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idK173829_s0_e2000

K173829.txt

purpose for submission

New device

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: k173829 B. Purpose for Submission: New device C. Measurand: Acid-β-glucocerebrosidase (ABG), acid-sphingomyelinase (ASM), acid-α-glucosidase (GAA), β-galactocerebrosidase (GALC), α-galactosidase A (GLA), α-L-iduronidase (IDUA) D. Type of Test: Quantitative mass spectrometric enzymatic activity assay E. Applicant: Wallac Oy, a subsidiary of PerkinElmer F. Proprietary and Established Names: NeoLSD MSMS kit G. Regulatory Information: 1. Regulation section: 862.1488 Lysosomal storage disorder newborn screening test system 2. Classification: II 3. Product code: PQW PQT PQU PQV 2 QCL QCM 4. Panel: Chemistry (75) H. Intended Use: 1. Intended use(s): See Indication(s) for use. 2. Indication(s) for use: The NeoLSD MSMS Kit is intended for the quantitative measurement of the activity of the enzymes acid-β-glucocerebrosidase (ABG), acid-sphingomyelinase (ASM), acid-α- glucosidase (GAA), β-galactocerebrosidase (GALC), α-galactosidase A (GLA), and α-L- iduronidase (IDUA) in dried blood spots (DBS) from newborn babies. The analysis of the enzymatic activity is intended as an aid in screening newborns for the following lysosomal storage disorders (LSD) respectively; Gaucher Disease, Niemann-Pick A/B Disease, Pompe Disease, Krabbe Disease, Fabry Disease, and mucopolysaccharidosis Type I (MPS I) Disease. 3. Special conditions for use statement(s): This test is not intended to diagnose lysosomal storage disorders. Test results are intended to be used in conjunction with other clinical and diagnostic findings, consistent with professional standards of practice, including confirmation by alternative methods, and clinical evaluation as appropriate. Known causes for anomalous analytical assay results are: - Sample not uniformly saturated with blood - Sample disk punched too close to the edge of the blood spot - Sample disk punched at the middle of the blood spot - Poorly collected specimens e.g. excessive milking or squeezing the puncture may cause hemolysis of the specimen or a mixture of tissue fluids with the specimen. Layering successive drops of blood in the specimen may affect the measured results. - Improperly dried specimens e.g. heating or stacking the specimen collection devices during the drying process - Humidity and moisture or exposure to direct sunlight are detrimental to the dried blood spot sample - Non-eluting blood spot due to deterioration of sample - Contamination of blood spot filter paper e.g. with fecal material 3 - It has been shown that female patients with the Fabry disorder may show normal GLA enzyme activities at birth but are later symptomatic - Hematocrit levels above 65% were found to interfere with the assay by increasing the measured ABG activity that could result in false negatives for Gaucher. Refer to the interference section for complete information about this interference. - Free (serum) hemoglobin above 16 g/dL was found to interfere with the assay by increasing the measured ABG, ASM and IDUA activity, that could result in false negative results for Gaucher, Niemann-Pick A/B, and mucopolysaccharidosis Type I (MPS I) Disease. Refer to the interference section for complete information about this interference. The NeoLSD MSMS kit may result in; - False negatives by not detecting Fabry disease in females - False positives by identifying pseudo deficiencies and carriers as affected for MPS I, Gaucher, and Pompe diseases - False negative by not detecting certain late onset forms for Pompe disease - False negatives by not detecting certain late onset forms for Fabry disease - Increase rate of false positives when the specimen is exposed to high temperature during shipping - The false negative rate is based on follow-up of subjects up to 4 years of age and on limited data from late onset forms of the disorders since it can take several years to identify a missed late onset case. - Certain late onset forms for Pompe disorder may have GAA enzymatic activity in the normal range and result in a false negative screening result. - Heterozygote female Fabry patients may present with normal GLA activity and not be detected by the NeoLSD MSMS kit. 4. Special instrument requirements: PerkinElmer TQD MSMS instrument system (k093916) I. Device Description: The NeoLSD MSMS kit consists of substrates, internal standards, and controls. The kit contains sufficient reagents and consumables to perform 960 assays (10 x 96-well plates). The contents of the kit are listed below: Component Contents Internal Standards Substrate Mix 1 vial or several vials of stable-isotope standards and designated substrates. The dried substrates and internal standards are a mixture of the 6 synthetic substrates, the corresponding 6 stable-isotope labeled internal standards, and sodium oleate DBS Controls C1, C2, C3 control levels on DBS cassettes, 4 manufactured from human blood with a hematocrit value of 45 - 50% Assay Buffer 1 bottle of 40 mL buffer, ready-for-use succinate buffered (pH 4.7) salt solution Extraction Solution Ethyl acetate Flow Solvent Reconstitution Solution The ready-for-use Flow Solvent contains acetonitrile, water, and formic acid Incubation / Sampling Plate 20 x 96-well microplate, U-bottomed Extraction Plate 10 x 96-deep well microplate Aluminum Foil Microplate Covers 10 x adhesive microplate covers Plate barcode labels 30 x plate barcodes J. Substantial Equivalence Information: 1. Predicate device name(s): SEEKER System 2. Predicate 510(k) number(s): DEN150035 3. Comparison with predicate: Similarities and Differences Item NeoLSD MSMS kit SEEKER System DEN150035 Indications for Use Quantitative measurement of the acid-β- glucocerebrosidase, acid-α- glucosidase, α-galactosidase A, and α-L-iduronidase in dried blood spots from newborn babies. The analysis of the enzymatic activity is intended as an aid in screening newborns for the following lysosomal storage disorders respectively; Gaucher Disease, Pompe Disease, Fabry Disease, and MPS I Disease. Same 5 Similarities and Differences Item NeoLSD MSMS kit SEEKER System DEN150035 Instrument / Software Platform PerkinElmer TQD instrument with MassLynx v4.1 firmware, with PerkinElmer 1525 sample pump, with PerkinElmer 2777c autosampler, with PerkinElmer NeoLynx v4.1 software and with the PerkinElmer MSMS Workstation Software Seeker Instrument with Spot Logic Software Measured enzymes IDUA GAA ABG GLA ASM GALC IDUA GAA ABG GLA Sample Type Punch from dried blood spot specimen Same Test Methodology Quantitative mass spectrometric enzymatic activity assay Quantitative fluorimetric enzymatic activity assay K. Standard/Guidance Document Referenced (if applicable): CLSI EP05-A3: Evaluation of precision of quantitative measurement procedures; Approved Guideline - Third Edition CLSI EP06-A: Evaluation of Linearity of Quantitative Measurement Procedures; A Statistical Approach; Approved Guideline CLSI EP07-A2: Interference Testing in Clinical Chemistry; Approved Guideline - Second Edition CLSI EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline- Second Edition CLSI EP25-A: Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline L. Test Principle: The NeoLSD MSMS kit evaluates enzyme activities by measuring the product generated when an enzyme reacts with a synthesized substrate to create a specific end product. The 6 activities of the six lysosomal enzymes present in a 3.2 mm punch from a dried blood spot are simultaneously measured by the NeoLSD MSMS assay. The punches are incubated with the assay reagent mixture which contains: · six substrates, one corresponding to each lysosomal enzyme · six stable-isotope mass-labeled internal standards (IS) each designed to chemically resemble each product generated · a buffer to maintain the reaction pH, and to carry inhibitors to limit activity from competing enzymes if present and additives to enhance the targeted enzyme reactions The amount of each product generated is directly proportional to the enzyme activity in the dried blood spot punch. The internal standards are deuterium labeled versions of the corresponding enzymatic products. The six enzymatic products and six internal standards are listed in the following table: Enzymatic product Molecular weight Internal Standard (IS) Molecular weight ABG P 383.34 ABG IS Purpose for submission:

idK173829_s0_e2000

K173829.txt

measurand

Acid-β-glucocerebrosidase (ABG), acid-sphingomyelinase (ASM), acid-α-glucosidase (GAA), β-galactocerebrosidase (GALC), α-galactosidase A (GLA), α-L-iduronidase (IDUA)

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: k173829 B. Purpose for Submission: New device C. Measurand: Acid-β-glucocerebrosidase (ABG), acid-sphingomyelinase (ASM), acid-α-glucosidase (GAA), β-galactocerebrosidase (GALC), α-galactosidase A (GLA), α-L-iduronidase (IDUA) D. Type of Test: Quantitative mass spectrometric enzymatic activity assay E. Applicant: Wallac Oy, a subsidiary of PerkinElmer F. Proprietary and Established Names: NeoLSD MSMS kit G. Regulatory Information: 1. Regulation section: 862.1488 Lysosomal storage disorder newborn screening test system 2. Classification: II 3. Product code: PQW PQT PQU PQV 2 QCL QCM 4. Panel: Chemistry (75) H. Intended Use: 1. Intended use(s): See Indication(s) for use. 2. Indication(s) for use: The NeoLSD MSMS Kit is intended for the quantitative measurement of the activity of the enzymes acid-β-glucocerebrosidase (ABG), acid-sphingomyelinase (ASM), acid-α- glucosidase (GAA), β-galactocerebrosidase (GALC), α-galactosidase A (GLA), and α-L- iduronidase (IDUA) in dried blood spots (DBS) from newborn babies. The analysis of the enzymatic activity is intended as an aid in screening newborns for the following lysosomal storage disorders (LSD) respectively; Gaucher Disease, Niemann-Pick A/B Disease, Pompe Disease, Krabbe Disease, Fabry Disease, and mucopolysaccharidosis Type I (MPS I) Disease. 3. Special conditions for use statement(s): This test is not intended to diagnose lysosomal storage disorders. Test results are intended to be used in conjunction with other clinical and diagnostic findings, consistent with professional standards of practice, including confirmation by alternative methods, and clinical evaluation as appropriate. Known causes for anomalous analytical assay results are: - Sample not uniformly saturated with blood - Sample disk punched too close to the edge of the blood spot - Sample disk punched at the middle of the blood spot - Poorly collected specimens e.g. excessive milking or squeezing the puncture may cause hemolysis of the specimen or a mixture of tissue fluids with the specimen. Layering successive drops of blood in the specimen may affect the measured results. - Improperly dried specimens e.g. heating or stacking the specimen collection devices during the drying process - Humidity and moisture or exposure to direct sunlight are detrimental to the dried blood spot sample - Non-eluting blood spot due to deterioration of sample - Contamination of blood spot filter paper e.g. with fecal material 3 - It has been shown that female patients with the Fabry disorder may show normal GLA enzyme activities at birth but are later symptomatic - Hematocrit levels above 65% were found to interfere with the assay by increasing the measured ABG activity that could result in false negatives for Gaucher. Refer to the interference section for complete information about this interference. - Free (serum) hemoglobin above 16 g/dL was found to interfere with the assay by increasing the measured ABG, ASM and IDUA activity, that could result in false negative results for Gaucher, Niemann-Pick A/B, and mucopolysaccharidosis Type I (MPS I) Disease. Refer to the interference section for complete information about this interference. The NeoLSD MSMS kit may result in; - False negatives by not detecting Fabry disease in females - False positives by identifying pseudo deficiencies and carriers as affected for MPS I, Gaucher, and Pompe diseases - False negative by not detecting certain late onset forms for Pompe disease - False negatives by not detecting certain late onset forms for Fabry disease - Increase rate of false positives when the specimen is exposed to high temperature during shipping - The false negative rate is based on follow-up of subjects up to 4 years of age and on limited data from late onset forms of the disorders since it can take several years to identify a missed late onset case. - Certain late onset forms for Pompe disorder may have GAA enzymatic activity in the normal range and result in a false negative screening result. - Heterozygote female Fabry patients may present with normal GLA activity and not be detected by the NeoLSD MSMS kit. 4. Special instrument requirements: PerkinElmer TQD MSMS instrument system (k093916) I. Device Description: The NeoLSD MSMS kit consists of substrates, internal standards, and controls. The kit contains sufficient reagents and consumables to perform 960 assays (10 x 96-well plates). The contents of the kit are listed below: Component Contents Internal Standards Substrate Mix 1 vial or several vials of stable-isotope standards and designated substrates. The dried substrates and internal standards are a mixture of the 6 synthetic substrates, the corresponding 6 stable-isotope labeled internal standards, and sodium oleate DBS Controls C1, C2, C3 control levels on DBS cassettes, 4 manufactured from human blood with a hematocrit value of 45 - 50% Assay Buffer 1 bottle of 40 mL buffer, ready-for-use succinate buffered (pH 4.7) salt solution Extraction Solution Ethyl acetate Flow Solvent Reconstitution Solution The ready-for-use Flow Solvent contains acetonitrile, water, and formic acid Incubation / Sampling Plate 20 x 96-well microplate, U-bottomed Extraction Plate 10 x 96-deep well microplate Aluminum Foil Microplate Covers 10 x adhesive microplate covers Plate barcode labels 30 x plate barcodes J. Substantial Equivalence Information: 1. Predicate device name(s): SEEKER System 2. Predicate 510(k) number(s): DEN150035 3. Comparison with predicate: Similarities and Differences Item NeoLSD MSMS kit SEEKER System DEN150035 Indications for Use Quantitative measurement of the acid-β- glucocerebrosidase, acid-α- glucosidase, α-galactosidase A, and α-L-iduronidase in dried blood spots from newborn babies. The analysis of the enzymatic activity is intended as an aid in screening newborns for the following lysosomal storage disorders respectively; Gaucher Disease, Pompe Disease, Fabry Disease, and MPS I Disease. Same 5 Similarities and Differences Item NeoLSD MSMS kit SEEKER System DEN150035 Instrument / Software Platform PerkinElmer TQD instrument with MassLynx v4.1 firmware, with PerkinElmer 1525 sample pump, with PerkinElmer 2777c autosampler, with PerkinElmer NeoLynx v4.1 software and with the PerkinElmer MSMS Workstation Software Seeker Instrument with Spot Logic Software Measured enzymes IDUA GAA ABG GLA ASM GALC IDUA GAA ABG GLA Sample Type Punch from dried blood spot specimen Same Test Methodology Quantitative mass spectrometric enzymatic activity assay Quantitative fluorimetric enzymatic activity assay K. Standard/Guidance Document Referenced (if applicable): CLSI EP05-A3: Evaluation of precision of quantitative measurement procedures; Approved Guideline - Third Edition CLSI EP06-A: Evaluation of Linearity of Quantitative Measurement Procedures; A Statistical Approach; Approved Guideline CLSI EP07-A2: Interference Testing in Clinical Chemistry; Approved Guideline - Second Edition CLSI EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline- Second Edition CLSI EP25-A: Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline L. Test Principle: The NeoLSD MSMS kit evaluates enzyme activities by measuring the product generated when an enzyme reacts with a synthesized substrate to create a specific end product. The 6 activities of the six lysosomal enzymes present in a 3.2 mm punch from a dried blood spot are simultaneously measured by the NeoLSD MSMS assay. The punches are incubated with the assay reagent mixture which contains: · six substrates, one corresponding to each lysosomal enzyme · six stable-isotope mass-labeled internal standards (IS) each designed to chemically resemble each product generated · a buffer to maintain the reaction pH, and to carry inhibitors to limit activity from competing enzymes if present and additives to enhance the targeted enzyme reactions The amount of each product generated is directly proportional to the enzyme activity in the dried blood spot punch. The internal standards are deuterium labeled versions of the corresponding enzymatic products. The six enzymatic products and six internal standards are listed in the following table: Enzymatic product Molecular weight Internal Standard (IS) Molecular weight ABG P 383.34 ABG IS Measurand:

idK173829_s0_e2000

K173829.txt

type of test

Quantitative mass spectrometric enzymatic activity assay

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: k173829 B. Purpose for Submission: New device C. Measurand: Acid-β-glucocerebrosidase (ABG), acid-sphingomyelinase (ASM), acid-α-glucosidase (GAA), β-galactocerebrosidase (GALC), α-galactosidase A (GLA), α-L-iduronidase (IDUA) D. Type of Test: Quantitative mass spectrometric enzymatic activity assay E. Applicant: Wallac Oy, a subsidiary of PerkinElmer F. Proprietary and Established Names: NeoLSD MSMS kit G. Regulatory Information: 1. Regulation section: 862.1488 Lysosomal storage disorder newborn screening test system 2. Classification: II 3. Product code: PQW PQT PQU PQV 2 QCL QCM 4. Panel: Chemistry (75) H. Intended Use: 1. Intended use(s): See Indication(s) for use. 2. Indication(s) for use: The NeoLSD MSMS Kit is intended for the quantitative measurement of the activity of the enzymes acid-β-glucocerebrosidase (ABG), acid-sphingomyelinase (ASM), acid-α- glucosidase (GAA), β-galactocerebrosidase (GALC), α-galactosidase A (GLA), and α-L- iduronidase (IDUA) in dried blood spots (DBS) from newborn babies. The analysis of the enzymatic activity is intended as an aid in screening newborns for the following lysosomal storage disorders (LSD) respectively; Gaucher Disease, Niemann-Pick A/B Disease, Pompe Disease, Krabbe Disease, Fabry Disease, and mucopolysaccharidosis Type I (MPS I) Disease. 3. Special conditions for use statement(s): This test is not intended to diagnose lysosomal storage disorders. Test results are intended to be used in conjunction with other clinical and diagnostic findings, consistent with professional standards of practice, including confirmation by alternative methods, and clinical evaluation as appropriate. Known causes for anomalous analytical assay results are: - Sample not uniformly saturated with blood - Sample disk punched too close to the edge of the blood spot - Sample disk punched at the middle of the blood spot - Poorly collected specimens e.g. excessive milking or squeezing the puncture may cause hemolysis of the specimen or a mixture of tissue fluids with the specimen. Layering successive drops of blood in the specimen may affect the measured results. - Improperly dried specimens e.g. heating or stacking the specimen collection devices during the drying process - Humidity and moisture or exposure to direct sunlight are detrimental to the dried blood spot sample - Non-eluting blood spot due to deterioration of sample - Contamination of blood spot filter paper e.g. with fecal material 3 - It has been shown that female patients with the Fabry disorder may show normal GLA enzyme activities at birth but are later symptomatic - Hematocrit levels above 65% were found to interfere with the assay by increasing the measured ABG activity that could result in false negatives for Gaucher. Refer to the interference section for complete information about this interference. - Free (serum) hemoglobin above 16 g/dL was found to interfere with the assay by increasing the measured ABG, ASM and IDUA activity, that could result in false negative results for Gaucher, Niemann-Pick A/B, and mucopolysaccharidosis Type I (MPS I) Disease. Refer to the interference section for complete information about this interference. The NeoLSD MSMS kit may result in; - False negatives by not detecting Fabry disease in females - False positives by identifying pseudo deficiencies and carriers as affected for MPS I, Gaucher, and Pompe diseases - False negative by not detecting certain late onset forms for Pompe disease - False negatives by not detecting certain late onset forms for Fabry disease - Increase rate of false positives when the specimen is exposed to high temperature during shipping - The false negative rate is based on follow-up of subjects up to 4 years of age and on limited data from late onset forms of the disorders since it can take several years to identify a missed late onset case. - Certain late onset forms for Pompe disorder may have GAA enzymatic activity in the normal range and result in a false negative screening result. - Heterozygote female Fabry patients may present with normal GLA activity and not be detected by the NeoLSD MSMS kit. 4. Special instrument requirements: PerkinElmer TQD MSMS instrument system (k093916) I. Device Description: The NeoLSD MSMS kit consists of substrates, internal standards, and controls. The kit contains sufficient reagents and consumables to perform 960 assays (10 x 96-well plates). The contents of the kit are listed below: Component Contents Internal Standards Substrate Mix 1 vial or several vials of stable-isotope standards and designated substrates. The dried substrates and internal standards are a mixture of the 6 synthetic substrates, the corresponding 6 stable-isotope labeled internal standards, and sodium oleate DBS Controls C1, C2, C3 control levels on DBS cassettes, 4 manufactured from human blood with a hematocrit value of 45 - 50% Assay Buffer 1 bottle of 40 mL buffer, ready-for-use succinate buffered (pH 4.7) salt solution Extraction Solution Ethyl acetate Flow Solvent Reconstitution Solution The ready-for-use Flow Solvent contains acetonitrile, water, and formic acid Incubation / Sampling Plate 20 x 96-well microplate, U-bottomed Extraction Plate 10 x 96-deep well microplate Aluminum Foil Microplate Covers 10 x adhesive microplate covers Plate barcode labels 30 x plate barcodes J. Substantial Equivalence Information: 1. Predicate device name(s): SEEKER System 2. Predicate 510(k) number(s): DEN150035 3. Comparison with predicate: Similarities and Differences Item NeoLSD MSMS kit SEEKER System DEN150035 Indications for Use Quantitative measurement of the acid-β- glucocerebrosidase, acid-α- glucosidase, α-galactosidase A, and α-L-iduronidase in dried blood spots from newborn babies. The analysis of the enzymatic activity is intended as an aid in screening newborns for the following lysosomal storage disorders respectively; Gaucher Disease, Pompe Disease, Fabry Disease, and MPS I Disease. Same 5 Similarities and Differences Item NeoLSD MSMS kit SEEKER System DEN150035 Instrument / Software Platform PerkinElmer TQD instrument with MassLynx v4.1 firmware, with PerkinElmer 1525 sample pump, with PerkinElmer 2777c autosampler, with PerkinElmer NeoLynx v4.1 software and with the PerkinElmer MSMS Workstation Software Seeker Instrument with Spot Logic Software Measured enzymes IDUA GAA ABG GLA ASM GALC IDUA GAA ABG GLA Sample Type Punch from dried blood spot specimen Same Test Methodology Quantitative mass spectrometric enzymatic activity assay Quantitative fluorimetric enzymatic activity assay K. Standard/Guidance Document Referenced (if applicable): CLSI EP05-A3: Evaluation of precision of quantitative measurement procedures; Approved Guideline - Third Edition CLSI EP06-A: Evaluation of Linearity of Quantitative Measurement Procedures; A Statistical Approach; Approved Guideline CLSI EP07-A2: Interference Testing in Clinical Chemistry; Approved Guideline - Second Edition CLSI EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline- Second Edition CLSI EP25-A: Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline L. Test Principle: The NeoLSD MSMS kit evaluates enzyme activities by measuring the product generated when an enzyme reacts with a synthesized substrate to create a specific end product. The 6 activities of the six lysosomal enzymes present in a 3.2 mm punch from a dried blood spot are simultaneously measured by the NeoLSD MSMS assay. The punches are incubated with the assay reagent mixture which contains: · six substrates, one corresponding to each lysosomal enzyme · six stable-isotope mass-labeled internal standards (IS) each designed to chemically resemble each product generated · a buffer to maintain the reaction pH, and to carry inhibitors to limit activity from competing enzymes if present and additives to enhance the targeted enzyme reactions The amount of each product generated is directly proportional to the enzyme activity in the dried blood spot punch. The internal standards are deuterium labeled versions of the corresponding enzymatic products. The six enzymatic products and six internal standards are listed in the following table: Enzymatic product Molecular weight Internal Standard (IS) Molecular weight ABG P 383.34 ABG IS Type of test:

idK173829_s0_e2000

K173829.txt

classification

II

k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: k173829 B. Purpose for Submission: New device C. Measurand: Acid-β-glucocerebrosidase (ABG), acid-sphingomyelinase (ASM), acid-α-glucosidase (GAA), β-galactocerebrosidase (GALC), α-galactosidase A (GLA), α-L-iduronidase (IDUA) D. Type of Test: Quantitative mass spectrometric enzymatic activity assay E. Applicant: Wallac Oy, a subsidiary of PerkinElmer F. Proprietary and Established Names: NeoLSD MSMS kit G. Regulatory Information: 1. Regulation section: 862.1488 Lysosomal storage disorder newborn screening test system 2. Classification: II 3. Product code: PQW PQT PQU PQV 2 QCL QCM 4. Panel: Chemistry (75) H. Intended Use: 1. Intended use(s): See Indication(s) for use. 2. Indication(s) for use: The NeoLSD MSMS Kit is intended for the quantitative measurement of the activity of the enzymes acid-β-glucocerebrosidase (ABG), acid-sphingomyelinase (ASM), acid-α- glucosidase (GAA), β-galactocerebrosidase (GALC), α-galactosidase A (GLA), and α-L- iduronidase (IDUA) in dried blood spots (DBS) from newborn babies. The analysis of the enzymatic activity is intended as an aid in screening newborns for the following lysosomal storage disorders (LSD) respectively; Gaucher Disease, Niemann-Pick A/B Disease, Pompe Disease, Krabbe Disease, Fabry Disease, and mucopolysaccharidosis Type I (MPS I) Disease. 3. Special conditions for use statement(s): This test is not intended to diagnose lysosomal storage disorders. Test results are intended to be used in conjunction with other clinical and diagnostic findings, consistent with professional standards of practice, including confirmation by alternative methods, and clinical evaluation as appropriate. Known causes for anomalous analytical assay results are: - Sample not uniformly saturated with blood - Sample disk punched too close to the edge of the blood spot - Sample disk punched at the middle of the blood spot - Poorly collected specimens e.g. excessive milking or squeezing the puncture may cause hemolysis of the specimen or a mixture of tissue fluids with the specimen. Layering successive drops of blood in the specimen may affect the measured results. - Improperly dried specimens e.g. heating or stacking the specimen collection devices during the drying process - Humidity and moisture or exposure to direct sunlight are detrimental to the dried blood spot sample - Non-eluting blood spot due to deterioration of sample - Contamination of blood spot filter paper e.g. with fecal material 3 - It has been shown that female patients with the Fabry disorder may show normal GLA enzyme activities at birth but are later symptomatic - Hematocrit levels above 65% were found to interfere with the assay by increasing the measured ABG activity that could result in false negatives for Gaucher. Refer to the interference section for complete information about this interference. - Free (serum) hemoglobin above 16 g/dL was found to interfere with the assay by increasing the measured ABG, ASM and IDUA activity, that could result in false negative results for Gaucher, Niemann-Pick A/B, and mucopolysaccharidosis Type I (MPS I) Disease. Refer to the interference section for complete information about this interference. The NeoLSD MSMS kit may result in; - False negatives by not detecting Fabry disease in females - False positives by identifying pseudo deficiencies and carriers as affected for MPS I, Gaucher, and Pompe diseases - False negative by not detecting certain late onset forms for Pompe disease - False negatives by not detecting certain late onset forms for Fabry disease - Increase rate of false positives when the specimen is exposed to high temperature during shipping - The false negative rate is based on follow-up of subjects up to 4 years of age and on limited data from late onset forms of the disorders since it can take several years to identify a missed late onset case. - Certain late onset forms for Pompe disorder may have GAA enzymatic activity in the normal range and result in a false negative screening result. - Heterozygote female Fabry patients may present with normal GLA activity and not be detected by the NeoLSD MSMS kit. 4. Special instrument requirements: PerkinElmer TQD MSMS instrument system (k093916) I. Device Description: The NeoLSD MSMS kit consists of substrates, internal standards, and controls. The kit contains sufficient reagents and consumables to perform 960 assays (10 x 96-well plates). The contents of the kit are listed below: Component Contents Internal Standards Substrate Mix 1 vial or several vials of stable-isotope standards and designated substrates. The dried substrates and internal standards are a mixture of the 6 synthetic substrates, the corresponding 6 stable-isotope labeled internal standards, and sodium oleate DBS Controls C1, C2, C3 control levels on DBS cassettes, 4 manufactured from human blood with a hematocrit value of 45 - 50% Assay Buffer 1 bottle of 40 mL buffer, ready-for-use succinate buffered (pH 4.7) salt solution Extraction Solution Ethyl acetate Flow Solvent Reconstitution Solution The ready-for-use Flow Solvent contains acetonitrile, water, and formic acid Incubation / Sampling Plate 20 x 96-well microplate, U-bottomed Extraction Plate 10 x 96-deep well microplate Aluminum Foil Microplate Covers 10 x adhesive microplate covers Plate barcode labels 30 x plate barcodes J. Substantial Equivalence Information: 1. Predicate device name(s): SEEKER System 2. Predicate 510(k) number(s): DEN150035 3. Comparison with predicate: Similarities and Differences Item NeoLSD MSMS kit SEEKER System DEN150035 Indications for Use Quantitative measurement of the acid-β- glucocerebrosidase, acid-α- glucosidase, α-galactosidase A, and α-L-iduronidase in dried blood spots from newborn babies. The analysis of the enzymatic activity is intended as an aid in screening newborns for the following lysosomal storage disorders respectively; Gaucher Disease, Pompe Disease, Fabry Disease, and MPS I Disease. Same 5 Similarities and Differences Item NeoLSD MSMS kit SEEKER System DEN150035 Instrument / Software Platform PerkinElmer TQD instrument with MassLynx v4.1 firmware, with PerkinElmer 1525 sample pump, with PerkinElmer 2777c autosampler, with PerkinElmer NeoLynx v4.1 software and with the PerkinElmer MSMS Workstation Software Seeker Instrument with Spot Logic Software Measured enzymes IDUA GAA ABG GLA ASM GALC IDUA GAA ABG GLA Sample Type Punch from dried blood spot specimen Same Test Methodology Quantitative mass spectrometric enzymatic activity assay Quantitative fluorimetric enzymatic activity assay K. Standard/Guidance Document Referenced (if applicable): CLSI EP05-A3: Evaluation of precision of quantitative measurement procedures; Approved Guideline - Third Edition CLSI EP06-A: Evaluation of Linearity of Quantitative Measurement Procedures; A Statistical Approach; Approved Guideline CLSI EP07-A2: Interference Testing in Clinical Chemistry; Approved Guideline - Second Edition CLSI EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline- Second Edition CLSI EP25-A: Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline L. Test Principle: The NeoLSD MSMS kit evaluates enzyme activities by measuring the product generated when an enzyme reacts with a synthesized substrate to create a specific end product. The 6 activities of the six lysosomal enzymes present in a 3.2 mm punch from a dried blood spot are simultaneously measured by the NeoLSD MSMS assay. The punches are incubated with the assay reagent mixture which contains: · six substrates, one corresponding to each lysosomal enzyme · six stable-isotope mass-labeled internal standards (IS) each designed to chemically resemble each product generated · a buffer to maintain the reaction pH, and to carry inhibitors to limit activity from competing enzymes if present and additives to enhance the targeted enzyme reactions The amount of each product generated is directly proportional to the enzyme activity in the dried blood spot punch. The internal standards are deuterium labeled versions of the corresponding enzymatic products. The six enzymatic products and six internal standards are listed in the following table: Enzymatic product Molecular weight Internal Standard (IS) Molecular weight ABG P 383.34 ABG IS Classification:

idK173829_s0_e2000

K173829.txt

panel

Chemistry (75)

(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: k173829 B. Purpose for Submission: New device C. Measurand: Acid-β-glucocerebrosidase (ABG), acid-sphingomyelinase (ASM), acid-α-glucosidase (GAA), β-galactocerebrosidase (GALC), α-galactosidase A (GLA), α-L-iduronidase (IDUA) D. Type of Test: Quantitative mass spectrometric enzymatic activity assay E. Applicant: Wallac Oy, a subsidiary of PerkinElmer F. Proprietary and Established Names: NeoLSD MSMS kit G. Regulatory Information: 1. Regulation section: 862.1488 Lysosomal storage disorder newborn screening test system 2. Classification: II 3. Product code: PQW PQT PQU PQV 2 QCL QCM 4. Panel: Chemistry (75) H. Intended Use: 1. Intended use(s): See Indication(s) for use. 2. Indication(s) for use: The NeoLSD MSMS Kit is intended for the quantitative measurement of the activity of the enzymes acid-β-glucocerebrosidase (ABG), acid-sphingomyelinase (ASM), acid-α- glucosidase (GAA), β-galactocerebrosidase (GALC), α-galactosidase A (GLA), and α-L- iduronidase (IDUA) in dried blood spots (DBS) from newborn babies. The analysis of the enzymatic activity is intended as an aid in screening newborns for the following lysosomal storage disorders (LSD) respectively; Gaucher Disease, Niemann-Pick A/B Disease, Pompe Disease, Krabbe Disease, Fabry Disease, and mucopolysaccharidosis Type I (MPS I) Disease. 3. Special conditions for use statement(s): This test is not intended to diagnose lysosomal storage disorders. Test results are intended to be used in conjunction with other clinical and diagnostic findings, consistent with professional standards of practice, including confirmation by alternative methods, and clinical evaluation as appropriate. Known causes for anomalous analytical assay results are: - Sample not uniformly saturated with blood - Sample disk punched too close to the edge of the blood spot - Sample disk punched at the middle of the blood spot - Poorly collected specimens e.g. excessive milking or squeezing the puncture may cause hemolysis of the specimen or a mixture of tissue fluids with the specimen. Layering successive drops of blood in the specimen may affect the measured results. - Improperly dried specimens e.g. heating or stacking the specimen collection devices during the drying process - Humidity and moisture or exposure to direct sunlight are detrimental to the dried blood spot sample - Non-eluting blood spot due to deterioration of sample - Contamination of blood spot filter paper e.g. with fecal material 3 - It has been shown that female patients with the Fabry disorder may show normal GLA enzyme activities at birth but are later symptomatic - Hematocrit levels above 65% were found to interfere with the assay by increasing the measured ABG activity that could result in false negatives for Gaucher. Refer to the interference section for complete information about this interference. - Free (serum) hemoglobin above 16 g/dL was found to interfere with the assay by increasing the measured ABG, ASM and IDUA activity, that could result in false negative results for Gaucher, Niemann-Pick A/B, and mucopolysaccharidosis Type I (MPS I) Disease. Refer to the interference section for complete information about this interference. The NeoLSD MSMS kit may result in; - False negatives by not detecting Fabry disease in females - False positives by identifying pseudo deficiencies and carriers as affected for MPS I, Gaucher, and Pompe diseases - False negative by not detecting certain late onset forms for Pompe disease - False negatives by not detecting certain late onset forms for Fabry disease - Increase rate of false positives when the specimen is exposed to high temperature during shipping - The false negative rate is based on follow-up of subjects up to 4 years of age and on limited data from late onset forms of the disorders since it can take several years to identify a missed late onset case. - Certain late onset forms for Pompe disorder may have GAA enzymatic activity in the normal range and result in a false negative screening result. - Heterozygote female Fabry patients may present with normal GLA activity and not be detected by the NeoLSD MSMS kit. 4. Special instrument requirements: PerkinElmer TQD MSMS instrument system (k093916) I. Device Description: The NeoLSD MSMS kit consists of substrates, internal standards, and controls. The kit contains sufficient reagents and consumables to perform 960 assays (10 x 96-well plates). The contents of the kit are listed below: Component Contents Internal Standards Substrate Mix 1 vial or several vials of stable-isotope standards and designated substrates. The dried substrates and internal standards are a mixture of the 6 synthetic substrates, the corresponding 6 stable-isotope labeled internal standards, and sodium oleate DBS Controls C1, C2, C3 control levels on DBS cassettes, 4 manufactured from human blood with a hematocrit value of 45 - 50% Assay Buffer 1 bottle of 40 mL buffer, ready-for-use succinate buffered (pH 4.7) salt solution Extraction Solution Ethyl acetate Flow Solvent Reconstitution Solution The ready-for-use Flow Solvent contains acetonitrile, water, and formic acid Incubation / Sampling Plate 20 x 96-well microplate, U-bottomed Extraction Plate 10 x 96-deep well microplate Aluminum Foil Microplate Covers 10 x adhesive microplate covers Plate barcode labels 30 x plate barcodes J. Substantial Equivalence Information: 1. Predicate device name(s): SEEKER System 2. Predicate 510(k) number(s): DEN150035 3. Comparison with predicate: Similarities and Differences Item NeoLSD MSMS kit SEEKER System DEN150035 Indications for Use Quantitative measurement of the acid-β- glucocerebrosidase, acid-α- glucosidase, α-galactosidase A, and α-L-iduronidase in dried blood spots from newborn babies. The analysis of the enzymatic activity is intended as an aid in screening newborns for the following lysosomal storage disorders respectively; Gaucher Disease, Pompe Disease, Fabry Disease, and MPS I Disease. Same 5 Similarities and Differences Item NeoLSD MSMS kit SEEKER System DEN150035 Instrument / Software Platform PerkinElmer TQD instrument with MassLynx v4.1 firmware, with PerkinElmer 1525 sample pump, with PerkinElmer 2777c autosampler, with PerkinElmer NeoLynx v4.1 software and with the PerkinElmer MSMS Workstation Software Seeker Instrument with Spot Logic Software Measured enzymes IDUA GAA ABG GLA ASM GALC IDUA GAA ABG GLA Sample Type Punch from dried blood spot specimen Same Test Methodology Quantitative mass spectrometric enzymatic activity assay Quantitative fluorimetric enzymatic activity assay K. Standard/Guidance Document Referenced (if applicable): CLSI EP05-A3: Evaluation of precision of quantitative measurement procedures; Approved Guideline - Third Edition CLSI EP06-A: Evaluation of Linearity of Quantitative Measurement Procedures; A Statistical Approach; Approved Guideline CLSI EP07-A2: Interference Testing in Clinical Chemistry; Approved Guideline - Second Edition CLSI EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline- Second Edition CLSI EP25-A: Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline L. Test Principle: The NeoLSD MSMS kit evaluates enzyme activities by measuring the product generated when an enzyme reacts with a synthesized substrate to create a specific end product. The 6 activities of the six lysosomal enzymes present in a 3.2 mm punch from a dried blood spot are simultaneously measured by the NeoLSD MSMS assay. The punches are incubated with the assay reagent mixture which contains: · six substrates, one corresponding to each lysosomal enzyme · six stable-isotope mass-labeled internal standards (IS) each designed to chemically resemble each product generated · a buffer to maintain the reaction pH, and to carry inhibitors to limit activity from competing enzymes if present and additives to enhance the targeted enzyme reactions The amount of each product generated is directly proportional to the enzyme activity in the dried blood spot punch. The internal standards are deuterium labeled versions of the corresponding enzymatic products. The six enzymatic products and six internal standards are listed in the following table: Enzymatic product Molecular weight Internal Standard (IS) Molecular weight ABG P 383.34 ABG IS Panel:

idK173829_s0_e2000

K173829.txt

intended use

See Indication(s) for use.

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: k173829 B. Purpose for Submission: New device C. Measurand: Acid-β-glucocerebrosidase (ABG), acid-sphingomyelinase (ASM), acid-α-glucosidase (GAA), β-galactocerebrosidase (GALC), α-galactosidase A (GLA), α-L-iduronidase (IDUA) D. Type of Test: Quantitative mass spectrometric enzymatic activity assay E. Applicant: Wallac Oy, a subsidiary of PerkinElmer F. Proprietary and Established Names: NeoLSD MSMS kit G. Regulatory Information: 1. Regulation section: 862.1488 Lysosomal storage disorder newborn screening test system 2. Classification: II 3. Product code: PQW PQT PQU PQV 2 QCL QCM 4. Panel: Chemistry (75) H. Intended Use: 1. Intended use(s): See Indication(s) for use. 2. Indication(s) for use: The NeoLSD MSMS Kit is intended for the quantitative measurement of the activity of the enzymes acid-β-glucocerebrosidase (ABG), acid-sphingomyelinase (ASM), acid-α- glucosidase (GAA), β-galactocerebrosidase (GALC), α-galactosidase A (GLA), and α-L- iduronidase (IDUA) in dried blood spots (DBS) from newborn babies. The analysis of the enzymatic activity is intended as an aid in screening newborns for the following lysosomal storage disorders (LSD) respectively; Gaucher Disease, Niemann-Pick A/B Disease, Pompe Disease, Krabbe Disease, Fabry Disease, and mucopolysaccharidosis Type I (MPS I) Disease. 3. Special conditions for use statement(s): This test is not intended to diagnose lysosomal storage disorders. Test results are intended to be used in conjunction with other clinical and diagnostic findings, consistent with professional standards of practice, including confirmation by alternative methods, and clinical evaluation as appropriate. Known causes for anomalous analytical assay results are: - Sample not uniformly saturated with blood - Sample disk punched too close to the edge of the blood spot - Sample disk punched at the middle of the blood spot - Poorly collected specimens e.g. excessive milking or squeezing the puncture may cause hemolysis of the specimen or a mixture of tissue fluids with the specimen. Layering successive drops of blood in the specimen may affect the measured results. - Improperly dried specimens e.g. heating or stacking the specimen collection devices during the drying process - Humidity and moisture or exposure to direct sunlight are detrimental to the dried blood spot sample - Non-eluting blood spot due to deterioration of sample - Contamination of blood spot filter paper e.g. with fecal material 3 - It has been shown that female patients with the Fabry disorder may show normal GLA enzyme activities at birth but are later symptomatic - Hematocrit levels above 65% were found to interfere with the assay by increasing the measured ABG activity that could result in false negatives for Gaucher. Refer to the interference section for complete information about this interference. - Free (serum) hemoglobin above 16 g/dL was found to interfere with the assay by increasing the measured ABG, ASM and IDUA activity, that could result in false negative results for Gaucher, Niemann-Pick A/B, and mucopolysaccharidosis Type I (MPS I) Disease. Refer to the interference section for complete information about this interference. The NeoLSD MSMS kit may result in; - False negatives by not detecting Fabry disease in females - False positives by identifying pseudo deficiencies and carriers as affected for MPS I, Gaucher, and Pompe diseases - False negative by not detecting certain late onset forms for Pompe disease - False negatives by not detecting certain late onset forms for Fabry disease - Increase rate of false positives when the specimen is exposed to high temperature during shipping - The false negative rate is based on follow-up of subjects up to 4 years of age and on limited data from late onset forms of the disorders since it can take several years to identify a missed late onset case. - Certain late onset forms for Pompe disorder may have GAA enzymatic activity in the normal range and result in a false negative screening result. - Heterozygote female Fabry patients may present with normal GLA activity and not be detected by the NeoLSD MSMS kit. 4. Special instrument requirements: PerkinElmer TQD MSMS instrument system (k093916) I. Device Description: The NeoLSD MSMS kit consists of substrates, internal standards, and controls. The kit contains sufficient reagents and consumables to perform 960 assays (10 x 96-well plates). The contents of the kit are listed below: Component Contents Internal Standards Substrate Mix 1 vial or several vials of stable-isotope standards and designated substrates. The dried substrates and internal standards are a mixture of the 6 synthetic substrates, the corresponding 6 stable-isotope labeled internal standards, and sodium oleate DBS Controls C1, C2, C3 control levels on DBS cassettes, 4 manufactured from human blood with a hematocrit value of 45 - 50% Assay Buffer 1 bottle of 40 mL buffer, ready-for-use succinate buffered (pH 4.7) salt solution Extraction Solution Ethyl acetate Flow Solvent Reconstitution Solution The ready-for-use Flow Solvent contains acetonitrile, water, and formic acid Incubation / Sampling Plate 20 x 96-well microplate, U-bottomed Extraction Plate 10 x 96-deep well microplate Aluminum Foil Microplate Covers 10 x adhesive microplate covers Plate barcode labels 30 x plate barcodes J. Substantial Equivalence Information: 1. Predicate device name(s): SEEKER System 2. Predicate 510(k) number(s): DEN150035 3. Comparison with predicate: Similarities and Differences Item NeoLSD MSMS kit SEEKER System DEN150035 Indications for Use Quantitative measurement of the acid-β- glucocerebrosidase, acid-α- glucosidase, α-galactosidase A, and α-L-iduronidase in dried blood spots from newborn babies. The analysis of the enzymatic activity is intended as an aid in screening newborns for the following lysosomal storage disorders respectively; Gaucher Disease, Pompe Disease, Fabry Disease, and MPS I Disease. Same 5 Similarities and Differences Item NeoLSD MSMS kit SEEKER System DEN150035 Instrument / Software Platform PerkinElmer TQD instrument with MassLynx v4.1 firmware, with PerkinElmer 1525 sample pump, with PerkinElmer 2777c autosampler, with PerkinElmer NeoLynx v4.1 software and with the PerkinElmer MSMS Workstation Software Seeker Instrument with Spot Logic Software Measured enzymes IDUA GAA ABG GLA ASM GALC IDUA GAA ABG GLA Sample Type Punch from dried blood spot specimen Same Test Methodology Quantitative mass spectrometric enzymatic activity assay Quantitative fluorimetric enzymatic activity assay K. Standard/Guidance Document Referenced (if applicable): CLSI EP05-A3: Evaluation of precision of quantitative measurement procedures; Approved Guideline - Third Edition CLSI EP06-A: Evaluation of Linearity of Quantitative Measurement Procedures; A Statistical Approach; Approved Guideline CLSI EP07-A2: Interference Testing in Clinical Chemistry; Approved Guideline - Second Edition CLSI EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline- Second Edition CLSI EP25-A: Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline L. Test Principle: The NeoLSD MSMS kit evaluates enzyme activities by measuring the product generated when an enzyme reacts with a synthesized substrate to create a specific end product. The 6 activities of the six lysosomal enzymes present in a 3.2 mm punch from a dried blood spot are simultaneously measured by the NeoLSD MSMS assay. The punches are incubated with the assay reagent mixture which contains: · six substrates, one corresponding to each lysosomal enzyme · six stable-isotope mass-labeled internal standards (IS) each designed to chemically resemble each product generated · a buffer to maintain the reaction pH, and to carry inhibitors to limit activity from competing enzymes if present and additives to enhance the targeted enzyme reactions The amount of each product generated is directly proportional to the enzyme activity in the dried blood spot punch. The internal standards are deuterium labeled versions of the corresponding enzymatic products. The six enzymatic products and six internal standards are listed in the following table: Enzymatic product Molecular weight Internal Standard (IS) Molecular weight ABG P 383.34 ABG IS Intended use:

idK173829_s0_e2000

K173829.txt

predicate device name

SEEKER System

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: k173829 B. Purpose for Submission: New device C. Measurand: Acid-β-glucocerebrosidase (ABG), acid-sphingomyelinase (ASM), acid-α-glucosidase (GAA), β-galactocerebrosidase (GALC), α-galactosidase A (GLA), α-L-iduronidase (IDUA) D. Type of Test: Quantitative mass spectrometric enzymatic activity assay E. Applicant: Wallac Oy, a subsidiary of PerkinElmer F. Proprietary and Established Names: NeoLSD MSMS kit G. Regulatory Information: 1. Regulation section: 862.1488 Lysosomal storage disorder newborn screening test system 2. Classification: II 3. Product code: PQW PQT PQU PQV 2 QCL QCM 4. Panel: Chemistry (75) H. Intended Use: 1. Intended use(s): See Indication(s) for use. 2. Indication(s) for use: The NeoLSD MSMS Kit is intended for the quantitative measurement of the activity of the enzymes acid-β-glucocerebrosidase (ABG), acid-sphingomyelinase (ASM), acid-α- glucosidase (GAA), β-galactocerebrosidase (GALC), α-galactosidase A (GLA), and α-L- iduronidase (IDUA) in dried blood spots (DBS) from newborn babies. The analysis of the enzymatic activity is intended as an aid in screening newborns for the following lysosomal storage disorders (LSD) respectively; Gaucher Disease, Niemann-Pick A/B Disease, Pompe Disease, Krabbe Disease, Fabry Disease, and mucopolysaccharidosis Type I (MPS I) Disease. 3. Special conditions for use statement(s): This test is not intended to diagnose lysosomal storage disorders. Test results are intended to be used in conjunction with other clinical and diagnostic findings, consistent with professional standards of practice, including confirmation by alternative methods, and clinical evaluation as appropriate. Known causes for anomalous analytical assay results are: - Sample not uniformly saturated with blood - Sample disk punched too close to the edge of the blood spot - Sample disk punched at the middle of the blood spot - Poorly collected specimens e.g. excessive milking or squeezing the puncture may cause hemolysis of the specimen or a mixture of tissue fluids with the specimen. Layering successive drops of blood in the specimen may affect the measured results. - Improperly dried specimens e.g. heating or stacking the specimen collection devices during the drying process - Humidity and moisture or exposure to direct sunlight are detrimental to the dried blood spot sample - Non-eluting blood spot due to deterioration of sample - Contamination of blood spot filter paper e.g. with fecal material 3 - It has been shown that female patients with the Fabry disorder may show normal GLA enzyme activities at birth but are later symptomatic - Hematocrit levels above 65% were found to interfere with the assay by increasing the measured ABG activity that could result in false negatives for Gaucher. Refer to the interference section for complete information about this interference. - Free (serum) hemoglobin above 16 g/dL was found to interfere with the assay by increasing the measured ABG, ASM and IDUA activity, that could result in false negative results for Gaucher, Niemann-Pick A/B, and mucopolysaccharidosis Type I (MPS I) Disease. Refer to the interference section for complete information about this interference. The NeoLSD MSMS kit may result in; - False negatives by not detecting Fabry disease in females - False positives by identifying pseudo deficiencies and carriers as affected for MPS I, Gaucher, and Pompe diseases - False negative by not detecting certain late onset forms for Pompe disease - False negatives by not detecting certain late onset forms for Fabry disease - Increase rate of false positives when the specimen is exposed to high temperature during shipping - The false negative rate is based on follow-up of subjects up to 4 years of age and on limited data from late onset forms of the disorders since it can take several years to identify a missed late onset case. - Certain late onset forms for Pompe disorder may have GAA enzymatic activity in the normal range and result in a false negative screening result. - Heterozygote female Fabry patients may present with normal GLA activity and not be detected by the NeoLSD MSMS kit. 4. Special instrument requirements: PerkinElmer TQD MSMS instrument system (k093916) I. Device Description: The NeoLSD MSMS kit consists of substrates, internal standards, and controls. The kit contains sufficient reagents and consumables to perform 960 assays (10 x 96-well plates). The contents of the kit are listed below: Component Contents Internal Standards Substrate Mix 1 vial or several vials of stable-isotope standards and designated substrates. The dried substrates and internal standards are a mixture of the 6 synthetic substrates, the corresponding 6 stable-isotope labeled internal standards, and sodium oleate DBS Controls C1, C2, C3 control levels on DBS cassettes, 4 manufactured from human blood with a hematocrit value of 45 - 50% Assay Buffer 1 bottle of 40 mL buffer, ready-for-use succinate buffered (pH 4.7) salt solution Extraction Solution Ethyl acetate Flow Solvent Reconstitution Solution The ready-for-use Flow Solvent contains acetonitrile, water, and formic acid Incubation / Sampling Plate 20 x 96-well microplate, U-bottomed Extraction Plate 10 x 96-deep well microplate Aluminum Foil Microplate Covers 10 x adhesive microplate covers Plate barcode labels 30 x plate barcodes J. Substantial Equivalence Information: 1. Predicate device name(s): SEEKER System 2. Predicate 510(k) number(s): DEN150035 3. Comparison with predicate: Similarities and Differences Item NeoLSD MSMS kit SEEKER System DEN150035 Indications for Use Quantitative measurement of the acid-β- glucocerebrosidase, acid-α- glucosidase, α-galactosidase A, and α-L-iduronidase in dried blood spots from newborn babies. The analysis of the enzymatic activity is intended as an aid in screening newborns for the following lysosomal storage disorders respectively; Gaucher Disease, Pompe Disease, Fabry Disease, and MPS I Disease. Same 5 Similarities and Differences Item NeoLSD MSMS kit SEEKER System DEN150035 Instrument / Software Platform PerkinElmer TQD instrument with MassLynx v4.1 firmware, with PerkinElmer 1525 sample pump, with PerkinElmer 2777c autosampler, with PerkinElmer NeoLynx v4.1 software and with the PerkinElmer MSMS Workstation Software Seeker Instrument with Spot Logic Software Measured enzymes IDUA GAA ABG GLA ASM GALC IDUA GAA ABG GLA Sample Type Punch from dried blood spot specimen Same Test Methodology Quantitative mass spectrometric enzymatic activity assay Quantitative fluorimetric enzymatic activity assay K. Standard/Guidance Document Referenced (if applicable): CLSI EP05-A3: Evaluation of precision of quantitative measurement procedures; Approved Guideline - Third Edition CLSI EP06-A: Evaluation of Linearity of Quantitative Measurement Procedures; A Statistical Approach; Approved Guideline CLSI EP07-A2: Interference Testing in Clinical Chemistry; Approved Guideline - Second Edition CLSI EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline- Second Edition CLSI EP25-A: Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline L. Test Principle: The NeoLSD MSMS kit evaluates enzyme activities by measuring the product generated when an enzyme reacts with a synthesized substrate to create a specific end product. The 6 activities of the six lysosomal enzymes present in a 3.2 mm punch from a dried blood spot are simultaneously measured by the NeoLSD MSMS assay. The punches are incubated with the assay reagent mixture which contains: · six substrates, one corresponding to each lysosomal enzyme · six stable-isotope mass-labeled internal standards (IS) each designed to chemically resemble each product generated · a buffer to maintain the reaction pH, and to carry inhibitors to limit activity from competing enzymes if present and additives to enhance the targeted enzyme reactions The amount of each product generated is directly proportional to the enzyme activity in the dried blood spot punch. The internal standards are deuterium labeled versions of the corresponding enzymatic products. The six enzymatic products and six internal standards are listed in the following table: Enzymatic product Molecular weight Internal Standard (IS) Molecular weight ABG P 383.34 ABG IS Predicate device name:

idK173829_s0_e2000

K173829.txt

applicant

Wallac Oy, a subsidiary of PerkinElmer

k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: k173829 B. Purpose for Submission: New device C. Measurand: Acid-β-glucocerebrosidase (ABG), acid-sphingomyelinase (ASM), acid-α-glucosidase (GAA), β-galactocerebrosidase (GALC), α-galactosidase A (GLA), α-L-iduronidase (IDUA) D. Type of Test: Quantitative mass spectrometric enzymatic activity assay E. Applicant: Wallac Oy, a subsidiary of PerkinElmer F. Proprietary and Established Names: NeoLSD MSMS kit G. Regulatory Information: 1. Regulation section: 862.1488 Lysosomal storage disorder newborn screening test system 2. Classification: II 3. Product code: PQW PQT PQU PQV 2 QCL QCM 4. Panel: Chemistry (75) H. Intended Use: 1. Intended use(s): See Indication(s) for use. 2. Indication(s) for use: The NeoLSD MSMS Kit is intended for the quantitative measurement of the activity of the enzymes acid-β-glucocerebrosidase (ABG), acid-sphingomyelinase (ASM), acid-α- glucosidase (GAA), β-galactocerebrosidase (GALC), α-galactosidase A (GLA), and α-L- iduronidase (IDUA) in dried blood spots (DBS) from newborn babies. The analysis of the enzymatic activity is intended as an aid in screening newborns for the following lysosomal storage disorders (LSD) respectively; Gaucher Disease, Niemann-Pick A/B Disease, Pompe Disease, Krabbe Disease, Fabry Disease, and mucopolysaccharidosis Type I (MPS I) Disease. 3. Special conditions for use statement(s): This test is not intended to diagnose lysosomal storage disorders. Test results are intended to be used in conjunction with other clinical and diagnostic findings, consistent with professional standards of practice, including confirmation by alternative methods, and clinical evaluation as appropriate. Known causes for anomalous analytical assay results are: - Sample not uniformly saturated with blood - Sample disk punched too close to the edge of the blood spot - Sample disk punched at the middle of the blood spot - Poorly collected specimens e.g. excessive milking or squeezing the puncture may cause hemolysis of the specimen or a mixture of tissue fluids with the specimen. Layering successive drops of blood in the specimen may affect the measured results. - Improperly dried specimens e.g. heating or stacking the specimen collection devices during the drying process - Humidity and moisture or exposure to direct sunlight are detrimental to the dried blood spot sample - Non-eluting blood spot due to deterioration of sample - Contamination of blood spot filter paper e.g. with fecal material 3 - It has been shown that female patients with the Fabry disorder may show normal GLA enzyme activities at birth but are later symptomatic - Hematocrit levels above 65% were found to interfere with the assay by increasing the measured ABG activity that could result in false negatives for Gaucher. Refer to the interference section for complete information about this interference. - Free (serum) hemoglobin above 16 g/dL was found to interfere with the assay by increasing the measured ABG, ASM and IDUA activity, that could result in false negative results for Gaucher, Niemann-Pick A/B, and mucopolysaccharidosis Type I (MPS I) Disease. Refer to the interference section for complete information about this interference. The NeoLSD MSMS kit may result in; - False negatives by not detecting Fabry disease in females - False positives by identifying pseudo deficiencies and carriers as affected for MPS I, Gaucher, and Pompe diseases - False negative by not detecting certain late onset forms for Pompe disease - False negatives by not detecting certain late onset forms for Fabry disease - Increase rate of false positives when the specimen is exposed to high temperature during shipping - The false negative rate is based on follow-up of subjects up to 4 years of age and on limited data from late onset forms of the disorders since it can take several years to identify a missed late onset case. - Certain late onset forms for Pompe disorder may have GAA enzymatic activity in the normal range and result in a false negative screening result. - Heterozygote female Fabry patients may present with normal GLA activity and not be detected by the NeoLSD MSMS kit. 4. Special instrument requirements: PerkinElmer TQD MSMS instrument system (k093916) I. Device Description: The NeoLSD MSMS kit consists of substrates, internal standards, and controls. The kit contains sufficient reagents and consumables to perform 960 assays (10 x 96-well plates). The contents of the kit are listed below: Component Contents Internal Standards Substrate Mix 1 vial or several vials of stable-isotope standards and designated substrates. The dried substrates and internal standards are a mixture of the 6 synthetic substrates, the corresponding 6 stable-isotope labeled internal standards, and sodium oleate DBS Controls C1, C2, C3 control levels on DBS cassettes, 4 manufactured from human blood with a hematocrit value of 45 - 50% Assay Buffer 1 bottle of 40 mL buffer, ready-for-use succinate buffered (pH 4.7) salt solution Extraction Solution Ethyl acetate Flow Solvent Reconstitution Solution The ready-for-use Flow Solvent contains acetonitrile, water, and formic acid Incubation / Sampling Plate 20 x 96-well microplate, U-bottomed Extraction Plate 10 x 96-deep well microplate Aluminum Foil Microplate Covers 10 x adhesive microplate covers Plate barcode labels 30 x plate barcodes J. Substantial Equivalence Information: 1. Predicate device name(s): SEEKER System 2. Predicate 510(k) number(s): DEN150035 3. Comparison with predicate: Similarities and Differences Item NeoLSD MSMS kit SEEKER System DEN150035 Indications for Use Quantitative measurement of the acid-β- glucocerebrosidase, acid-α- glucosidase, α-galactosidase A, and α-L-iduronidase in dried blood spots from newborn babies. The analysis of the enzymatic activity is intended as an aid in screening newborns for the following lysosomal storage disorders respectively; Gaucher Disease, Pompe Disease, Fabry Disease, and MPS I Disease. Same 5 Similarities and Differences Item NeoLSD MSMS kit SEEKER System DEN150035 Instrument / Software Platform PerkinElmer TQD instrument with MassLynx v4.1 firmware, with PerkinElmer 1525 sample pump, with PerkinElmer 2777c autosampler, with PerkinElmer NeoLynx v4.1 software and with the PerkinElmer MSMS Workstation Software Seeker Instrument with Spot Logic Software Measured enzymes IDUA GAA ABG GLA ASM GALC IDUA GAA ABG GLA Sample Type Punch from dried blood spot specimen Same Test Methodology Quantitative mass spectrometric enzymatic activity assay Quantitative fluorimetric enzymatic activity assay K. Standard/Guidance Document Referenced (if applicable): CLSI EP05-A3: Evaluation of precision of quantitative measurement procedures; Approved Guideline - Third Edition CLSI EP06-A: Evaluation of Linearity of Quantitative Measurement Procedures; A Statistical Approach; Approved Guideline CLSI EP07-A2: Interference Testing in Clinical Chemistry; Approved Guideline - Second Edition CLSI EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline- Second Edition CLSI EP25-A: Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline L. Test Principle: The NeoLSD MSMS kit evaluates enzyme activities by measuring the product generated when an enzyme reacts with a synthesized substrate to create a specific end product. The 6 activities of the six lysosomal enzymes present in a 3.2 mm punch from a dried blood spot are simultaneously measured by the NeoLSD MSMS assay. The punches are incubated with the assay reagent mixture which contains: · six substrates, one corresponding to each lysosomal enzyme · six stable-isotope mass-labeled internal standards (IS) each designed to chemically resemble each product generated · a buffer to maintain the reaction pH, and to carry inhibitors to limit activity from competing enzymes if present and additives to enhance the targeted enzyme reactions The amount of each product generated is directly proportional to the enzyme activity in the dried blood spot punch. The internal standards are deuterium labeled versions of the corresponding enzymatic products. The six enzymatic products and six internal standards are listed in the following table: Enzymatic product Molecular weight Internal Standard (IS) Molecular weight ABG P 383.34 ABG IS Applicant:

idK173829_s0_e2000

K173829.txt

proprietary and established names

NeoLSD MSMS kit

ANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: k173829 B. Purpose for Submission: New device C. Measurand: Acid-β-glucocerebrosidase (ABG), acid-sphingomyelinase (ASM), acid-α-glucosidase (GAA), β-galactocerebrosidase (GALC), α-galactosidase A (GLA), α-L-iduronidase (IDUA) D. Type of Test: Quantitative mass spectrometric enzymatic activity assay E. Applicant: Wallac Oy, a subsidiary of PerkinElmer F. Proprietary and Established Names: NeoLSD MSMS kit G. Regulatory Information: 1. Regulation section: 862.1488 Lysosomal storage disorder newborn screening test system 2. Classification: II 3. Product code: PQW PQT PQU PQV 2 QCL QCM 4. Panel: Chemistry (75) H. Intended Use: 1. Intended use(s): See Indication(s) for use. 2. Indication(s) for use: The NeoLSD MSMS Kit is intended for the quantitative measurement of the activity of the enzymes acid-β-glucocerebrosidase (ABG), acid-sphingomyelinase (ASM), acid-α- glucosidase (GAA), β-galactocerebrosidase (GALC), α-galactosidase A (GLA), and α-L- iduronidase (IDUA) in dried blood spots (DBS) from newborn babies. The analysis of the enzymatic activity is intended as an aid in screening newborns for the following lysosomal storage disorders (LSD) respectively; Gaucher Disease, Niemann-Pick A/B Disease, Pompe Disease, Krabbe Disease, Fabry Disease, and mucopolysaccharidosis Type I (MPS I) Disease. 3. Special conditions for use statement(s): This test is not intended to diagnose lysosomal storage disorders. Test results are intended to be used in conjunction with other clinical and diagnostic findings, consistent with professional standards of practice, including confirmation by alternative methods, and clinical evaluation as appropriate. Known causes for anomalous analytical assay results are: - Sample not uniformly saturated with blood - Sample disk punched too close to the edge of the blood spot - Sample disk punched at the middle of the blood spot - Poorly collected specimens e.g. excessive milking or squeezing the puncture may cause hemolysis of the specimen or a mixture of tissue fluids with the specimen. Layering successive drops of blood in the specimen may affect the measured results. - Improperly dried specimens e.g. heating or stacking the specimen collection devices during the drying process - Humidity and moisture or exposure to direct sunlight are detrimental to the dried blood spot sample - Non-eluting blood spot due to deterioration of sample - Contamination of blood spot filter paper e.g. with fecal material 3 - It has been shown that female patients with the Fabry disorder may show normal GLA enzyme activities at birth but are later symptomatic - Hematocrit levels above 65% were found to interfere with the assay by increasing the measured ABG activity that could result in false negatives for Gaucher. Refer to the interference section for complete information about this interference. - Free (serum) hemoglobin above 16 g/dL was found to interfere with the assay by increasing the measured ABG, ASM and IDUA activity, that could result in false negative results for Gaucher, Niemann-Pick A/B, and mucopolysaccharidosis Type I (MPS I) Disease. Refer to the interference section for complete information about this interference. The NeoLSD MSMS kit may result in; - False negatives by not detecting Fabry disease in females - False positives by identifying pseudo deficiencies and carriers as affected for MPS I, Gaucher, and Pompe diseases - False negative by not detecting certain late onset forms for Pompe disease - False negatives by not detecting certain late onset forms for Fabry disease - Increase rate of false positives when the specimen is exposed to high temperature during shipping - The false negative rate is based on follow-up of subjects up to 4 years of age and on limited data from late onset forms of the disorders since it can take several years to identify a missed late onset case. - Certain late onset forms for Pompe disorder may have GAA enzymatic activity in the normal range and result in a false negative screening result. - Heterozygote female Fabry patients may present with normal GLA activity and not be detected by the NeoLSD MSMS kit. 4. Special instrument requirements: PerkinElmer TQD MSMS instrument system (k093916) I. Device Description: The NeoLSD MSMS kit consists of substrates, internal standards, and controls. The kit contains sufficient reagents and consumables to perform 960 assays (10 x 96-well plates). The contents of the kit are listed below: Component Contents Internal Standards Substrate Mix 1 vial or several vials of stable-isotope standards and designated substrates. The dried substrates and internal standards are a mixture of the 6 synthetic substrates, the corresponding 6 stable-isotope labeled internal standards, and sodium oleate DBS Controls C1, C2, C3 control levels on DBS cassettes, 4 manufactured from human blood with a hematocrit value of 45 - 50% Assay Buffer 1 bottle of 40 mL buffer, ready-for-use succinate buffered (pH 4.7) salt solution Extraction Solution Ethyl acetate Flow Solvent Reconstitution Solution The ready-for-use Flow Solvent contains acetonitrile, water, and formic acid Incubation / Sampling Plate 20 x 96-well microplate, U-bottomed Extraction Plate 10 x 96-deep well microplate Aluminum Foil Microplate Covers 10 x adhesive microplate covers Plate barcode labels 30 x plate barcodes J. Substantial Equivalence Information: 1. Predicate device name(s): SEEKER System 2. Predicate 510(k) number(s): DEN150035 3. Comparison with predicate: Similarities and Differences Item NeoLSD MSMS kit SEEKER System DEN150035 Indications for Use Quantitative measurement of the acid-β- glucocerebrosidase, acid-α- glucosidase, α-galactosidase A, and α-L-iduronidase in dried blood spots from newborn babies. The analysis of the enzymatic activity is intended as an aid in screening newborns for the following lysosomal storage disorders respectively; Gaucher Disease, Pompe Disease, Fabry Disease, and MPS I Disease. Same 5 Similarities and Differences Item NeoLSD MSMS kit SEEKER System DEN150035 Instrument / Software Platform PerkinElmer TQD instrument with MassLynx v4.1 firmware, with PerkinElmer 1525 sample pump, with PerkinElmer 2777c autosampler, with PerkinElmer NeoLynx v4.1 software and with the PerkinElmer MSMS Workstation Software Seeker Instrument with Spot Logic Software Measured enzymes IDUA GAA ABG GLA ASM GALC IDUA GAA ABG GLA Sample Type Punch from dried blood spot specimen Same Test Methodology Quantitative mass spectrometric enzymatic activity assay Quantitative fluorimetric enzymatic activity assay K. Standard/Guidance Document Referenced (if applicable): CLSI EP05-A3: Evaluation of precision of quantitative measurement procedures; Approved Guideline - Third Edition CLSI EP06-A: Evaluation of Linearity of Quantitative Measurement Procedures; A Statistical Approach; Approved Guideline CLSI EP07-A2: Interference Testing in Clinical Chemistry; Approved Guideline - Second Edition CLSI EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline- Second Edition CLSI EP25-A: Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline L. Test Principle: The NeoLSD MSMS kit evaluates enzyme activities by measuring the product generated when an enzyme reacts with a synthesized substrate to create a specific end product. The 6 activities of the six lysosomal enzymes present in a 3.2 mm punch from a dried blood spot are simultaneously measured by the NeoLSD MSMS assay. The punches are incubated with the assay reagent mixture which contains: · six substrates, one corresponding to each lysosomal enzyme · six stable-isotope mass-labeled internal standards (IS) each designed to chemically resemble each product generated · a buffer to maintain the reaction pH, and to carry inhibitors to limit activity from competing enzymes if present and additives to enhance the targeted enzyme reactions The amount of each product generated is directly proportional to the enzyme activity in the dried blood spot punch. The internal standards are deuterium labeled versions of the corresponding enzymatic products. The six enzymatic products and six internal standards are listed in the following table: Enzymatic product Molecular weight Internal Standard (IS) Molecular weight ABG P 383.34 ABG IS Proprietary and established names:

idK173829_s0_e2000

K173829.txt

regulation section

862.1488 Lysosomal storage disorder newborn screening test system

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: k173829 B. Purpose for Submission: New device C. Measurand: Acid-β-glucocerebrosidase (ABG), acid-sphingomyelinase (ASM), acid-α-glucosidase (GAA), β-galactocerebrosidase (GALC), α-galactosidase A (GLA), α-L-iduronidase (IDUA) D. Type of Test: Quantitative mass spectrometric enzymatic activity assay E. Applicant: Wallac Oy, a subsidiary of PerkinElmer F. Proprietary and Established Names: NeoLSD MSMS kit G. Regulatory Information: 1. Regulation section: 862.1488 Lysosomal storage disorder newborn screening test system 2. Classification: II 3. Product code: PQW PQT PQU PQV 2 QCL QCM 4. Panel: Chemistry (75) H. Intended Use: 1. Intended use(s): See Indication(s) for use. 2. Indication(s) for use: The NeoLSD MSMS Kit is intended for the quantitative measurement of the activity of the enzymes acid-β-glucocerebrosidase (ABG), acid-sphingomyelinase (ASM), acid-α- glucosidase (GAA), β-galactocerebrosidase (GALC), α-galactosidase A (GLA), and α-L- iduronidase (IDUA) in dried blood spots (DBS) from newborn babies. The analysis of the enzymatic activity is intended as an aid in screening newborns for the following lysosomal storage disorders (LSD) respectively; Gaucher Disease, Niemann-Pick A/B Disease, Pompe Disease, Krabbe Disease, Fabry Disease, and mucopolysaccharidosis Type I (MPS I) Disease. 3. Special conditions for use statement(s): This test is not intended to diagnose lysosomal storage disorders. Test results are intended to be used in conjunction with other clinical and diagnostic findings, consistent with professional standards of practice, including confirmation by alternative methods, and clinical evaluation as appropriate. Known causes for anomalous analytical assay results are: - Sample not uniformly saturated with blood - Sample disk punched too close to the edge of the blood spot - Sample disk punched at the middle of the blood spot - Poorly collected specimens e.g. excessive milking or squeezing the puncture may cause hemolysis of the specimen or a mixture of tissue fluids with the specimen. Layering successive drops of blood in the specimen may affect the measured results. - Improperly dried specimens e.g. heating or stacking the specimen collection devices during the drying process - Humidity and moisture or exposure to direct sunlight are detrimental to the dried blood spot sample - Non-eluting blood spot due to deterioration of sample - Contamination of blood spot filter paper e.g. with fecal material 3 - It has been shown that female patients with the Fabry disorder may show normal GLA enzyme activities at birth but are later symptomatic - Hematocrit levels above 65% were found to interfere with the assay by increasing the measured ABG activity that could result in false negatives for Gaucher. Refer to the interference section for complete information about this interference. - Free (serum) hemoglobin above 16 g/dL was found to interfere with the assay by increasing the measured ABG, ASM and IDUA activity, that could result in false negative results for Gaucher, Niemann-Pick A/B, and mucopolysaccharidosis Type I (MPS I) Disease. Refer to the interference section for complete information about this interference. The NeoLSD MSMS kit may result in; - False negatives by not detecting Fabry disease in females - False positives by identifying pseudo deficiencies and carriers as affected for MPS I, Gaucher, and Pompe diseases - False negative by not detecting certain late onset forms for Pompe disease - False negatives by not detecting certain late onset forms for Fabry disease - Increase rate of false positives when the specimen is exposed to high temperature during shipping - The false negative rate is based on follow-up of subjects up to 4 years of age and on limited data from late onset forms of the disorders since it can take several years to identify a missed late onset case. - Certain late onset forms for Pompe disorder may have GAA enzymatic activity in the normal range and result in a false negative screening result. - Heterozygote female Fabry patients may present with normal GLA activity and not be detected by the NeoLSD MSMS kit. 4. Special instrument requirements: PerkinElmer TQD MSMS instrument system (k093916) I. Device Description: The NeoLSD MSMS kit consists of substrates, internal standards, and controls. The kit contains sufficient reagents and consumables to perform 960 assays (10 x 96-well plates). The contents of the kit are listed below: Component Contents Internal Standards Substrate Mix 1 vial or several vials of stable-isotope standards and designated substrates. The dried substrates and internal standards are a mixture of the 6 synthetic substrates, the corresponding 6 stable-isotope labeled internal standards, and sodium oleate DBS Controls C1, C2, C3 control levels on DBS cassettes, 4 manufactured from human blood with a hematocrit value of 45 - 50% Assay Buffer 1 bottle of 40 mL buffer, ready-for-use succinate buffered (pH 4.7) salt solution Extraction Solution Ethyl acetate Flow Solvent Reconstitution Solution The ready-for-use Flow Solvent contains acetonitrile, water, and formic acid Incubation / Sampling Plate 20 x 96-well microplate, U-bottomed Extraction Plate 10 x 96-deep well microplate Aluminum Foil Microplate Covers 10 x adhesive microplate covers Plate barcode labels 30 x plate barcodes J. Substantial Equivalence Information: 1. Predicate device name(s): SEEKER System 2. Predicate 510(k) number(s): DEN150035 3. Comparison with predicate: Similarities and Differences Item NeoLSD MSMS kit SEEKER System DEN150035 Indications for Use Quantitative measurement of the acid-β- glucocerebrosidase, acid-α- glucosidase, α-galactosidase A, and α-L-iduronidase in dried blood spots from newborn babies. The analysis of the enzymatic activity is intended as an aid in screening newborns for the following lysosomal storage disorders respectively; Gaucher Disease, Pompe Disease, Fabry Disease, and MPS I Disease. Same 5 Similarities and Differences Item NeoLSD MSMS kit SEEKER System DEN150035 Instrument / Software Platform PerkinElmer TQD instrument with MassLynx v4.1 firmware, with PerkinElmer 1525 sample pump, with PerkinElmer 2777c autosampler, with PerkinElmer NeoLynx v4.1 software and with the PerkinElmer MSMS Workstation Software Seeker Instrument with Spot Logic Software Measured enzymes IDUA GAA ABG GLA ASM GALC IDUA GAA ABG GLA Sample Type Punch from dried blood spot specimen Same Test Methodology Quantitative mass spectrometric enzymatic activity assay Quantitative fluorimetric enzymatic activity assay K. Standard/Guidance Document Referenced (if applicable): CLSI EP05-A3: Evaluation of precision of quantitative measurement procedures; Approved Guideline - Third Edition CLSI EP06-A: Evaluation of Linearity of Quantitative Measurement Procedures; A Statistical Approach; Approved Guideline CLSI EP07-A2: Interference Testing in Clinical Chemistry; Approved Guideline - Second Edition CLSI EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline- Second Edition CLSI EP25-A: Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline L. Test Principle: The NeoLSD MSMS kit evaluates enzyme activities by measuring the product generated when an enzyme reacts with a synthesized substrate to create a specific end product. The 6 activities of the six lysosomal enzymes present in a 3.2 mm punch from a dried blood spot are simultaneously measured by the NeoLSD MSMS assay. The punches are incubated with the assay reagent mixture which contains: · six substrates, one corresponding to each lysosomal enzyme · six stable-isotope mass-labeled internal standards (IS) each designed to chemically resemble each product generated · a buffer to maintain the reaction pH, and to carry inhibitors to limit activity from competing enzymes if present and additives to enhance the targeted enzyme reactions The amount of each product generated is directly proportional to the enzyme activity in the dried blood spot punch. The internal standards are deuterium labeled versions of the corresponding enzymatic products. The six enzymatic products and six internal standards are listed in the following table: Enzymatic product Molecular weight Internal Standard (IS) Molecular weight ABG P 383.34 ABG IS Regulation section:

idK173829_s8000_e10000

K173829.txt

proposed labeling

The labeling is sufficient and it satisfies the requirements of 21 CFR Parts 801 and 809, as applicable and the special controls for this device type under 21 CFR 862.1488.

stored between 5-17 years. The NeoLSD MSMS kit cut-off values have not been not validated for babies older than 4 days old. Older samples should be tested using cut-off values validated for newborns greater than 4 days old. 4. Clinical cut-off: See other clinical supportive data (3.c.) above. 5. Expected values/Reference range: The labeling states that each laboratory should establish its own reference range and cut- off values. The descriptive statistics from the Danish Section for Neonatal Screening, Department of Clinical Biochemistry and Immunology, Statens Serum Institute (SSI) are summarized below for each enzyme for 5041 presumed unaffected newborns. All values are in µmol/L/hour. Enzyme n Enzyme activity (μmol/L/h) Range Mean Median Lower percentiles 0.1% 0.2% 0.3% ABG 5041 2.07 - 66.3 10.35 9.60 2.85 3.16 3.33 ASM 5041 1.64 - 35.2 6.38 5.86 2.12 2.21 2.37 GALC 5041 0.22 - 54.9 3.63 3.10 0.43 0.52 0.56 IDUA 5041 0.45 - 35.4 7.55 7.25 2.06 2.55 2.62 GLA 5041 1.48 - 94.8 11.06 9.72 3.04 3.37 3.62 GAA 5041 1.55 - 34.8 9.28 8.74 2.33 2.69 2.92 Additional newborn population distributions were determined at two different newborn screening laboratories in the United States. Site A analyzed 5251 and Site B analyzed 5053 presumed unaffected newborn dried blood spot specimens submitted for routine testing. Descriptive statistics for the samples are shown in the tables. Samples tested in Site A and Site B were collected from newborns of ≤ 4 days and ≤ 7 days, respectively. All values are in µmol/L/hour. 18 Site A: Enzyme n Enzyme activity (µmol/L/h) Range Mean Median Lower percentiles 0.1% 0.2% 0.3% ABG 5251 1.39 – 77.9 10.52 9.67 2.00 2.16 2.36 ASM 5251 1.10 – 24.3 4.70 4.44 1.49 1.60 1.64 GALC 5251 0.52 – 85.0 5.49 4.63 0.86 0.96 1.02 IDUA 5251 0.09 – 18.7 6.31 6.08 0.85 1.40 1.56 GLA 5251 1.69 – 121 16.91 14.39 3.44 4.42 4.89 GAA 5251 0.75 - 43.0 10.21 9.62 2.16 2.38 2.56 Site B: Enzyme n Enzyme activity (µmol/L/h) Range Mean Median Lower percentiles 0.1% 0.2% 0.3% ABG 5053 1.68 – 76.5 11.4 10.4 2.94 3.23 3.33 ASM 5053 1.02 – 28.4 5.44 5.13 1.71 1.79 1.98 GALC 5053 0.53 – 33.0 4.67 4.20 0.68 0.82 0.86 IDUA 5053 0.9 – 21.8 6.65 6.39 1.59 1.98 2.09 GLA 5053 0.96 – 59.5 13.3 12.0 3.99 4.33 4.43 GAA 5053 1.11 – 36.4 11.0 10.4 2.53 2.88 3.37 N. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Parts 801 and 809, as applicable and the special controls for this device type under 21 CFR 862.1488. O. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Proposed labeling:

idK173829_s8000_e10000

K173829.txt

conclusion

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

repository samples stored between 5-17 years. The NeoLSD MSMS kit cut-off values have not been not validated for babies older than 4 days old. Older samples should be tested using cut-off values validated for newborns greater than 4 days old. 4. Clinical cut-off: See other clinical supportive data (3.c.) above. 5. Expected values/Reference range: The labeling states that each laboratory should establish its own reference range and cut- off values. The descriptive statistics from the Danish Section for Neonatal Screening, Department of Clinical Biochemistry and Immunology, Statens Serum Institute (SSI) are summarized below for each enzyme for 5041 presumed unaffected newborns. All values are in µmol/L/hour. Enzyme n Enzyme activity (μmol/L/h) Range Mean Median Lower percentiles 0.1% 0.2% 0.3% ABG 5041 2.07 - 66.3 10.35 9.60 2.85 3.16 3.33 ASM 5041 1.64 - 35.2 6.38 5.86 2.12 2.21 2.37 GALC 5041 0.22 - 54.9 3.63 3.10 0.43 0.52 0.56 IDUA 5041 0.45 - 35.4 7.55 7.25 2.06 2.55 2.62 GLA 5041 1.48 - 94.8 11.06 9.72 3.04 3.37 3.62 GAA 5041 1.55 - 34.8 9.28 8.74 2.33 2.69 2.92 Additional newborn population distributions were determined at two different newborn screening laboratories in the United States. Site A analyzed 5251 and Site B analyzed 5053 presumed unaffected newborn dried blood spot specimens submitted for routine testing. Descriptive statistics for the samples are shown in the tables. Samples tested in Site A and Site B were collected from newborns of ≤ 4 days and ≤ 7 days, respectively. All values are in µmol/L/hour. 18 Site A: Enzyme n Enzyme activity (µmol/L/h) Range Mean Median Lower percentiles 0.1% 0.2% 0.3% ABG 5251 1.39 – 77.9 10.52 9.67 2.00 2.16 2.36 ASM 5251 1.10 – 24.3 4.70 4.44 1.49 1.60 1.64 GALC 5251 0.52 – 85.0 5.49 4.63 0.86 0.96 1.02 IDUA 5251 0.09 – 18.7 6.31 6.08 0.85 1.40 1.56 GLA 5251 1.69 – 121 16.91 14.39 3.44 4.42 4.89 GAA 5251 0.75 - 43.0 10.21 9.62 2.16 2.38 2.56 Site B: Enzyme n Enzyme activity (µmol/L/h) Range Mean Median Lower percentiles 0.1% 0.2% 0.3% ABG 5053 1.68 – 76.5 11.4 10.4 2.94 3.23 3.33 ASM 5053 1.02 – 28.4 5.44 5.13 1.71 1.79 1.98 GALC 5053 0.53 – 33.0 4.67 4.20 0.68 0.82 0.86 IDUA 5053 0.9 – 21.8 6.65 6.39 1.59 1.98 2.09 GLA 5053 0.96 – 59.5 13.3 12.0 3.99 4.33 4.43 GAA 5053 1.11 – 36.4 11.0 10.4 2.53 2.88 3.37 N. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Parts 801 and 809, as applicable and the special controls for this device type under 21 CFR 862.1488. O. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Conclusion:

idK160538_s0_e2000

K160538.txt

purpose for submission

Clearance of a new device

STANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K160538 B. Purpose for Submission: Clearance of a new device C. Manufacturer and Instrument Name: Sysmex America Inc., Sysmex® XN-L Automated Hematology Analyzer D. Type of Test or Tests Performed: The XN-L analyzer classifies and enumerates the following parameters in whole blood: WBC, RBC, HGB, HCT, MCV, MCH, MCHC, PLT, NEUT%/#, LYMPH%/#, MONO%/#, EO%/#, BASO%/#, IG%/#, RDW-CV, RDW-SD, MPV, RET%/#, IRF, RET-He and has a Body Fluid mode for body fluids. The Body Fluid mode enumerates the WBC-BF, RBC-BF, MN%/#, PMN%/#, and TC-BF# parameters in CSF, peritoneal, pleural and synovial fluids. E. System Descriptions: 1. Device Description: The Sysmex XN-L analyzer is a quantitative multi-parameter automated hematology analyzer intended for in vitro diagnostic use in screening patient populations found in clinical laboratories. The XN-L analyzer classifies and enumerates whole blood and body fluid parameters by means of electrical impedance, laser light scattering, and fluorescent labeling. Tests are performed on whole blood samples collected in K2 or K3 EDTA anticoagulant and body fluids (peritoneal, pleural and synovial) collected in K2EDTA anticoagulant and cerebrospinal fluid that is not collected in anticoagulant. The instrument consists of two principal units: (1) Main Unit which will aspirate, dilute, mix, and analyze whole blood and body fluid samples and (2) Pneumatic Unit which supplies pressure and vacuum to the analyzer. The XN-L has an external monitor with touch screen capability that is used to operate the instrument and process data from the Main Unit. The monitor also allows operator interfacing with the instrument by use of a panel keyboard 2. Principles of Operation: The XN-L analyzer performs analysis using the following methods: DC Sheath Flow 2 Detection method, Flow Cytometry method using a semiconductor laser, and SLS (cyanide-free sodium lauryl sulfate) hemoglobin method. Particle characterization and identification is based on detection of forward scatter, fluorescence, and adaptive cluster analysis. The XN-L analyzer automatically classifies cells from whole blood and body fluids and carries out all processes automatically from aspiration of the sample to result output. 3. Modes of Operation: Does the applicant’s device contain the ability to transmit data to a computer, webserver, or mobile device? Yes ___X____ or No ________ Does the applicant’s device transmit data to a computer, webserver, or mobile device using wireless transmission? Yes ________ or No ___X____ 4. Specimen Identification: Specimen identification input is manual (by operator) or by barcode reader 5. Specimen Sampling and Handling: There are two modes of sample introduction: (1) Sampler Mode; (2) Manual Mode. In the Sampler Mode the operator loads the sample tubes into a rack, which is then automatically transported and analyzed by the instrument. This mode automatically mixes, aspirates, and analyzes samples without removing their caps. The Sampler Mode is used for processing of whole blood samples. In the Manual Mode, there are two sample tube holders: (1) Normal sample tube holder; (2) Micro collection tube holder. In this mode the operator loads and mixes the samples tubes individually by hand. The samples in the Manual Mode can be analyzed with the cap on or off. The Manual Mode is used for processing whole blood and body fluid samples. 6. Calibration: The XN CALTM calibrator (K160585) is used for calibration of the instrument for WBC, RBC, HGB, HCT, PLT and RET. XN CAL is used for the calibration and calibration verification of Sysmex XN series (XN-10, XN-11, XN-20, XN-21, XN-L) analyzers. Calibration is performed as needed (e.g., when QC data is fluctuating) to ensure accuracy of the system. 7. Quality Control: The XN-L CHECK (K160586) is used as quality control (three levels) for Sysmex XN-L 3 analyzers. XN-L CHECK™ is an in-vitro diagnostic product that contains the following: stabilized red blood cell component(s), stabilized white blood cell component(s), and stabilized platelet component(s) in a preservative medium. XN CHECK (K160590) is used as quality control (three levels) for Sysmex XN series (XN-10, XN-11, XN-20, XN-21, XN-L) analyzers. XN CHECK™ is an in-vitro diagnostic product that contains the following: stabilized red blood cell component(s), stabilized white blood cell component(s), stabilized platelet component(s), and stabilized nucleated red blood cell component(s) in a preservative medium. XN CHECK BF (K160588) is used as quality control (two levels) for Sysmex XN series (XN-10, XN-11, XN-20, XN-21, XN-L) analyzers. Assayed parameters include: WBC- BF, RBC-BF, MN%, PMN%, TC-BF#. 8. Software: FDA has reviewed applicant’s Hazard Analysis and Software Development processes for this line of product types: Yes___X____ or No________ F. Regulatory Information: 1. Regulation section: 21 CFR 864.5220, Automated differential cell counter 2. Classification: Class II 3 Product code: GKZ, Counter, differential cell 4. Panel: Hematology (81) G. Intended Use: 1. Indication(s) for Use: The Sysmex XN-L analyzer is a quantitative multi-parameter automated hematology analyzer intended for in vitro diagnostic use in screening patient populations found in clinical laboratories. The XN-L analyzer classifies and enumerates the following 4 parameters in venous and capillary whole blood: WBC, RBC, HGB, HCT, MCV, MCH,MCHC, PLT, NEUT%/#, LYMPH%/#, MONO%/#, EO%/#, BASO%/#, IG%/#, RDW-CV, RDW-SD, MPV, RET%/#,IRF, RET-He and has a Body Fluid mode for body fluids. The Body Fluid mode enumerates the WBC-BF, RBC-BF, MN%/#, PMN%/#, and TC-BF# parameters in cerebrospinal, peritoneal, pleural, and synovial fluids. Whole blood should be collected in K2 or K3EDTA anticoagulant and peritoneal, pleural, and synovial fluids in K2EDTA anticoagulant to prevent clotting of fluid. The use of anticoagulants with CSF specimens is neither required nor recommended. The performance of this device has not been established in pediatric patients under the age of 2 years. 2. Special Conditions for Use Statement(s): For prescription use only. H. Substantial Equivalence Information: 1. Predicate Device Name(s) and 510(k) numbers: Sysmex XN-Series (XN-10, XN-20) Automated Hematology Analyzer, K112605 2. Comparison with Predicate Device: Similarities Item Device: XN-L Predicate: XN-Series (XN- 10)a K112605 Intended Use The Sysmex® XN-L analyzer is a quantitative multi-parameter automated hematology analyzer intended for in vitro diagnostic use in screening patient populations found in clinical laboratories. The XN-L analyzer classifies and enumerates the following parameters in whole blood: WBC, RBC, HGB, HCT, MCV, MCH, MCHC, PLT, NEUT%/#, LYMPH%/#, MONO%/#, EO%/#, BASO%/#, IG%/#, RDW-CV, RDW-SD,MPV, RET%/#, IRF, RET-He and has a Body Fluid mode for body fluids. The Body Fluid mode enumerates the WBCBF, RBC-BF, MN%/#, PMN%/#, and TC-BF# parameters in CSF, peritoneal, pleural and synovial fluids. Whole blood should The XN-Series modules (XN- 10, XN-20) are quantitative multi-parameter automated hematology analyzers intended for in vitro diagnostic use in screening patient populations found in clinical laboratories. The XN- Series modules Purpose for submission:

idK160538_s0_e2000

K160538.txt

type of test

The XN-L analyzer classifies and enumerates the following parameters in whole blood: WBC, RBC, HGB, HCT, MCV, MCH, MCHC, PLT, NEUT%/#, LYMPH%/#, MONO%/#, EO%/#, BASO%/#, IG%/#, RDW-CV, RDW-SD, MPV, RET%/#, IRF, RET-He and has a Body Fluid mode for body fluids. The Body Fluid mode enumerates the WBC-BF, RBC-BF, MN%/#, PMN%/#, and TC-BF# parameters in CSF, peritoneal, pleural and synovial fluids.

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K160538 B. Purpose for Submission: Clearance of a new device C. Manufacturer and Instrument Name: Sysmex America Inc., Sysmex® XN-L Automated Hematology Analyzer D. Type of Test or Tests Performed: The XN-L analyzer classifies and enumerates the following parameters in whole blood: WBC, RBC, HGB, HCT, MCV, MCH, MCHC, PLT, NEUT%/#, LYMPH%/#, MONO%/#, EO%/#, BASO%/#, IG%/#, RDW-CV, RDW-SD, MPV, RET%/#, IRF, RET-He and has a Body Fluid mode for body fluids. The Body Fluid mode enumerates the WBC-BF, RBC-BF, MN%/#, PMN%/#, and TC-BF# parameters in CSF, peritoneal, pleural and synovial fluids. E. System Descriptions: 1. Device Description: The Sysmex XN-L analyzer is a quantitative multi-parameter automated hematology analyzer intended for in vitro diagnostic use in screening patient populations found in clinical laboratories. The XN-L analyzer classifies and enumerates whole blood and body fluid parameters by means of electrical impedance, laser light scattering, and fluorescent labeling. Tests are performed on whole blood samples collected in K2 or K3 EDTA anticoagulant and body fluids (peritoneal, pleural and synovial) collected in K2EDTA anticoagulant and cerebrospinal fluid that is not collected in anticoagulant. The instrument consists of two principal units: (1) Main Unit which will aspirate, dilute, mix, and analyze whole blood and body fluid samples and (2) Pneumatic Unit which supplies pressure and vacuum to the analyzer. The XN-L has an external monitor with touch screen capability that is used to operate the instrument and process data from the Main Unit. The monitor also allows operator interfacing with the instrument by use of a panel keyboard 2. Principles of Operation: The XN-L analyzer performs analysis using the following methods: DC Sheath Flow 2 Detection method, Flow Cytometry method using a semiconductor laser, and SLS (cyanide-free sodium lauryl sulfate) hemoglobin method. Particle characterization and identification is based on detection of forward scatter, fluorescence, and adaptive cluster analysis. The XN-L analyzer automatically classifies cells from whole blood and body fluids and carries out all processes automatically from aspiration of the sample to result output. 3. Modes of Operation: Does the applicant’s device contain the ability to transmit data to a computer, webserver, or mobile device? Yes ___X____ or No ________ Does the applicant’s device transmit data to a computer, webserver, or mobile device using wireless transmission? Yes ________ or No ___X____ 4. Specimen Identification: Specimen identification input is manual (by operator) or by barcode reader 5. Specimen Sampling and Handling: There are two modes of sample introduction: (1) Sampler Mode; (2) Manual Mode. In the Sampler Mode the operator loads the sample tubes into a rack, which is then automatically transported and analyzed by the instrument. This mode automatically mixes, aspirates, and analyzes samples without removing their caps. The Sampler Mode is used for processing of whole blood samples. In the Manual Mode, there are two sample tube holders: (1) Normal sample tube holder; (2) Micro collection tube holder. In this mode the operator loads and mixes the samples tubes individually by hand. The samples in the Manual Mode can be analyzed with the cap on or off. The Manual Mode is used for processing whole blood and body fluid samples. 6. Calibration: The XN CALTM calibrator (K160585) is used for calibration of the instrument for WBC, RBC, HGB, HCT, PLT and RET. XN CAL is used for the calibration and calibration verification of Sysmex XN series (XN-10, XN-11, XN-20, XN-21, XN-L) analyzers. Calibration is performed as needed (e.g., when QC data is fluctuating) to ensure accuracy of the system. 7. Quality Control: The XN-L CHECK (K160586) is used as quality control (three levels) for Sysmex XN-L 3 analyzers. XN-L CHECK™ is an in-vitro diagnostic product that contains the following: stabilized red blood cell component(s), stabilized white blood cell component(s), and stabilized platelet component(s) in a preservative medium. XN CHECK (K160590) is used as quality control (three levels) for Sysmex XN series (XN-10, XN-11, XN-20, XN-21, XN-L) analyzers. XN CHECK™ is an in-vitro diagnostic product that contains the following: stabilized red blood cell component(s), stabilized white blood cell component(s), stabilized platelet component(s), and stabilized nucleated red blood cell component(s) in a preservative medium. XN CHECK BF (K160588) is used as quality control (two levels) for Sysmex XN series (XN-10, XN-11, XN-20, XN-21, XN-L) analyzers. Assayed parameters include: WBC- BF, RBC-BF, MN%, PMN%, TC-BF#. 8. Software: FDA has reviewed applicant’s Hazard Analysis and Software Development processes for this line of product types: Yes___X____ or No________ F. Regulatory Information: 1. Regulation section: 21 CFR 864.5220, Automated differential cell counter 2. Classification: Class II 3 Product code: GKZ, Counter, differential cell 4. Panel: Hematology (81) G. Intended Use: 1. Indication(s) for Use: The Sysmex XN-L analyzer is a quantitative multi-parameter automated hematology analyzer intended for in vitro diagnostic use in screening patient populations found in clinical laboratories. The XN-L analyzer classifies and enumerates the following 4 parameters in venous and capillary whole blood: WBC, RBC, HGB, HCT, MCV, MCH,MCHC, PLT, NEUT%/#, LYMPH%/#, MONO%/#, EO%/#, BASO%/#, IG%/#, RDW-CV, RDW-SD, MPV, RET%/#,IRF, RET-He and has a Body Fluid mode for body fluids. The Body Fluid mode enumerates the WBC-BF, RBC-BF, MN%/#, PMN%/#, and TC-BF# parameters in cerebrospinal, peritoneal, pleural, and synovial fluids. Whole blood should be collected in K2 or K3EDTA anticoagulant and peritoneal, pleural, and synovial fluids in K2EDTA anticoagulant to prevent clotting of fluid. The use of anticoagulants with CSF specimens is neither required nor recommended. The performance of this device has not been established in pediatric patients under the age of 2 years. 2. Special Conditions for Use Statement(s): For prescription use only. H. Substantial Equivalence Information: 1. Predicate Device Name(s) and 510(k) numbers: Sysmex XN-Series (XN-10, XN-20) Automated Hematology Analyzer, K112605 2. Comparison with Predicate Device: Similarities Item Device: XN-L Predicate: XN-Series (XN- 10)a K112605 Intended Use The Sysmex® XN-L analyzer is a quantitative multi-parameter automated hematology analyzer intended for in vitro diagnostic use in screening patient populations found in clinical laboratories. The XN-L analyzer classifies and enumerates the following parameters in whole blood: WBC, RBC, HGB, HCT, MCV, MCH, MCHC, PLT, NEUT%/#, LYMPH%/#, MONO%/#, EO%/#, BASO%/#, IG%/#, RDW-CV, RDW-SD,MPV, RET%/#, IRF, RET-He and has a Body Fluid mode for body fluids. The Body Fluid mode enumerates the WBCBF, RBC-BF, MN%/#, PMN%/#, and TC-BF# parameters in CSF, peritoneal, pleural and synovial fluids. Whole blood should The XN-Series modules (XN- 10, XN-20) are quantitative multi-parameter automated hematology analyzers intended for in vitro diagnostic use in screening patient populations found in clinical laboratories. The XN- Series modules Type of test:

idK160538_s0_e2000

K160538.txt

classification

Class II

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K160538 B. Purpose for Submission: Clearance of a new device C. Manufacturer and Instrument Name: Sysmex America Inc., Sysmex® XN-L Automated Hematology Analyzer D. Type of Test or Tests Performed: The XN-L analyzer classifies and enumerates the following parameters in whole blood: WBC, RBC, HGB, HCT, MCV, MCH, MCHC, PLT, NEUT%/#, LYMPH%/#, MONO%/#, EO%/#, BASO%/#, IG%/#, RDW-CV, RDW-SD, MPV, RET%/#, IRF, RET-He and has a Body Fluid mode for body fluids. The Body Fluid mode enumerates the WBC-BF, RBC-BF, MN%/#, PMN%/#, and TC-BF# parameters in CSF, peritoneal, pleural and synovial fluids. E. System Descriptions: 1. Device Description: The Sysmex XN-L analyzer is a quantitative multi-parameter automated hematology analyzer intended for in vitro diagnostic use in screening patient populations found in clinical laboratories. The XN-L analyzer classifies and enumerates whole blood and body fluid parameters by means of electrical impedance, laser light scattering, and fluorescent labeling. Tests are performed on whole blood samples collected in K2 or K3 EDTA anticoagulant and body fluids (peritoneal, pleural and synovial) collected in K2EDTA anticoagulant and cerebrospinal fluid that is not collected in anticoagulant. The instrument consists of two principal units: (1) Main Unit which will aspirate, dilute, mix, and analyze whole blood and body fluid samples and (2) Pneumatic Unit which supplies pressure and vacuum to the analyzer. The XN-L has an external monitor with touch screen capability that is used to operate the instrument and process data from the Main Unit. The monitor also allows operator interfacing with the instrument by use of a panel keyboard 2. Principles of Operation: The XN-L analyzer performs analysis using the following methods: DC Sheath Flow 2 Detection method, Flow Cytometry method using a semiconductor laser, and SLS (cyanide-free sodium lauryl sulfate) hemoglobin method. Particle characterization and identification is based on detection of forward scatter, fluorescence, and adaptive cluster analysis. The XN-L analyzer automatically classifies cells from whole blood and body fluids and carries out all processes automatically from aspiration of the sample to result output. 3. Modes of Operation: Does the applicant’s device contain the ability to transmit data to a computer, webserver, or mobile device? Yes ___X____ or No ________ Does the applicant’s device transmit data to a computer, webserver, or mobile device using wireless transmission? Yes ________ or No ___X____ 4. Specimen Identification: Specimen identification input is manual (by operator) or by barcode reader 5. Specimen Sampling and Handling: There are two modes of sample introduction: (1) Sampler Mode; (2) Manual Mode. In the Sampler Mode the operator loads the sample tubes into a rack, which is then automatically transported and analyzed by the instrument. This mode automatically mixes, aspirates, and analyzes samples without removing their caps. The Sampler Mode is used for processing of whole blood samples. In the Manual Mode, there are two sample tube holders: (1) Normal sample tube holder; (2) Micro collection tube holder. In this mode the operator loads and mixes the samples tubes individually by hand. The samples in the Manual Mode can be analyzed with the cap on or off. The Manual Mode is used for processing whole blood and body fluid samples. 6. Calibration: The XN CALTM calibrator (K160585) is used for calibration of the instrument for WBC, RBC, HGB, HCT, PLT and RET. XN CAL is used for the calibration and calibration verification of Sysmex XN series (XN-10, XN-11, XN-20, XN-21, XN-L) analyzers. Calibration is performed as needed (e.g., when QC data is fluctuating) to ensure accuracy of the system. 7. Quality Control: The XN-L CHECK (K160586) is used as quality control (three levels) for Sysmex XN-L 3 analyzers. XN-L CHECK™ is an in-vitro diagnostic product that contains the following: stabilized red blood cell component(s), stabilized white blood cell component(s), and stabilized platelet component(s) in a preservative medium. XN CHECK (K160590) is used as quality control (three levels) for Sysmex XN series (XN-10, XN-11, XN-20, XN-21, XN-L) analyzers. XN CHECK™ is an in-vitro diagnostic product that contains the following: stabilized red blood cell component(s), stabilized white blood cell component(s), stabilized platelet component(s), and stabilized nucleated red blood cell component(s) in a preservative medium. XN CHECK BF (K160588) is used as quality control (two levels) for Sysmex XN series (XN-10, XN-11, XN-20, XN-21, XN-L) analyzers. Assayed parameters include: WBC- BF, RBC-BF, MN%, PMN%, TC-BF#. 8. Software: FDA has reviewed applicant’s Hazard Analysis and Software Development processes for this line of product types: Yes___X____ or No________ F. Regulatory Information: 1. Regulation section: 21 CFR 864.5220, Automated differential cell counter 2. Classification: Class II 3 Product code: GKZ, Counter, differential cell 4. Panel: Hematology (81) G. Intended Use: 1. Indication(s) for Use: The Sysmex XN-L analyzer is a quantitative multi-parameter automated hematology analyzer intended for in vitro diagnostic use in screening patient populations found in clinical laboratories. The XN-L analyzer classifies and enumerates the following 4 parameters in venous and capillary whole blood: WBC, RBC, HGB, HCT, MCV, MCH,MCHC, PLT, NEUT%/#, LYMPH%/#, MONO%/#, EO%/#, BASO%/#, IG%/#, RDW-CV, RDW-SD, MPV, RET%/#,IRF, RET-He and has a Body Fluid mode for body fluids. The Body Fluid mode enumerates the WBC-BF, RBC-BF, MN%/#, PMN%/#, and TC-BF# parameters in cerebrospinal, peritoneal, pleural, and synovial fluids. Whole blood should be collected in K2 or K3EDTA anticoagulant and peritoneal, pleural, and synovial fluids in K2EDTA anticoagulant to prevent clotting of fluid. The use of anticoagulants with CSF specimens is neither required nor recommended. The performance of this device has not been established in pediatric patients under the age of 2 years. 2. Special Conditions for Use Statement(s): For prescription use only. H. Substantial Equivalence Information: 1. Predicate Device Name(s) and 510(k) numbers: Sysmex XN-Series (XN-10, XN-20) Automated Hematology Analyzer, K112605 2. Comparison with Predicate Device: Similarities Item Device: XN-L Predicate: XN-Series (XN- 10)a K112605 Intended Use The Sysmex® XN-L analyzer is a quantitative multi-parameter automated hematology analyzer intended for in vitro diagnostic use in screening patient populations found in clinical laboratories. The XN-L analyzer classifies and enumerates the following parameters in whole blood: WBC, RBC, HGB, HCT, MCV, MCH, MCHC, PLT, NEUT%/#, LYMPH%/#, MONO%/#, EO%/#, BASO%/#, IG%/#, RDW-CV, RDW-SD,MPV, RET%/#, IRF, RET-He and has a Body Fluid mode for body fluids. The Body Fluid mode enumerates the WBCBF, RBC-BF, MN%/#, PMN%/#, and TC-BF# parameters in CSF, peritoneal, pleural and synovial fluids. Whole blood should The XN-Series modules (XN- 10, XN-20) are quantitative multi-parameter automated hematology analyzers intended for in vitro diagnostic use in screening patient populations found in clinical laboratories. The XN- Series modules Classification:

idK160538_s0_e2000

K160538.txt

product code

GKZ, Counter, differential cell

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K160538 B. Purpose for Submission: Clearance of a new device C. Manufacturer and Instrument Name: Sysmex America Inc., Sysmex® XN-L Automated Hematology Analyzer D. Type of Test or Tests Performed: The XN-L analyzer classifies and enumerates the following parameters in whole blood: WBC, RBC, HGB, HCT, MCV, MCH, MCHC, PLT, NEUT%/#, LYMPH%/#, MONO%/#, EO%/#, BASO%/#, IG%/#, RDW-CV, RDW-SD, MPV, RET%/#, IRF, RET-He and has a Body Fluid mode for body fluids. The Body Fluid mode enumerates the WBC-BF, RBC-BF, MN%/#, PMN%/#, and TC-BF# parameters in CSF, peritoneal, pleural and synovial fluids. E. System Descriptions: 1. Device Description: The Sysmex XN-L analyzer is a quantitative multi-parameter automated hematology analyzer intended for in vitro diagnostic use in screening patient populations found in clinical laboratories. The XN-L analyzer classifies and enumerates whole blood and body fluid parameters by means of electrical impedance, laser light scattering, and fluorescent labeling. Tests are performed on whole blood samples collected in K2 or K3 EDTA anticoagulant and body fluids (peritoneal, pleural and synovial) collected in K2EDTA anticoagulant and cerebrospinal fluid that is not collected in anticoagulant. The instrument consists of two principal units: (1) Main Unit which will aspirate, dilute, mix, and analyze whole blood and body fluid samples and (2) Pneumatic Unit which supplies pressure and vacuum to the analyzer. The XN-L has an external monitor with touch screen capability that is used to operate the instrument and process data from the Main Unit. The monitor also allows operator interfacing with the instrument by use of a panel keyboard 2. Principles of Operation: The XN-L analyzer performs analysis using the following methods: DC Sheath Flow 2 Detection method, Flow Cytometry method using a semiconductor laser, and SLS (cyanide-free sodium lauryl sulfate) hemoglobin method. Particle characterization and identification is based on detection of forward scatter, fluorescence, and adaptive cluster analysis. The XN-L analyzer automatically classifies cells from whole blood and body fluids and carries out all processes automatically from aspiration of the sample to result output. 3. Modes of Operation: Does the applicant’s device contain the ability to transmit data to a computer, webserver, or mobile device? Yes ___X____ or No ________ Does the applicant’s device transmit data to a computer, webserver, or mobile device using wireless transmission? Yes ________ or No ___X____ 4. Specimen Identification: Specimen identification input is manual (by operator) or by barcode reader 5. Specimen Sampling and Handling: There are two modes of sample introduction: (1) Sampler Mode; (2) Manual Mode. In the Sampler Mode the operator loads the sample tubes into a rack, which is then automatically transported and analyzed by the instrument. This mode automatically mixes, aspirates, and analyzes samples without removing their caps. The Sampler Mode is used for processing of whole blood samples. In the Manual Mode, there are two sample tube holders: (1) Normal sample tube holder; (2) Micro collection tube holder. In this mode the operator loads and mixes the samples tubes individually by hand. The samples in the Manual Mode can be analyzed with the cap on or off. The Manual Mode is used for processing whole blood and body fluid samples. 6. Calibration: The XN CALTM calibrator (K160585) is used for calibration of the instrument for WBC, RBC, HGB, HCT, PLT and RET. XN CAL is used for the calibration and calibration verification of Sysmex XN series (XN-10, XN-11, XN-20, XN-21, XN-L) analyzers. Calibration is performed as needed (e.g., when QC data is fluctuating) to ensure accuracy of the system. 7. Quality Control: The XN-L CHECK (K160586) is used as quality control (three levels) for Sysmex XN-L 3 analyzers. XN-L CHECK™ is an in-vitro diagnostic product that contains the following: stabilized red blood cell component(s), stabilized white blood cell component(s), and stabilized platelet component(s) in a preservative medium. XN CHECK (K160590) is used as quality control (three levels) for Sysmex XN series (XN-10, XN-11, XN-20, XN-21, XN-L) analyzers. XN CHECK™ is an in-vitro diagnostic product that contains the following: stabilized red blood cell component(s), stabilized white blood cell component(s), stabilized platelet component(s), and stabilized nucleated red blood cell component(s) in a preservative medium. XN CHECK BF (K160588) is used as quality control (two levels) for Sysmex XN series (XN-10, XN-11, XN-20, XN-21, XN-L) analyzers. Assayed parameters include: WBC- BF, RBC-BF, MN%, PMN%, TC-BF#. 8. Software: FDA has reviewed applicant’s Hazard Analysis and Software Development processes for this line of product types: Yes___X____ or No________ F. Regulatory Information: 1. Regulation section: 21 CFR 864.5220, Automated differential cell counter 2. Classification: Class II 3 Product code: GKZ, Counter, differential cell 4. Panel: Hematology (81) G. Intended Use: 1. Indication(s) for Use: The Sysmex XN-L analyzer is a quantitative multi-parameter automated hematology analyzer intended for in vitro diagnostic use in screening patient populations found in clinical laboratories. The XN-L analyzer classifies and enumerates the following 4 parameters in venous and capillary whole blood: WBC, RBC, HGB, HCT, MCV, MCH,MCHC, PLT, NEUT%/#, LYMPH%/#, MONO%/#, EO%/#, BASO%/#, IG%/#, RDW-CV, RDW-SD, MPV, RET%/#,IRF, RET-He and has a Body Fluid mode for body fluids. The Body Fluid mode enumerates the WBC-BF, RBC-BF, MN%/#, PMN%/#, and TC-BF# parameters in cerebrospinal, peritoneal, pleural, and synovial fluids. Whole blood should be collected in K2 or K3EDTA anticoagulant and peritoneal, pleural, and synovial fluids in K2EDTA anticoagulant to prevent clotting of fluid. The use of anticoagulants with CSF specimens is neither required nor recommended. The performance of this device has not been established in pediatric patients under the age of 2 years. 2. Special Conditions for Use Statement(s): For prescription use only. H. Substantial Equivalence Information: 1. Predicate Device Name(s) and 510(k) numbers: Sysmex XN-Series (XN-10, XN-20) Automated Hematology Analyzer, K112605 2. Comparison with Predicate Device: Similarities Item Device: XN-L Predicate: XN-Series (XN- 10)a K112605 Intended Use The Sysmex® XN-L analyzer is a quantitative multi-parameter automated hematology analyzer intended for in vitro diagnostic use in screening patient populations found in clinical laboratories. The XN-L analyzer classifies and enumerates the following parameters in whole blood: WBC, RBC, HGB, HCT, MCV, MCH, MCHC, PLT, NEUT%/#, LYMPH%/#, MONO%/#, EO%/#, BASO%/#, IG%/#, RDW-CV, RDW-SD,MPV, RET%/#, IRF, RET-He and has a Body Fluid mode for body fluids. The Body Fluid mode enumerates the WBCBF, RBC-BF, MN%/#, PMN%/#, and TC-BF# parameters in CSF, peritoneal, pleural and synovial fluids. Whole blood should The XN-Series modules (XN- 10, XN-20) are quantitative multi-parameter automated hematology analyzers intended for in vitro diagnostic use in screening patient populations found in clinical laboratories. The XN- Series modules Product code:

idK160538_s0_e2000

K160538.txt

panel

Hematology (81)

k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K160538 B. Purpose for Submission: Clearance of a new device C. Manufacturer and Instrument Name: Sysmex America Inc., Sysmex® XN-L Automated Hematology Analyzer D. Type of Test or Tests Performed: The XN-L analyzer classifies and enumerates the following parameters in whole blood: WBC, RBC, HGB, HCT, MCV, MCH, MCHC, PLT, NEUT%/#, LYMPH%/#, MONO%/#, EO%/#, BASO%/#, IG%/#, RDW-CV, RDW-SD, MPV, RET%/#, IRF, RET-He and has a Body Fluid mode for body fluids. The Body Fluid mode enumerates the WBC-BF, RBC-BF, MN%/#, PMN%/#, and TC-BF# parameters in CSF, peritoneal, pleural and synovial fluids. E. System Descriptions: 1. Device Description: The Sysmex XN-L analyzer is a quantitative multi-parameter automated hematology analyzer intended for in vitro diagnostic use in screening patient populations found in clinical laboratories. The XN-L analyzer classifies and enumerates whole blood and body fluid parameters by means of electrical impedance, laser light scattering, and fluorescent labeling. Tests are performed on whole blood samples collected in K2 or K3 EDTA anticoagulant and body fluids (peritoneal, pleural and synovial) collected in K2EDTA anticoagulant and cerebrospinal fluid that is not collected in anticoagulant. The instrument consists of two principal units: (1) Main Unit which will aspirate, dilute, mix, and analyze whole blood and body fluid samples and (2) Pneumatic Unit which supplies pressure and vacuum to the analyzer. The XN-L has an external monitor with touch screen capability that is used to operate the instrument and process data from the Main Unit. The monitor also allows operator interfacing with the instrument by use of a panel keyboard 2. Principles of Operation: The XN-L analyzer performs analysis using the following methods: DC Sheath Flow 2 Detection method, Flow Cytometry method using a semiconductor laser, and SLS (cyanide-free sodium lauryl sulfate) hemoglobin method. Particle characterization and identification is based on detection of forward scatter, fluorescence, and adaptive cluster analysis. The XN-L analyzer automatically classifies cells from whole blood and body fluids and carries out all processes automatically from aspiration of the sample to result output. 3. Modes of Operation: Does the applicant’s device contain the ability to transmit data to a computer, webserver, or mobile device? Yes ___X____ or No ________ Does the applicant’s device transmit data to a computer, webserver, or mobile device using wireless transmission? Yes ________ or No ___X____ 4. Specimen Identification: Specimen identification input is manual (by operator) or by barcode reader 5. Specimen Sampling and Handling: There are two modes of sample introduction: (1) Sampler Mode; (2) Manual Mode. In the Sampler Mode the operator loads the sample tubes into a rack, which is then automatically transported and analyzed by the instrument. This mode automatically mixes, aspirates, and analyzes samples without removing their caps. The Sampler Mode is used for processing of whole blood samples. In the Manual Mode, there are two sample tube holders: (1) Normal sample tube holder; (2) Micro collection tube holder. In this mode the operator loads and mixes the samples tubes individually by hand. The samples in the Manual Mode can be analyzed with the cap on or off. The Manual Mode is used for processing whole blood and body fluid samples. 6. Calibration: The XN CALTM calibrator (K160585) is used for calibration of the instrument for WBC, RBC, HGB, HCT, PLT and RET. XN CAL is used for the calibration and calibration verification of Sysmex XN series (XN-10, XN-11, XN-20, XN-21, XN-L) analyzers. Calibration is performed as needed (e.g., when QC data is fluctuating) to ensure accuracy of the system. 7. Quality Control: The XN-L CHECK (K160586) is used as quality control (three levels) for Sysmex XN-L 3 analyzers. XN-L CHECK™ is an in-vitro diagnostic product that contains the following: stabilized red blood cell component(s), stabilized white blood cell component(s), and stabilized platelet component(s) in a preservative medium. XN CHECK (K160590) is used as quality control (three levels) for Sysmex XN series (XN-10, XN-11, XN-20, XN-21, XN-L) analyzers. XN CHECK™ is an in-vitro diagnostic product that contains the following: stabilized red blood cell component(s), stabilized white blood cell component(s), stabilized platelet component(s), and stabilized nucleated red blood cell component(s) in a preservative medium. XN CHECK BF (K160588) is used as quality control (two levels) for Sysmex XN series (XN-10, XN-11, XN-20, XN-21, XN-L) analyzers. Assayed parameters include: WBC- BF, RBC-BF, MN%, PMN%, TC-BF#. 8. Software: FDA has reviewed applicant’s Hazard Analysis and Software Development processes for this line of product types: Yes___X____ or No________ F. Regulatory Information: 1. Regulation section: 21 CFR 864.5220, Automated differential cell counter 2. Classification: Class II 3 Product code: GKZ, Counter, differential cell 4. Panel: Hematology (81) G. Intended Use: 1. Indication(s) for Use: The Sysmex XN-L analyzer is a quantitative multi-parameter automated hematology analyzer intended for in vitro diagnostic use in screening patient populations found in clinical laboratories. The XN-L analyzer classifies and enumerates the following 4 parameters in venous and capillary whole blood: WBC, RBC, HGB, HCT, MCV, MCH,MCHC, PLT, NEUT%/#, LYMPH%/#, MONO%/#, EO%/#, BASO%/#, IG%/#, RDW-CV, RDW-SD, MPV, RET%/#,IRF, RET-He and has a Body Fluid mode for body fluids. The Body Fluid mode enumerates the WBC-BF, RBC-BF, MN%/#, PMN%/#, and TC-BF# parameters in cerebrospinal, peritoneal, pleural, and synovial fluids. Whole blood should be collected in K2 or K3EDTA anticoagulant and peritoneal, pleural, and synovial fluids in K2EDTA anticoagulant to prevent clotting of fluid. The use of anticoagulants with CSF specimens is neither required nor recommended. The performance of this device has not been established in pediatric patients under the age of 2 years. 2. Special Conditions for Use Statement(s): For prescription use only. H. Substantial Equivalence Information: 1. Predicate Device Name(s) and 510(k) numbers: Sysmex XN-Series (XN-10, XN-20) Automated Hematology Analyzer, K112605 2. Comparison with Predicate Device: Similarities Item Device: XN-L Predicate: XN-Series (XN- 10)a K112605 Intended Use The Sysmex® XN-L analyzer is a quantitative multi-parameter automated hematology analyzer intended for in vitro diagnostic use in screening patient populations found in clinical laboratories. The XN-L analyzer classifies and enumerates the following parameters in whole blood: WBC, RBC, HGB, HCT, MCV, MCH, MCHC, PLT, NEUT%/#, LYMPH%/#, MONO%/#, EO%/#, BASO%/#, IG%/#, RDW-CV, RDW-SD,MPV, RET%/#, IRF, RET-He and has a Body Fluid mode for body fluids. The Body Fluid mode enumerates the WBCBF, RBC-BF, MN%/#, PMN%/#, and TC-BF# parameters in CSF, peritoneal, pleural and synovial fluids. Whole blood should The XN-Series modules (XN- 10, XN-20) are quantitative multi-parameter automated hematology analyzers intended for in vitro diagnostic use in screening patient populations found in clinical laboratories. The XN- Series modules Panel:

idK160538_s0_e2000

K160538.txt

predicate device name

Sysmex XN-Series (XN-10, XN-20) Automated Hematology Analyzer

STANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K160538 B. Purpose for Submission: Clearance of a new device C. Manufacturer and Instrument Name: Sysmex America Inc., Sysmex® XN-L Automated Hematology Analyzer D. Type of Test or Tests Performed: The XN-L analyzer classifies and enumerates the following parameters in whole blood: WBC, RBC, HGB, HCT, MCV, MCH, MCHC, PLT, NEUT%/#, LYMPH%/#, MONO%/#, EO%/#, BASO%/#, IG%/#, RDW-CV, RDW-SD, MPV, RET%/#, IRF, RET-He and has a Body Fluid mode for body fluids. The Body Fluid mode enumerates the WBC-BF, RBC-BF, MN%/#, PMN%/#, and TC-BF# parameters in CSF, peritoneal, pleural and synovial fluids. E. System Descriptions: 1. Device Description: The Sysmex XN-L analyzer is a quantitative multi-parameter automated hematology analyzer intended for in vitro diagnostic use in screening patient populations found in clinical laboratories. The XN-L analyzer classifies and enumerates whole blood and body fluid parameters by means of electrical impedance, laser light scattering, and fluorescent labeling. Tests are performed on whole blood samples collected in K2 or K3 EDTA anticoagulant and body fluids (peritoneal, pleural and synovial) collected in K2EDTA anticoagulant and cerebrospinal fluid that is not collected in anticoagulant. The instrument consists of two principal units: (1) Main Unit which will aspirate, dilute, mix, and analyze whole blood and body fluid samples and (2) Pneumatic Unit which supplies pressure and vacuum to the analyzer. The XN-L has an external monitor with touch screen capability that is used to operate the instrument and process data from the Main Unit. The monitor also allows operator interfacing with the instrument by use of a panel keyboard 2. Principles of Operation: The XN-L analyzer performs analysis using the following methods: DC Sheath Flow 2 Detection method, Flow Cytometry method using a semiconductor laser, and SLS (cyanide-free sodium lauryl sulfate) hemoglobin method. Particle characterization and identification is based on detection of forward scatter, fluorescence, and adaptive cluster analysis. The XN-L analyzer automatically classifies cells from whole blood and body fluids and carries out all processes automatically from aspiration of the sample to result output. 3. Modes of Operation: Does the applicant’s device contain the ability to transmit data to a computer, webserver, or mobile device? Yes ___X____ or No ________ Does the applicant’s device transmit data to a computer, webserver, or mobile device using wireless transmission? Yes ________ or No ___X____ 4. Specimen Identification: Specimen identification input is manual (by operator) or by barcode reader 5. Specimen Sampling and Handling: There are two modes of sample introduction: (1) Sampler Mode; (2) Manual Mode. In the Sampler Mode the operator loads the sample tubes into a rack, which is then automatically transported and analyzed by the instrument. This mode automatically mixes, aspirates, and analyzes samples without removing their caps. The Sampler Mode is used for processing of whole blood samples. In the Manual Mode, there are two sample tube holders: (1) Normal sample tube holder; (2) Micro collection tube holder. In this mode the operator loads and mixes the samples tubes individually by hand. The samples in the Manual Mode can be analyzed with the cap on or off. The Manual Mode is used for processing whole blood and body fluid samples. 6. Calibration: The XN CALTM calibrator (K160585) is used for calibration of the instrument for WBC, RBC, HGB, HCT, PLT and RET. XN CAL is used for the calibration and calibration verification of Sysmex XN series (XN-10, XN-11, XN-20, XN-21, XN-L) analyzers. Calibration is performed as needed (e.g., when QC data is fluctuating) to ensure accuracy of the system. 7. Quality Control: The XN-L CHECK (K160586) is used as quality control (three levels) for Sysmex XN-L 3 analyzers. XN-L CHECK™ is an in-vitro diagnostic product that contains the following: stabilized red blood cell component(s), stabilized white blood cell component(s), and stabilized platelet component(s) in a preservative medium. XN CHECK (K160590) is used as quality control (three levels) for Sysmex XN series (XN-10, XN-11, XN-20, XN-21, XN-L) analyzers. XN CHECK™ is an in-vitro diagnostic product that contains the following: stabilized red blood cell component(s), stabilized white blood cell component(s), stabilized platelet component(s), and stabilized nucleated red blood cell component(s) in a preservative medium. XN CHECK BF (K160588) is used as quality control (two levels) for Sysmex XN series (XN-10, XN-11, XN-20, XN-21, XN-L) analyzers. Assayed parameters include: WBC- BF, RBC-BF, MN%, PMN%, TC-BF#. 8. Software: FDA has reviewed applicant’s Hazard Analysis and Software Development processes for this line of product types: Yes___X____ or No________ F. Regulatory Information: 1. Regulation section: 21 CFR 864.5220, Automated differential cell counter 2. Classification: Class II 3 Product code: GKZ, Counter, differential cell 4. Panel: Hematology (81) G. Intended Use: 1. Indication(s) for Use: The Sysmex XN-L analyzer is a quantitative multi-parameter automated hematology analyzer intended for in vitro diagnostic use in screening patient populations found in clinical laboratories. The XN-L analyzer classifies and enumerates the following 4 parameters in venous and capillary whole blood: WBC, RBC, HGB, HCT, MCV, MCH,MCHC, PLT, NEUT%/#, LYMPH%/#, MONO%/#, EO%/#, BASO%/#, IG%/#, RDW-CV, RDW-SD, MPV, RET%/#,IRF, RET-He and has a Body Fluid mode for body fluids. The Body Fluid mode enumerates the WBC-BF, RBC-BF, MN%/#, PMN%/#, and TC-BF# parameters in cerebrospinal, peritoneal, pleural, and synovial fluids. Whole blood should be collected in K2 or K3EDTA anticoagulant and peritoneal, pleural, and synovial fluids in K2EDTA anticoagulant to prevent clotting of fluid. The use of anticoagulants with CSF specimens is neither required nor recommended. The performance of this device has not been established in pediatric patients under the age of 2 years. 2. Special Conditions for Use Statement(s): For prescription use only. H. Substantial Equivalence Information: 1. Predicate Device Name(s) and 510(k) numbers: Sysmex XN-Series (XN-10, XN-20) Automated Hematology Analyzer, K112605 2. Comparison with Predicate Device: Similarities Item Device: XN-L Predicate: XN-Series (XN- 10)a K112605 Intended Use The Sysmex® XN-L analyzer is a quantitative multi-parameter automated hematology analyzer intended for in vitro diagnostic use in screening patient populations found in clinical laboratories. The XN-L analyzer classifies and enumerates the following parameters in whole blood: WBC, RBC, HGB, HCT, MCV, MCH, MCHC, PLT, NEUT%/#, LYMPH%/#, MONO%/#, EO%/#, BASO%/#, IG%/#, RDW-CV, RDW-SD,MPV, RET%/#, IRF, RET-He and has a Body Fluid mode for body fluids. The Body Fluid mode enumerates the WBCBF, RBC-BF, MN%/#, PMN%/#, and TC-BF# parameters in CSF, peritoneal, pleural and synovial fluids. Whole blood should The XN-Series modules (XN- 10, XN-20) are quantitative multi-parameter automated hematology analyzers intended for in vitro diagnostic use in screening patient populations found in clinical laboratories. The XN- Series modules Predicate device name:

idK160538_s0_e2000

K160538.txt

applicant

Sysmex America Inc.

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K160538 B. Purpose for Submission: Clearance of a new device C. Manufacturer and Instrument Name: Sysmex America Inc., Sysmex® XN-L Automated Hematology Analyzer D. Type of Test or Tests Performed: The XN-L analyzer classifies and enumerates the following parameters in whole blood: WBC, RBC, HGB, HCT, MCV, MCH, MCHC, PLT, NEUT%/#, LYMPH%/#, MONO%/#, EO%/#, BASO%/#, IG%/#, RDW-CV, RDW-SD, MPV, RET%/#, IRF, RET-He and has a Body Fluid mode for body fluids. The Body Fluid mode enumerates the WBC-BF, RBC-BF, MN%/#, PMN%/#, and TC-BF# parameters in CSF, peritoneal, pleural and synovial fluids. E. System Descriptions: 1. Device Description: The Sysmex XN-L analyzer is a quantitative multi-parameter automated hematology analyzer intended for in vitro diagnostic use in screening patient populations found in clinical laboratories. The XN-L analyzer classifies and enumerates whole blood and body fluid parameters by means of electrical impedance, laser light scattering, and fluorescent labeling. Tests are performed on whole blood samples collected in K2 or K3 EDTA anticoagulant and body fluids (peritoneal, pleural and synovial) collected in K2EDTA anticoagulant and cerebrospinal fluid that is not collected in anticoagulant. The instrument consists of two principal units: (1) Main Unit which will aspirate, dilute, mix, and analyze whole blood and body fluid samples and (2) Pneumatic Unit which supplies pressure and vacuum to the analyzer. The XN-L has an external monitor with touch screen capability that is used to operate the instrument and process data from the Main Unit. The monitor also allows operator interfacing with the instrument by use of a panel keyboard 2. Principles of Operation: The XN-L analyzer performs analysis using the following methods: DC Sheath Flow 2 Detection method, Flow Cytometry method using a semiconductor laser, and SLS (cyanide-free sodium lauryl sulfate) hemoglobin method. Particle characterization and identification is based on detection of forward scatter, fluorescence, and adaptive cluster analysis. The XN-L analyzer automatically classifies cells from whole blood and body fluids and carries out all processes automatically from aspiration of the sample to result output. 3. Modes of Operation: Does the applicant’s device contain the ability to transmit data to a computer, webserver, or mobile device? Yes ___X____ or No ________ Does the applicant’s device transmit data to a computer, webserver, or mobile device using wireless transmission? Yes ________ or No ___X____ 4. Specimen Identification: Specimen identification input is manual (by operator) or by barcode reader 5. Specimen Sampling and Handling: There are two modes of sample introduction: (1) Sampler Mode; (2) Manual Mode. In the Sampler Mode the operator loads the sample tubes into a rack, which is then automatically transported and analyzed by the instrument. This mode automatically mixes, aspirates, and analyzes samples without removing their caps. The Sampler Mode is used for processing of whole blood samples. In the Manual Mode, there are two sample tube holders: (1) Normal sample tube holder; (2) Micro collection tube holder. In this mode the operator loads and mixes the samples tubes individually by hand. The samples in the Manual Mode can be analyzed with the cap on or off. The Manual Mode is used for processing whole blood and body fluid samples. 6. Calibration: The XN CALTM calibrator (K160585) is used for calibration of the instrument for WBC, RBC, HGB, HCT, PLT and RET. XN CAL is used for the calibration and calibration verification of Sysmex XN series (XN-10, XN-11, XN-20, XN-21, XN-L) analyzers. Calibration is performed as needed (e.g., when QC data is fluctuating) to ensure accuracy of the system. 7. Quality Control: The XN-L CHECK (K160586) is used as quality control (three levels) for Sysmex XN-L 3 analyzers. XN-L CHECK™ is an in-vitro diagnostic product that contains the following: stabilized red blood cell component(s), stabilized white blood cell component(s), and stabilized platelet component(s) in a preservative medium. XN CHECK (K160590) is used as quality control (three levels) for Sysmex XN series (XN-10, XN-11, XN-20, XN-21, XN-L) analyzers. XN CHECK™ is an in-vitro diagnostic product that contains the following: stabilized red blood cell component(s), stabilized white blood cell component(s), stabilized platelet component(s), and stabilized nucleated red blood cell component(s) in a preservative medium. XN CHECK BF (K160588) is used as quality control (two levels) for Sysmex XN series (XN-10, XN-11, XN-20, XN-21, XN-L) analyzers. Assayed parameters include: WBC- BF, RBC-BF, MN%, PMN%, TC-BF#. 8. Software: FDA has reviewed applicant’s Hazard Analysis and Software Development processes for this line of product types: Yes___X____ or No________ F. Regulatory Information: 1. Regulation section: 21 CFR 864.5220, Automated differential cell counter 2. Classification: Class II 3 Product code: GKZ, Counter, differential cell 4. Panel: Hematology (81) G. Intended Use: 1. Indication(s) for Use: The Sysmex XN-L analyzer is a quantitative multi-parameter automated hematology analyzer intended for in vitro diagnostic use in screening patient populations found in clinical laboratories. The XN-L analyzer classifies and enumerates the following 4 parameters in venous and capillary whole blood: WBC, RBC, HGB, HCT, MCV, MCH,MCHC, PLT, NEUT%/#, LYMPH%/#, MONO%/#, EO%/#, BASO%/#, IG%/#, RDW-CV, RDW-SD, MPV, RET%/#,IRF, RET-He and has a Body Fluid mode for body fluids. The Body Fluid mode enumerates the WBC-BF, RBC-BF, MN%/#, PMN%/#, and TC-BF# parameters in cerebrospinal, peritoneal, pleural, and synovial fluids. Whole blood should be collected in K2 or K3EDTA anticoagulant and peritoneal, pleural, and synovial fluids in K2EDTA anticoagulant to prevent clotting of fluid. The use of anticoagulants with CSF specimens is neither required nor recommended. The performance of this device has not been established in pediatric patients under the age of 2 years. 2. Special Conditions for Use Statement(s): For prescription use only. H. Substantial Equivalence Information: 1. Predicate Device Name(s) and 510(k) numbers: Sysmex XN-Series (XN-10, XN-20) Automated Hematology Analyzer, K112605 2. Comparison with Predicate Device: Similarities Item Device: XN-L Predicate: XN-Series (XN- 10)a K112605 Intended Use The Sysmex® XN-L analyzer is a quantitative multi-parameter automated hematology analyzer intended for in vitro diagnostic use in screening patient populations found in clinical laboratories. The XN-L analyzer classifies and enumerates the following parameters in whole blood: WBC, RBC, HGB, HCT, MCV, MCH, MCHC, PLT, NEUT%/#, LYMPH%/#, MONO%/#, EO%/#, BASO%/#, IG%/#, RDW-CV, RDW-SD,MPV, RET%/#, IRF, RET-He and has a Body Fluid mode for body fluids. The Body Fluid mode enumerates the WBCBF, RBC-BF, MN%/#, PMN%/#, and TC-BF# parameters in CSF, peritoneal, pleural and synovial fluids. Whole blood should The XN-Series modules (XN- 10, XN-20) are quantitative multi-parameter automated hematology analyzers intended for in vitro diagnostic use in screening patient populations found in clinical laboratories. The XN- Series modules Applicant:

idK160538_s0_e2000

K160538.txt

regulation section

21 CFR 864.5220, Automated differential cell counter

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K160538 B. Purpose for Submission: Clearance of a new device C. Manufacturer and Instrument Name: Sysmex America Inc., Sysmex® XN-L Automated Hematology Analyzer D. Type of Test or Tests Performed: The XN-L analyzer classifies and enumerates the following parameters in whole blood: WBC, RBC, HGB, HCT, MCV, MCH, MCHC, PLT, NEUT%/#, LYMPH%/#, MONO%/#, EO%/#, BASO%/#, IG%/#, RDW-CV, RDW-SD, MPV, RET%/#, IRF, RET-He and has a Body Fluid mode for body fluids. The Body Fluid mode enumerates the WBC-BF, RBC-BF, MN%/#, PMN%/#, and TC-BF# parameters in CSF, peritoneal, pleural and synovial fluids. E. System Descriptions: 1. Device Description: The Sysmex XN-L analyzer is a quantitative multi-parameter automated hematology analyzer intended for in vitro diagnostic use in screening patient populations found in clinical laboratories. The XN-L analyzer classifies and enumerates whole blood and body fluid parameters by means of electrical impedance, laser light scattering, and fluorescent labeling. Tests are performed on whole blood samples collected in K2 or K3 EDTA anticoagulant and body fluids (peritoneal, pleural and synovial) collected in K2EDTA anticoagulant and cerebrospinal fluid that is not collected in anticoagulant. The instrument consists of two principal units: (1) Main Unit which will aspirate, dilute, mix, and analyze whole blood and body fluid samples and (2) Pneumatic Unit which supplies pressure and vacuum to the analyzer. The XN-L has an external monitor with touch screen capability that is used to operate the instrument and process data from the Main Unit. The monitor also allows operator interfacing with the instrument by use of a panel keyboard 2. Principles of Operation: The XN-L analyzer performs analysis using the following methods: DC Sheath Flow 2 Detection method, Flow Cytometry method using a semiconductor laser, and SLS (cyanide-free sodium lauryl sulfate) hemoglobin method. Particle characterization and identification is based on detection of forward scatter, fluorescence, and adaptive cluster analysis. The XN-L analyzer automatically classifies cells from whole blood and body fluids and carries out all processes automatically from aspiration of the sample to result output. 3. Modes of Operation: Does the applicant’s device contain the ability to transmit data to a computer, webserver, or mobile device? Yes ___X____ or No ________ Does the applicant’s device transmit data to a computer, webserver, or mobile device using wireless transmission? Yes ________ or No ___X____ 4. Specimen Identification: Specimen identification input is manual (by operator) or by barcode reader 5. Specimen Sampling and Handling: There are two modes of sample introduction: (1) Sampler Mode; (2) Manual Mode. In the Sampler Mode the operator loads the sample tubes into a rack, which is then automatically transported and analyzed by the instrument. This mode automatically mixes, aspirates, and analyzes samples without removing their caps. The Sampler Mode is used for processing of whole blood samples. In the Manual Mode, there are two sample tube holders: (1) Normal sample tube holder; (2) Micro collection tube holder. In this mode the operator loads and mixes the samples tubes individually by hand. The samples in the Manual Mode can be analyzed with the cap on or off. The Manual Mode is used for processing whole blood and body fluid samples. 6. Calibration: The XN CALTM calibrator (K160585) is used for calibration of the instrument for WBC, RBC, HGB, HCT, PLT and RET. XN CAL is used for the calibration and calibration verification of Sysmex XN series (XN-10, XN-11, XN-20, XN-21, XN-L) analyzers. Calibration is performed as needed (e.g., when QC data is fluctuating) to ensure accuracy of the system. 7. Quality Control: The XN-L CHECK (K160586) is used as quality control (three levels) for Sysmex XN-L 3 analyzers. XN-L CHECK™ is an in-vitro diagnostic product that contains the following: stabilized red blood cell component(s), stabilized white blood cell component(s), and stabilized platelet component(s) in a preservative medium. XN CHECK (K160590) is used as quality control (three levels) for Sysmex XN series (XN-10, XN-11, XN-20, XN-21, XN-L) analyzers. XN CHECK™ is an in-vitro diagnostic product that contains the following: stabilized red blood cell component(s), stabilized white blood cell component(s), stabilized platelet component(s), and stabilized nucleated red blood cell component(s) in a preservative medium. XN CHECK BF (K160588) is used as quality control (two levels) for Sysmex XN series (XN-10, XN-11, XN-20, XN-21, XN-L) analyzers. Assayed parameters include: WBC- BF, RBC-BF, MN%, PMN%, TC-BF#. 8. Software: FDA has reviewed applicant’s Hazard Analysis and Software Development processes for this line of product types: Yes___X____ or No________ F. Regulatory Information: 1. Regulation section: 21 CFR 864.5220, Automated differential cell counter 2. Classification: Class II 3 Product code: GKZ, Counter, differential cell 4. Panel: Hematology (81) G. Intended Use: 1. Indication(s) for Use: The Sysmex XN-L analyzer is a quantitative multi-parameter automated hematology analyzer intended for in vitro diagnostic use in screening patient populations found in clinical laboratories. The XN-L analyzer classifies and enumerates the following 4 parameters in venous and capillary whole blood: WBC, RBC, HGB, HCT, MCV, MCH,MCHC, PLT, NEUT%/#, LYMPH%/#, MONO%/#, EO%/#, BASO%/#, IG%/#, RDW-CV, RDW-SD, MPV, RET%/#,IRF, RET-He and has a Body Fluid mode for body fluids. The Body Fluid mode enumerates the WBC-BF, RBC-BF, MN%/#, PMN%/#, and TC-BF# parameters in cerebrospinal, peritoneal, pleural, and synovial fluids. Whole blood should be collected in K2 or K3EDTA anticoagulant and peritoneal, pleural, and synovial fluids in K2EDTA anticoagulant to prevent clotting of fluid. The use of anticoagulants with CSF specimens is neither required nor recommended. The performance of this device has not been established in pediatric patients under the age of 2 years. 2. Special Conditions for Use Statement(s): For prescription use only. H. Substantial Equivalence Information: 1. Predicate Device Name(s) and 510(k) numbers: Sysmex XN-Series (XN-10, XN-20) Automated Hematology Analyzer, K112605 2. Comparison with Predicate Device: Similarities Item Device: XN-L Predicate: XN-Series (XN- 10)a K112605 Intended Use The Sysmex® XN-L analyzer is a quantitative multi-parameter automated hematology analyzer intended for in vitro diagnostic use in screening patient populations found in clinical laboratories. The XN-L analyzer classifies and enumerates the following parameters in whole blood: WBC, RBC, HGB, HCT, MCV, MCH, MCHC, PLT, NEUT%/#, LYMPH%/#, MONO%/#, EO%/#, BASO%/#, IG%/#, RDW-CV, RDW-SD,MPV, RET%/#, IRF, RET-He and has a Body Fluid mode for body fluids. The Body Fluid mode enumerates the WBCBF, RBC-BF, MN%/#, PMN%/#, and TC-BF# parameters in CSF, peritoneal, pleural and synovial fluids. Whole blood should The XN-Series modules (XN- 10, XN-20) are quantitative multi-parameter automated hematology analyzers intended for in vitro diagnostic use in screening patient populations found in clinical laboratories. The XN- Series modules Regulation section:

idK160538_s18000_e20000

K160538.txt

proposed labeling

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

Manual Mode Normal Tube Position and within 2 hours of analysis, the samples were transferred to micro collection tubes (without additive) and analyzed in the Manual Mode Micro-collection Tube Position. 2. Whole Blood Pre-dilute Mode Normal Tube to Micro-tube Comparison A total of 40 residual K2EDTA (4 mL tubes) anticoagulated whole blood samples were used to determine the equivalency between the Pre-dilute Mode Normal Tube Position and the Pre-dilute Mode Micro-collection tube position. Pre-diluted samples (1:7) were prepared for each sample by dispensing 420 μL of the analyzer diluent into plain top tubes (4 mL tubes) then adding 70 μL of whole blood and mixing 10 times by gentle inversion. The plain top 4 mL tubes were run in singlet in the Pre-dilute Mode normal tube position. Immediately following, the samples were mixed 10 times then transferred to micro-collection tubes (without additive) and analyzed in the Pre- dilute Mode micro-collection tube position (Cap Off). Results in the mode are automatically multiplied by 7 before results are displayed, therefore no additional calculation is required. 3. Low WBC (LWBC) Mode Normal Tube Position to Micro Tube Comparison- Whole Blood A total of 40 residual K2EDTA anticoagulated whole blood samples and 20 LWBC samples were used to determine the equivalency between the LWBC Mode Normal tube position and the LWBC Mode micro-collection tube position. The original K2EDTA sample tube was hand mixed by gentle inversion 10 times and run in the singlet in the LWBC Mode Normal tube position on the XN-L analyzer. Immediately following, the samples were mixed 10 times then transferred to micro-collection tubes (without additive) and analyzed in the LWBC Mode micro-collection tube position (Cap Off). E. Determination of limit of Blank, lower limits of detection and quantitation: Whole Blood Limit of Blank The Limit of Blank (LoB) for WBC, RBC, HGB, HCT and PLT was determined using the system diluent as a blank sample. A total of 12 repeated measurements using one blank sample were tested on four XN-L analyzers over a period of 5 days for a total of 60 measurements per analyzer (12 reps x 1 sample x 4 analyzers x 5 24 days) for each parameter. Testing was conducted in the Whole Blood Manual Mode in accordance with CLSI EP17-A2. The results obtained from all four analyzers were used to calculate the Mean, SD, and LoB for each parameter. The results of the LoB are included in the table below. Limit of Detection and Quantitation The Limit of Detection (LoD) for the WBC, RBC, HGB, HCT and PLT parameters were determined using venous whole blood K2EDTA anticoagulated samples diluted with system diluent to create four low concentration samples not exceeding three times the manufacturer’s claimed limit of blank for WBC, RBC, HGB, HCT, PLT, for a predicate device which is 0.10, 0.02, 0.1, 10, 0.001 and 0.003, respectively. Samples were tested in replicates of five measurements over three days using two XN-L analyzers for a total of 60 measurements for each parameter. Samples were mixed by gentle hand inversion 10 times and analyzed in Whole Blood Mode in accordance with CLSI EP17-A2. The measurements obtained from all analyzers were used to calculate the Mean, SD, and LoD for each parameter. The results of the LoD and LoQ are included in the following table below. [Whole Blood] mode Parameters Limit of blank (LoB) Limit of detection (LoD) Limit of quantitation (LoQ) Units WBC*1 0.00 0.01 0.03 x 103/μL RBC 0.00 0.00 0.00 x 106/μL HGB 0.0 0.0 0.0 g/dL PLT 0 0 1 x 103/μL HCT 0.0 0.0 0.0 % *1 The white blood cell count measured from the WDF channel. (CBC+DIFF mode) Body Fluids Limit of Blank The LoB for WBC-BF, RBC-BF and TC-BF was determined using the system diluent as a blank sample. A total of 12 repeated measurements using one blank sample were tested on four XN-L analyzers over a period of 5 days for a total of 60 measurements per analyzer (12 reps x 1 sample x 4 analyzers x 5 days) for each parameter. Testing was conducted in the Body Fluid Mode by one operator in accordance with the CLSI EP17-A2 approved guideline. The results obtained from all four analyzers were used to calculate the Mean, SD, and LoB for each parameter. The results of the LoB are included in the table below. Limits of Detection and Quantitation The LoD for the WBC-BF, RBC-BF and TC-BF parameters were determined using 25 body fluid samples diluted with system diluent to create four low concentration samples not exceeding three times the manufacture’s claimed limit of blank for BC- BF/TC-BF and RBC-BF for a predicate device which is 0.10, 0.02, 0.1, 10, 0.001 and 0.003, respectively. Samples were tested in replicates of five measurements over 3 days using two XN-L analyzers for a total of 60 measurements for each parameter. Samples were mixed by gentle hand inversion 10 times and analyzed in the Body Fluid Manual Mode and tested in accordance with CLSI EP17-A2. The measurements obtained from all analyzers were used to calculate the Mean, SD, and LoD for each parameter. The results of the LoD and LoQ are included in the following table below. [Body Fluid] Mode Parameters Limit of blank (LoB) Limit of detection (LoD) Limit of quantitation (LoQ) Units WBC-BF 0.000 0.002 0.004 x 103/μL RBC-BF 0.000 0.000 0.001 x 103/μL TC-BF# 0.000 0.002 0.004 x 103/μL K. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. L. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Proposed labeling:

idK160538_s18000_e20000

K160538.txt

conclusion

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

in the Manual Mode Normal Tube Position and within 2 hours of analysis, the samples were transferred to micro collection tubes (without additive) and analyzed in the Manual Mode Micro-collection Tube Position. 2. Whole Blood Pre-dilute Mode Normal Tube to Micro-tube Comparison A total of 40 residual K2EDTA (4 mL tubes) anticoagulated whole blood samples were used to determine the equivalency between the Pre-dilute Mode Normal Tube Position and the Pre-dilute Mode Micro-collection tube position. Pre-diluted samples (1:7) were prepared for each sample by dispensing 420 μL of the analyzer diluent into plain top tubes (4 mL tubes) then adding 70 μL of whole blood and mixing 10 times by gentle inversion. The plain top 4 mL tubes were run in singlet in the Pre-dilute Mode normal tube position. Immediately following, the samples were mixed 10 times then transferred to micro-collection tubes (without additive) and analyzed in the Pre- dilute Mode micro-collection tube position (Cap Off). Results in the mode are automatically multiplied by 7 before results are displayed, therefore no additional calculation is required. 3. Low WBC (LWBC) Mode Normal Tube Position to Micro Tube Comparison- Whole Blood A total of 40 residual K2EDTA anticoagulated whole blood samples and 20 LWBC samples were used to determine the equivalency between the LWBC Mode Normal tube position and the LWBC Mode micro-collection tube position. The original K2EDTA sample tube was hand mixed by gentle inversion 10 times and run in the singlet in the LWBC Mode Normal tube position on the XN-L analyzer. Immediately following, the samples were mixed 10 times then transferred to micro-collection tubes (without additive) and analyzed in the LWBC Mode micro-collection tube position (Cap Off). E. Determination of limit of Blank, lower limits of detection and quantitation: Whole Blood Limit of Blank The Limit of Blank (LoB) for WBC, RBC, HGB, HCT and PLT was determined using the system diluent as a blank sample. A total of 12 repeated measurements using one blank sample were tested on four XN-L analyzers over a period of 5 days for a total of 60 measurements per analyzer (12 reps x 1 sample x 4 analyzers x 5 24 days) for each parameter. Testing was conducted in the Whole Blood Manual Mode in accordance with CLSI EP17-A2. The results obtained from all four analyzers were used to calculate the Mean, SD, and LoB for each parameter. The results of the LoB are included in the table below. Limit of Detection and Quantitation The Limit of Detection (LoD) for the WBC, RBC, HGB, HCT and PLT parameters were determined using venous whole blood K2EDTA anticoagulated samples diluted with system diluent to create four low concentration samples not exceeding three times the manufacturer’s claimed limit of blank for WBC, RBC, HGB, HCT, PLT, for a predicate device which is 0.10, 0.02, 0.1, 10, 0.001 and 0.003, respectively. Samples were tested in replicates of five measurements over three days using two XN-L analyzers for a total of 60 measurements for each parameter. Samples were mixed by gentle hand inversion 10 times and analyzed in Whole Blood Mode in accordance with CLSI EP17-A2. The measurements obtained from all analyzers were used to calculate the Mean, SD, and LoD for each parameter. The results of the LoD and LoQ are included in the following table below. [Whole Blood] mode Parameters Limit of blank (LoB) Limit of detection (LoD) Limit of quantitation (LoQ) Units WBC*1 0.00 0.01 0.03 x 103/μL RBC 0.00 0.00 0.00 x 106/μL HGB 0.0 0.0 0.0 g/dL PLT 0 0 1 x 103/μL HCT 0.0 0.0 0.0 % *1 The white blood cell count measured from the WDF channel. (CBC+DIFF mode) Body Fluids Limit of Blank The LoB for WBC-BF, RBC-BF and TC-BF was determined using the system diluent as a blank sample. A total of 12 repeated measurements using one blank sample were tested on four XN-L analyzers over a period of 5 days for a total of 60 measurements per analyzer (12 reps x 1 sample x 4 analyzers x 5 days) for each parameter. Testing was conducted in the Body Fluid Mode by one operator in accordance with the CLSI EP17-A2 approved guideline. The results obtained from all four analyzers were used to calculate the Mean, SD, and LoB for each parameter. The results of the LoB are included in the table below. Limits of Detection and Quantitation The LoD for the WBC-BF, RBC-BF and TC-BF parameters were determined using 25 body fluid samples diluted with system diluent to create four low concentration samples not exceeding three times the manufacture’s claimed limit of blank for BC- BF/TC-BF and RBC-BF for a predicate device which is 0.10, 0.02, 0.1, 10, 0.001 and 0.003, respectively. Samples were tested in replicates of five measurements over 3 days using two XN-L analyzers for a total of 60 measurements for each parameter. Samples were mixed by gentle hand inversion 10 times and analyzed in the Body Fluid Manual Mode and tested in accordance with CLSI EP17-A2. The measurements obtained from all analyzers were used to calculate the Mean, SD, and LoD for each parameter. The results of the LoD and LoQ are included in the following table below. [Body Fluid] Mode Parameters Limit of blank (LoB) Limit of detection (LoD) Limit of quantitation (LoQ) Units WBC-BF 0.000 0.002 0.004 x 103/μL RBC-BF 0.000 0.000 0.001 x 103/μL TC-BF# 0.000 0.002 0.004 x 103/μL K. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. L. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Conclusion:

idK161714_s0_e2000

K161714.txt

purpose for submission

New device

ANTIAL EQUIVALENCE DETERMINATION DECISION MEMORANDUM ASSAY ONLY TEMPLATE A. 510(k) Number: k161714 B. Purpose for Submission: New device C. Measurand: Barbiturates D. Type of Test: Homogenous Enzyme Immunoassay, Qualitative and Semi-quantitative. E. Applicant: Immunalysis Corporation F. Proprietary and Established Names: Immunalysis Barbiturates Urine Enzyme Immunoassay Immunalysis Multi-Drug Calibrators G. Regulatory Information: 1. Regulation section: 1 21 CFR 862.3150 Barbiturate test system 21 CFR 862.3200, Clinical toxicology calibrator 2. Classification: Class II 3. Product code: DIS DKB 4. Panel: 2 Toxicology (91) H. Intended Use: 1. Intended use(s): Refer to Indications for Use below 2. Indication(s) for use: Immunalysis Barbiturates Urine Enzyme Immunoassay The Immunalysis Barbiturates Urine Enzyme Immunoassay is a homogeneous enzyme immunoassay with a cutoff of 200 ng/mL. The assay is intended for use in laboratories for the qualitative and semi-quantitative analysis of Barbiturates in human urine with automated clinical chemistry analyzers. This assay is calibrated against Secobarbital. This in vitro diagnostic device is for prescription use only. The semi-quantitative mode is for purposes of enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as Gas Chromatography/ Mass Spectrometry (GC-MS) or Liquid Chromatography/ Tandem Mass Spectrometry (LC-MS/MS) or permitting laboratories to establish quality control procedures. The Immunalysis Barbiturates Urine Enzyme Immunoassay provides only a preliminary analytical test result. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. GC-MS or LC-MS/MS is the preferred confirmatory method. Clinical consideration and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are used. lmmunalysis Multi-Drug Calibrators: The lmmunalysis Multi-Drug Calibrators are intended for in vitro diagnostic use for the calibration of assays for the following analytes: Benzoylecgonine, Methamphetamine, Morphine, PCP, Secobarbital and Oxazepam. The calibrators are designed for prescription use with immunoassays. 3. Special conditions for use statement(s): For prescription use only. 4. Special instrument requirements: Performance data was obtained using the Beckman AU400e clinical chemistry analyzer. I. Device Description: The Immunalysis Barbiturates Urine Enzyme Immunoassay Kit reagents are provided as ready to use liquids and consist of the following reagents: · The Antibody/ Substrate Reagent (Reagent A; 25, 100, or 500 mL) contains a recombinant antibody to Secobarbital, a mouse monoclonal antibody to Secobarbital, glucose-6-phosphate (G6P) and nicotinamide adenine dinucleotide (NAD) in HEPES buffer with Sodium Azide as a preservative. · The Enzyme Conjugate Reagent (Reagent E; 25, 100, or 500 mL) contains glucose-6- phosphate dehydrogenase (G6PDH) labeled with Barbiturates in HEPES buffer with Sodium Azide as a preservative. Immunalysis Multi-Drug Calibrators are provided separately, as five individual, liquid ready-to use drug levels (15 mL or 25 mL). J. Substantial Equivalence Information: 1. Predicate device name(s): 3 DRI Barbiturates EIA Assay 2. Predicate 510(k) number(s): k955928 3. Comparison with predicate: Similarities - Reagent Item Candidate Device – Immunalysis Barbiturates Urine Enzyme Immunoassay Predicate Device – DRI Barbiturates EIA Assay k955928 Intended Use Same For the qualitative and semiquantitative determination of the presence of Barbiturates in human urine Assay cutoff Same 200 ng/mL Calibrator compound Same Secobarbital Assay type Same Homogeneous enzyme immunoassay, qualitative and semi-quantitative Storage conditions Same 2° - 8° C 4 Differences - Reagent Item Candidate Device – Immunalysis Barbiturates Urine Enzyme Immunoassay Predicate Device – DRI Barbiturates EIA Assay k955928 Calibrators Provided separately Provided with assay Controls Provided separately Provided with assay Antibody type Recombinant and mouse monoclonal Mouse monoclonal Similarities - Calibrators Item Candidate Device – Immunalysis Multi-Drug Calibrators (MDC) Predicate Device – Calibrators included with DRI Barbiturates EIA Assay k955928 Calibrator drug Same Secobarbital Differences - Calibrators Item Candidate Device – Immunalysis Negative and Multi-Drug Calibrators (MDC) Predicate Device – Calibrators included with DRI Barbiturates EIA Assay k955928 Calibrator Levels Calibrator levels at 0 100, 200, 500 and 1000 ng/mL Calibrator levels at 0, 200, and 1000 ng/mL K. Standard/Guidance Document Referenced (if applicable): · CLSI EP5-A3: Evaluation of Precision Performance of Quantitative Measurement Methods · CLSI EP 7-A3: Interference Testing in Clinical Chemistry. · ISO 14971 Second edition 2007-03-01, Medical devices – application of risk management to medical devices · EN ISO 14971:2012 Medical devices. Application of risk management to medical devices L. Test Principle: This assay uses a recombinant and a mouse monoclonal antibody, both directed against Secobarbital. The assay is based on the competition of Barbiturates labeled enzyme glucose- 6-phosphate dehydrogenase (G6PDH) and the free drug in the urine sample for the fixed amount of antibody binding sites. In the absence of the free drug in the sample, the antibody binds the drug enzyme conjugate and enzyme activity is inhibited. This creates a dose response relationship between drug concentration in the urine and enzyme activity. The enzyme G6PDH activity is determined at 340 nm spectrophotometrically by the conversion of Nicotinamide Adenine Dinucleotide (NAD) to NADH. M. Performance Characteristics (if/when applicable): 1. Analytical performance: 5 a. Precision/Reproducibility: A precision/cutoff characterization study was performed over 20 days, with two runs per day in duplicate (n=80) on calibrators (100 and 200 ng/mL), controls (150 and 250 ng/mL) and drug-free negative urine samples spiked with secobarbital to concentrations of 50, 300, 350, and 400 ng/mL. The spiked concentrations were confirmed by mass spectrometry (MS). The concentrations and results of the study are summarized below: Qualitative Analysis Concentration (ng/mL) % of cutoff # of determinations Result 0 -100% 80 80 neg / 0 pos 50 -75% 80 80 neg / 0 pos 100 -50% 80 80 neg / 0 pos 150 -25% 80 80 neg / 0 pos 200 Cutoff 80 33 neg / 47 pos 250 +25% 80 0 neg / 80 pos 300 +50% 80 0 neg / 80 pos 350 +75% 80 0 neg / 80 pos 400 +100% 80 0 neg / 80 pos Semi -quantitative Analysis Concentration (ng/mL) % of cutoff # of determinations Result 0 -100% 80 80 neg / 0 pos 50 -75% 80 80 neg / 0 pos 100 -50% 80 80 neg / 0 pos 150 -25% 80 80 neg / 0 pos 200 Cutoff 80 23 neg / 57 pos 250 +25% 80 0 neg / 80 pos 300 +50% 80 0 neg / 80 pos 350 +75% 80 0 neg / 80 pos 400 +100% 80 0 neg / 80 pos b. Linearity/assay reportable range: A linearity study in the semi-quantitative mode was conducted by spiking a drug-free urine pool with a high concentration of Secobarbital and generating serial dilutions to achieve concentrations ranging from 0 ng/mL to 1100 ng/mL. The 0 ng/mL sample utilized drug free urine and was not achieved through serial dilution. Each concentration was tested in triplicate and drug recovery calculated using the mean concentration of the replicates. The results are summarized below: 6 Linearity/Recovery Expected Concentration (ng/mL) Mean Concentration (ng/mL) Recovery (%) 0 -0.6 n/a 100 93.2 93.2 200 196.0 98.0 300 314.7 104.9 400 418.1 104.5 500 487.9 97.6 600 604.1 100.7 700 724.2 103.5 800 819.3 102.4 900 891.2 99.0 1000 968.7 96.9 1100 981.8 89.3 c. Traceability, Stability, Expected values (controls, calibrators, or methods): Traceability The secobarbital Purpose for submission:

idK161714_s0_e2000

K161714.txt

measurand

Barbiturates

ANTIAL EQUIVALENCE DETERMINATION DECISION MEMORANDUM ASSAY ONLY TEMPLATE A. 510(k) Number: k161714 B. Purpose for Submission: New device C. Measurand: Barbiturates D. Type of Test: Homogenous Enzyme Immunoassay, Qualitative and Semi-quantitative. E. Applicant: Immunalysis Corporation F. Proprietary and Established Names: Immunalysis Barbiturates Urine Enzyme Immunoassay Immunalysis Multi-Drug Calibrators G. Regulatory Information: 1. Regulation section: 1 21 CFR 862.3150 Barbiturate test system 21 CFR 862.3200, Clinical toxicology calibrator 2. Classification: Class II 3. Product code: DIS DKB 4. Panel: 2 Toxicology (91) H. Intended Use: 1. Intended use(s): Refer to Indications for Use below 2. Indication(s) for use: Immunalysis Barbiturates Urine Enzyme Immunoassay The Immunalysis Barbiturates Urine Enzyme Immunoassay is a homogeneous enzyme immunoassay with a cutoff of 200 ng/mL. The assay is intended for use in laboratories for the qualitative and semi-quantitative analysis of Barbiturates in human urine with automated clinical chemistry analyzers. This assay is calibrated against Secobarbital. This in vitro diagnostic device is for prescription use only. The semi-quantitative mode is for purposes of enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as Gas Chromatography/ Mass Spectrometry (GC-MS) or Liquid Chromatography/ Tandem Mass Spectrometry (LC-MS/MS) or permitting laboratories to establish quality control procedures. The Immunalysis Barbiturates Urine Enzyme Immunoassay provides only a preliminary analytical test result. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. GC-MS or LC-MS/MS is the preferred confirmatory method. Clinical consideration and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are used. lmmunalysis Multi-Drug Calibrators: The lmmunalysis Multi-Drug Calibrators are intended for in vitro diagnostic use for the calibration of assays for the following analytes: Benzoylecgonine, Methamphetamine, Morphine, PCP, Secobarbital and Oxazepam. The calibrators are designed for prescription use with immunoassays. 3. Special conditions for use statement(s): For prescription use only. 4. Special instrument requirements: Performance data was obtained using the Beckman AU400e clinical chemistry analyzer. I. Device Description: The Immunalysis Barbiturates Urine Enzyme Immunoassay Kit reagents are provided as ready to use liquids and consist of the following reagents: · The Antibody/ Substrate Reagent (Reagent A; 25, 100, or 500 mL) contains a recombinant antibody to Secobarbital, a mouse monoclonal antibody to Secobarbital, glucose-6-phosphate (G6P) and nicotinamide adenine dinucleotide (NAD) in HEPES buffer with Sodium Azide as a preservative. · The Enzyme Conjugate Reagent (Reagent E; 25, 100, or 500 mL) contains glucose-6- phosphate dehydrogenase (G6PDH) labeled with Barbiturates in HEPES buffer with Sodium Azide as a preservative. Immunalysis Multi-Drug Calibrators are provided separately, as five individual, liquid ready-to use drug levels (15 mL or 25 mL). J. Substantial Equivalence Information: 1. Predicate device name(s): 3 DRI Barbiturates EIA Assay 2. Predicate 510(k) number(s): k955928 3. Comparison with predicate: Similarities - Reagent Item Candidate Device – Immunalysis Barbiturates Urine Enzyme Immunoassay Predicate Device – DRI Barbiturates EIA Assay k955928 Intended Use Same For the qualitative and semiquantitative determination of the presence of Barbiturates in human urine Assay cutoff Same 200 ng/mL Calibrator compound Same Secobarbital Assay type Same Homogeneous enzyme immunoassay, qualitative and semi-quantitative Storage conditions Same 2° - 8° C 4 Differences - Reagent Item Candidate Device – Immunalysis Barbiturates Urine Enzyme Immunoassay Predicate Device – DRI Barbiturates EIA Assay k955928 Calibrators Provided separately Provided with assay Controls Provided separately Provided with assay Antibody type Recombinant and mouse monoclonal Mouse monoclonal Similarities - Calibrators Item Candidate Device – Immunalysis Multi-Drug Calibrators (MDC) Predicate Device – Calibrators included with DRI Barbiturates EIA Assay k955928 Calibrator drug Same Secobarbital Differences - Calibrators Item Candidate Device – Immunalysis Negative and Multi-Drug Calibrators (MDC) Predicate Device – Calibrators included with DRI Barbiturates EIA Assay k955928 Calibrator Levels Calibrator levels at 0 100, 200, 500 and 1000 ng/mL Calibrator levels at 0, 200, and 1000 ng/mL K. Standard/Guidance Document Referenced (if applicable): · CLSI EP5-A3: Evaluation of Precision Performance of Quantitative Measurement Methods · CLSI EP 7-A3: Interference Testing in Clinical Chemistry. · ISO 14971 Second edition 2007-03-01, Medical devices – application of risk management to medical devices · EN ISO 14971:2012 Medical devices. Application of risk management to medical devices L. Test Principle: This assay uses a recombinant and a mouse monoclonal antibody, both directed against Secobarbital. The assay is based on the competition of Barbiturates labeled enzyme glucose- 6-phosphate dehydrogenase (G6PDH) and the free drug in the urine sample for the fixed amount of antibody binding sites. In the absence of the free drug in the sample, the antibody binds the drug enzyme conjugate and enzyme activity is inhibited. This creates a dose response relationship between drug concentration in the urine and enzyme activity. The enzyme G6PDH activity is determined at 340 nm spectrophotometrically by the conversion of Nicotinamide Adenine Dinucleotide (NAD) to NADH. M. Performance Characteristics (if/when applicable): 1. Analytical performance: 5 a. Precision/Reproducibility: A precision/cutoff characterization study was performed over 20 days, with two runs per day in duplicate (n=80) on calibrators (100 and 200 ng/mL), controls (150 and 250 ng/mL) and drug-free negative urine samples spiked with secobarbital to concentrations of 50, 300, 350, and 400 ng/mL. The spiked concentrations were confirmed by mass spectrometry (MS). The concentrations and results of the study are summarized below: Qualitative Analysis Concentration (ng/mL) % of cutoff # of determinations Result 0 -100% 80 80 neg / 0 pos 50 -75% 80 80 neg / 0 pos 100 -50% 80 80 neg / 0 pos 150 -25% 80 80 neg / 0 pos 200 Cutoff 80 33 neg / 47 pos 250 +25% 80 0 neg / 80 pos 300 +50% 80 0 neg / 80 pos 350 +75% 80 0 neg / 80 pos 400 +100% 80 0 neg / 80 pos Semi -quantitative Analysis Concentration (ng/mL) % of cutoff # of determinations Result 0 -100% 80 80 neg / 0 pos 50 -75% 80 80 neg / 0 pos 100 -50% 80 80 neg / 0 pos 150 -25% 80 80 neg / 0 pos 200 Cutoff 80 23 neg / 57 pos 250 +25% 80 0 neg / 80 pos 300 +50% 80 0 neg / 80 pos 350 +75% 80 0 neg / 80 pos 400 +100% 80 0 neg / 80 pos b. Linearity/assay reportable range: A linearity study in the semi-quantitative mode was conducted by spiking a drug-free urine pool with a high concentration of Secobarbital and generating serial dilutions to achieve concentrations ranging from 0 ng/mL to 1100 ng/mL. The 0 ng/mL sample utilized drug free urine and was not achieved through serial dilution. Each concentration was tested in triplicate and drug recovery calculated using the mean concentration of the replicates. The results are summarized below: 6 Linearity/Recovery Expected Concentration (ng/mL) Mean Concentration (ng/mL) Recovery (%) 0 -0.6 n/a 100 93.2 93.2 200 196.0 98.0 300 314.7 104.9 400 418.1 104.5 500 487.9 97.6 600 604.1 100.7 700 724.2 103.5 800 819.3 102.4 900 891.2 99.0 1000 968.7 96.9 1100 981.8 89.3 c. Traceability, Stability, Expected values (controls, calibrators, or methods): Traceability The secobarbital Measurand:

idK161714_s0_e2000

K161714.txt

type of test

Homogenous Enzyme Immunoassay, Qualitative and Semi-quantitative.

STANTIAL EQUIVALENCE DETERMINATION DECISION MEMORANDUM ASSAY ONLY TEMPLATE A. 510(k) Number: k161714 B. Purpose for Submission: New device C. Measurand: Barbiturates D. Type of Test: Homogenous Enzyme Immunoassay, Qualitative and Semi-quantitative. E. Applicant: Immunalysis Corporation F. Proprietary and Established Names: Immunalysis Barbiturates Urine Enzyme Immunoassay Immunalysis Multi-Drug Calibrators G. Regulatory Information: 1. Regulation section: 1 21 CFR 862.3150 Barbiturate test system 21 CFR 862.3200, Clinical toxicology calibrator 2. Classification: Class II 3. Product code: DIS DKB 4. Panel: 2 Toxicology (91) H. Intended Use: 1. Intended use(s): Refer to Indications for Use below 2. Indication(s) for use: Immunalysis Barbiturates Urine Enzyme Immunoassay The Immunalysis Barbiturates Urine Enzyme Immunoassay is a homogeneous enzyme immunoassay with a cutoff of 200 ng/mL. The assay is intended for use in laboratories for the qualitative and semi-quantitative analysis of Barbiturates in human urine with automated clinical chemistry analyzers. This assay is calibrated against Secobarbital. This in vitro diagnostic device is for prescription use only. The semi-quantitative mode is for purposes of enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as Gas Chromatography/ Mass Spectrometry (GC-MS) or Liquid Chromatography/ Tandem Mass Spectrometry (LC-MS/MS) or permitting laboratories to establish quality control procedures. The Immunalysis Barbiturates Urine Enzyme Immunoassay provides only a preliminary analytical test result. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. GC-MS or LC-MS/MS is the preferred confirmatory method. Clinical consideration and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are used. lmmunalysis Multi-Drug Calibrators: The lmmunalysis Multi-Drug Calibrators are intended for in vitro diagnostic use for the calibration of assays for the following analytes: Benzoylecgonine, Methamphetamine, Morphine, PCP, Secobarbital and Oxazepam. The calibrators are designed for prescription use with immunoassays. 3. Special conditions for use statement(s): For prescription use only. 4. Special instrument requirements: Performance data was obtained using the Beckman AU400e clinical chemistry analyzer. I. Device Description: The Immunalysis Barbiturates Urine Enzyme Immunoassay Kit reagents are provided as ready to use liquids and consist of the following reagents: · The Antibody/ Substrate Reagent (Reagent A; 25, 100, or 500 mL) contains a recombinant antibody to Secobarbital, a mouse monoclonal antibody to Secobarbital, glucose-6-phosphate (G6P) and nicotinamide adenine dinucleotide (NAD) in HEPES buffer with Sodium Azide as a preservative. · The Enzyme Conjugate Reagent (Reagent E; 25, 100, or 500 mL) contains glucose-6- phosphate dehydrogenase (G6PDH) labeled with Barbiturates in HEPES buffer with Sodium Azide as a preservative. Immunalysis Multi-Drug Calibrators are provided separately, as five individual, liquid ready-to use drug levels (15 mL or 25 mL). J. Substantial Equivalence Information: 1. Predicate device name(s): 3 DRI Barbiturates EIA Assay 2. Predicate 510(k) number(s): k955928 3. Comparison with predicate: Similarities - Reagent Item Candidate Device – Immunalysis Barbiturates Urine Enzyme Immunoassay Predicate Device – DRI Barbiturates EIA Assay k955928 Intended Use Same For the qualitative and semiquantitative determination of the presence of Barbiturates in human urine Assay cutoff Same 200 ng/mL Calibrator compound Same Secobarbital Assay type Same Homogeneous enzyme immunoassay, qualitative and semi-quantitative Storage conditions Same 2° - 8° C 4 Differences - Reagent Item Candidate Device – Immunalysis Barbiturates Urine Enzyme Immunoassay Predicate Device – DRI Barbiturates EIA Assay k955928 Calibrators Provided separately Provided with assay Controls Provided separately Provided with assay Antibody type Recombinant and mouse monoclonal Mouse monoclonal Similarities - Calibrators Item Candidate Device – Immunalysis Multi-Drug Calibrators (MDC) Predicate Device – Calibrators included with DRI Barbiturates EIA Assay k955928 Calibrator drug Same Secobarbital Differences - Calibrators Item Candidate Device – Immunalysis Negative and Multi-Drug Calibrators (MDC) Predicate Device – Calibrators included with DRI Barbiturates EIA Assay k955928 Calibrator Levels Calibrator levels at 0 100, 200, 500 and 1000 ng/mL Calibrator levels at 0, 200, and 1000 ng/mL K. Standard/Guidance Document Referenced (if applicable): · CLSI EP5-A3: Evaluation of Precision Performance of Quantitative Measurement Methods · CLSI EP 7-A3: Interference Testing in Clinical Chemistry. · ISO 14971 Second edition 2007-03-01, Medical devices – application of risk management to medical devices · EN ISO 14971:2012 Medical devices. Application of risk management to medical devices L. Test Principle: This assay uses a recombinant and a mouse monoclonal antibody, both directed against Secobarbital. The assay is based on the competition of Barbiturates labeled enzyme glucose- 6-phosphate dehydrogenase (G6PDH) and the free drug in the urine sample for the fixed amount of antibody binding sites. In the absence of the free drug in the sample, the antibody binds the drug enzyme conjugate and enzyme activity is inhibited. This creates a dose response relationship between drug concentration in the urine and enzyme activity. The enzyme G6PDH activity is determined at 340 nm spectrophotometrically by the conversion of Nicotinamide Adenine Dinucleotide (NAD) to NADH. M. Performance Characteristics (if/when applicable): 1. Analytical performance: 5 a. Precision/Reproducibility: A precision/cutoff characterization study was performed over 20 days, with two runs per day in duplicate (n=80) on calibrators (100 and 200 ng/mL), controls (150 and 250 ng/mL) and drug-free negative urine samples spiked with secobarbital to concentrations of 50, 300, 350, and 400 ng/mL. The spiked concentrations were confirmed by mass spectrometry (MS). The concentrations and results of the study are summarized below: Qualitative Analysis Concentration (ng/mL) % of cutoff # of determinations Result 0 -100% 80 80 neg / 0 pos 50 -75% 80 80 neg / 0 pos 100 -50% 80 80 neg / 0 pos 150 -25% 80 80 neg / 0 pos 200 Cutoff 80 33 neg / 47 pos 250 +25% 80 0 neg / 80 pos 300 +50% 80 0 neg / 80 pos 350 +75% 80 0 neg / 80 pos 400 +100% 80 0 neg / 80 pos Semi -quantitative Analysis Concentration (ng/mL) % of cutoff # of determinations Result 0 -100% 80 80 neg / 0 pos 50 -75% 80 80 neg / 0 pos 100 -50% 80 80 neg / 0 pos 150 -25% 80 80 neg / 0 pos 200 Cutoff 80 23 neg / 57 pos 250 +25% 80 0 neg / 80 pos 300 +50% 80 0 neg / 80 pos 350 +75% 80 0 neg / 80 pos 400 +100% 80 0 neg / 80 pos b. Linearity/assay reportable range: A linearity study in the semi-quantitative mode was conducted by spiking a drug-free urine pool with a high concentration of Secobarbital and generating serial dilutions to achieve concentrations ranging from 0 ng/mL to 1100 ng/mL. The 0 ng/mL sample utilized drug free urine and was not achieved through serial dilution. Each concentration was tested in triplicate and drug recovery calculated using the mean concentration of the replicates. The results are summarized below: 6 Linearity/Recovery Expected Concentration (ng/mL) Mean Concentration (ng/mL) Recovery (%) 0 -0.6 n/a 100 93.2 93.2 200 196.0 98.0 300 314.7 104.9 400 418.1 104.5 500 487.9 97.6 600 604.1 100.7 700 724.2 103.5 800 819.3 102.4 900 891.2 99.0 1000 968.7 96.9 1100 981.8 89.3 c. Traceability, Stability, Expected values (controls, calibrators, or methods): Traceability The secobarbital Type of test:

idK161714_s0_e2000

K161714.txt

classification

Class II

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION MEMORANDUM ASSAY ONLY TEMPLATE A. 510(k) Number: k161714 B. Purpose for Submission: New device C. Measurand: Barbiturates D. Type of Test: Homogenous Enzyme Immunoassay, Qualitative and Semi-quantitative. E. Applicant: Immunalysis Corporation F. Proprietary and Established Names: Immunalysis Barbiturates Urine Enzyme Immunoassay Immunalysis Multi-Drug Calibrators G. Regulatory Information: 1. Regulation section: 1 21 CFR 862.3150 Barbiturate test system 21 CFR 862.3200, Clinical toxicology calibrator 2. Classification: Class II 3. Product code: DIS DKB 4. Panel: 2 Toxicology (91) H. Intended Use: 1. Intended use(s): Refer to Indications for Use below 2. Indication(s) for use: Immunalysis Barbiturates Urine Enzyme Immunoassay The Immunalysis Barbiturates Urine Enzyme Immunoassay is a homogeneous enzyme immunoassay with a cutoff of 200 ng/mL. The assay is intended for use in laboratories for the qualitative and semi-quantitative analysis of Barbiturates in human urine with automated clinical chemistry analyzers. This assay is calibrated against Secobarbital. This in vitro diagnostic device is for prescription use only. The semi-quantitative mode is for purposes of enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as Gas Chromatography/ Mass Spectrometry (GC-MS) or Liquid Chromatography/ Tandem Mass Spectrometry (LC-MS/MS) or permitting laboratories to establish quality control procedures. The Immunalysis Barbiturates Urine Enzyme Immunoassay provides only a preliminary analytical test result. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. GC-MS or LC-MS/MS is the preferred confirmatory method. Clinical consideration and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are used. lmmunalysis Multi-Drug Calibrators: The lmmunalysis Multi-Drug Calibrators are intended for in vitro diagnostic use for the calibration of assays for the following analytes: Benzoylecgonine, Methamphetamine, Morphine, PCP, Secobarbital and Oxazepam. The calibrators are designed for prescription use with immunoassays. 3. Special conditions for use statement(s): For prescription use only. 4. Special instrument requirements: Performance data was obtained using the Beckman AU400e clinical chemistry analyzer. I. Device Description: The Immunalysis Barbiturates Urine Enzyme Immunoassay Kit reagents are provided as ready to use liquids and consist of the following reagents: · The Antibody/ Substrate Reagent (Reagent A; 25, 100, or 500 mL) contains a recombinant antibody to Secobarbital, a mouse monoclonal antibody to Secobarbital, glucose-6-phosphate (G6P) and nicotinamide adenine dinucleotide (NAD) in HEPES buffer with Sodium Azide as a preservative. · The Enzyme Conjugate Reagent (Reagent E; 25, 100, or 500 mL) contains glucose-6- phosphate dehydrogenase (G6PDH) labeled with Barbiturates in HEPES buffer with Sodium Azide as a preservative. Immunalysis Multi-Drug Calibrators are provided separately, as five individual, liquid ready-to use drug levels (15 mL or 25 mL). J. Substantial Equivalence Information: 1. Predicate device name(s): 3 DRI Barbiturates EIA Assay 2. Predicate 510(k) number(s): k955928 3. Comparison with predicate: Similarities - Reagent Item Candidate Device – Immunalysis Barbiturates Urine Enzyme Immunoassay Predicate Device – DRI Barbiturates EIA Assay k955928 Intended Use Same For the qualitative and semiquantitative determination of the presence of Barbiturates in human urine Assay cutoff Same 200 ng/mL Calibrator compound Same Secobarbital Assay type Same Homogeneous enzyme immunoassay, qualitative and semi-quantitative Storage conditions Same 2° - 8° C 4 Differences - Reagent Item Candidate Device – Immunalysis Barbiturates Urine Enzyme Immunoassay Predicate Device – DRI Barbiturates EIA Assay k955928 Calibrators Provided separately Provided with assay Controls Provided separately Provided with assay Antibody type Recombinant and mouse monoclonal Mouse monoclonal Similarities - Calibrators Item Candidate Device – Immunalysis Multi-Drug Calibrators (MDC) Predicate Device – Calibrators included with DRI Barbiturates EIA Assay k955928 Calibrator drug Same Secobarbital Differences - Calibrators Item Candidate Device – Immunalysis Negative and Multi-Drug Calibrators (MDC) Predicate Device – Calibrators included with DRI Barbiturates EIA Assay k955928 Calibrator Levels Calibrator levels at 0 100, 200, 500 and 1000 ng/mL Calibrator levels at 0, 200, and 1000 ng/mL K. Standard/Guidance Document Referenced (if applicable): · CLSI EP5-A3: Evaluation of Precision Performance of Quantitative Measurement Methods · CLSI EP 7-A3: Interference Testing in Clinical Chemistry. · ISO 14971 Second edition 2007-03-01, Medical devices – application of risk management to medical devices · EN ISO 14971:2012 Medical devices. Application of risk management to medical devices L. Test Principle: This assay uses a recombinant and a mouse monoclonal antibody, both directed against Secobarbital. The assay is based on the competition of Barbiturates labeled enzyme glucose- 6-phosphate dehydrogenase (G6PDH) and the free drug in the urine sample for the fixed amount of antibody binding sites. In the absence of the free drug in the sample, the antibody binds the drug enzyme conjugate and enzyme activity is inhibited. This creates a dose response relationship between drug concentration in the urine and enzyme activity. The enzyme G6PDH activity is determined at 340 nm spectrophotometrically by the conversion of Nicotinamide Adenine Dinucleotide (NAD) to NADH. M. Performance Characteristics (if/when applicable): 1. Analytical performance: 5 a. Precision/Reproducibility: A precision/cutoff characterization study was performed over 20 days, with two runs per day in duplicate (n=80) on calibrators (100 and 200 ng/mL), controls (150 and 250 ng/mL) and drug-free negative urine samples spiked with secobarbital to concentrations of 50, 300, 350, and 400 ng/mL. The spiked concentrations were confirmed by mass spectrometry (MS). The concentrations and results of the study are summarized below: Qualitative Analysis Concentration (ng/mL) % of cutoff # of determinations Result 0 -100% 80 80 neg / 0 pos 50 -75% 80 80 neg / 0 pos 100 -50% 80 80 neg / 0 pos 150 -25% 80 80 neg / 0 pos 200 Cutoff 80 33 neg / 47 pos 250 +25% 80 0 neg / 80 pos 300 +50% 80 0 neg / 80 pos 350 +75% 80 0 neg / 80 pos 400 +100% 80 0 neg / 80 pos Semi -quantitative Analysis Concentration (ng/mL) % of cutoff # of determinations Result 0 -100% 80 80 neg / 0 pos 50 -75% 80 80 neg / 0 pos 100 -50% 80 80 neg / 0 pos 150 -25% 80 80 neg / 0 pos 200 Cutoff 80 23 neg / 57 pos 250 +25% 80 0 neg / 80 pos 300 +50% 80 0 neg / 80 pos 350 +75% 80 0 neg / 80 pos 400 +100% 80 0 neg / 80 pos b. Linearity/assay reportable range: A linearity study in the semi-quantitative mode was conducted by spiking a drug-free urine pool with a high concentration of Secobarbital and generating serial dilutions to achieve concentrations ranging from 0 ng/mL to 1100 ng/mL. The 0 ng/mL sample utilized drug free urine and was not achieved through serial dilution. Each concentration was tested in triplicate and drug recovery calculated using the mean concentration of the replicates. The results are summarized below: 6 Linearity/Recovery Expected Concentration (ng/mL) Mean Concentration (ng/mL) Recovery (%) 0 -0.6 n/a 100 93.2 93.2 200 196.0 98.0 300 314.7 104.9 400 418.1 104.5 500 487.9 97.6 600 604.1 100.7 700 724.2 103.5 800 819.3 102.4 900 891.2 99.0 1000 968.7 96.9 1100 981.8 89.3 c. Traceability, Stability, Expected values (controls, calibrators, or methods): Traceability The secobarbital Classification:

idK161714_s0_e2000

K161714.txt

panel

Toxicology (91)

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION MEMORANDUM ASSAY ONLY TEMPLATE A. 510(k) Number: k161714 B. Purpose for Submission: New device C. Measurand: Barbiturates D. Type of Test: Homogenous Enzyme Immunoassay, Qualitative and Semi-quantitative. E. Applicant: Immunalysis Corporation F. Proprietary and Established Names: Immunalysis Barbiturates Urine Enzyme Immunoassay Immunalysis Multi-Drug Calibrators G. Regulatory Information: 1. Regulation section: 1 21 CFR 862.3150 Barbiturate test system 21 CFR 862.3200, Clinical toxicology calibrator 2. Classification: Class II 3. Product code: DIS DKB 4. Panel: 2 Toxicology (91) H. Intended Use: 1. Intended use(s): Refer to Indications for Use below 2. Indication(s) for use: Immunalysis Barbiturates Urine Enzyme Immunoassay The Immunalysis Barbiturates Urine Enzyme Immunoassay is a homogeneous enzyme immunoassay with a cutoff of 200 ng/mL. The assay is intended for use in laboratories for the qualitative and semi-quantitative analysis of Barbiturates in human urine with automated clinical chemistry analyzers. This assay is calibrated against Secobarbital. This in vitro diagnostic device is for prescription use only. The semi-quantitative mode is for purposes of enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as Gas Chromatography/ Mass Spectrometry (GC-MS) or Liquid Chromatography/ Tandem Mass Spectrometry (LC-MS/MS) or permitting laboratories to establish quality control procedures. The Immunalysis Barbiturates Urine Enzyme Immunoassay provides only a preliminary analytical test result. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. GC-MS or LC-MS/MS is the preferred confirmatory method. Clinical consideration and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are used. lmmunalysis Multi-Drug Calibrators: The lmmunalysis Multi-Drug Calibrators are intended for in vitro diagnostic use for the calibration of assays for the following analytes: Benzoylecgonine, Methamphetamine, Morphine, PCP, Secobarbital and Oxazepam. The calibrators are designed for prescription use with immunoassays. 3. Special conditions for use statement(s): For prescription use only. 4. Special instrument requirements: Performance data was obtained using the Beckman AU400e clinical chemistry analyzer. I. Device Description: The Immunalysis Barbiturates Urine Enzyme Immunoassay Kit reagents are provided as ready to use liquids and consist of the following reagents: · The Antibody/ Substrate Reagent (Reagent A; 25, 100, or 500 mL) contains a recombinant antibody to Secobarbital, a mouse monoclonal antibody to Secobarbital, glucose-6-phosphate (G6P) and nicotinamide adenine dinucleotide (NAD) in HEPES buffer with Sodium Azide as a preservative. · The Enzyme Conjugate Reagent (Reagent E; 25, 100, or 500 mL) contains glucose-6- phosphate dehydrogenase (G6PDH) labeled with Barbiturates in HEPES buffer with Sodium Azide as a preservative. Immunalysis Multi-Drug Calibrators are provided separately, as five individual, liquid ready-to use drug levels (15 mL or 25 mL). J. Substantial Equivalence Information: 1. Predicate device name(s): 3 DRI Barbiturates EIA Assay 2. Predicate 510(k) number(s): k955928 3. Comparison with predicate: Similarities - Reagent Item Candidate Device – Immunalysis Barbiturates Urine Enzyme Immunoassay Predicate Device – DRI Barbiturates EIA Assay k955928 Intended Use Same For the qualitative and semiquantitative determination of the presence of Barbiturates in human urine Assay cutoff Same 200 ng/mL Calibrator compound Same Secobarbital Assay type Same Homogeneous enzyme immunoassay, qualitative and semi-quantitative Storage conditions Same 2° - 8° C 4 Differences - Reagent Item Candidate Device – Immunalysis Barbiturates Urine Enzyme Immunoassay Predicate Device – DRI Barbiturates EIA Assay k955928 Calibrators Provided separately Provided with assay Controls Provided separately Provided with assay Antibody type Recombinant and mouse monoclonal Mouse monoclonal Similarities - Calibrators Item Candidate Device – Immunalysis Multi-Drug Calibrators (MDC) Predicate Device – Calibrators included with DRI Barbiturates EIA Assay k955928 Calibrator drug Same Secobarbital Differences - Calibrators Item Candidate Device – Immunalysis Negative and Multi-Drug Calibrators (MDC) Predicate Device – Calibrators included with DRI Barbiturates EIA Assay k955928 Calibrator Levels Calibrator levels at 0 100, 200, 500 and 1000 ng/mL Calibrator levels at 0, 200, and 1000 ng/mL K. Standard/Guidance Document Referenced (if applicable): · CLSI EP5-A3: Evaluation of Precision Performance of Quantitative Measurement Methods · CLSI EP 7-A3: Interference Testing in Clinical Chemistry. · ISO 14971 Second edition 2007-03-01, Medical devices – application of risk management to medical devices · EN ISO 14971:2012 Medical devices. Application of risk management to medical devices L. Test Principle: This assay uses a recombinant and a mouse monoclonal antibody, both directed against Secobarbital. The assay is based on the competition of Barbiturates labeled enzyme glucose- 6-phosphate dehydrogenase (G6PDH) and the free drug in the urine sample for the fixed amount of antibody binding sites. In the absence of the free drug in the sample, the antibody binds the drug enzyme conjugate and enzyme activity is inhibited. This creates a dose response relationship between drug concentration in the urine and enzyme activity. The enzyme G6PDH activity is determined at 340 nm spectrophotometrically by the conversion of Nicotinamide Adenine Dinucleotide (NAD) to NADH. M. Performance Characteristics (if/when applicable): 1. Analytical performance: 5 a. Precision/Reproducibility: A precision/cutoff characterization study was performed over 20 days, with two runs per day in duplicate (n=80) on calibrators (100 and 200 ng/mL), controls (150 and 250 ng/mL) and drug-free negative urine samples spiked with secobarbital to concentrations of 50, 300, 350, and 400 ng/mL. The spiked concentrations were confirmed by mass spectrometry (MS). The concentrations and results of the study are summarized below: Qualitative Analysis Concentration (ng/mL) % of cutoff # of determinations Result 0 -100% 80 80 neg / 0 pos 50 -75% 80 80 neg / 0 pos 100 -50% 80 80 neg / 0 pos 150 -25% 80 80 neg / 0 pos 200 Cutoff 80 33 neg / 47 pos 250 +25% 80 0 neg / 80 pos 300 +50% 80 0 neg / 80 pos 350 +75% 80 0 neg / 80 pos 400 +100% 80 0 neg / 80 pos Semi -quantitative Analysis Concentration (ng/mL) % of cutoff # of determinations Result 0 -100% 80 80 neg / 0 pos 50 -75% 80 80 neg / 0 pos 100 -50% 80 80 neg / 0 pos 150 -25% 80 80 neg / 0 pos 200 Cutoff 80 23 neg / 57 pos 250 +25% 80 0 neg / 80 pos 300 +50% 80 0 neg / 80 pos 350 +75% 80 0 neg / 80 pos 400 +100% 80 0 neg / 80 pos b. Linearity/assay reportable range: A linearity study in the semi-quantitative mode was conducted by spiking a drug-free urine pool with a high concentration of Secobarbital and generating serial dilutions to achieve concentrations ranging from 0 ng/mL to 1100 ng/mL. The 0 ng/mL sample utilized drug free urine and was not achieved through serial dilution. Each concentration was tested in triplicate and drug recovery calculated using the mean concentration of the replicates. The results are summarized below: 6 Linearity/Recovery Expected Concentration (ng/mL) Mean Concentration (ng/mL) Recovery (%) 0 -0.6 n/a 100 93.2 93.2 200 196.0 98.0 300 314.7 104.9 400 418.1 104.5 500 487.9 97.6 600 604.1 100.7 700 724.2 103.5 800 819.3 102.4 900 891.2 99.0 1000 968.7 96.9 1100 981.8 89.3 c. Traceability, Stability, Expected values (controls, calibrators, or methods): Traceability The secobarbital Panel:

idK161714_s0_e2000

K161714.txt

intended use

Refer to Indications for Use below

STANTIAL EQUIVALENCE DETERMINATION DECISION MEMORANDUM ASSAY ONLY TEMPLATE A. 510(k) Number: k161714 B. Purpose for Submission: New device C. Measurand: Barbiturates D. Type of Test: Homogenous Enzyme Immunoassay, Qualitative and Semi-quantitative. E. Applicant: Immunalysis Corporation F. Proprietary and Established Names: Immunalysis Barbiturates Urine Enzyme Immunoassay Immunalysis Multi-Drug Calibrators G. Regulatory Information: 1. Regulation section: 1 21 CFR 862.3150 Barbiturate test system 21 CFR 862.3200, Clinical toxicology calibrator 2. Classification: Class II 3. Product code: DIS DKB 4. Panel: 2 Toxicology (91) H. Intended Use: 1. Intended use(s): Refer to Indications for Use below 2. Indication(s) for use: Immunalysis Barbiturates Urine Enzyme Immunoassay The Immunalysis Barbiturates Urine Enzyme Immunoassay is a homogeneous enzyme immunoassay with a cutoff of 200 ng/mL. The assay is intended for use in laboratories for the qualitative and semi-quantitative analysis of Barbiturates in human urine with automated clinical chemistry analyzers. This assay is calibrated against Secobarbital. This in vitro diagnostic device is for prescription use only. The semi-quantitative mode is for purposes of enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as Gas Chromatography/ Mass Spectrometry (GC-MS) or Liquid Chromatography/ Tandem Mass Spectrometry (LC-MS/MS) or permitting laboratories to establish quality control procedures. The Immunalysis Barbiturates Urine Enzyme Immunoassay provides only a preliminary analytical test result. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. GC-MS or LC-MS/MS is the preferred confirmatory method. Clinical consideration and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are used. lmmunalysis Multi-Drug Calibrators: The lmmunalysis Multi-Drug Calibrators are intended for in vitro diagnostic use for the calibration of assays for the following analytes: Benzoylecgonine, Methamphetamine, Morphine, PCP, Secobarbital and Oxazepam. The calibrators are designed for prescription use with immunoassays. 3. Special conditions for use statement(s): For prescription use only. 4. Special instrument requirements: Performance data was obtained using the Beckman AU400e clinical chemistry analyzer. I. Device Description: The Immunalysis Barbiturates Urine Enzyme Immunoassay Kit reagents are provided as ready to use liquids and consist of the following reagents: · The Antibody/ Substrate Reagent (Reagent A; 25, 100, or 500 mL) contains a recombinant antibody to Secobarbital, a mouse monoclonal antibody to Secobarbital, glucose-6-phosphate (G6P) and nicotinamide adenine dinucleotide (NAD) in HEPES buffer with Sodium Azide as a preservative. · The Enzyme Conjugate Reagent (Reagent E; 25, 100, or 500 mL) contains glucose-6- phosphate dehydrogenase (G6PDH) labeled with Barbiturates in HEPES buffer with Sodium Azide as a preservative. Immunalysis Multi-Drug Calibrators are provided separately, as five individual, liquid ready-to use drug levels (15 mL or 25 mL). J. Substantial Equivalence Information: 1. Predicate device name(s): 3 DRI Barbiturates EIA Assay 2. Predicate 510(k) number(s): k955928 3. Comparison with predicate: Similarities - Reagent Item Candidate Device – Immunalysis Barbiturates Urine Enzyme Immunoassay Predicate Device – DRI Barbiturates EIA Assay k955928 Intended Use Same For the qualitative and semiquantitative determination of the presence of Barbiturates in human urine Assay cutoff Same 200 ng/mL Calibrator compound Same Secobarbital Assay type Same Homogeneous enzyme immunoassay, qualitative and semi-quantitative Storage conditions Same 2° - 8° C 4 Differences - Reagent Item Candidate Device – Immunalysis Barbiturates Urine Enzyme Immunoassay Predicate Device – DRI Barbiturates EIA Assay k955928 Calibrators Provided separately Provided with assay Controls Provided separately Provided with assay Antibody type Recombinant and mouse monoclonal Mouse monoclonal Similarities - Calibrators Item Candidate Device – Immunalysis Multi-Drug Calibrators (MDC) Predicate Device – Calibrators included with DRI Barbiturates EIA Assay k955928 Calibrator drug Same Secobarbital Differences - Calibrators Item Candidate Device – Immunalysis Negative and Multi-Drug Calibrators (MDC) Predicate Device – Calibrators included with DRI Barbiturates EIA Assay k955928 Calibrator Levels Calibrator levels at 0 100, 200, 500 and 1000 ng/mL Calibrator levels at 0, 200, and 1000 ng/mL K. Standard/Guidance Document Referenced (if applicable): · CLSI EP5-A3: Evaluation of Precision Performance of Quantitative Measurement Methods · CLSI EP 7-A3: Interference Testing in Clinical Chemistry. · ISO 14971 Second edition 2007-03-01, Medical devices – application of risk management to medical devices · EN ISO 14971:2012 Medical devices. Application of risk management to medical devices L. Test Principle: This assay uses a recombinant and a mouse monoclonal antibody, both directed against Secobarbital. The assay is based on the competition of Barbiturates labeled enzyme glucose- 6-phosphate dehydrogenase (G6PDH) and the free drug in the urine sample for the fixed amount of antibody binding sites. In the absence of the free drug in the sample, the antibody binds the drug enzyme conjugate and enzyme activity is inhibited. This creates a dose response relationship between drug concentration in the urine and enzyme activity. The enzyme G6PDH activity is determined at 340 nm spectrophotometrically by the conversion of Nicotinamide Adenine Dinucleotide (NAD) to NADH. M. Performance Characteristics (if/when applicable): 1. Analytical performance: 5 a. Precision/Reproducibility: A precision/cutoff characterization study was performed over 20 days, with two runs per day in duplicate (n=80) on calibrators (100 and 200 ng/mL), controls (150 and 250 ng/mL) and drug-free negative urine samples spiked with secobarbital to concentrations of 50, 300, 350, and 400 ng/mL. The spiked concentrations were confirmed by mass spectrometry (MS). The concentrations and results of the study are summarized below: Qualitative Analysis Concentration (ng/mL) % of cutoff # of determinations Result 0 -100% 80 80 neg / 0 pos 50 -75% 80 80 neg / 0 pos 100 -50% 80 80 neg / 0 pos 150 -25% 80 80 neg / 0 pos 200 Cutoff 80 33 neg / 47 pos 250 +25% 80 0 neg / 80 pos 300 +50% 80 0 neg / 80 pos 350 +75% 80 0 neg / 80 pos 400 +100% 80 0 neg / 80 pos Semi -quantitative Analysis Concentration (ng/mL) % of cutoff # of determinations Result 0 -100% 80 80 neg / 0 pos 50 -75% 80 80 neg / 0 pos 100 -50% 80 80 neg / 0 pos 150 -25% 80 80 neg / 0 pos 200 Cutoff 80 23 neg / 57 pos 250 +25% 80 0 neg / 80 pos 300 +50% 80 0 neg / 80 pos 350 +75% 80 0 neg / 80 pos 400 +100% 80 0 neg / 80 pos b. Linearity/assay reportable range: A linearity study in the semi-quantitative mode was conducted by spiking a drug-free urine pool with a high concentration of Secobarbital and generating serial dilutions to achieve concentrations ranging from 0 ng/mL to 1100 ng/mL. The 0 ng/mL sample utilized drug free urine and was not achieved through serial dilution. Each concentration was tested in triplicate and drug recovery calculated using the mean concentration of the replicates. The results are summarized below: 6 Linearity/Recovery Expected Concentration (ng/mL) Mean Concentration (ng/mL) Recovery (%) 0 -0.6 n/a 100 93.2 93.2 200 196.0 98.0 300 314.7 104.9 400 418.1 104.5 500 487.9 97.6 600 604.1 100.7 700 724.2 103.5 800 819.3 102.4 900 891.2 99.0 1000 968.7 96.9 1100 981.8 89.3 c. Traceability, Stability, Expected values (controls, calibrators, or methods): Traceability The secobarbital Intended use:

idK161714_s0_e2000

K161714.txt

predicate device name

DRI Barbiturates EIA Assay

ANTIAL EQUIVALENCE DETERMINATION DECISION MEMORANDUM ASSAY ONLY TEMPLATE A. 510(k) Number: k161714 B. Purpose for Submission: New device C. Measurand: Barbiturates D. Type of Test: Homogenous Enzyme Immunoassay, Qualitative and Semi-quantitative. E. Applicant: Immunalysis Corporation F. Proprietary and Established Names: Immunalysis Barbiturates Urine Enzyme Immunoassay Immunalysis Multi-Drug Calibrators G. Regulatory Information: 1. Regulation section: 1 21 CFR 862.3150 Barbiturate test system 21 CFR 862.3200, Clinical toxicology calibrator 2. Classification: Class II 3. Product code: DIS DKB 4. Panel: 2 Toxicology (91) H. Intended Use: 1. Intended use(s): Refer to Indications for Use below 2. Indication(s) for use: Immunalysis Barbiturates Urine Enzyme Immunoassay The Immunalysis Barbiturates Urine Enzyme Immunoassay is a homogeneous enzyme immunoassay with a cutoff of 200 ng/mL. The assay is intended for use in laboratories for the qualitative and semi-quantitative analysis of Barbiturates in human urine with automated clinical chemistry analyzers. This assay is calibrated against Secobarbital. This in vitro diagnostic device is for prescription use only. The semi-quantitative mode is for purposes of enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as Gas Chromatography/ Mass Spectrometry (GC-MS) or Liquid Chromatography/ Tandem Mass Spectrometry (LC-MS/MS) or permitting laboratories to establish quality control procedures. The Immunalysis Barbiturates Urine Enzyme Immunoassay provides only a preliminary analytical test result. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. GC-MS or LC-MS/MS is the preferred confirmatory method. Clinical consideration and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are used. lmmunalysis Multi-Drug Calibrators: The lmmunalysis Multi-Drug Calibrators are intended for in vitro diagnostic use for the calibration of assays for the following analytes: Benzoylecgonine, Methamphetamine, Morphine, PCP, Secobarbital and Oxazepam. The calibrators are designed for prescription use with immunoassays. 3. Special conditions for use statement(s): For prescription use only. 4. Special instrument requirements: Performance data was obtained using the Beckman AU400e clinical chemistry analyzer. I. Device Description: The Immunalysis Barbiturates Urine Enzyme Immunoassay Kit reagents are provided as ready to use liquids and consist of the following reagents: · The Antibody/ Substrate Reagent (Reagent A; 25, 100, or 500 mL) contains a recombinant antibody to Secobarbital, a mouse monoclonal antibody to Secobarbital, glucose-6-phosphate (G6P) and nicotinamide adenine dinucleotide (NAD) in HEPES buffer with Sodium Azide as a preservative. · The Enzyme Conjugate Reagent (Reagent E; 25, 100, or 500 mL) contains glucose-6- phosphate dehydrogenase (G6PDH) labeled with Barbiturates in HEPES buffer with Sodium Azide as a preservative. Immunalysis Multi-Drug Calibrators are provided separately, as five individual, liquid ready-to use drug levels (15 mL or 25 mL). J. Substantial Equivalence Information: 1. Predicate device name(s): 3 DRI Barbiturates EIA Assay 2. Predicate 510(k) number(s): k955928 3. Comparison with predicate: Similarities - Reagent Item Candidate Device – Immunalysis Barbiturates Urine Enzyme Immunoassay Predicate Device – DRI Barbiturates EIA Assay k955928 Intended Use Same For the qualitative and semiquantitative determination of the presence of Barbiturates in human urine Assay cutoff Same 200 ng/mL Calibrator compound Same Secobarbital Assay type Same Homogeneous enzyme immunoassay, qualitative and semi-quantitative Storage conditions Same 2° - 8° C 4 Differences - Reagent Item Candidate Device – Immunalysis Barbiturates Urine Enzyme Immunoassay Predicate Device – DRI Barbiturates EIA Assay k955928 Calibrators Provided separately Provided with assay Controls Provided separately Provided with assay Antibody type Recombinant and mouse monoclonal Mouse monoclonal Similarities - Calibrators Item Candidate Device – Immunalysis Multi-Drug Calibrators (MDC) Predicate Device – Calibrators included with DRI Barbiturates EIA Assay k955928 Calibrator drug Same Secobarbital Differences - Calibrators Item Candidate Device – Immunalysis Negative and Multi-Drug Calibrators (MDC) Predicate Device – Calibrators included with DRI Barbiturates EIA Assay k955928 Calibrator Levels Calibrator levels at 0 100, 200, 500 and 1000 ng/mL Calibrator levels at 0, 200, and 1000 ng/mL K. Standard/Guidance Document Referenced (if applicable): · CLSI EP5-A3: Evaluation of Precision Performance of Quantitative Measurement Methods · CLSI EP 7-A3: Interference Testing in Clinical Chemistry. · ISO 14971 Second edition 2007-03-01, Medical devices – application of risk management to medical devices · EN ISO 14971:2012 Medical devices. Application of risk management to medical devices L. Test Principle: This assay uses a recombinant and a mouse monoclonal antibody, both directed against Secobarbital. The assay is based on the competition of Barbiturates labeled enzyme glucose- 6-phosphate dehydrogenase (G6PDH) and the free drug in the urine sample for the fixed amount of antibody binding sites. In the absence of the free drug in the sample, the antibody binds the drug enzyme conjugate and enzyme activity is inhibited. This creates a dose response relationship between drug concentration in the urine and enzyme activity. The enzyme G6PDH activity is determined at 340 nm spectrophotometrically by the conversion of Nicotinamide Adenine Dinucleotide (NAD) to NADH. M. Performance Characteristics (if/when applicable): 1. Analytical performance: 5 a. Precision/Reproducibility: A precision/cutoff characterization study was performed over 20 days, with two runs per day in duplicate (n=80) on calibrators (100 and 200 ng/mL), controls (150 and 250 ng/mL) and drug-free negative urine samples spiked with secobarbital to concentrations of 50, 300, 350, and 400 ng/mL. The spiked concentrations were confirmed by mass spectrometry (MS). The concentrations and results of the study are summarized below: Qualitative Analysis Concentration (ng/mL) % of cutoff # of determinations Result 0 -100% 80 80 neg / 0 pos 50 -75% 80 80 neg / 0 pos 100 -50% 80 80 neg / 0 pos 150 -25% 80 80 neg / 0 pos 200 Cutoff 80 33 neg / 47 pos 250 +25% 80 0 neg / 80 pos 300 +50% 80 0 neg / 80 pos 350 +75% 80 0 neg / 80 pos 400 +100% 80 0 neg / 80 pos Semi -quantitative Analysis Concentration (ng/mL) % of cutoff # of determinations Result 0 -100% 80 80 neg / 0 pos 50 -75% 80 80 neg / 0 pos 100 -50% 80 80 neg / 0 pos 150 -25% 80 80 neg / 0 pos 200 Cutoff 80 23 neg / 57 pos 250 +25% 80 0 neg / 80 pos 300 +50% 80 0 neg / 80 pos 350 +75% 80 0 neg / 80 pos 400 +100% 80 0 neg / 80 pos b. Linearity/assay reportable range: A linearity study in the semi-quantitative mode was conducted by spiking a drug-free urine pool with a high concentration of Secobarbital and generating serial dilutions to achieve concentrations ranging from 0 ng/mL to 1100 ng/mL. The 0 ng/mL sample utilized drug free urine and was not achieved through serial dilution. Each concentration was tested in triplicate and drug recovery calculated using the mean concentration of the replicates. The results are summarized below: 6 Linearity/Recovery Expected Concentration (ng/mL) Mean Concentration (ng/mL) Recovery (%) 0 -0.6 n/a 100 93.2 93.2 200 196.0 98.0 300 314.7 104.9 400 418.1 104.5 500 487.9 97.6 600 604.1 100.7 700 724.2 103.5 800 819.3 102.4 900 891.2 99.0 1000 968.7 96.9 1100 981.8 89.3 c. Traceability, Stability, Expected values (controls, calibrators, or methods): Traceability The secobarbital Predicate device name:

idK161714_s0_e2000

K161714.txt

applicant

Immunalysis Corporation

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION MEMORANDUM ASSAY ONLY TEMPLATE A. 510(k) Number: k161714 B. Purpose for Submission: New device C. Measurand: Barbiturates D. Type of Test: Homogenous Enzyme Immunoassay, Qualitative and Semi-quantitative. E. Applicant: Immunalysis Corporation F. Proprietary and Established Names: Immunalysis Barbiturates Urine Enzyme Immunoassay Immunalysis Multi-Drug Calibrators G. Regulatory Information: 1. Regulation section: 1 21 CFR 862.3150 Barbiturate test system 21 CFR 862.3200, Clinical toxicology calibrator 2. Classification: Class II 3. Product code: DIS DKB 4. Panel: 2 Toxicology (91) H. Intended Use: 1. Intended use(s): Refer to Indications for Use below 2. Indication(s) for use: Immunalysis Barbiturates Urine Enzyme Immunoassay The Immunalysis Barbiturates Urine Enzyme Immunoassay is a homogeneous enzyme immunoassay with a cutoff of 200 ng/mL. The assay is intended for use in laboratories for the qualitative and semi-quantitative analysis of Barbiturates in human urine with automated clinical chemistry analyzers. This assay is calibrated against Secobarbital. This in vitro diagnostic device is for prescription use only. The semi-quantitative mode is for purposes of enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as Gas Chromatography/ Mass Spectrometry (GC-MS) or Liquid Chromatography/ Tandem Mass Spectrometry (LC-MS/MS) or permitting laboratories to establish quality control procedures. The Immunalysis Barbiturates Urine Enzyme Immunoassay provides only a preliminary analytical test result. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. GC-MS or LC-MS/MS is the preferred confirmatory method. Clinical consideration and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are used. lmmunalysis Multi-Drug Calibrators: The lmmunalysis Multi-Drug Calibrators are intended for in vitro diagnostic use for the calibration of assays for the following analytes: Benzoylecgonine, Methamphetamine, Morphine, PCP, Secobarbital and Oxazepam. The calibrators are designed for prescription use with immunoassays. 3. Special conditions for use statement(s): For prescription use only. 4. Special instrument requirements: Performance data was obtained using the Beckman AU400e clinical chemistry analyzer. I. Device Description: The Immunalysis Barbiturates Urine Enzyme Immunoassay Kit reagents are provided as ready to use liquids and consist of the following reagents: · The Antibody/ Substrate Reagent (Reagent A; 25, 100, or 500 mL) contains a recombinant antibody to Secobarbital, a mouse monoclonal antibody to Secobarbital, glucose-6-phosphate (G6P) and nicotinamide adenine dinucleotide (NAD) in HEPES buffer with Sodium Azide as a preservative. · The Enzyme Conjugate Reagent (Reagent E; 25, 100, or 500 mL) contains glucose-6- phosphate dehydrogenase (G6PDH) labeled with Barbiturates in HEPES buffer with Sodium Azide as a preservative. Immunalysis Multi-Drug Calibrators are provided separately, as five individual, liquid ready-to use drug levels (15 mL or 25 mL). J. Substantial Equivalence Information: 1. Predicate device name(s): 3 DRI Barbiturates EIA Assay 2. Predicate 510(k) number(s): k955928 3. Comparison with predicate: Similarities - Reagent Item Candidate Device – Immunalysis Barbiturates Urine Enzyme Immunoassay Predicate Device – DRI Barbiturates EIA Assay k955928 Intended Use Same For the qualitative and semiquantitative determination of the presence of Barbiturates in human urine Assay cutoff Same 200 ng/mL Calibrator compound Same Secobarbital Assay type Same Homogeneous enzyme immunoassay, qualitative and semi-quantitative Storage conditions Same 2° - 8° C 4 Differences - Reagent Item Candidate Device – Immunalysis Barbiturates Urine Enzyme Immunoassay Predicate Device – DRI Barbiturates EIA Assay k955928 Calibrators Provided separately Provided with assay Controls Provided separately Provided with assay Antibody type Recombinant and mouse monoclonal Mouse monoclonal Similarities - Calibrators Item Candidate Device – Immunalysis Multi-Drug Calibrators (MDC) Predicate Device – Calibrators included with DRI Barbiturates EIA Assay k955928 Calibrator drug Same Secobarbital Differences - Calibrators Item Candidate Device – Immunalysis Negative and Multi-Drug Calibrators (MDC) Predicate Device – Calibrators included with DRI Barbiturates EIA Assay k955928 Calibrator Levels Calibrator levels at 0 100, 200, 500 and 1000 ng/mL Calibrator levels at 0, 200, and 1000 ng/mL K. Standard/Guidance Document Referenced (if applicable): · CLSI EP5-A3: Evaluation of Precision Performance of Quantitative Measurement Methods · CLSI EP 7-A3: Interference Testing in Clinical Chemistry. · ISO 14971 Second edition 2007-03-01, Medical devices – application of risk management to medical devices · EN ISO 14971:2012 Medical devices. Application of risk management to medical devices L. Test Principle: This assay uses a recombinant and a mouse monoclonal antibody, both directed against Secobarbital. The assay is based on the competition of Barbiturates labeled enzyme glucose- 6-phosphate dehydrogenase (G6PDH) and the free drug in the urine sample for the fixed amount of antibody binding sites. In the absence of the free drug in the sample, the antibody binds the drug enzyme conjugate and enzyme activity is inhibited. This creates a dose response relationship between drug concentration in the urine and enzyme activity. The enzyme G6PDH activity is determined at 340 nm spectrophotometrically by the conversion of Nicotinamide Adenine Dinucleotide (NAD) to NADH. M. Performance Characteristics (if/when applicable): 1. Analytical performance: 5 a. Precision/Reproducibility: A precision/cutoff characterization study was performed over 20 days, with two runs per day in duplicate (n=80) on calibrators (100 and 200 ng/mL), controls (150 and 250 ng/mL) and drug-free negative urine samples spiked with secobarbital to concentrations of 50, 300, 350, and 400 ng/mL. The spiked concentrations were confirmed by mass spectrometry (MS). The concentrations and results of the study are summarized below: Qualitative Analysis Concentration (ng/mL) % of cutoff # of determinations Result 0 -100% 80 80 neg / 0 pos 50 -75% 80 80 neg / 0 pos 100 -50% 80 80 neg / 0 pos 150 -25% 80 80 neg / 0 pos 200 Cutoff 80 33 neg / 47 pos 250 +25% 80 0 neg / 80 pos 300 +50% 80 0 neg / 80 pos 350 +75% 80 0 neg / 80 pos 400 +100% 80 0 neg / 80 pos Semi -quantitative Analysis Concentration (ng/mL) % of cutoff # of determinations Result 0 -100% 80 80 neg / 0 pos 50 -75% 80 80 neg / 0 pos 100 -50% 80 80 neg / 0 pos 150 -25% 80 80 neg / 0 pos 200 Cutoff 80 23 neg / 57 pos 250 +25% 80 0 neg / 80 pos 300 +50% 80 0 neg / 80 pos 350 +75% 80 0 neg / 80 pos 400 +100% 80 0 neg / 80 pos b. Linearity/assay reportable range: A linearity study in the semi-quantitative mode was conducted by spiking a drug-free urine pool with a high concentration of Secobarbital and generating serial dilutions to achieve concentrations ranging from 0 ng/mL to 1100 ng/mL. The 0 ng/mL sample utilized drug free urine and was not achieved through serial dilution. Each concentration was tested in triplicate and drug recovery calculated using the mean concentration of the replicates. The results are summarized below: 6 Linearity/Recovery Expected Concentration (ng/mL) Mean Concentration (ng/mL) Recovery (%) 0 -0.6 n/a 100 93.2 93.2 200 196.0 98.0 300 314.7 104.9 400 418.1 104.5 500 487.9 97.6 600 604.1 100.7 700 724.2 103.5 800 819.3 102.4 900 891.2 99.0 1000 968.7 96.9 1100 981.8 89.3 c. Traceability, Stability, Expected values (controls, calibrators, or methods): Traceability The secobarbital Applicant:

idK161714_s4000_e6000

K161714.txt

proposed labeling

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

Sufentanil Citrate 50,000 Negative Positive Tapentadol 100,000 Negative Positive Temazepam 100,000 Negative Positive Theophylline 100,000 Negative Positive Thioridazine 100,000 Negative Positive Triazolam 100,000 Negative Positive 12 Structurally Unrelated Compounds (for 200 ng/mL cutoff) Compound Concentration Tested (ng/mL) -25% Cutoff (150 ng/mL) +25% Cutoff (250 ng/mL) Result Result Trifluoromethylphenyl- piperazine 100,000 Negative Positive Trimipramine 100,000 Negative Positive Trazodone 100,000 Negative Positive Venlafaxine 100,000 Negative Positive Verapamil 100,000 Negative Positive Zolpidem Tartrate 100,000 Negative Positive Endogenous compounds. Potential interference from endogenous compounds was evaluated in the qualitative and semi-quantitative modes by spiking these compounds into drug free urine containing secobarbital at ± 25% of the 200 ng/mL cutoff (150 ng/mL and 250 ng/mL, respectively). The results were the same for the qualitative and semi-quantitative modes and are summarized below: Compound Concentratio n Tested (ng/mL) -25% Cutoff (150 ng/mL) +25% Cutoff (250ng/mL) Acetone 1.0 g/dL Negative Positive Ascorbic Acid 1.5 g/dL Negative Positive Bilirubin 0.002 g/dL Negative Positive Creatinine 0.5 g/dL Negative Positive Ethanol 1.0 g/dL Negative Positive Galactose 0.01 g/dL Negative Positive γ-Globulin 0.5 g/dL Negative Positive Glucose 2.0 g/dL Negative Positive Hemoglobin 0.115 g/dL Negative Positive Human Serum Albumin 0.5 g/dL Negative Positive Oxalic Acid 0.1 g/dL Negative Positive Riboflavin 0.0075 g/dL Negative Positive Sodium Azide 1% w/v Negative Positive Sodium Chloride 6.0 g/dL Negative Positive Sodium Fluoride 1% w/v Negative Positive Urea 6.0 g/dL Negative Positive Boric Acid. Boric Acid was also evaluated, and at a concentration of 1% w/v was found to cause false negative results at both the +25% and +50% (250 ng/mL and 300 ng/mL, respectively) at the 200 ng/mL cutoff in both the qualitative and semiquantitative modes. The following statement is provided in the limitations section of the labeling: “Boric Acid at 1% w/v may cause false negative results. Boric Acid is not recommended as a preservative for urine”. pH and Specific Gravity. To evaluate potential interference from the pH of urine, 13 device performance in the qualitative and semi-quantitative modes was tested using a range of urine pH values (3.0, 4.0, 5.0, 6.0, 7.0, 8.0, 9.0, 10.0 and 11.0). All test samples were prepared in drug free urine containing secobarbital at ± 25% of the 200 ng/mL cutoff (150 ng/mL and 250 ng/mL, respectively). No positive or negative interference was observed at urine pH values ranging from 3.0 to 11.0 for the qualitative and semi-quantitative modes. To evaluate potential interference from the specific gravity of urine, device performance in the qualitative and semi-quantitative modes was tested using a range of urine specific gravity values (1.000, 1.002, 1.005, 1.010, 1.015, 1.020, 1.025 and 1.030). All test samples were prepared in drug free urine containing secobarbital at ± 25% of the 200 ng/mL cutoff (150 ng/mL and 250 ng/mL, respectively). No positive or negative interference was observed at urine specific gravity values ranging from 1.000 to 1.030 for the qualitative and semi-quantitative modes. f. Assay cut-off: Characterization of how the device performs analytically around the claimed cutoff concentration of 200 ng/mL is described in the precision section, M.1.a. above. 2. Comparison studies: a. Method comparison with predicate device: The method comparison study was performed in-house using unaltered, clinical urine samples obtained from clinical testing laboratories. A total of 96 samples were analyzed. Each sample was run in singlicate on a Beckman Coulter AU400e Chemistry Analyzer and the result was compared to that obtained by liquid chromatography/mass spectroscopy (LC/MS-MS). The results were the same for the qualitative and semi-quantitative modes and are summarized below. Candidate Device Results vs. stratified LC/MS-MS Values 14 Candidate Device Results Negative by the predicate device or less than half the cutoff concentration by GC/MS analysis Near Cutoff Negative (Between 50% below the cutoff and the cutoff concentration) Near Cutoff Positive (Between the cutoff and 50% above the cutoff concentration) High Positive (greater than 50% above the cutoff concentration) Positive 0 0 8 44 Negative 36 8 0 0 % Agreement among positives is 52/52 = 100% % Agreement among negatives is 44/44 = 100% b. Matrix comparison: Not applicable. Urine is the only claimed matrix for the candidate device. 3. Clinical studies: a. Clinical Sensitivity: Not applicable. b. Clinical specificity: Not applicable. c. Other clinical supportive data (when a. and b. are not applicable): Not applicable. 4. Clinical cut-off: Not applicable. 5. Expected values/Reference range: Not applicable. N. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. O. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. 15 Proposed labeling:

idK161714_s4000_e6000

K161714.txt

conclusion

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

Negative Positive Sufentanil Citrate 50,000 Negative Positive Tapentadol 100,000 Negative Positive Temazepam 100,000 Negative Positive Theophylline 100,000 Negative Positive Thioridazine 100,000 Negative Positive Triazolam 100,000 Negative Positive 12 Structurally Unrelated Compounds (for 200 ng/mL cutoff) Compound Concentration Tested (ng/mL) -25% Cutoff (150 ng/mL) +25% Cutoff (250 ng/mL) Result Result Trifluoromethylphenyl- piperazine 100,000 Negative Positive Trimipramine 100,000 Negative Positive Trazodone 100,000 Negative Positive Venlafaxine 100,000 Negative Positive Verapamil 100,000 Negative Positive Zolpidem Tartrate 100,000 Negative Positive Endogenous compounds. Potential interference from endogenous compounds was evaluated in the qualitative and semi-quantitative modes by spiking these compounds into drug free urine containing secobarbital at ± 25% of the 200 ng/mL cutoff (150 ng/mL and 250 ng/mL, respectively). The results were the same for the qualitative and semi-quantitative modes and are summarized below: Compound Concentratio n Tested (ng/mL) -25% Cutoff (150 ng/mL) +25% Cutoff (250ng/mL) Acetone 1.0 g/dL Negative Positive Ascorbic Acid 1.5 g/dL Negative Positive Bilirubin 0.002 g/dL Negative Positive Creatinine 0.5 g/dL Negative Positive Ethanol 1.0 g/dL Negative Positive Galactose 0.01 g/dL Negative Positive γ-Globulin 0.5 g/dL Negative Positive Glucose 2.0 g/dL Negative Positive Hemoglobin 0.115 g/dL Negative Positive Human Serum Albumin 0.5 g/dL Negative Positive Oxalic Acid 0.1 g/dL Negative Positive Riboflavin 0.0075 g/dL Negative Positive Sodium Azide 1% w/v Negative Positive Sodium Chloride 6.0 g/dL Negative Positive Sodium Fluoride 1% w/v Negative Positive Urea 6.0 g/dL Negative Positive Boric Acid. Boric Acid was also evaluated, and at a concentration of 1% w/v was found to cause false negative results at both the +25% and +50% (250 ng/mL and 300 ng/mL, respectively) at the 200 ng/mL cutoff in both the qualitative and semiquantitative modes. The following statement is provided in the limitations section of the labeling: “Boric Acid at 1% w/v may cause false negative results. Boric Acid is not recommended as a preservative for urine”. pH and Specific Gravity. To evaluate potential interference from the pH of urine, 13 device performance in the qualitative and semi-quantitative modes was tested using a range of urine pH values (3.0, 4.0, 5.0, 6.0, 7.0, 8.0, 9.0, 10.0 and 11.0). All test samples were prepared in drug free urine containing secobarbital at ± 25% of the 200 ng/mL cutoff (150 ng/mL and 250 ng/mL, respectively). No positive or negative interference was observed at urine pH values ranging from 3.0 to 11.0 for the qualitative and semi-quantitative modes. To evaluate potential interference from the specific gravity of urine, device performance in the qualitative and semi-quantitative modes was tested using a range of urine specific gravity values (1.000, 1.002, 1.005, 1.010, 1.015, 1.020, 1.025 and 1.030). All test samples were prepared in drug free urine containing secobarbital at ± 25% of the 200 ng/mL cutoff (150 ng/mL and 250 ng/mL, respectively). No positive or negative interference was observed at urine specific gravity values ranging from 1.000 to 1.030 for the qualitative and semi-quantitative modes. f. Assay cut-off: Characterization of how the device performs analytically around the claimed cutoff concentration of 200 ng/mL is described in the precision section, M.1.a. above. 2. Comparison studies: a. Method comparison with predicate device: The method comparison study was performed in-house using unaltered, clinical urine samples obtained from clinical testing laboratories. A total of 96 samples were analyzed. Each sample was run in singlicate on a Beckman Coulter AU400e Chemistry Analyzer and the result was compared to that obtained by liquid chromatography/mass spectroscopy (LC/MS-MS). The results were the same for the qualitative and semi-quantitative modes and are summarized below. Candidate Device Results vs. stratified LC/MS-MS Values 14 Candidate Device Results Negative by the predicate device or less than half the cutoff concentration by GC/MS analysis Near Cutoff Negative (Between 50% below the cutoff and the cutoff concentration) Near Cutoff Positive (Between the cutoff and 50% above the cutoff concentration) High Positive (greater than 50% above the cutoff concentration) Positive 0 0 8 44 Negative 36 8 0 0 % Agreement among positives is 52/52 = 100% % Agreement among negatives is 44/44 = 100% b. Matrix comparison: Not applicable. Urine is the only claimed matrix for the candidate device. 3. Clinical studies: a. Clinical Sensitivity: Not applicable. b. Clinical specificity: Not applicable. c. Other clinical supportive data (when a. and b. are not applicable): Not applicable. 4. Clinical cut-off: Not applicable. 5. Expected values/Reference range: Not applicable. N. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. O. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. 15 Conclusion:

idK162688_s0_e2000

K162688.txt

purpose for submission

To expand the use of previously cleared assay reagents for Coagulation Factor V Deficient Plasma, Coagulation Factor VII Deficient Plasma, Protein C Reagent, and Berichrom® Protein C to the Sysmex® CS-2100i automated blood coagulation analyzer.

ANTIAL EQUIVALENCE DETERMINATION DECISION MEMORANDUM 1 A. 510(k) Number: K162688 B. Purpose for Submission: To expand the use of previously cleared assay reagents for Coagulation Factor V Deficient Plasma, Coagulation Factor VII Deficient Plasma, Protein C Reagent, and Berichrom® Protein C to the Sysmex® CS-2100i automated blood coagulation analyzer. C. Measurand: Factor V activity using Coagulation Factor V Deficient Plasman with Dade® Innovin®; factor VII activity using Coagulation Factor VII Deficient Plasma with Dade® Innovin®; protein C activity using Protein C Reagent and protein C activity using Berichrom® Protein C. All measurands are reported as percent (%)of norm. D. Type of Test: Factor V activity using Coagulation Factor V with Dade® Innovin®, factor VII activity using Coagulation Factor VII with Dade® Innovin®, and protein C using Protein C Reagent are quantitative clot-based applications. Protein C using Berichrom® Protein C is a quantitative chromogenic application. E. Applicant: Siemens Healthcare Diagnostics Product GmbH F. Proprietary and Established Names: Sysmex® CS-2100i Automated Blood Coagulation Analyzer Coagulation Factor V Deficient Plasma Coagulation Factor II, VII and X Deficient Plasmas Protein C Reagent Berichrom® Protein C Note: The performance of Coagulation Factor II Deficient Plasma and Coagulation Factor X Deficient Plasma was not evaluated in this premarket notification. G. Regulatory Information: 1. Regulation section: 2 Device Regulation Section Sysmex® CS-2100i 21 CFR 864.5425, Multipurpose system for in vitro coagulation studies Coagulation Factor V Deficient Plasma 21 CFR 864.7290, Factor deficiency test Coagulation Factor VII Deficient Plasma Protein C Reagent Berichrom® Protein C 2. Classification: Class II 3. Product code: Device Product Code Sysmex® CS-5100 JPA, System, multipurpose for in vitro coagulation studies Coagulation Factor V Deficient Plasma GJT, Plasma, coagulation factor deficient Coagulation Factor II, VII and X Deficient Plasma Protein C Reagent GGP, Test, qualitative and quantitative factor deficiency Berichrom® Protein C 4. Panel: Hematology (81) H. Intended Use: 1. Intended use(s): The Sysmex CS-2100i is a fully automated blood coagulation analyzer intended for in vitro diagnostic use using plasma collected from venous blood samples in 3.2% sodium citrate tubes to analyze clotting, chromogenic and immunoassay methods in the clinical laboratory. For determination of: - Prothrombin Time (PT) seconds and PT INR with Dade® Innovin® - Activated Partial Thromboplastin Time (APTT) with Dade® Actin® FSL - Fibrinogen (Fbg) with Dade® Thrombin Reagent - Coagulation Factor V with Dade® Innovin® - Coagulation Factor VII with Dade® Innovin® - Protein C with Protein C Reagent - Antithrombin (AT) with INNOVANCE® Antithrombin - Protein C with Berichrom® Protein C - D-dimer with INNOVANCE® D-Dimer The performance of this device has not been established in neonate and pediatric patient populations. For Coagulation Factor V Deficient Plasma 3 In vitro diagnostic reagent for the determination of the activity of factor V in human plasma. For Coagulation Factor VII Deficient Plasma In vitro diagnostic reagent for the determination of the activity of coagulation factor II (prothrombin), coagulation factor VII and coagulation factor X in human plasma by coagulometric methods. For Protein C Reagent Protein C Reagent is a coagulation test for the quantitative determination of protein C activity in human plasma. For Berichrom® Protein C For the quantitative determination of functionally active protein C using a chromogenic substrate as an aid in the diagnosis of inherited and acquired deficiencies. 2. Indication(s) for use: Same as Intended Use(s) above 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: Sysmex CS-2100i I. Device Description: The Sysmex CS-2100i is a standalone automated blood coagulation analyzer which analyzes venous plasma samples collected in 3.2% sodium citrate using clotting, chromogenic and immunoassay methods. Results are displayed on the Information Processing Unit (IPU) screen and can be printed on external printers or transmitted to a host computer. The instrument is capable of measuring the assays in a normal mode and a micro-sample mode. Coagulation Factor V and VII Deficient Plasmas Coagulation Factor V Deficient Plasma and Coagulation Factor VII Deficient Plasma are lyophilized human plasmas with a residual factor V or VII activity ≤ 1%. Each deficient plasma contains mannitol as a stabilizer. Berichrom® Protein C 4 The Berichrom® Protein C kit is comprised of the following: Protein C Activator, Substrate Reagent, and Hepes Buffer Solution (activator diluent). Protein C Reagent The Protein C Reagent kit includes: lyophilized Protein C Activator (with snake venom extract), APTT Reagent for Protein C, and lyophilized Protein C Deficient Plasma. J. Substantial Equivalence Information: 1. Predicate device name(s): Sysmex® Automated Coagulation Analyzer CA-1500 2. Predicate 510(k) number(s): K011235 The performance of the Coagulation Factor V with Dade® Innovin® and Coagulation Factor VII with Dade® Innovin® applications on the Sysmex® CA-1500 was evaluated in K993299. The performance of Protein C Reagent and Berichrom® Protein C in combination with the Sysmex® CA-1500 was evaluated in K000649 and K001645, respectively. 3. Comparison with predicate: Similarities Item Device Sysmex® CS-2100i Predicate Sysmex® CA-1500 Intended Use The Sysmex® CS-2100i is a fully automated blood coagulation analyzer intended for in vitro diagnostic use using plasma collected from venous blood samples in 3.2% sodium citrate tubes to analyze clotting, chromogenic and immunoassay methods in the clinical laboratory. For determination of: · Prothrombin Time (PT) seconds and PT INR with Dade® Innovin® · Activated Partial Thromboplastin The intended use of the Sysmex® CA-1500 is as a fully automated, computerized blood plasma coagulation analyzer for in vitro diagnostic use in clinical laboratories. The instrument uses citrated human plasma to perform the following parameters and calculated parameters: Clotting Analysis Parameters: Prothrombin Time (PT); Activated Partial Thromboplastin Time (APTT); Fibrinogen (Clauss); Batroxobin Time; 5 Similarities Item Device Sysmex® CS-2100i Predicate Sysmex® CA-1500 Time (APTT) with Dade® Actin® FSL · Fibrinogen (Fbg) with Dade® Thrombin Reagent · Coagulation Factor V with Dade® Innovin® · Coagulation Factor VII with Dade® Innovin® · Protein C with Protein C Reagent · Antithrombin (AT) with INNOVANCE® Antithrombin · Protein C with Berichrom® Protein C · D-dimer with INNOVANCE® D- Dimer The performance of this device has not been established in neonate and pediatric patient populations. Extrinsic Factors (II, V, VII, X); Intrinsic Factors (VIII, IX, XI, XII); Protein C Chromogenic Analysis Parameters: Antithrombin III; Factor VIII; Plasminogen; Heparin; Protein C; α2-Antiplasmin Immunologic Analysis Parameters: D-dimer Calculated Parameters: PT Ratio; PT INR; PT %; Derived Fibrinogen; Factor Assays % Activity Clinical Reportable Range Coagulation Factor V with Dade® Innovin® 6.0 to 149.0% of norm; Coagulation Factor VII with Dade® Innovin® 6.0 to 149.0% of norm; Protein C with Protein C Reagent 10.1 to 131.0% of norm Same Sample Type 3.2% sodium citrate venous plasma Same Specimen Processing Automatic Pipetting and Dilution Same Random access Yes Same Liquid Level Sensing Yes – reagent and sample Same Bar Code Reader Sample and reagent Same Sampling Capabilities Normal and Micro Mode Same Sample Volumes (Plasma) Coagulation Factor V with Dade® Innovin® (5 μL) Coagulation Factor VII with Dade® Innovin® (5 μL) Protein C with Protein C Reagent (5 μL Purpose for submission:

idK162688_s0_e2000

K162688.txt

measurand

Factor V activity using Coagulation Factor V Deficient Plasman with Dade® Innovin®; factor VII activity using Coagulation Factor VII Deficient Plasma with Dade® Innovin®; protein C activity using Protein C Reagent and protein C activity using Berichrom® Protein C. All measurands are reported as percent (%)of norm.

ANTIAL EQUIVALENCE DETERMINATION DECISION MEMORANDUM 1 A. 510(k) Number: K162688 B. Purpose for Submission: To expand the use of previously cleared assay reagents for Coagulation Factor V Deficient Plasma, Coagulation Factor VII Deficient Plasma, Protein C Reagent, and Berichrom® Protein C to the Sysmex® CS-2100i automated blood coagulation analyzer. C. Measurand: Factor V activity using Coagulation Factor V Deficient Plasman with Dade® Innovin®; factor VII activity using Coagulation Factor VII Deficient Plasma with Dade® Innovin®; protein C activity using Protein C Reagent and protein C activity using Berichrom® Protein C. All measurands are reported as percent (%)of norm. D. Type of Test: Factor V activity using Coagulation Factor V with Dade® Innovin®, factor VII activity using Coagulation Factor VII with Dade® Innovin®, and protein C using Protein C Reagent are quantitative clot-based applications. Protein C using Berichrom® Protein C is a quantitative chromogenic application. E. Applicant: Siemens Healthcare Diagnostics Product GmbH F. Proprietary and Established Names: Sysmex® CS-2100i Automated Blood Coagulation Analyzer Coagulation Factor V Deficient Plasma Coagulation Factor II, VII and X Deficient Plasmas Protein C Reagent Berichrom® Protein C Note: The performance of Coagulation Factor II Deficient Plasma and Coagulation Factor X Deficient Plasma was not evaluated in this premarket notification. G. Regulatory Information: 1. Regulation section: 2 Device Regulation Section Sysmex® CS-2100i 21 CFR 864.5425, Multipurpose system for in vitro coagulation studies Coagulation Factor V Deficient Plasma 21 CFR 864.7290, Factor deficiency test Coagulation Factor VII Deficient Plasma Protein C Reagent Berichrom® Protein C 2. Classification: Class II 3. Product code: Device Product Code Sysmex® CS-5100 JPA, System, multipurpose for in vitro coagulation studies Coagulation Factor V Deficient Plasma GJT, Plasma, coagulation factor deficient Coagulation Factor II, VII and X Deficient Plasma Protein C Reagent GGP, Test, qualitative and quantitative factor deficiency Berichrom® Protein C 4. Panel: Hematology (81) H. Intended Use: 1. Intended use(s): The Sysmex CS-2100i is a fully automated blood coagulation analyzer intended for in vitro diagnostic use using plasma collected from venous blood samples in 3.2% sodium citrate tubes to analyze clotting, chromogenic and immunoassay methods in the clinical laboratory. For determination of: - Prothrombin Time (PT) seconds and PT INR with Dade® Innovin® - Activated Partial Thromboplastin Time (APTT) with Dade® Actin® FSL - Fibrinogen (Fbg) with Dade® Thrombin Reagent - Coagulation Factor V with Dade® Innovin® - Coagulation Factor VII with Dade® Innovin® - Protein C with Protein C Reagent - Antithrombin (AT) with INNOVANCE® Antithrombin - Protein C with Berichrom® Protein C - D-dimer with INNOVANCE® D-Dimer The performance of this device has not been established in neonate and pediatric patient populations. For Coagulation Factor V Deficient Plasma 3 In vitro diagnostic reagent for the determination of the activity of factor V in human plasma. For Coagulation Factor VII Deficient Plasma In vitro diagnostic reagent for the determination of the activity of coagulation factor II (prothrombin), coagulation factor VII and coagulation factor X in human plasma by coagulometric methods. For Protein C Reagent Protein C Reagent is a coagulation test for the quantitative determination of protein C activity in human plasma. For Berichrom® Protein C For the quantitative determination of functionally active protein C using a chromogenic substrate as an aid in the diagnosis of inherited and acquired deficiencies. 2. Indication(s) for use: Same as Intended Use(s) above 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: Sysmex CS-2100i I. Device Description: The Sysmex CS-2100i is a standalone automated blood coagulation analyzer which analyzes venous plasma samples collected in 3.2% sodium citrate using clotting, chromogenic and immunoassay methods. Results are displayed on the Information Processing Unit (IPU) screen and can be printed on external printers or transmitted to a host computer. The instrument is capable of measuring the assays in a normal mode and a micro-sample mode. Coagulation Factor V and VII Deficient Plasmas Coagulation Factor V Deficient Plasma and Coagulation Factor VII Deficient Plasma are lyophilized human plasmas with a residual factor V or VII activity ≤ 1%. Each deficient plasma contains mannitol as a stabilizer. Berichrom® Protein C 4 The Berichrom® Protein C kit is comprised of the following: Protein C Activator, Substrate Reagent, and Hepes Buffer Solution (activator diluent). Protein C Reagent The Protein C Reagent kit includes: lyophilized Protein C Activator (with snake venom extract), APTT Reagent for Protein C, and lyophilized Protein C Deficient Plasma. J. Substantial Equivalence Information: 1. Predicate device name(s): Sysmex® Automated Coagulation Analyzer CA-1500 2. Predicate 510(k) number(s): K011235 The performance of the Coagulation Factor V with Dade® Innovin® and Coagulation Factor VII with Dade® Innovin® applications on the Sysmex® CA-1500 was evaluated in K993299. The performance of Protein C Reagent and Berichrom® Protein C in combination with the Sysmex® CA-1500 was evaluated in K000649 and K001645, respectively. 3. Comparison with predicate: Similarities Item Device Sysmex® CS-2100i Predicate Sysmex® CA-1500 Intended Use The Sysmex® CS-2100i is a fully automated blood coagulation analyzer intended for in vitro diagnostic use using plasma collected from venous blood samples in 3.2% sodium citrate tubes to analyze clotting, chromogenic and immunoassay methods in the clinical laboratory. For determination of: · Prothrombin Time (PT) seconds and PT INR with Dade® Innovin® · Activated Partial Thromboplastin The intended use of the Sysmex® CA-1500 is as a fully automated, computerized blood plasma coagulation analyzer for in vitro diagnostic use in clinical laboratories. The instrument uses citrated human plasma to perform the following parameters and calculated parameters: Clotting Analysis Parameters: Prothrombin Time (PT); Activated Partial Thromboplastin Time (APTT); Fibrinogen (Clauss); Batroxobin Time; 5 Similarities Item Device Sysmex® CS-2100i Predicate Sysmex® CA-1500 Time (APTT) with Dade® Actin® FSL · Fibrinogen (Fbg) with Dade® Thrombin Reagent · Coagulation Factor V with Dade® Innovin® · Coagulation Factor VII with Dade® Innovin® · Protein C with Protein C Reagent · Antithrombin (AT) with INNOVANCE® Antithrombin · Protein C with Berichrom® Protein C · D-dimer with INNOVANCE® D- Dimer The performance of this device has not been established in neonate and pediatric patient populations. Extrinsic Factors (II, V, VII, X); Intrinsic Factors (VIII, IX, XI, XII); Protein C Chromogenic Analysis Parameters: Antithrombin III; Factor VIII; Plasminogen; Heparin; Protein C; α2-Antiplasmin Immunologic Analysis Parameters: D-dimer Calculated Parameters: PT Ratio; PT INR; PT %; Derived Fibrinogen; Factor Assays % Activity Clinical Reportable Range Coagulation Factor V with Dade® Innovin® 6.0 to 149.0% of norm; Coagulation Factor VII with Dade® Innovin® 6.0 to 149.0% of norm; Protein C with Protein C Reagent 10.1 to 131.0% of norm Same Sample Type 3.2% sodium citrate venous plasma Same Specimen Processing Automatic Pipetting and Dilution Same Random access Yes Same Liquid Level Sensing Yes – reagent and sample Same Bar Code Reader Sample and reagent Same Sampling Capabilities Normal and Micro Mode Same Sample Volumes (Plasma) Coagulation Factor V with Dade® Innovin® (5 μL) Coagulation Factor VII with Dade® Innovin® (5 μL) Protein C with Protein C Reagent (5 μL Measurand:

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type of test

Factor V activity using Coagulation Factor V with Dade® Innovin®, factor VII activity using Coagulation Factor VII with Dade® Innovin®, and protein C using Protein C Reagent are quantitative clot-based applications. Protein C using Berichrom® Protein C is a quantitative chromogenic application.

STANTIAL EQUIVALENCE DETERMINATION DECISION MEMORANDUM 1 A. 510(k) Number: K162688 B. Purpose for Submission: To expand the use of previously cleared assay reagents for Coagulation Factor V Deficient Plasma, Coagulation Factor VII Deficient Plasma, Protein C Reagent, and Berichrom® Protein C to the Sysmex® CS-2100i automated blood coagulation analyzer. C. Measurand: Factor V activity using Coagulation Factor V Deficient Plasman with Dade® Innovin®; factor VII activity using Coagulation Factor VII Deficient Plasma with Dade® Innovin®; protein C activity using Protein C Reagent and protein C activity using Berichrom® Protein C. All measurands are reported as percent (%)of norm. D. Type of Test: Factor V activity using Coagulation Factor V with Dade® Innovin®, factor VII activity using Coagulation Factor VII with Dade® Innovin®, and protein C using Protein C Reagent are quantitative clot-based applications. Protein C using Berichrom® Protein C is a quantitative chromogenic application. E. Applicant: Siemens Healthcare Diagnostics Product GmbH F. Proprietary and Established Names: Sysmex® CS-2100i Automated Blood Coagulation Analyzer Coagulation Factor V Deficient Plasma Coagulation Factor II, VII and X Deficient Plasmas Protein C Reagent Berichrom® Protein C Note: The performance of Coagulation Factor II Deficient Plasma and Coagulation Factor X Deficient Plasma was not evaluated in this premarket notification. G. Regulatory Information: 1. Regulation section: 2 Device Regulation Section Sysmex® CS-2100i 21 CFR 864.5425, Multipurpose system for in vitro coagulation studies Coagulation Factor V Deficient Plasma 21 CFR 864.7290, Factor deficiency test Coagulation Factor VII Deficient Plasma Protein C Reagent Berichrom® Protein C 2. Classification: Class II 3. Product code: Device Product Code Sysmex® CS-5100 JPA, System, multipurpose for in vitro coagulation studies Coagulation Factor V Deficient Plasma GJT, Plasma, coagulation factor deficient Coagulation Factor II, VII and X Deficient Plasma Protein C Reagent GGP, Test, qualitative and quantitative factor deficiency Berichrom® Protein C 4. Panel: Hematology (81) H. Intended Use: 1. Intended use(s): The Sysmex CS-2100i is a fully automated blood coagulation analyzer intended for in vitro diagnostic use using plasma collected from venous blood samples in 3.2% sodium citrate tubes to analyze clotting, chromogenic and immunoassay methods in the clinical laboratory. For determination of: - Prothrombin Time (PT) seconds and PT INR with Dade® Innovin® - Activated Partial Thromboplastin Time (APTT) with Dade® Actin® FSL - Fibrinogen (Fbg) with Dade® Thrombin Reagent - Coagulation Factor V with Dade® Innovin® - Coagulation Factor VII with Dade® Innovin® - Protein C with Protein C Reagent - Antithrombin (AT) with INNOVANCE® Antithrombin - Protein C with Berichrom® Protein C - D-dimer with INNOVANCE® D-Dimer The performance of this device has not been established in neonate and pediatric patient populations. For Coagulation Factor V Deficient Plasma 3 In vitro diagnostic reagent for the determination of the activity of factor V in human plasma. For Coagulation Factor VII Deficient Plasma In vitro diagnostic reagent for the determination of the activity of coagulation factor II (prothrombin), coagulation factor VII and coagulation factor X in human plasma by coagulometric methods. For Protein C Reagent Protein C Reagent is a coagulation test for the quantitative determination of protein C activity in human plasma. For Berichrom® Protein C For the quantitative determination of functionally active protein C using a chromogenic substrate as an aid in the diagnosis of inherited and acquired deficiencies. 2. Indication(s) for use: Same as Intended Use(s) above 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: Sysmex CS-2100i I. Device Description: The Sysmex CS-2100i is a standalone automated blood coagulation analyzer which analyzes venous plasma samples collected in 3.2% sodium citrate using clotting, chromogenic and immunoassay methods. Results are displayed on the Information Processing Unit (IPU) screen and can be printed on external printers or transmitted to a host computer. The instrument is capable of measuring the assays in a normal mode and a micro-sample mode. Coagulation Factor V and VII Deficient Plasmas Coagulation Factor V Deficient Plasma and Coagulation Factor VII Deficient Plasma are lyophilized human plasmas with a residual factor V or VII activity ≤ 1%. Each deficient plasma contains mannitol as a stabilizer. Berichrom® Protein C 4 The Berichrom® Protein C kit is comprised of the following: Protein C Activator, Substrate Reagent, and Hepes Buffer Solution (activator diluent). Protein C Reagent The Protein C Reagent kit includes: lyophilized Protein C Activator (with snake venom extract), APTT Reagent for Protein C, and lyophilized Protein C Deficient Plasma. J. Substantial Equivalence Information: 1. Predicate device name(s): Sysmex® Automated Coagulation Analyzer CA-1500 2. Predicate 510(k) number(s): K011235 The performance of the Coagulation Factor V with Dade® Innovin® and Coagulation Factor VII with Dade® Innovin® applications on the Sysmex® CA-1500 was evaluated in K993299. The performance of Protein C Reagent and Berichrom® Protein C in combination with the Sysmex® CA-1500 was evaluated in K000649 and K001645, respectively. 3. Comparison with predicate: Similarities Item Device Sysmex® CS-2100i Predicate Sysmex® CA-1500 Intended Use The Sysmex® CS-2100i is a fully automated blood coagulation analyzer intended for in vitro diagnostic use using plasma collected from venous blood samples in 3.2% sodium citrate tubes to analyze clotting, chromogenic and immunoassay methods in the clinical laboratory. For determination of: · Prothrombin Time (PT) seconds and PT INR with Dade® Innovin® · Activated Partial Thromboplastin The intended use of the Sysmex® CA-1500 is as a fully automated, computerized blood plasma coagulation analyzer for in vitro diagnostic use in clinical laboratories. The instrument uses citrated human plasma to perform the following parameters and calculated parameters: Clotting Analysis Parameters: Prothrombin Time (PT); Activated Partial Thromboplastin Time (APTT); Fibrinogen (Clauss); Batroxobin Time; 5 Similarities Item Device Sysmex® CS-2100i Predicate Sysmex® CA-1500 Time (APTT) with Dade® Actin® FSL · Fibrinogen (Fbg) with Dade® Thrombin Reagent · Coagulation Factor V with Dade® Innovin® · Coagulation Factor VII with Dade® Innovin® · Protein C with Protein C Reagent · Antithrombin (AT) with INNOVANCE® Antithrombin · Protein C with Berichrom® Protein C · D-dimer with INNOVANCE® D- Dimer The performance of this device has not been established in neonate and pediatric patient populations. Extrinsic Factors (II, V, VII, X); Intrinsic Factors (VIII, IX, XI, XII); Protein C Chromogenic Analysis Parameters: Antithrombin III; Factor VIII; Plasminogen; Heparin; Protein C; α2-Antiplasmin Immunologic Analysis Parameters: D-dimer Calculated Parameters: PT Ratio; PT INR; PT %; Derived Fibrinogen; Factor Assays % Activity Clinical Reportable Range Coagulation Factor V with Dade® Innovin® 6.0 to 149.0% of norm; Coagulation Factor VII with Dade® Innovin® 6.0 to 149.0% of norm; Protein C with Protein C Reagent 10.1 to 131.0% of norm Same Sample Type 3.2% sodium citrate venous plasma Same Specimen Processing Automatic Pipetting and Dilution Same Random access Yes Same Liquid Level Sensing Yes – reagent and sample Same Bar Code Reader Sample and reagent Same Sampling Capabilities Normal and Micro Mode Same Sample Volumes (Plasma) Coagulation Factor V with Dade® Innovin® (5 μL) Coagulation Factor VII with Dade® Innovin® (5 μL) Protein C with Protein C Reagent (5 μL Type of test:

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classification

Class II

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION MEMORANDUM 1 A. 510(k) Number: K162688 B. Purpose for Submission: To expand the use of previously cleared assay reagents for Coagulation Factor V Deficient Plasma, Coagulation Factor VII Deficient Plasma, Protein C Reagent, and Berichrom® Protein C to the Sysmex® CS-2100i automated blood coagulation analyzer. C. Measurand: Factor V activity using Coagulation Factor V Deficient Plasman with Dade® Innovin®; factor VII activity using Coagulation Factor VII Deficient Plasma with Dade® Innovin®; protein C activity using Protein C Reagent and protein C activity using Berichrom® Protein C. All measurands are reported as percent (%)of norm. D. Type of Test: Factor V activity using Coagulation Factor V with Dade® Innovin®, factor VII activity using Coagulation Factor VII with Dade® Innovin®, and protein C using Protein C Reagent are quantitative clot-based applications. Protein C using Berichrom® Protein C is a quantitative chromogenic application. E. Applicant: Siemens Healthcare Diagnostics Product GmbH F. Proprietary and Established Names: Sysmex® CS-2100i Automated Blood Coagulation Analyzer Coagulation Factor V Deficient Plasma Coagulation Factor II, VII and X Deficient Plasmas Protein C Reagent Berichrom® Protein C Note: The performance of Coagulation Factor II Deficient Plasma and Coagulation Factor X Deficient Plasma was not evaluated in this premarket notification. G. Regulatory Information: 1. Regulation section: 2 Device Regulation Section Sysmex® CS-2100i 21 CFR 864.5425, Multipurpose system for in vitro coagulation studies Coagulation Factor V Deficient Plasma 21 CFR 864.7290, Factor deficiency test Coagulation Factor VII Deficient Plasma Protein C Reagent Berichrom® Protein C 2. Classification: Class II 3. Product code: Device Product Code Sysmex® CS-5100 JPA, System, multipurpose for in vitro coagulation studies Coagulation Factor V Deficient Plasma GJT, Plasma, coagulation factor deficient Coagulation Factor II, VII and X Deficient Plasma Protein C Reagent GGP, Test, qualitative and quantitative factor deficiency Berichrom® Protein C 4. Panel: Hematology (81) H. Intended Use: 1. Intended use(s): The Sysmex CS-2100i is a fully automated blood coagulation analyzer intended for in vitro diagnostic use using plasma collected from venous blood samples in 3.2% sodium citrate tubes to analyze clotting, chromogenic and immunoassay methods in the clinical laboratory. For determination of: - Prothrombin Time (PT) seconds and PT INR with Dade® Innovin® - Activated Partial Thromboplastin Time (APTT) with Dade® Actin® FSL - Fibrinogen (Fbg) with Dade® Thrombin Reagent - Coagulation Factor V with Dade® Innovin® - Coagulation Factor VII with Dade® Innovin® - Protein C with Protein C Reagent - Antithrombin (AT) with INNOVANCE® Antithrombin - Protein C with Berichrom® Protein C - D-dimer with INNOVANCE® D-Dimer The performance of this device has not been established in neonate and pediatric patient populations. For Coagulation Factor V Deficient Plasma 3 In vitro diagnostic reagent for the determination of the activity of factor V in human plasma. For Coagulation Factor VII Deficient Plasma In vitro diagnostic reagent for the determination of the activity of coagulation factor II (prothrombin), coagulation factor VII and coagulation factor X in human plasma by coagulometric methods. For Protein C Reagent Protein C Reagent is a coagulation test for the quantitative determination of protein C activity in human plasma. For Berichrom® Protein C For the quantitative determination of functionally active protein C using a chromogenic substrate as an aid in the diagnosis of inherited and acquired deficiencies. 2. Indication(s) for use: Same as Intended Use(s) above 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: Sysmex CS-2100i I. Device Description: The Sysmex CS-2100i is a standalone automated blood coagulation analyzer which analyzes venous plasma samples collected in 3.2% sodium citrate using clotting, chromogenic and immunoassay methods. Results are displayed on the Information Processing Unit (IPU) screen and can be printed on external printers or transmitted to a host computer. The instrument is capable of measuring the assays in a normal mode and a micro-sample mode. Coagulation Factor V and VII Deficient Plasmas Coagulation Factor V Deficient Plasma and Coagulation Factor VII Deficient Plasma are lyophilized human plasmas with a residual factor V or VII activity ≤ 1%. Each deficient plasma contains mannitol as a stabilizer. Berichrom® Protein C 4 The Berichrom® Protein C kit is comprised of the following: Protein C Activator, Substrate Reagent, and Hepes Buffer Solution (activator diluent). Protein C Reagent The Protein C Reagent kit includes: lyophilized Protein C Activator (with snake venom extract), APTT Reagent for Protein C, and lyophilized Protein C Deficient Plasma. J. Substantial Equivalence Information: 1. Predicate device name(s): Sysmex® Automated Coagulation Analyzer CA-1500 2. Predicate 510(k) number(s): K011235 The performance of the Coagulation Factor V with Dade® Innovin® and Coagulation Factor VII with Dade® Innovin® applications on the Sysmex® CA-1500 was evaluated in K993299. The performance of Protein C Reagent and Berichrom® Protein C in combination with the Sysmex® CA-1500 was evaluated in K000649 and K001645, respectively. 3. Comparison with predicate: Similarities Item Device Sysmex® CS-2100i Predicate Sysmex® CA-1500 Intended Use The Sysmex® CS-2100i is a fully automated blood coagulation analyzer intended for in vitro diagnostic use using plasma collected from venous blood samples in 3.2% sodium citrate tubes to analyze clotting, chromogenic and immunoassay methods in the clinical laboratory. For determination of: · Prothrombin Time (PT) seconds and PT INR with Dade® Innovin® · Activated Partial Thromboplastin The intended use of the Sysmex® CA-1500 is as a fully automated, computerized blood plasma coagulation analyzer for in vitro diagnostic use in clinical laboratories. The instrument uses citrated human plasma to perform the following parameters and calculated parameters: Clotting Analysis Parameters: Prothrombin Time (PT); Activated Partial Thromboplastin Time (APTT); Fibrinogen (Clauss); Batroxobin Time; 5 Similarities Item Device Sysmex® CS-2100i Predicate Sysmex® CA-1500 Time (APTT) with Dade® Actin® FSL · Fibrinogen (Fbg) with Dade® Thrombin Reagent · Coagulation Factor V with Dade® Innovin® · Coagulation Factor VII with Dade® Innovin® · Protein C with Protein C Reagent · Antithrombin (AT) with INNOVANCE® Antithrombin · Protein C with Berichrom® Protein C · D-dimer with INNOVANCE® D- Dimer The performance of this device has not been established in neonate and pediatric patient populations. Extrinsic Factors (II, V, VII, X); Intrinsic Factors (VIII, IX, XI, XII); Protein C Chromogenic Analysis Parameters: Antithrombin III; Factor VIII; Plasminogen; Heparin; Protein C; α2-Antiplasmin Immunologic Analysis Parameters: D-dimer Calculated Parameters: PT Ratio; PT INR; PT %; Derived Fibrinogen; Factor Assays % Activity Clinical Reportable Range Coagulation Factor V with Dade® Innovin® 6.0 to 149.0% of norm; Coagulation Factor VII with Dade® Innovin® 6.0 to 149.0% of norm; Protein C with Protein C Reagent 10.1 to 131.0% of norm Same Sample Type 3.2% sodium citrate venous plasma Same Specimen Processing Automatic Pipetting and Dilution Same Random access Yes Same Liquid Level Sensing Yes – reagent and sample Same Bar Code Reader Sample and reagent Same Sampling Capabilities Normal and Micro Mode Same Sample Volumes (Plasma) Coagulation Factor V with Dade® Innovin® (5 μL) Coagulation Factor VII with Dade® Innovin® (5 μL) Protein C with Protein C Reagent (5 μL Classification:

idK162688_s0_e2000

K162688.txt

panel

Hematology (81)

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION MEMORANDUM 1 A. 510(k) Number: K162688 B. Purpose for Submission: To expand the use of previously cleared assay reagents for Coagulation Factor V Deficient Plasma, Coagulation Factor VII Deficient Plasma, Protein C Reagent, and Berichrom® Protein C to the Sysmex® CS-2100i automated blood coagulation analyzer. C. Measurand: Factor V activity using Coagulation Factor V Deficient Plasman with Dade® Innovin®; factor VII activity using Coagulation Factor VII Deficient Plasma with Dade® Innovin®; protein C activity using Protein C Reagent and protein C activity using Berichrom® Protein C. All measurands are reported as percent (%)of norm. D. Type of Test: Factor V activity using Coagulation Factor V with Dade® Innovin®, factor VII activity using Coagulation Factor VII with Dade® Innovin®, and protein C using Protein C Reagent are quantitative clot-based applications. Protein C using Berichrom® Protein C is a quantitative chromogenic application. E. Applicant: Siemens Healthcare Diagnostics Product GmbH F. Proprietary and Established Names: Sysmex® CS-2100i Automated Blood Coagulation Analyzer Coagulation Factor V Deficient Plasma Coagulation Factor II, VII and X Deficient Plasmas Protein C Reagent Berichrom® Protein C Note: The performance of Coagulation Factor II Deficient Plasma and Coagulation Factor X Deficient Plasma was not evaluated in this premarket notification. G. Regulatory Information: 1. Regulation section: 2 Device Regulation Section Sysmex® CS-2100i 21 CFR 864.5425, Multipurpose system for in vitro coagulation studies Coagulation Factor V Deficient Plasma 21 CFR 864.7290, Factor deficiency test Coagulation Factor VII Deficient Plasma Protein C Reagent Berichrom® Protein C 2. Classification: Class II 3. Product code: Device Product Code Sysmex® CS-5100 JPA, System, multipurpose for in vitro coagulation studies Coagulation Factor V Deficient Plasma GJT, Plasma, coagulation factor deficient Coagulation Factor II, VII and X Deficient Plasma Protein C Reagent GGP, Test, qualitative and quantitative factor deficiency Berichrom® Protein C 4. Panel: Hematology (81) H. Intended Use: 1. Intended use(s): The Sysmex CS-2100i is a fully automated blood coagulation analyzer intended for in vitro diagnostic use using plasma collected from venous blood samples in 3.2% sodium citrate tubes to analyze clotting, chromogenic and immunoassay methods in the clinical laboratory. For determination of: - Prothrombin Time (PT) seconds and PT INR with Dade® Innovin® - Activated Partial Thromboplastin Time (APTT) with Dade® Actin® FSL - Fibrinogen (Fbg) with Dade® Thrombin Reagent - Coagulation Factor V with Dade® Innovin® - Coagulation Factor VII with Dade® Innovin® - Protein C with Protein C Reagent - Antithrombin (AT) with INNOVANCE® Antithrombin - Protein C with Berichrom® Protein C - D-dimer with INNOVANCE® D-Dimer The performance of this device has not been established in neonate and pediatric patient populations. For Coagulation Factor V Deficient Plasma 3 In vitro diagnostic reagent for the determination of the activity of factor V in human plasma. For Coagulation Factor VII Deficient Plasma In vitro diagnostic reagent for the determination of the activity of coagulation factor II (prothrombin), coagulation factor VII and coagulation factor X in human plasma by coagulometric methods. For Protein C Reagent Protein C Reagent is a coagulation test for the quantitative determination of protein C activity in human plasma. For Berichrom® Protein C For the quantitative determination of functionally active protein C using a chromogenic substrate as an aid in the diagnosis of inherited and acquired deficiencies. 2. Indication(s) for use: Same as Intended Use(s) above 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: Sysmex CS-2100i I. Device Description: The Sysmex CS-2100i is a standalone automated blood coagulation analyzer which analyzes venous plasma samples collected in 3.2% sodium citrate using clotting, chromogenic and immunoassay methods. Results are displayed on the Information Processing Unit (IPU) screen and can be printed on external printers or transmitted to a host computer. The instrument is capable of measuring the assays in a normal mode and a micro-sample mode. Coagulation Factor V and VII Deficient Plasmas Coagulation Factor V Deficient Plasma and Coagulation Factor VII Deficient Plasma are lyophilized human plasmas with a residual factor V or VII activity ≤ 1%. Each deficient plasma contains mannitol as a stabilizer. Berichrom® Protein C 4 The Berichrom® Protein C kit is comprised of the following: Protein C Activator, Substrate Reagent, and Hepes Buffer Solution (activator diluent). Protein C Reagent The Protein C Reagent kit includes: lyophilized Protein C Activator (with snake venom extract), APTT Reagent for Protein C, and lyophilized Protein C Deficient Plasma. J. Substantial Equivalence Information: 1. Predicate device name(s): Sysmex® Automated Coagulation Analyzer CA-1500 2. Predicate 510(k) number(s): K011235 The performance of the Coagulation Factor V with Dade® Innovin® and Coagulation Factor VII with Dade® Innovin® applications on the Sysmex® CA-1500 was evaluated in K993299. The performance of Protein C Reagent and Berichrom® Protein C in combination with the Sysmex® CA-1500 was evaluated in K000649 and K001645, respectively. 3. Comparison with predicate: Similarities Item Device Sysmex® CS-2100i Predicate Sysmex® CA-1500 Intended Use The Sysmex® CS-2100i is a fully automated blood coagulation analyzer intended for in vitro diagnostic use using plasma collected from venous blood samples in 3.2% sodium citrate tubes to analyze clotting, chromogenic and immunoassay methods in the clinical laboratory. For determination of: · Prothrombin Time (PT) seconds and PT INR with Dade® Innovin® · Activated Partial Thromboplastin The intended use of the Sysmex® CA-1500 is as a fully automated, computerized blood plasma coagulation analyzer for in vitro diagnostic use in clinical laboratories. The instrument uses citrated human plasma to perform the following parameters and calculated parameters: Clotting Analysis Parameters: Prothrombin Time (PT); Activated Partial Thromboplastin Time (APTT); Fibrinogen (Clauss); Batroxobin Time; 5 Similarities Item Device Sysmex® CS-2100i Predicate Sysmex® CA-1500 Time (APTT) with Dade® Actin® FSL · Fibrinogen (Fbg) with Dade® Thrombin Reagent · Coagulation Factor V with Dade® Innovin® · Coagulation Factor VII with Dade® Innovin® · Protein C with Protein C Reagent · Antithrombin (AT) with INNOVANCE® Antithrombin · Protein C with Berichrom® Protein C · D-dimer with INNOVANCE® D- Dimer The performance of this device has not been established in neonate and pediatric patient populations. Extrinsic Factors (II, V, VII, X); Intrinsic Factors (VIII, IX, XI, XII); Protein C Chromogenic Analysis Parameters: Antithrombin III; Factor VIII; Plasminogen; Heparin; Protein C; α2-Antiplasmin Immunologic Analysis Parameters: D-dimer Calculated Parameters: PT Ratio; PT INR; PT %; Derived Fibrinogen; Factor Assays % Activity Clinical Reportable Range Coagulation Factor V with Dade® Innovin® 6.0 to 149.0% of norm; Coagulation Factor VII with Dade® Innovin® 6.0 to 149.0% of norm; Protein C with Protein C Reagent 10.1 to 131.0% of norm Same Sample Type 3.2% sodium citrate venous plasma Same Specimen Processing Automatic Pipetting and Dilution Same Random access Yes Same Liquid Level Sensing Yes – reagent and sample Same Bar Code Reader Sample and reagent Same Sampling Capabilities Normal and Micro Mode Same Sample Volumes (Plasma) Coagulation Factor V with Dade® Innovin® (5 μL) Coagulation Factor VII with Dade® Innovin® (5 μL) Protein C with Protein C Reagent (5 μL Panel:

idK162688_s0_e2000

K162688.txt

predicate device name

Sysmex® Automated Coagulation Analyzer CA-1500

ANTIAL EQUIVALENCE DETERMINATION DECISION MEMORANDUM 1 A. 510(k) Number: K162688 B. Purpose for Submission: To expand the use of previously cleared assay reagents for Coagulation Factor V Deficient Plasma, Coagulation Factor VII Deficient Plasma, Protein C Reagent, and Berichrom® Protein C to the Sysmex® CS-2100i automated blood coagulation analyzer. C. Measurand: Factor V activity using Coagulation Factor V Deficient Plasman with Dade® Innovin®; factor VII activity using Coagulation Factor VII Deficient Plasma with Dade® Innovin®; protein C activity using Protein C Reagent and protein C activity using Berichrom® Protein C. All measurands are reported as percent (%)of norm. D. Type of Test: Factor V activity using Coagulation Factor V with Dade® Innovin®, factor VII activity using Coagulation Factor VII with Dade® Innovin®, and protein C using Protein C Reagent are quantitative clot-based applications. Protein C using Berichrom® Protein C is a quantitative chromogenic application. E. Applicant: Siemens Healthcare Diagnostics Product GmbH F. Proprietary and Established Names: Sysmex® CS-2100i Automated Blood Coagulation Analyzer Coagulation Factor V Deficient Plasma Coagulation Factor II, VII and X Deficient Plasmas Protein C Reagent Berichrom® Protein C Note: The performance of Coagulation Factor II Deficient Plasma and Coagulation Factor X Deficient Plasma was not evaluated in this premarket notification. G. Regulatory Information: 1. Regulation section: 2 Device Regulation Section Sysmex® CS-2100i 21 CFR 864.5425, Multipurpose system for in vitro coagulation studies Coagulation Factor V Deficient Plasma 21 CFR 864.7290, Factor deficiency test Coagulation Factor VII Deficient Plasma Protein C Reagent Berichrom® Protein C 2. Classification: Class II 3. Product code: Device Product Code Sysmex® CS-5100 JPA, System, multipurpose for in vitro coagulation studies Coagulation Factor V Deficient Plasma GJT, Plasma, coagulation factor deficient Coagulation Factor II, VII and X Deficient Plasma Protein C Reagent GGP, Test, qualitative and quantitative factor deficiency Berichrom® Protein C 4. Panel: Hematology (81) H. Intended Use: 1. Intended use(s): The Sysmex CS-2100i is a fully automated blood coagulation analyzer intended for in vitro diagnostic use using plasma collected from venous blood samples in 3.2% sodium citrate tubes to analyze clotting, chromogenic and immunoassay methods in the clinical laboratory. For determination of: - Prothrombin Time (PT) seconds and PT INR with Dade® Innovin® - Activated Partial Thromboplastin Time (APTT) with Dade® Actin® FSL - Fibrinogen (Fbg) with Dade® Thrombin Reagent - Coagulation Factor V with Dade® Innovin® - Coagulation Factor VII with Dade® Innovin® - Protein C with Protein C Reagent - Antithrombin (AT) with INNOVANCE® Antithrombin - Protein C with Berichrom® Protein C - D-dimer with INNOVANCE® D-Dimer The performance of this device has not been established in neonate and pediatric patient populations. For Coagulation Factor V Deficient Plasma 3 In vitro diagnostic reagent for the determination of the activity of factor V in human plasma. For Coagulation Factor VII Deficient Plasma In vitro diagnostic reagent for the determination of the activity of coagulation factor II (prothrombin), coagulation factor VII and coagulation factor X in human plasma by coagulometric methods. For Protein C Reagent Protein C Reagent is a coagulation test for the quantitative determination of protein C activity in human plasma. For Berichrom® Protein C For the quantitative determination of functionally active protein C using a chromogenic substrate as an aid in the diagnosis of inherited and acquired deficiencies. 2. Indication(s) for use: Same as Intended Use(s) above 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: Sysmex CS-2100i I. Device Description: The Sysmex CS-2100i is a standalone automated blood coagulation analyzer which analyzes venous plasma samples collected in 3.2% sodium citrate using clotting, chromogenic and immunoassay methods. Results are displayed on the Information Processing Unit (IPU) screen and can be printed on external printers or transmitted to a host computer. The instrument is capable of measuring the assays in a normal mode and a micro-sample mode. Coagulation Factor V and VII Deficient Plasmas Coagulation Factor V Deficient Plasma and Coagulation Factor VII Deficient Plasma are lyophilized human plasmas with a residual factor V or VII activity ≤ 1%. Each deficient plasma contains mannitol as a stabilizer. Berichrom® Protein C 4 The Berichrom® Protein C kit is comprised of the following: Protein C Activator, Substrate Reagent, and Hepes Buffer Solution (activator diluent). Protein C Reagent The Protein C Reagent kit includes: lyophilized Protein C Activator (with snake venom extract), APTT Reagent for Protein C, and lyophilized Protein C Deficient Plasma. J. Substantial Equivalence Information: 1. Predicate device name(s): Sysmex® Automated Coagulation Analyzer CA-1500 2. Predicate 510(k) number(s): K011235 The performance of the Coagulation Factor V with Dade® Innovin® and Coagulation Factor VII with Dade® Innovin® applications on the Sysmex® CA-1500 was evaluated in K993299. The performance of Protein C Reagent and Berichrom® Protein C in combination with the Sysmex® CA-1500 was evaluated in K000649 and K001645, respectively. 3. Comparison with predicate: Similarities Item Device Sysmex® CS-2100i Predicate Sysmex® CA-1500 Intended Use The Sysmex® CS-2100i is a fully automated blood coagulation analyzer intended for in vitro diagnostic use using plasma collected from venous blood samples in 3.2% sodium citrate tubes to analyze clotting, chromogenic and immunoassay methods in the clinical laboratory. For determination of: · Prothrombin Time (PT) seconds and PT INR with Dade® Innovin® · Activated Partial Thromboplastin The intended use of the Sysmex® CA-1500 is as a fully automated, computerized blood plasma coagulation analyzer for in vitro diagnostic use in clinical laboratories. The instrument uses citrated human plasma to perform the following parameters and calculated parameters: Clotting Analysis Parameters: Prothrombin Time (PT); Activated Partial Thromboplastin Time (APTT); Fibrinogen (Clauss); Batroxobin Time; 5 Similarities Item Device Sysmex® CS-2100i Predicate Sysmex® CA-1500 Time (APTT) with Dade® Actin® FSL · Fibrinogen (Fbg) with Dade® Thrombin Reagent · Coagulation Factor V with Dade® Innovin® · Coagulation Factor VII with Dade® Innovin® · Protein C with Protein C Reagent · Antithrombin (AT) with INNOVANCE® Antithrombin · Protein C with Berichrom® Protein C · D-dimer with INNOVANCE® D- Dimer The performance of this device has not been established in neonate and pediatric patient populations. Extrinsic Factors (II, V, VII, X); Intrinsic Factors (VIII, IX, XI, XII); Protein C Chromogenic Analysis Parameters: Antithrombin III; Factor VIII; Plasminogen; Heparin; Protein C; α2-Antiplasmin Immunologic Analysis Parameters: D-dimer Calculated Parameters: PT Ratio; PT INR; PT %; Derived Fibrinogen; Factor Assays % Activity Clinical Reportable Range Coagulation Factor V with Dade® Innovin® 6.0 to 149.0% of norm; Coagulation Factor VII with Dade® Innovin® 6.0 to 149.0% of norm; Protein C with Protein C Reagent 10.1 to 131.0% of norm Same Sample Type 3.2% sodium citrate venous plasma Same Specimen Processing Automatic Pipetting and Dilution Same Random access Yes Same Liquid Level Sensing Yes – reagent and sample Same Bar Code Reader Sample and reagent Same Sampling Capabilities Normal and Micro Mode Same Sample Volumes (Plasma) Coagulation Factor V with Dade® Innovin® (5 μL) Coagulation Factor VII with Dade® Innovin® (5 μL) Protein C with Protein C Reagent (5 μL Predicate device name:

idK162688_s0_e2000

K162688.txt

applicant

Siemens Healthcare Diagnostics Product GmbH

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION MEMORANDUM 1 A. 510(k) Number: K162688 B. Purpose for Submission: To expand the use of previously cleared assay reagents for Coagulation Factor V Deficient Plasma, Coagulation Factor VII Deficient Plasma, Protein C Reagent, and Berichrom® Protein C to the Sysmex® CS-2100i automated blood coagulation analyzer. C. Measurand: Factor V activity using Coagulation Factor V Deficient Plasman with Dade® Innovin®; factor VII activity using Coagulation Factor VII Deficient Plasma with Dade® Innovin®; protein C activity using Protein C Reagent and protein C activity using Berichrom® Protein C. All measurands are reported as percent (%)of norm. D. Type of Test: Factor V activity using Coagulation Factor V with Dade® Innovin®, factor VII activity using Coagulation Factor VII with Dade® Innovin®, and protein C using Protein C Reagent are quantitative clot-based applications. Protein C using Berichrom® Protein C is a quantitative chromogenic application. E. Applicant: Siemens Healthcare Diagnostics Product GmbH F. Proprietary and Established Names: Sysmex® CS-2100i Automated Blood Coagulation Analyzer Coagulation Factor V Deficient Plasma Coagulation Factor II, VII and X Deficient Plasmas Protein C Reagent Berichrom® Protein C Note: The performance of Coagulation Factor II Deficient Plasma and Coagulation Factor X Deficient Plasma was not evaluated in this premarket notification. G. Regulatory Information: 1. Regulation section: 2 Device Regulation Section Sysmex® CS-2100i 21 CFR 864.5425, Multipurpose system for in vitro coagulation studies Coagulation Factor V Deficient Plasma 21 CFR 864.7290, Factor deficiency test Coagulation Factor VII Deficient Plasma Protein C Reagent Berichrom® Protein C 2. Classification: Class II 3. Product code: Device Product Code Sysmex® CS-5100 JPA, System, multipurpose for in vitro coagulation studies Coagulation Factor V Deficient Plasma GJT, Plasma, coagulation factor deficient Coagulation Factor II, VII and X Deficient Plasma Protein C Reagent GGP, Test, qualitative and quantitative factor deficiency Berichrom® Protein C 4. Panel: Hematology (81) H. Intended Use: 1. Intended use(s): The Sysmex CS-2100i is a fully automated blood coagulation analyzer intended for in vitro diagnostic use using plasma collected from venous blood samples in 3.2% sodium citrate tubes to analyze clotting, chromogenic and immunoassay methods in the clinical laboratory. For determination of: - Prothrombin Time (PT) seconds and PT INR with Dade® Innovin® - Activated Partial Thromboplastin Time (APTT) with Dade® Actin® FSL - Fibrinogen (Fbg) with Dade® Thrombin Reagent - Coagulation Factor V with Dade® Innovin® - Coagulation Factor VII with Dade® Innovin® - Protein C with Protein C Reagent - Antithrombin (AT) with INNOVANCE® Antithrombin - Protein C with Berichrom® Protein C - D-dimer with INNOVANCE® D-Dimer The performance of this device has not been established in neonate and pediatric patient populations. For Coagulation Factor V Deficient Plasma 3 In vitro diagnostic reagent for the determination of the activity of factor V in human plasma. For Coagulation Factor VII Deficient Plasma In vitro diagnostic reagent for the determination of the activity of coagulation factor II (prothrombin), coagulation factor VII and coagulation factor X in human plasma by coagulometric methods. For Protein C Reagent Protein C Reagent is a coagulation test for the quantitative determination of protein C activity in human plasma. For Berichrom® Protein C For the quantitative determination of functionally active protein C using a chromogenic substrate as an aid in the diagnosis of inherited and acquired deficiencies. 2. Indication(s) for use: Same as Intended Use(s) above 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: Sysmex CS-2100i I. Device Description: The Sysmex CS-2100i is a standalone automated blood coagulation analyzer which analyzes venous plasma samples collected in 3.2% sodium citrate using clotting, chromogenic and immunoassay methods. Results are displayed on the Information Processing Unit (IPU) screen and can be printed on external printers or transmitted to a host computer. The instrument is capable of measuring the assays in a normal mode and a micro-sample mode. Coagulation Factor V and VII Deficient Plasmas Coagulation Factor V Deficient Plasma and Coagulation Factor VII Deficient Plasma are lyophilized human plasmas with a residual factor V or VII activity ≤ 1%. Each deficient plasma contains mannitol as a stabilizer. Berichrom® Protein C 4 The Berichrom® Protein C kit is comprised of the following: Protein C Activator, Substrate Reagent, and Hepes Buffer Solution (activator diluent). Protein C Reagent The Protein C Reagent kit includes: lyophilized Protein C Activator (with snake venom extract), APTT Reagent for Protein C, and lyophilized Protein C Deficient Plasma. J. Substantial Equivalence Information: 1. Predicate device name(s): Sysmex® Automated Coagulation Analyzer CA-1500 2. Predicate 510(k) number(s): K011235 The performance of the Coagulation Factor V with Dade® Innovin® and Coagulation Factor VII with Dade® Innovin® applications on the Sysmex® CA-1500 was evaluated in K993299. The performance of Protein C Reagent and Berichrom® Protein C in combination with the Sysmex® CA-1500 was evaluated in K000649 and K001645, respectively. 3. Comparison with predicate: Similarities Item Device Sysmex® CS-2100i Predicate Sysmex® CA-1500 Intended Use The Sysmex® CS-2100i is a fully automated blood coagulation analyzer intended for in vitro diagnostic use using plasma collected from venous blood samples in 3.2% sodium citrate tubes to analyze clotting, chromogenic and immunoassay methods in the clinical laboratory. For determination of: · Prothrombin Time (PT) seconds and PT INR with Dade® Innovin® · Activated Partial Thromboplastin The intended use of the Sysmex® CA-1500 is as a fully automated, computerized blood plasma coagulation analyzer for in vitro diagnostic use in clinical laboratories. The instrument uses citrated human plasma to perform the following parameters and calculated parameters: Clotting Analysis Parameters: Prothrombin Time (PT); Activated Partial Thromboplastin Time (APTT); Fibrinogen (Clauss); Batroxobin Time; 5 Similarities Item Device Sysmex® CS-2100i Predicate Sysmex® CA-1500 Time (APTT) with Dade® Actin® FSL · Fibrinogen (Fbg) with Dade® Thrombin Reagent · Coagulation Factor V with Dade® Innovin® · Coagulation Factor VII with Dade® Innovin® · Protein C with Protein C Reagent · Antithrombin (AT) with INNOVANCE® Antithrombin · Protein C with Berichrom® Protein C · D-dimer with INNOVANCE® D- Dimer The performance of this device has not been established in neonate and pediatric patient populations. Extrinsic Factors (II, V, VII, X); Intrinsic Factors (VIII, IX, XI, XII); Protein C Chromogenic Analysis Parameters: Antithrombin III; Factor VIII; Plasminogen; Heparin; Protein C; α2-Antiplasmin Immunologic Analysis Parameters: D-dimer Calculated Parameters: PT Ratio; PT INR; PT %; Derived Fibrinogen; Factor Assays % Activity Clinical Reportable Range Coagulation Factor V with Dade® Innovin® 6.0 to 149.0% of norm; Coagulation Factor VII with Dade® Innovin® 6.0 to 149.0% of norm; Protein C with Protein C Reagent 10.1 to 131.0% of norm Same Sample Type 3.2% sodium citrate venous plasma Same Specimen Processing Automatic Pipetting and Dilution Same Random access Yes Same Liquid Level Sensing Yes – reagent and sample Same Bar Code Reader Sample and reagent Same Sampling Capabilities Normal and Micro Mode Same Sample Volumes (Plasma) Coagulation Factor V with Dade® Innovin® (5 μL) Coagulation Factor VII with Dade® Innovin® (5 μL) Protein C with Protein C Reagent (5 μL Applicant:

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proposed labeling

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

________ or No ____X____ 2. Software: FDA has reviewed applicant’s Hazard Analysis and software development processes for this line of product types: Yes _____X___ or No ________ The Hazard Analysis and Software Development processes were reviewed in premarket notification K150678. The technological characteristics cleared in K150678 remain unchanged; therefore, additional software analysis was not required to support substantial equivalence in this premarket notification. 3. Specimen Identification: 17 Manual entry and barcode reader 4. Specimen Sampling and Handling: Cap piercer for the normal mode. Cap piercing not allowed for a micro-mode. 5. Calibration: Calibration is performed using Standard Human Plasma (SHP) as an automated function of the Sysmex® CS-2100i. A new standard curve must be established when changing reagent lot, post-major maintenance or service, if indicated by quality control results, and when required according to laboratory control procedures and government regulations. 6. Quality Control: Quality control testing using Control Plasma N and Control Plasma P should be performed at least every 8 hours during intervals of patient testing. Controls should be run after a new standard curve is established and after each change of reagent. Patient test results should not be reported if controls are out of range. P. Other Supportive Instrument Performance Characteristics Data Not Covered In The “Performance Characteristics” Section above: 1. Dilution Study The Sysmex CS-2100i analyzer offers additional dilution options for each application carried out by an auto-dilution mode: - Auto-dilution mode 1:2 or 2:1 processing mode for Factor V and Factor VII - Auto-dilution mode 1:2 for Protein C applications. These automatic dilution options are carried out when measurement results are observed outside the analytical measuring range (AMR) —auto-dilution mode (1:2) for results above the AMR and the 2:1 processing mode for results below the AMR. In addition to automatic dilution settings, the Sysmex CS-2100i analyzer also provides a "dilution analysis" on demand to the user, as listed in the application sheets. The auto-dilution study was carried out with one analyzer and one reagent lot with three different plasma pools between assay measuring range (AMR) and clinical reportable range (CRR). At least five manual dilutions with the same dilution factor and the method specific dilution medium were prepared and measured on the analyzer in five replicates. The same samples, but undiluted, were measured upon auto-dilution by the instrument. All observed maximum deviations in the dilution analysis study were below the pre-defined acceptance criteria. 2. Normal Mode versus Micro Mode The Sysmex 2100i has two analysis modes: normal and micro. In the normal-sample mode, samples for all the analyses including re-analyses are taken into the instrument at the same time and analyzed using capped sample tube analysis. Automatic re-analysis can also be performed. In the micro-sample mode, the sample volume from samples set in the sampler or STAT holder is taken into the instrument through a secondary dispensing sample probe and analyzed. The micro-sample mode cannot be used with capped sample tubes. This analysis mode can also be performed with less sample volume than normal mode. However, automatic re-analysis cannot be performed. The comparison study between micro versus normal mode was conducted for each application using 60 samples covering clinical reportable ranges, measured with one reagent lot on one Sysmex CS-2100i analyzer and the predicate instrument. The study results met pre-defined acceptance criteria and demonstrated acceptable comparability between micro versus normal mode. 3. Carryover studies Reagent carryover 18 The Sysmex CS-2100i analyzer has one reagent pipettor. The reagent carryover study investigated whether a reagent or a test component of a donor application may affect an acceptor application. A combination of donor and acceptor applications was tested in a defined sequence. One normal plasma pool and one pathological plasma pool were used as test samples. The reagent carryover studies data showed no cross-contamination caused between one application into another. Sample carryover The sample volume transferred is critical for potential carryover effects. A donor was a test sample with the highest possible analyte concentration that might interfere in the subsequent assay. An acceptor was a low analyte concentration test sample measured after the measurements of the donor assay. If sample carryover occurs the results of the acceptor assay show interference. The donor and acceptor assay measurements were performed in a defined sequence. The data supported lack of sample cross-contamination. Q. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. R. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. 19 Proposed labeling:

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K162688.txt

conclusion

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

? Yes ________ or No ____X____ 2. Software: FDA has reviewed applicant’s Hazard Analysis and software development processes for this line of product types: Yes _____X___ or No ________ The Hazard Analysis and Software Development processes were reviewed in premarket notification K150678. The technological characteristics cleared in K150678 remain unchanged; therefore, additional software analysis was not required to support substantial equivalence in this premarket notification. 3. Specimen Identification: 17 Manual entry and barcode reader 4. Specimen Sampling and Handling: Cap piercer for the normal mode. Cap piercing not allowed for a micro-mode. 5. Calibration: Calibration is performed using Standard Human Plasma (SHP) as an automated function of the Sysmex® CS-2100i. A new standard curve must be established when changing reagent lot, post-major maintenance or service, if indicated by quality control results, and when required according to laboratory control procedures and government regulations. 6. Quality Control: Quality control testing using Control Plasma N and Control Plasma P should be performed at least every 8 hours during intervals of patient testing. Controls should be run after a new standard curve is established and after each change of reagent. Patient test results should not be reported if controls are out of range. P. Other Supportive Instrument Performance Characteristics Data Not Covered In The “Performance Characteristics” Section above: 1. Dilution Study The Sysmex CS-2100i analyzer offers additional dilution options for each application carried out by an auto-dilution mode: - Auto-dilution mode 1:2 or 2:1 processing mode for Factor V and Factor VII - Auto-dilution mode 1:2 for Protein C applications. These automatic dilution options are carried out when measurement results are observed outside the analytical measuring range (AMR) —auto-dilution mode (1:2) for results above the AMR and the 2:1 processing mode for results below the AMR. In addition to automatic dilution settings, the Sysmex CS-2100i analyzer also provides a "dilution analysis" on demand to the user, as listed in the application sheets. The auto-dilution study was carried out with one analyzer and one reagent lot with three different plasma pools between assay measuring range (AMR) and clinical reportable range (CRR). At least five manual dilutions with the same dilution factor and the method specific dilution medium were prepared and measured on the analyzer in five replicates. The same samples, but undiluted, were measured upon auto-dilution by the instrument. All observed maximum deviations in the dilution analysis study were below the pre-defined acceptance criteria. 2. Normal Mode versus Micro Mode The Sysmex 2100i has two analysis modes: normal and micro. In the normal-sample mode, samples for all the analyses including re-analyses are taken into the instrument at the same time and analyzed using capped sample tube analysis. Automatic re-analysis can also be performed. In the micro-sample mode, the sample volume from samples set in the sampler or STAT holder is taken into the instrument through a secondary dispensing sample probe and analyzed. The micro-sample mode cannot be used with capped sample tubes. This analysis mode can also be performed with less sample volume than normal mode. However, automatic re-analysis cannot be performed. The comparison study between micro versus normal mode was conducted for each application using 60 samples covering clinical reportable ranges, measured with one reagent lot on one Sysmex CS-2100i analyzer and the predicate instrument. The study results met pre-defined acceptance criteria and demonstrated acceptable comparability between micro versus normal mode. 3. Carryover studies Reagent carryover 18 The Sysmex CS-2100i analyzer has one reagent pipettor. The reagent carryover study investigated whether a reagent or a test component of a donor application may affect an acceptor application. A combination of donor and acceptor applications was tested in a defined sequence. One normal plasma pool and one pathological plasma pool were used as test samples. The reagent carryover studies data showed no cross-contamination caused between one application into another. Sample carryover The sample volume transferred is critical for potential carryover effects. A donor was a test sample with the highest possible analyte concentration that might interfere in the subsequent assay. An acceptor was a low analyte concentration test sample measured after the measurements of the donor assay. If sample carryover occurs the results of the acceptor assay show interference. The donor and acceptor assay measurements were performed in a defined sequence. The data supported lack of sample cross-contamination. Q. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. R. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. 19 Conclusion:

idK193024_s0_e2000

K193024.txt

purpose for submission

To obtain a substantial equivalence determination for the addition of Lefamulin to the Sensititre 20-24 hour Haemophilus influenzae/Streptococcus pneumoniae MIC or Breakpoint, Susceptibility System with Lefamulin in the dilution range of 0.008 – 16 ug/mL

New Hampshire Avenue Silver Spring, MD 20993-0002 www.fda.gov 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY I Background Information: A 510(k) Number K193024 B Applicant Thermo Fisher Scientific C Proprietary and Established Names Sensititre 20-24 hour Haemophilus influenzae/Streptococcus pneumoniae MIC or Breakpoint, Susceptibility System with Lefamulin in the dilution range of 0.008-16 µg/mL D Regulatory Information Product Code(s) Classification Regulation Section Panel JWY, LRG, LTT Class II 21 CFR 866.1640 - Antimicrobial Susceptibility Test Powder MI - Microbiology II Submission/Device Overview: A Purpose for Submission: To obtain a substantial equivalence determination for the addition of Lefamulin to the Sensititre 20-24 hour Haemophilus influenzae/Streptococcus pneumoniae MIC or Breakpoint, Susceptibility System with Lefamulin in the dilution range of 0.008 – 16 ug/mL B Measurand: Lefamulin in the dilution range of 0.008 – 16 μg/mL C Type of Test: Quantitative Antimicrobial Susceptibility Test (AST), growth-based detection III Intended Use/Indications for Use: K193024 - Page 2 of 11 A Intended Use(s): See Indications for Use below. B Indication(s) for Use: The Sensititre 20 - 24 hour Haemophilus influenzae/Streptococcus pneumoniae MIC or Breakpoint Susceptibility System is an in vitro diagnostic product for clinical susceptibility testing of H. influenzae, Streptococcus pneumoniae, and Streptococcus spp. This 510(k) is for Lefamulin in the dilution range of 0.008 - 16 ug/mL for testing Streptococcus spp. and Haemophilus influenzae on the Sensititre 20 - 24 hour MIC panel. Lefamulin has been shown to be active both clinically and in vitro against the following organisms according to the FDA drug label: Streptococcus pneumoniae Haemophilus influenzae C Special Conditions for Use Statement(s): Rx - For Prescription Use Only The performance of lefamulin with Haemophilus influenzae and Streptococcus pneumoniae was evaluated using the AIM autoinoculator only. The use of an alternative inoculation system when testing lefamulin has not been evaluated. The reading of lefamulin results for S. pneumoniae was performed using the AutoReader (OptiRead) and VIZION reading methods. The reading of lefamulin results for Haemophilus influenzae was only performed by VIZION method. The use of alternative reading methods when testing lefamulin has not been evaluated. The ability of the Sensititre system to detect resistance to Lefamulin in the following species is unknown because non-susceptible strains were not available at the time of comparative testing: S. pneumoniae and H. influenzae. Isolates yielding Lefamulin MIC results suggestive of a non- susceptible interpretive category should be submitted to a reference laboratory. Due to the lack of an intermediate category and observed trending towards higher dilutions for Lefamulin, testing of H. influenzae have resulted in major discrepancies for isolates that are otherwise within essential agreement for the reference method. Testing should be repeated using an alternative testing/reference method prior to reporting results for H. influenzae when the Sensititre with the VIZION is 4 μg/mL. D Special Instrument Requirements: Sensititre AIM for device inoculation K193024 - Page 3 of 11 Sensititre VIZION or OptiRead for plate reading (results for Haemophilus influenzae are interpreted using VIZION only) IV Device/System Characteristics: A Device Description: Sensititre MIC Susceptibility MIC panels are multi-well microtiter plates, dosed with dried, stabilized antimicrobials. It is a miniaturized version of the classic broth dilution method and can provide both qualitative and quantitative susceptibility results. After inoculation, plates are sealed with an adhesive seal, incubated at 34 – 36 °C for 20 – 24 hours and examined for bacterial growth. Antimicrobial susceptibility test results can be determined by reading growth using the digital viewing device (VIZION) or automatically on an autoreader (OptiRead) using fluorescence. B Principle of Operation: The Sensititre 20 - 24 hour Haemophilus influenzae/Streptococcus pneumoniae system includes multi-well plastic microtiter plates that contain doubled dilutions of antibacterial agents. Each plate includes antimicrobial agents at appropriate dilutions. Results can be read by the digital device, VIZION, or by use of an automated reader, OptiRead (Streptococcus spp. only). The VIZION allows the panel image to be displayed on a touch screen directly from a video camera and allows the user to visually determine MIC results. The Sensititre OptiRead utilizes fluorescence technology to read the microbroth dilution plates after 20 to 24 hours incubation. The technology involves the detection of bacterial growth by monitoring the activity of specific surface enzymes produced by the test organism. Growth is determined by generating a fluorescent product from a fluorogenic substrate. The substrate is prepared by conjugating a fluorescent compound to the specific enzyme substrates with a bond which prevents fluorescence. The enzymatic action of the bacterial surface enzymes on the substrate cleaves the bond releasing fluorescence. The amount of fluorescence detected is directly related to bacterial growth. The MIC is determined by observing the lowest dilution of antimicrobial agent that inhibits growth of the organism. The substrate can be added to the inoculum broth which is dispensed into the test plate at the same time as the test organism, or, the plates can be prepared with the substrate already added to each micro-well. V Substantial Equivalence Information: A Predicate Device Name(s): Sensititre 20-24 hour Haemophilus influenzae/Streptococcus pneumoniae MIC or Breakpoint Susceptibility System with Omadacycline in the dilution range of 0.008 - 32 ug/mL B Predicate 510(k) Number(s): K183324 K193024 - Page 4 of 11 C Comparison with Predicate(s): Table 1: Comparison with the Predicate Device & Predicate Device(s): Device K193024 Predicate K183324 Device Trade Name Sensititre Haemophilus/Streptococcus pneumoniae (HP) MIC Plates with Lefamulin Sensititre Haemophilus/Streptococcus pneumoniae (HP) MIC Plates with Omadacycline General Device Characteristic Similarities Intended Use/Indications For Use The Sensititre Haemophilus influenzae/Streptococcus pneumoniae plates are in vitro diagnostic products for clinical susceptibility testing of Haemophilus influenzae, Streptococcus pneumoniae, and Streptococcus species. Same Test Panel 96 well plate is dosed with selected antimicrobial agents and substrate for the fluorescent reads, then dried. The bacterial suspension in the appropriate broth is used to rehydrate the plate. Same Test Organism Haemophilus influenzae, Streptococcus pneumoniae, and Streptococcus spp. Same Reading Methods for Streptococcus spp. Results can be read using the following methods: 1) Automatically with the OptiRead (fluorescent substrate technology) 2) On the VIZION (digital viewing device) Same Reading Methods for Haemophilus Results can be read using the VIZION (digital viewing device) only Same Incubation 20-24 hours, 35 ± 1° C Same Inoculation Media CAMHBT + LHB (Streptococcus spp.), HTM broth (H. influenzae) Same General Device Characteristic Differences Antimicrobial Agent Lefamulin Omadacycline K193024 - Page 5 of 11 Concentration Range 0.008 – 16 µg/mL 0.008 – 32 µg/mL VI Standards/Guidance Documents Referenced: Guidance for Industry and FDA - Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems – August 28, 2009. CLSI. Performance Standards for Antimicrobial Susceptibility Testing. 29th ed. CLSI supplement M100. Wayne, PA: Clinical and Laboratory Standards Institute; 2019. CLSI. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically. 11th ed. CLSI standard M07. Wayne, PA: Clinical and Laboratory Standards Institute; 2018. VII Performance Characteristics (if/when applicable): A Analytical Performance: 1. Precision/Reproducibility: A reproducibility study was performed at four sites using a panel comprised of 10 isolates of Streptococcus spp.: S. pneumoniae (three isolates), S. pyogenes (one isolate), S. agalactiae (two isolates), S. anginosus (two isolates), S. mitis (one isolate), Purpose for submission:

idK193024_s0_e2000

K193024.txt

measurand

Lefamulin in the dilution range of 0.008 – 16 μg/mL

New Hampshire Avenue Silver Spring, MD 20993-0002 www.fda.gov 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY I Background Information: A 510(k) Number K193024 B Applicant Thermo Fisher Scientific C Proprietary and Established Names Sensititre 20-24 hour Haemophilus influenzae/Streptococcus pneumoniae MIC or Breakpoint, Susceptibility System with Lefamulin in the dilution range of 0.008-16 µg/mL D Regulatory Information Product Code(s) Classification Regulation Section Panel JWY, LRG, LTT Class II 21 CFR 866.1640 - Antimicrobial Susceptibility Test Powder MI - Microbiology II Submission/Device Overview: A Purpose for Submission: To obtain a substantial equivalence determination for the addition of Lefamulin to the Sensititre 20-24 hour Haemophilus influenzae/Streptococcus pneumoniae MIC or Breakpoint, Susceptibility System with Lefamulin in the dilution range of 0.008 – 16 ug/mL B Measurand: Lefamulin in the dilution range of 0.008 – 16 μg/mL C Type of Test: Quantitative Antimicrobial Susceptibility Test (AST), growth-based detection III Intended Use/Indications for Use: K193024 - Page 2 of 11 A Intended Use(s): See Indications for Use below. B Indication(s) for Use: The Sensititre 20 - 24 hour Haemophilus influenzae/Streptococcus pneumoniae MIC or Breakpoint Susceptibility System is an in vitro diagnostic product for clinical susceptibility testing of H. influenzae, Streptococcus pneumoniae, and Streptococcus spp. This 510(k) is for Lefamulin in the dilution range of 0.008 - 16 ug/mL for testing Streptococcus spp. and Haemophilus influenzae on the Sensititre 20 - 24 hour MIC panel. Lefamulin has been shown to be active both clinically and in vitro against the following organisms according to the FDA drug label: Streptococcus pneumoniae Haemophilus influenzae C Special Conditions for Use Statement(s): Rx - For Prescription Use Only The performance of lefamulin with Haemophilus influenzae and Streptococcus pneumoniae was evaluated using the AIM autoinoculator only. The use of an alternative inoculation system when testing lefamulin has not been evaluated. The reading of lefamulin results for S. pneumoniae was performed using the AutoReader (OptiRead) and VIZION reading methods. The reading of lefamulin results for Haemophilus influenzae was only performed by VIZION method. The use of alternative reading methods when testing lefamulin has not been evaluated. The ability of the Sensititre system to detect resistance to Lefamulin in the following species is unknown because non-susceptible strains were not available at the time of comparative testing: S. pneumoniae and H. influenzae. Isolates yielding Lefamulin MIC results suggestive of a non- susceptible interpretive category should be submitted to a reference laboratory. Due to the lack of an intermediate category and observed trending towards higher dilutions for Lefamulin, testing of H. influenzae have resulted in major discrepancies for isolates that are otherwise within essential agreement for the reference method. Testing should be repeated using an alternative testing/reference method prior to reporting results for H. influenzae when the Sensititre with the VIZION is 4 μg/mL. D Special Instrument Requirements: Sensititre AIM for device inoculation K193024 - Page 3 of 11 Sensititre VIZION or OptiRead for plate reading (results for Haemophilus influenzae are interpreted using VIZION only) IV Device/System Characteristics: A Device Description: Sensititre MIC Susceptibility MIC panels are multi-well microtiter plates, dosed with dried, stabilized antimicrobials. It is a miniaturized version of the classic broth dilution method and can provide both qualitative and quantitative susceptibility results. After inoculation, plates are sealed with an adhesive seal, incubated at 34 – 36 °C for 20 – 24 hours and examined for bacterial growth. Antimicrobial susceptibility test results can be determined by reading growth using the digital viewing device (VIZION) or automatically on an autoreader (OptiRead) using fluorescence. B Principle of Operation: The Sensititre 20 - 24 hour Haemophilus influenzae/Streptococcus pneumoniae system includes multi-well plastic microtiter plates that contain doubled dilutions of antibacterial agents. Each plate includes antimicrobial agents at appropriate dilutions. Results can be read by the digital device, VIZION, or by use of an automated reader, OptiRead (Streptococcus spp. only). The VIZION allows the panel image to be displayed on a touch screen directly from a video camera and allows the user to visually determine MIC results. The Sensititre OptiRead utilizes fluorescence technology to read the microbroth dilution plates after 20 to 24 hours incubation. The technology involves the detection of bacterial growth by monitoring the activity of specific surface enzymes produced by the test organism. Growth is determined by generating a fluorescent product from a fluorogenic substrate. The substrate is prepared by conjugating a fluorescent compound to the specific enzyme substrates with a bond which prevents fluorescence. The enzymatic action of the bacterial surface enzymes on the substrate cleaves the bond releasing fluorescence. The amount of fluorescence detected is directly related to bacterial growth. The MIC is determined by observing the lowest dilution of antimicrobial agent that inhibits growth of the organism. The substrate can be added to the inoculum broth which is dispensed into the test plate at the same time as the test organism, or, the plates can be prepared with the substrate already added to each micro-well. V Substantial Equivalence Information: A Predicate Device Name(s): Sensititre 20-24 hour Haemophilus influenzae/Streptococcus pneumoniae MIC or Breakpoint Susceptibility System with Omadacycline in the dilution range of 0.008 - 32 ug/mL B Predicate 510(k) Number(s): K183324 K193024 - Page 4 of 11 C Comparison with Predicate(s): Table 1: Comparison with the Predicate Device & Predicate Device(s): Device K193024 Predicate K183324 Device Trade Name Sensititre Haemophilus/Streptococcus pneumoniae (HP) MIC Plates with Lefamulin Sensititre Haemophilus/Streptococcus pneumoniae (HP) MIC Plates with Omadacycline General Device Characteristic Similarities Intended Use/Indications For Use The Sensititre Haemophilus influenzae/Streptococcus pneumoniae plates are in vitro diagnostic products for clinical susceptibility testing of Haemophilus influenzae, Streptococcus pneumoniae, and Streptococcus species. Same Test Panel 96 well plate is dosed with selected antimicrobial agents and substrate for the fluorescent reads, then dried. The bacterial suspension in the appropriate broth is used to rehydrate the plate. Same Test Organism Haemophilus influenzae, Streptococcus pneumoniae, and Streptococcus spp. Same Reading Methods for Streptococcus spp. Results can be read using the following methods: 1) Automatically with the OptiRead (fluorescent substrate technology) 2) On the VIZION (digital viewing device) Same Reading Methods for Haemophilus Results can be read using the VIZION (digital viewing device) only Same Incubation 20-24 hours, 35 ± 1° C Same Inoculation Media CAMHBT + LHB (Streptococcus spp.), HTM broth (H. influenzae) Same General Device Characteristic Differences Antimicrobial Agent Lefamulin Omadacycline K193024 - Page 5 of 11 Concentration Range 0.008 – 16 µg/mL 0.008 – 32 µg/mL VI Standards/Guidance Documents Referenced: Guidance for Industry and FDA - Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems – August 28, 2009. CLSI. Performance Standards for Antimicrobial Susceptibility Testing. 29th ed. CLSI supplement M100. Wayne, PA: Clinical and Laboratory Standards Institute; 2019. CLSI. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically. 11th ed. CLSI standard M07. Wayne, PA: Clinical and Laboratory Standards Institute; 2018. VII Performance Characteristics (if/when applicable): A Analytical Performance: 1. Precision/Reproducibility: A reproducibility study was performed at four sites using a panel comprised of 10 isolates of Streptococcus spp.: S. pneumoniae (three isolates), S. pyogenes (one isolate), S. agalactiae (two isolates), S. anginosus (two isolates), S. mitis (one isolate), Measurand:

idK193024_s0_e2000

K193024.txt

type of test

Quantitative Antimicrobial Susceptibility Test (AST), growth-based detection

03 New Hampshire Avenue Silver Spring, MD 20993-0002 www.fda.gov 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY I Background Information: A 510(k) Number K193024 B Applicant Thermo Fisher Scientific C Proprietary and Established Names Sensititre 20-24 hour Haemophilus influenzae/Streptococcus pneumoniae MIC or Breakpoint, Susceptibility System with Lefamulin in the dilution range of 0.008-16 µg/mL D Regulatory Information Product Code(s) Classification Regulation Section Panel JWY, LRG, LTT Class II 21 CFR 866.1640 - Antimicrobial Susceptibility Test Powder MI - Microbiology II Submission/Device Overview: A Purpose for Submission: To obtain a substantial equivalence determination for the addition of Lefamulin to the Sensititre 20-24 hour Haemophilus influenzae/Streptococcus pneumoniae MIC or Breakpoint, Susceptibility System with Lefamulin in the dilution range of 0.008 – 16 ug/mL B Measurand: Lefamulin in the dilution range of 0.008 – 16 μg/mL C Type of Test: Quantitative Antimicrobial Susceptibility Test (AST), growth-based detection III Intended Use/Indications for Use: K193024 - Page 2 of 11 A Intended Use(s): See Indications for Use below. B Indication(s) for Use: The Sensititre 20 - 24 hour Haemophilus influenzae/Streptococcus pneumoniae MIC or Breakpoint Susceptibility System is an in vitro diagnostic product for clinical susceptibility testing of H. influenzae, Streptococcus pneumoniae, and Streptococcus spp. This 510(k) is for Lefamulin in the dilution range of 0.008 - 16 ug/mL for testing Streptococcus spp. and Haemophilus influenzae on the Sensititre 20 - 24 hour MIC panel. Lefamulin has been shown to be active both clinically and in vitro against the following organisms according to the FDA drug label: Streptococcus pneumoniae Haemophilus influenzae C Special Conditions for Use Statement(s): Rx - For Prescription Use Only The performance of lefamulin with Haemophilus influenzae and Streptococcus pneumoniae was evaluated using the AIM autoinoculator only. The use of an alternative inoculation system when testing lefamulin has not been evaluated. The reading of lefamulin results for S. pneumoniae was performed using the AutoReader (OptiRead) and VIZION reading methods. The reading of lefamulin results for Haemophilus influenzae was only performed by VIZION method. The use of alternative reading methods when testing lefamulin has not been evaluated. The ability of the Sensititre system to detect resistance to Lefamulin in the following species is unknown because non-susceptible strains were not available at the time of comparative testing: S. pneumoniae and H. influenzae. Isolates yielding Lefamulin MIC results suggestive of a non- susceptible interpretive category should be submitted to a reference laboratory. Due to the lack of an intermediate category and observed trending towards higher dilutions for Lefamulin, testing of H. influenzae have resulted in major discrepancies for isolates that are otherwise within essential agreement for the reference method. Testing should be repeated using an alternative testing/reference method prior to reporting results for H. influenzae when the Sensititre with the VIZION is 4 μg/mL. D Special Instrument Requirements: Sensititre AIM for device inoculation K193024 - Page 3 of 11 Sensititre VIZION or OptiRead for plate reading (results for Haemophilus influenzae are interpreted using VIZION only) IV Device/System Characteristics: A Device Description: Sensititre MIC Susceptibility MIC panels are multi-well microtiter plates, dosed with dried, stabilized antimicrobials. It is a miniaturized version of the classic broth dilution method and can provide both qualitative and quantitative susceptibility results. After inoculation, plates are sealed with an adhesive seal, incubated at 34 – 36 °C for 20 – 24 hours and examined for bacterial growth. Antimicrobial susceptibility test results can be determined by reading growth using the digital viewing device (VIZION) or automatically on an autoreader (OptiRead) using fluorescence. B Principle of Operation: The Sensititre 20 - 24 hour Haemophilus influenzae/Streptococcus pneumoniae system includes multi-well plastic microtiter plates that contain doubled dilutions of antibacterial agents. Each plate includes antimicrobial agents at appropriate dilutions. Results can be read by the digital device, VIZION, or by use of an automated reader, OptiRead (Streptococcus spp. only). The VIZION allows the panel image to be displayed on a touch screen directly from a video camera and allows the user to visually determine MIC results. The Sensititre OptiRead utilizes fluorescence technology to read the microbroth dilution plates after 20 to 24 hours incubation. The technology involves the detection of bacterial growth by monitoring the activity of specific surface enzymes produced by the test organism. Growth is determined by generating a fluorescent product from a fluorogenic substrate. The substrate is prepared by conjugating a fluorescent compound to the specific enzyme substrates with a bond which prevents fluorescence. The enzymatic action of the bacterial surface enzymes on the substrate cleaves the bond releasing fluorescence. The amount of fluorescence detected is directly related to bacterial growth. The MIC is determined by observing the lowest dilution of antimicrobial agent that inhibits growth of the organism. The substrate can be added to the inoculum broth which is dispensed into the test plate at the same time as the test organism, or, the plates can be prepared with the substrate already added to each micro-well. V Substantial Equivalence Information: A Predicate Device Name(s): Sensititre 20-24 hour Haemophilus influenzae/Streptococcus pneumoniae MIC or Breakpoint Susceptibility System with Omadacycline in the dilution range of 0.008 - 32 ug/mL B Predicate 510(k) Number(s): K183324 K193024 - Page 4 of 11 C Comparison with Predicate(s): Table 1: Comparison with the Predicate Device & Predicate Device(s): Device K193024 Predicate K183324 Device Trade Name Sensititre Haemophilus/Streptococcus pneumoniae (HP) MIC Plates with Lefamulin Sensititre Haemophilus/Streptococcus pneumoniae (HP) MIC Plates with Omadacycline General Device Characteristic Similarities Intended Use/Indications For Use The Sensititre Haemophilus influenzae/Streptococcus pneumoniae plates are in vitro diagnostic products for clinical susceptibility testing of Haemophilus influenzae, Streptococcus pneumoniae, and Streptococcus species. Same Test Panel 96 well plate is dosed with selected antimicrobial agents and substrate for the fluorescent reads, then dried. The bacterial suspension in the appropriate broth is used to rehydrate the plate. Same Test Organism Haemophilus influenzae, Streptococcus pneumoniae, and Streptococcus spp. Same Reading Methods for Streptococcus spp. Results can be read using the following methods: 1) Automatically with the OptiRead (fluorescent substrate technology) 2) On the VIZION (digital viewing device) Same Reading Methods for Haemophilus Results can be read using the VIZION (digital viewing device) only Same Incubation 20-24 hours, 35 ± 1° C Same Inoculation Media CAMHBT + LHB (Streptococcus spp.), HTM broth (H. influenzae) Same General Device Characteristic Differences Antimicrobial Agent Lefamulin Omadacycline K193024 - Page 5 of 11 Concentration Range 0.008 – 16 µg/mL 0.008 – 32 µg/mL VI Standards/Guidance Documents Referenced: Guidance for Industry and FDA - Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems – August 28, 2009. CLSI. Performance Standards for Antimicrobial Susceptibility Testing. 29th ed. CLSI supplement M100. Wayne, PA: Clinical and Laboratory Standards Institute; 2019. CLSI. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically. 11th ed. CLSI standard M07. Wayne, PA: Clinical and Laboratory Standards Institute; 2018. VII Performance Characteristics (if/when applicable): A Analytical Performance: 1. Precision/Reproducibility: A reproducibility study was performed at four sites using a panel comprised of 10 isolates of Streptococcus spp.: S. pneumoniae (three isolates), S. pyogenes (one isolate), S. agalactiae (two isolates), S. anginosus (two isolates), S. mitis (one isolate), Type of test:

idK193024_s0_e2000

K193024.txt

classification

Class II

10903 New Hampshire Avenue Silver Spring, MD 20993-0002 www.fda.gov 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY I Background Information: A 510(k) Number K193024 B Applicant Thermo Fisher Scientific C Proprietary and Established Names Sensititre 20-24 hour Haemophilus influenzae/Streptococcus pneumoniae MIC or Breakpoint, Susceptibility System with Lefamulin in the dilution range of 0.008-16 µg/mL D Regulatory Information Product Code(s) Classification Regulation Section Panel JWY, LRG, LTT Class II 21 CFR 866.1640 - Antimicrobial Susceptibility Test Powder MI - Microbiology II Submission/Device Overview: A Purpose for Submission: To obtain a substantial equivalence determination for the addition of Lefamulin to the Sensititre 20-24 hour Haemophilus influenzae/Streptococcus pneumoniae MIC or Breakpoint, Susceptibility System with Lefamulin in the dilution range of 0.008 – 16 ug/mL B Measurand: Lefamulin in the dilution range of 0.008 – 16 μg/mL C Type of Test: Quantitative Antimicrobial Susceptibility Test (AST), growth-based detection III Intended Use/Indications for Use: K193024 - Page 2 of 11 A Intended Use(s): See Indications for Use below. B Indication(s) for Use: The Sensititre 20 - 24 hour Haemophilus influenzae/Streptococcus pneumoniae MIC or Breakpoint Susceptibility System is an in vitro diagnostic product for clinical susceptibility testing of H. influenzae, Streptococcus pneumoniae, and Streptococcus spp. This 510(k) is for Lefamulin in the dilution range of 0.008 - 16 ug/mL for testing Streptococcus spp. and Haemophilus influenzae on the Sensititre 20 - 24 hour MIC panel. Lefamulin has been shown to be active both clinically and in vitro against the following organisms according to the FDA drug label: Streptococcus pneumoniae Haemophilus influenzae C Special Conditions for Use Statement(s): Rx - For Prescription Use Only The performance of lefamulin with Haemophilus influenzae and Streptococcus pneumoniae was evaluated using the AIM autoinoculator only. The use of an alternative inoculation system when testing lefamulin has not been evaluated. The reading of lefamulin results for S. pneumoniae was performed using the AutoReader (OptiRead) and VIZION reading methods. The reading of lefamulin results for Haemophilus influenzae was only performed by VIZION method. The use of alternative reading methods when testing lefamulin has not been evaluated. The ability of the Sensititre system to detect resistance to Lefamulin in the following species is unknown because non-susceptible strains were not available at the time of comparative testing: S. pneumoniae and H. influenzae. Isolates yielding Lefamulin MIC results suggestive of a non- susceptible interpretive category should be submitted to a reference laboratory. Due to the lack of an intermediate category and observed trending towards higher dilutions for Lefamulin, testing of H. influenzae have resulted in major discrepancies for isolates that are otherwise within essential agreement for the reference method. Testing should be repeated using an alternative testing/reference method prior to reporting results for H. influenzae when the Sensititre with the VIZION is 4 μg/mL. D Special Instrument Requirements: Sensititre AIM for device inoculation K193024 - Page 3 of 11 Sensititre VIZION or OptiRead for plate reading (results for Haemophilus influenzae are interpreted using VIZION only) IV Device/System Characteristics: A Device Description: Sensititre MIC Susceptibility MIC panels are multi-well microtiter plates, dosed with dried, stabilized antimicrobials. It is a miniaturized version of the classic broth dilution method and can provide both qualitative and quantitative susceptibility results. After inoculation, plates are sealed with an adhesive seal, incubated at 34 – 36 °C for 20 – 24 hours and examined for bacterial growth. Antimicrobial susceptibility test results can be determined by reading growth using the digital viewing device (VIZION) or automatically on an autoreader (OptiRead) using fluorescence. B Principle of Operation: The Sensititre 20 - 24 hour Haemophilus influenzae/Streptococcus pneumoniae system includes multi-well plastic microtiter plates that contain doubled dilutions of antibacterial agents. Each plate includes antimicrobial agents at appropriate dilutions. Results can be read by the digital device, VIZION, or by use of an automated reader, OptiRead (Streptococcus spp. only). The VIZION allows the panel image to be displayed on a touch screen directly from a video camera and allows the user to visually determine MIC results. The Sensititre OptiRead utilizes fluorescence technology to read the microbroth dilution plates after 20 to 24 hours incubation. The technology involves the detection of bacterial growth by monitoring the activity of specific surface enzymes produced by the test organism. Growth is determined by generating a fluorescent product from a fluorogenic substrate. The substrate is prepared by conjugating a fluorescent compound to the specific enzyme substrates with a bond which prevents fluorescence. The enzymatic action of the bacterial surface enzymes on the substrate cleaves the bond releasing fluorescence. The amount of fluorescence detected is directly related to bacterial growth. The MIC is determined by observing the lowest dilution of antimicrobial agent that inhibits growth of the organism. The substrate can be added to the inoculum broth which is dispensed into the test plate at the same time as the test organism, or, the plates can be prepared with the substrate already added to each micro-well. V Substantial Equivalence Information: A Predicate Device Name(s): Sensititre 20-24 hour Haemophilus influenzae/Streptococcus pneumoniae MIC or Breakpoint Susceptibility System with Omadacycline in the dilution range of 0.008 - 32 ug/mL B Predicate 510(k) Number(s): K183324 K193024 - Page 4 of 11 C Comparison with Predicate(s): Table 1: Comparison with the Predicate Device & Predicate Device(s): Device K193024 Predicate K183324 Device Trade Name Sensititre Haemophilus/Streptococcus pneumoniae (HP) MIC Plates with Lefamulin Sensititre Haemophilus/Streptococcus pneumoniae (HP) MIC Plates with Omadacycline General Device Characteristic Similarities Intended Use/Indications For Use The Sensititre Haemophilus influenzae/Streptococcus pneumoniae plates are in vitro diagnostic products for clinical susceptibility testing of Haemophilus influenzae, Streptococcus pneumoniae, and Streptococcus species. Same Test Panel 96 well plate is dosed with selected antimicrobial agents and substrate for the fluorescent reads, then dried. The bacterial suspension in the appropriate broth is used to rehydrate the plate. Same Test Organism Haemophilus influenzae, Streptococcus pneumoniae, and Streptococcus spp. Same Reading Methods for Streptococcus spp. Results can be read using the following methods: 1) Automatically with the OptiRead (fluorescent substrate technology) 2) On the VIZION (digital viewing device) Same Reading Methods for Haemophilus Results can be read using the VIZION (digital viewing device) only Same Incubation 20-24 hours, 35 ± 1° C Same Inoculation Media CAMHBT + LHB (Streptococcus spp.), HTM broth (H. influenzae) Same General Device Characteristic Differences Antimicrobial Agent Lefamulin Omadacycline K193024 - Page 5 of 11 Concentration Range 0.008 – 16 µg/mL 0.008 – 32 µg/mL VI Standards/Guidance Documents Referenced: Guidance for Industry and FDA - Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems – August 28, 2009. CLSI. Performance Standards for Antimicrobial Susceptibility Testing. 29th ed. CLSI supplement M100. Wayne, PA: Clinical and Laboratory Standards Institute; 2019. CLSI. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically. 11th ed. CLSI standard M07. Wayne, PA: Clinical and Laboratory Standards Institute; 2018. VII Performance Characteristics (if/when applicable): A Analytical Performance: 1. Precision/Reproducibility: A reproducibility study was performed at four sites using a panel comprised of 10 isolates of Streptococcus spp.: S. pneumoniae (three isolates), S. pyogenes (one isolate), S. agalactiae (two isolates), S. anginosus (two isolates), S. mitis (one isolate), Classification:

idK193024_s0_e2000

K193024.txt

product code

JWY, LRG, LTT

10903 New Hampshire Avenue Silver Spring, MD 20993-0002 www.fda.gov 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY I Background Information: A 510(k) Number K193024 B Applicant Thermo Fisher Scientific C Proprietary and Established Names Sensititre 20-24 hour Haemophilus influenzae/Streptococcus pneumoniae MIC or Breakpoint, Susceptibility System with Lefamulin in the dilution range of 0.008-16 µg/mL D Regulatory Information Product Code(s) Classification Regulation Section Panel JWY, LRG, LTT Class II 21 CFR 866.1640 - Antimicrobial Susceptibility Test Powder MI - Microbiology II Submission/Device Overview: A Purpose for Submission: To obtain a substantial equivalence determination for the addition of Lefamulin to the Sensititre 20-24 hour Haemophilus influenzae/Streptococcus pneumoniae MIC or Breakpoint, Susceptibility System with Lefamulin in the dilution range of 0.008 – 16 ug/mL B Measurand: Lefamulin in the dilution range of 0.008 – 16 μg/mL C Type of Test: Quantitative Antimicrobial Susceptibility Test (AST), growth-based detection III Intended Use/Indications for Use: K193024 - Page 2 of 11 A Intended Use(s): See Indications for Use below. B Indication(s) for Use: The Sensititre 20 - 24 hour Haemophilus influenzae/Streptococcus pneumoniae MIC or Breakpoint Susceptibility System is an in vitro diagnostic product for clinical susceptibility testing of H. influenzae, Streptococcus pneumoniae, and Streptococcus spp. This 510(k) is for Lefamulin in the dilution range of 0.008 - 16 ug/mL for testing Streptococcus spp. and Haemophilus influenzae on the Sensititre 20 - 24 hour MIC panel. Lefamulin has been shown to be active both clinically and in vitro against the following organisms according to the FDA drug label: Streptococcus pneumoniae Haemophilus influenzae C Special Conditions for Use Statement(s): Rx - For Prescription Use Only The performance of lefamulin with Haemophilus influenzae and Streptococcus pneumoniae was evaluated using the AIM autoinoculator only. The use of an alternative inoculation system when testing lefamulin has not been evaluated. The reading of lefamulin results for S. pneumoniae was performed using the AutoReader (OptiRead) and VIZION reading methods. The reading of lefamulin results for Haemophilus influenzae was only performed by VIZION method. The use of alternative reading methods when testing lefamulin has not been evaluated. The ability of the Sensititre system to detect resistance to Lefamulin in the following species is unknown because non-susceptible strains were not available at the time of comparative testing: S. pneumoniae and H. influenzae. Isolates yielding Lefamulin MIC results suggestive of a non- susceptible interpretive category should be submitted to a reference laboratory. Due to the lack of an intermediate category and observed trending towards higher dilutions for Lefamulin, testing of H. influenzae have resulted in major discrepancies for isolates that are otherwise within essential agreement for the reference method. Testing should be repeated using an alternative testing/reference method prior to reporting results for H. influenzae when the Sensititre with the VIZION is 4 μg/mL. D Special Instrument Requirements: Sensititre AIM for device inoculation K193024 - Page 3 of 11 Sensititre VIZION or OptiRead for plate reading (results for Haemophilus influenzae are interpreted using VIZION only) IV Device/System Characteristics: A Device Description: Sensititre MIC Susceptibility MIC panels are multi-well microtiter plates, dosed with dried, stabilized antimicrobials. It is a miniaturized version of the classic broth dilution method and can provide both qualitative and quantitative susceptibility results. After inoculation, plates are sealed with an adhesive seal, incubated at 34 – 36 °C for 20 – 24 hours and examined for bacterial growth. Antimicrobial susceptibility test results can be determined by reading growth using the digital viewing device (VIZION) or automatically on an autoreader (OptiRead) using fluorescence. B Principle of Operation: The Sensititre 20 - 24 hour Haemophilus influenzae/Streptococcus pneumoniae system includes multi-well plastic microtiter plates that contain doubled dilutions of antibacterial agents. Each plate includes antimicrobial agents at appropriate dilutions. Results can be read by the digital device, VIZION, or by use of an automated reader, OptiRead (Streptococcus spp. only). The VIZION allows the panel image to be displayed on a touch screen directly from a video camera and allows the user to visually determine MIC results. The Sensititre OptiRead utilizes fluorescence technology to read the microbroth dilution plates after 20 to 24 hours incubation. The technology involves the detection of bacterial growth by monitoring the activity of specific surface enzymes produced by the test organism. Growth is determined by generating a fluorescent product from a fluorogenic substrate. The substrate is prepared by conjugating a fluorescent compound to the specific enzyme substrates with a bond which prevents fluorescence. The enzymatic action of the bacterial surface enzymes on the substrate cleaves the bond releasing fluorescence. The amount of fluorescence detected is directly related to bacterial growth. The MIC is determined by observing the lowest dilution of antimicrobial agent that inhibits growth of the organism. The substrate can be added to the inoculum broth which is dispensed into the test plate at the same time as the test organism, or, the plates can be prepared with the substrate already added to each micro-well. V Substantial Equivalence Information: A Predicate Device Name(s): Sensititre 20-24 hour Haemophilus influenzae/Streptococcus pneumoniae MIC or Breakpoint Susceptibility System with Omadacycline in the dilution range of 0.008 - 32 ug/mL B Predicate 510(k) Number(s): K183324 K193024 - Page 4 of 11 C Comparison with Predicate(s): Table 1: Comparison with the Predicate Device & Predicate Device(s): Device K193024 Predicate K183324 Device Trade Name Sensititre Haemophilus/Streptococcus pneumoniae (HP) MIC Plates with Lefamulin Sensititre Haemophilus/Streptococcus pneumoniae (HP) MIC Plates with Omadacycline General Device Characteristic Similarities Intended Use/Indications For Use The Sensititre Haemophilus influenzae/Streptococcus pneumoniae plates are in vitro diagnostic products for clinical susceptibility testing of Haemophilus influenzae, Streptococcus pneumoniae, and Streptococcus species. Same Test Panel 96 well plate is dosed with selected antimicrobial agents and substrate for the fluorescent reads, then dried. The bacterial suspension in the appropriate broth is used to rehydrate the plate. Same Test Organism Haemophilus influenzae, Streptococcus pneumoniae, and Streptococcus spp. Same Reading Methods for Streptococcus spp. Results can be read using the following methods: 1) Automatically with the OptiRead (fluorescent substrate technology) 2) On the VIZION (digital viewing device) Same Reading Methods for Haemophilus Results can be read using the VIZION (digital viewing device) only Same Incubation 20-24 hours, 35 ± 1° C Same Inoculation Media CAMHBT + LHB (Streptococcus spp.), HTM broth (H. influenzae) Same General Device Characteristic Differences Antimicrobial Agent Lefamulin Omadacycline K193024 - Page 5 of 11 Concentration Range 0.008 – 16 µg/mL 0.008 – 32 µg/mL VI Standards/Guidance Documents Referenced: Guidance for Industry and FDA - Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems – August 28, 2009. CLSI. Performance Standards for Antimicrobial Susceptibility Testing. 29th ed. CLSI supplement M100. Wayne, PA: Clinical and Laboratory Standards Institute; 2019. CLSI. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically. 11th ed. CLSI standard M07. Wayne, PA: Clinical and Laboratory Standards Institute; 2018. VII Performance Characteristics (if/when applicable): A Analytical Performance: 1. Precision/Reproducibility: A reproducibility study was performed at four sites using a panel comprised of 10 isolates of Streptococcus spp.: S. pneumoniae (three isolates), S. pyogenes (one isolate), S. agalactiae (two isolates), S. anginosus (two isolates), S. mitis (one isolate), Product code:

idK193024_s0_e2000

K193024.txt

panel

MI - Microbiology

Administration 10903 New Hampshire Avenue Silver Spring, MD 20993-0002 www.fda.gov 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY I Background Information: A 510(k) Number K193024 B Applicant Thermo Fisher Scientific C Proprietary and Established Names Sensititre 20-24 hour Haemophilus influenzae/Streptococcus pneumoniae MIC or Breakpoint, Susceptibility System with Lefamulin in the dilution range of 0.008-16 µg/mL D Regulatory Information Product Code(s) Classification Regulation Section Panel JWY, LRG, LTT Class II 21 CFR 866.1640 - Antimicrobial Susceptibility Test Powder MI - Microbiology II Submission/Device Overview: A Purpose for Submission: To obtain a substantial equivalence determination for the addition of Lefamulin to the Sensititre 20-24 hour Haemophilus influenzae/Streptococcus pneumoniae MIC or Breakpoint, Susceptibility System with Lefamulin in the dilution range of 0.008 – 16 ug/mL B Measurand: Lefamulin in the dilution range of 0.008 – 16 μg/mL C Type of Test: Quantitative Antimicrobial Susceptibility Test (AST), growth-based detection III Intended Use/Indications for Use: K193024 - Page 2 of 11 A Intended Use(s): See Indications for Use below. B Indication(s) for Use: The Sensititre 20 - 24 hour Haemophilus influenzae/Streptococcus pneumoniae MIC or Breakpoint Susceptibility System is an in vitro diagnostic product for clinical susceptibility testing of H. influenzae, Streptococcus pneumoniae, and Streptococcus spp. This 510(k) is for Lefamulin in the dilution range of 0.008 - 16 ug/mL for testing Streptococcus spp. and Haemophilus influenzae on the Sensititre 20 - 24 hour MIC panel. Lefamulin has been shown to be active both clinically and in vitro against the following organisms according to the FDA drug label: Streptococcus pneumoniae Haemophilus influenzae C Special Conditions for Use Statement(s): Rx - For Prescription Use Only The performance of lefamulin with Haemophilus influenzae and Streptococcus pneumoniae was evaluated using the AIM autoinoculator only. The use of an alternative inoculation system when testing lefamulin has not been evaluated. The reading of lefamulin results for S. pneumoniae was performed using the AutoReader (OptiRead) and VIZION reading methods. The reading of lefamulin results for Haemophilus influenzae was only performed by VIZION method. The use of alternative reading methods when testing lefamulin has not been evaluated. The ability of the Sensititre system to detect resistance to Lefamulin in the following species is unknown because non-susceptible strains were not available at the time of comparative testing: S. pneumoniae and H. influenzae. Isolates yielding Lefamulin MIC results suggestive of a non- susceptible interpretive category should be submitted to a reference laboratory. Due to the lack of an intermediate category and observed trending towards higher dilutions for Lefamulin, testing of H. influenzae have resulted in major discrepancies for isolates that are otherwise within essential agreement for the reference method. Testing should be repeated using an alternative testing/reference method prior to reporting results for H. influenzae when the Sensititre with the VIZION is 4 μg/mL. D Special Instrument Requirements: Sensititre AIM for device inoculation K193024 - Page 3 of 11 Sensititre VIZION or OptiRead for plate reading (results for Haemophilus influenzae are interpreted using VIZION only) IV Device/System Characteristics: A Device Description: Sensititre MIC Susceptibility MIC panels are multi-well microtiter plates, dosed with dried, stabilized antimicrobials. It is a miniaturized version of the classic broth dilution method and can provide both qualitative and quantitative susceptibility results. After inoculation, plates are sealed with an adhesive seal, incubated at 34 – 36 °C for 20 – 24 hours and examined for bacterial growth. Antimicrobial susceptibility test results can be determined by reading growth using the digital viewing device (VIZION) or automatically on an autoreader (OptiRead) using fluorescence. B Principle of Operation: The Sensititre 20 - 24 hour Haemophilus influenzae/Streptococcus pneumoniae system includes multi-well plastic microtiter plates that contain doubled dilutions of antibacterial agents. Each plate includes antimicrobial agents at appropriate dilutions. Results can be read by the digital device, VIZION, or by use of an automated reader, OptiRead (Streptococcus spp. only). The VIZION allows the panel image to be displayed on a touch screen directly from a video camera and allows the user to visually determine MIC results. The Sensititre OptiRead utilizes fluorescence technology to read the microbroth dilution plates after 20 to 24 hours incubation. The technology involves the detection of bacterial growth by monitoring the activity of specific surface enzymes produced by the test organism. Growth is determined by generating a fluorescent product from a fluorogenic substrate. The substrate is prepared by conjugating a fluorescent compound to the specific enzyme substrates with a bond which prevents fluorescence. The enzymatic action of the bacterial surface enzymes on the substrate cleaves the bond releasing fluorescence. The amount of fluorescence detected is directly related to bacterial growth. The MIC is determined by observing the lowest dilution of antimicrobial agent that inhibits growth of the organism. The substrate can be added to the inoculum broth which is dispensed into the test plate at the same time as the test organism, or, the plates can be prepared with the substrate already added to each micro-well. V Substantial Equivalence Information: A Predicate Device Name(s): Sensititre 20-24 hour Haemophilus influenzae/Streptococcus pneumoniae MIC or Breakpoint Susceptibility System with Omadacycline in the dilution range of 0.008 - 32 ug/mL B Predicate 510(k) Number(s): K183324 K193024 - Page 4 of 11 C Comparison with Predicate(s): Table 1: Comparison with the Predicate Device & Predicate Device(s): Device K193024 Predicate K183324 Device Trade Name Sensititre Haemophilus/Streptococcus pneumoniae (HP) MIC Plates with Lefamulin Sensititre Haemophilus/Streptococcus pneumoniae (HP) MIC Plates with Omadacycline General Device Characteristic Similarities Intended Use/Indications For Use The Sensititre Haemophilus influenzae/Streptococcus pneumoniae plates are in vitro diagnostic products for clinical susceptibility testing of Haemophilus influenzae, Streptococcus pneumoniae, and Streptococcus species. Same Test Panel 96 well plate is dosed with selected antimicrobial agents and substrate for the fluorescent reads, then dried. The bacterial suspension in the appropriate broth is used to rehydrate the plate. Same Test Organism Haemophilus influenzae, Streptococcus pneumoniae, and Streptococcus spp. Same Reading Methods for Streptococcus spp. Results can be read using the following methods: 1) Automatically with the OptiRead (fluorescent substrate technology) 2) On the VIZION (digital viewing device) Same Reading Methods for Haemophilus Results can be read using the VIZION (digital viewing device) only Same Incubation 20-24 hours, 35 ± 1° C Same Inoculation Media CAMHBT + LHB (Streptococcus spp.), HTM broth (H. influenzae) Same General Device Characteristic Differences Antimicrobial Agent Lefamulin Omadacycline K193024 - Page 5 of 11 Concentration Range 0.008 – 16 µg/mL 0.008 – 32 µg/mL VI Standards/Guidance Documents Referenced: Guidance for Industry and FDA - Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems – August 28, 2009. CLSI. Performance Standards for Antimicrobial Susceptibility Testing. 29th ed. CLSI supplement M100. Wayne, PA: Clinical and Laboratory Standards Institute; 2019. CLSI. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically. 11th ed. CLSI standard M07. Wayne, PA: Clinical and Laboratory Standards Institute; 2018. VII Performance Characteristics (if/when applicable): A Analytical Performance: 1. Precision/Reproducibility: A reproducibility study was performed at four sites using a panel comprised of 10 isolates of Streptococcus spp.: S. pneumoniae (three isolates), S. pyogenes (one isolate), S. agalactiae (two isolates), S. anginosus (two isolates), S. mitis (one isolate), Panel:

idK193024_s0_e2000

K193024.txt

intended use

See Indications for Use below.

03 New Hampshire Avenue Silver Spring, MD 20993-0002 www.fda.gov 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY I Background Information: A 510(k) Number K193024 B Applicant Thermo Fisher Scientific C Proprietary and Established Names Sensititre 20-24 hour Haemophilus influenzae/Streptococcus pneumoniae MIC or Breakpoint, Susceptibility System with Lefamulin in the dilution range of 0.008-16 µg/mL D Regulatory Information Product Code(s) Classification Regulation Section Panel JWY, LRG, LTT Class II 21 CFR 866.1640 - Antimicrobial Susceptibility Test Powder MI - Microbiology II Submission/Device Overview: A Purpose for Submission: To obtain a substantial equivalence determination for the addition of Lefamulin to the Sensititre 20-24 hour Haemophilus influenzae/Streptococcus pneumoniae MIC or Breakpoint, Susceptibility System with Lefamulin in the dilution range of 0.008 – 16 ug/mL B Measurand: Lefamulin in the dilution range of 0.008 – 16 μg/mL C Type of Test: Quantitative Antimicrobial Susceptibility Test (AST), growth-based detection III Intended Use/Indications for Use: K193024 - Page 2 of 11 A Intended Use(s): See Indications for Use below. B Indication(s) for Use: The Sensititre 20 - 24 hour Haemophilus influenzae/Streptococcus pneumoniae MIC or Breakpoint Susceptibility System is an in vitro diagnostic product for clinical susceptibility testing of H. influenzae, Streptococcus pneumoniae, and Streptococcus spp. This 510(k) is for Lefamulin in the dilution range of 0.008 - 16 ug/mL for testing Streptococcus spp. and Haemophilus influenzae on the Sensititre 20 - 24 hour MIC panel. Lefamulin has been shown to be active both clinically and in vitro against the following organisms according to the FDA drug label: Streptococcus pneumoniae Haemophilus influenzae C Special Conditions for Use Statement(s): Rx - For Prescription Use Only The performance of lefamulin with Haemophilus influenzae and Streptococcus pneumoniae was evaluated using the AIM autoinoculator only. The use of an alternative inoculation system when testing lefamulin has not been evaluated. The reading of lefamulin results for S. pneumoniae was performed using the AutoReader (OptiRead) and VIZION reading methods. The reading of lefamulin results for Haemophilus influenzae was only performed by VIZION method. The use of alternative reading methods when testing lefamulin has not been evaluated. The ability of the Sensititre system to detect resistance to Lefamulin in the following species is unknown because non-susceptible strains were not available at the time of comparative testing: S. pneumoniae and H. influenzae. Isolates yielding Lefamulin MIC results suggestive of a non- susceptible interpretive category should be submitted to a reference laboratory. Due to the lack of an intermediate category and observed trending towards higher dilutions for Lefamulin, testing of H. influenzae have resulted in major discrepancies for isolates that are otherwise within essential agreement for the reference method. Testing should be repeated using an alternative testing/reference method prior to reporting results for H. influenzae when the Sensititre with the VIZION is 4 μg/mL. D Special Instrument Requirements: Sensititre AIM for device inoculation K193024 - Page 3 of 11 Sensititre VIZION or OptiRead for plate reading (results for Haemophilus influenzae are interpreted using VIZION only) IV Device/System Characteristics: A Device Description: Sensititre MIC Susceptibility MIC panels are multi-well microtiter plates, dosed with dried, stabilized antimicrobials. It is a miniaturized version of the classic broth dilution method and can provide both qualitative and quantitative susceptibility results. After inoculation, plates are sealed with an adhesive seal, incubated at 34 – 36 °C for 20 – 24 hours and examined for bacterial growth. Antimicrobial susceptibility test results can be determined by reading growth using the digital viewing device (VIZION) or automatically on an autoreader (OptiRead) using fluorescence. B Principle of Operation: The Sensititre 20 - 24 hour Haemophilus influenzae/Streptococcus pneumoniae system includes multi-well plastic microtiter plates that contain doubled dilutions of antibacterial agents. Each plate includes antimicrobial agents at appropriate dilutions. Results can be read by the digital device, VIZION, or by use of an automated reader, OptiRead (Streptococcus spp. only). The VIZION allows the panel image to be displayed on a touch screen directly from a video camera and allows the user to visually determine MIC results. The Sensititre OptiRead utilizes fluorescence technology to read the microbroth dilution plates after 20 to 24 hours incubation. The technology involves the detection of bacterial growth by monitoring the activity of specific surface enzymes produced by the test organism. Growth is determined by generating a fluorescent product from a fluorogenic substrate. The substrate is prepared by conjugating a fluorescent compound to the specific enzyme substrates with a bond which prevents fluorescence. The enzymatic action of the bacterial surface enzymes on the substrate cleaves the bond releasing fluorescence. The amount of fluorescence detected is directly related to bacterial growth. The MIC is determined by observing the lowest dilution of antimicrobial agent that inhibits growth of the organism. The substrate can be added to the inoculum broth which is dispensed into the test plate at the same time as the test organism, or, the plates can be prepared with the substrate already added to each micro-well. V Substantial Equivalence Information: A Predicate Device Name(s): Sensititre 20-24 hour Haemophilus influenzae/Streptococcus pneumoniae MIC or Breakpoint Susceptibility System with Omadacycline in the dilution range of 0.008 - 32 ug/mL B Predicate 510(k) Number(s): K183324 K193024 - Page 4 of 11 C Comparison with Predicate(s): Table 1: Comparison with the Predicate Device & Predicate Device(s): Device K193024 Predicate K183324 Device Trade Name Sensititre Haemophilus/Streptococcus pneumoniae (HP) MIC Plates with Lefamulin Sensititre Haemophilus/Streptococcus pneumoniae (HP) MIC Plates with Omadacycline General Device Characteristic Similarities Intended Use/Indications For Use The Sensititre Haemophilus influenzae/Streptococcus pneumoniae plates are in vitro diagnostic products for clinical susceptibility testing of Haemophilus influenzae, Streptococcus pneumoniae, and Streptococcus species. Same Test Panel 96 well plate is dosed with selected antimicrobial agents and substrate for the fluorescent reads, then dried. The bacterial suspension in the appropriate broth is used to rehydrate the plate. Same Test Organism Haemophilus influenzae, Streptococcus pneumoniae, and Streptococcus spp. Same Reading Methods for Streptococcus spp. Results can be read using the following methods: 1) Automatically with the OptiRead (fluorescent substrate technology) 2) On the VIZION (digital viewing device) Same Reading Methods for Haemophilus Results can be read using the VIZION (digital viewing device) only Same Incubation 20-24 hours, 35 ± 1° C Same Inoculation Media CAMHBT + LHB (Streptococcus spp.), HTM broth (H. influenzae) Same General Device Characteristic Differences Antimicrobial Agent Lefamulin Omadacycline K193024 - Page 5 of 11 Concentration Range 0.008 – 16 µg/mL 0.008 – 32 µg/mL VI Standards/Guidance Documents Referenced: Guidance for Industry and FDA - Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems – August 28, 2009. CLSI. Performance Standards for Antimicrobial Susceptibility Testing. 29th ed. CLSI supplement M100. Wayne, PA: Clinical and Laboratory Standards Institute; 2019. CLSI. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically. 11th ed. CLSI standard M07. Wayne, PA: Clinical and Laboratory Standards Institute; 2018. VII Performance Characteristics (if/when applicable): A Analytical Performance: 1. Precision/Reproducibility: A reproducibility study was performed at four sites using a panel comprised of 10 isolates of Streptococcus spp.: S. pneumoniae (three isolates), S. pyogenes (one isolate), S. agalactiae (two isolates), S. anginosus (two isolates), S. mitis (one isolate), Intended use:

idK193024_s0_e2000

K193024.txt

applicant

Thermo Fisher Scientific

10903 New Hampshire Avenue Silver Spring, MD 20993-0002 www.fda.gov 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY I Background Information: A 510(k) Number K193024 B Applicant Thermo Fisher Scientific C Proprietary and Established Names Sensititre 20-24 hour Haemophilus influenzae/Streptococcus pneumoniae MIC or Breakpoint, Susceptibility System with Lefamulin in the dilution range of 0.008-16 µg/mL D Regulatory Information Product Code(s) Classification Regulation Section Panel JWY, LRG, LTT Class II 21 CFR 866.1640 - Antimicrobial Susceptibility Test Powder MI - Microbiology II Submission/Device Overview: A Purpose for Submission: To obtain a substantial equivalence determination for the addition of Lefamulin to the Sensititre 20-24 hour Haemophilus influenzae/Streptococcus pneumoniae MIC or Breakpoint, Susceptibility System with Lefamulin in the dilution range of 0.008 – 16 ug/mL B Measurand: Lefamulin in the dilution range of 0.008 – 16 μg/mL C Type of Test: Quantitative Antimicrobial Susceptibility Test (AST), growth-based detection III Intended Use/Indications for Use: K193024 - Page 2 of 11 A Intended Use(s): See Indications for Use below. B Indication(s) for Use: The Sensititre 20 - 24 hour Haemophilus influenzae/Streptococcus pneumoniae MIC or Breakpoint Susceptibility System is an in vitro diagnostic product for clinical susceptibility testing of H. influenzae, Streptococcus pneumoniae, and Streptococcus spp. This 510(k) is for Lefamulin in the dilution range of 0.008 - 16 ug/mL for testing Streptococcus spp. and Haemophilus influenzae on the Sensititre 20 - 24 hour MIC panel. Lefamulin has been shown to be active both clinically and in vitro against the following organisms according to the FDA drug label: Streptococcus pneumoniae Haemophilus influenzae C Special Conditions for Use Statement(s): Rx - For Prescription Use Only The performance of lefamulin with Haemophilus influenzae and Streptococcus pneumoniae was evaluated using the AIM autoinoculator only. The use of an alternative inoculation system when testing lefamulin has not been evaluated. The reading of lefamulin results for S. pneumoniae was performed using the AutoReader (OptiRead) and VIZION reading methods. The reading of lefamulin results for Haemophilus influenzae was only performed by VIZION method. The use of alternative reading methods when testing lefamulin has not been evaluated. The ability of the Sensititre system to detect resistance to Lefamulin in the following species is unknown because non-susceptible strains were not available at the time of comparative testing: S. pneumoniae and H. influenzae. Isolates yielding Lefamulin MIC results suggestive of a non- susceptible interpretive category should be submitted to a reference laboratory. Due to the lack of an intermediate category and observed trending towards higher dilutions for Lefamulin, testing of H. influenzae have resulted in major discrepancies for isolates that are otherwise within essential agreement for the reference method. Testing should be repeated using an alternative testing/reference method prior to reporting results for H. influenzae when the Sensititre with the VIZION is 4 μg/mL. D Special Instrument Requirements: Sensititre AIM for device inoculation K193024 - Page 3 of 11 Sensititre VIZION or OptiRead for plate reading (results for Haemophilus influenzae are interpreted using VIZION only) IV Device/System Characteristics: A Device Description: Sensititre MIC Susceptibility MIC panels are multi-well microtiter plates, dosed with dried, stabilized antimicrobials. It is a miniaturized version of the classic broth dilution method and can provide both qualitative and quantitative susceptibility results. After inoculation, plates are sealed with an adhesive seal, incubated at 34 – 36 °C for 20 – 24 hours and examined for bacterial growth. Antimicrobial susceptibility test results can be determined by reading growth using the digital viewing device (VIZION) or automatically on an autoreader (OptiRead) using fluorescence. B Principle of Operation: The Sensititre 20 - 24 hour Haemophilus influenzae/Streptococcus pneumoniae system includes multi-well plastic microtiter plates that contain doubled dilutions of antibacterial agents. Each plate includes antimicrobial agents at appropriate dilutions. Results can be read by the digital device, VIZION, or by use of an automated reader, OptiRead (Streptococcus spp. only). The VIZION allows the panel image to be displayed on a touch screen directly from a video camera and allows the user to visually determine MIC results. The Sensititre OptiRead utilizes fluorescence technology to read the microbroth dilution plates after 20 to 24 hours incubation. The technology involves the detection of bacterial growth by monitoring the activity of specific surface enzymes produced by the test organism. Growth is determined by generating a fluorescent product from a fluorogenic substrate. The substrate is prepared by conjugating a fluorescent compound to the specific enzyme substrates with a bond which prevents fluorescence. The enzymatic action of the bacterial surface enzymes on the substrate cleaves the bond releasing fluorescence. The amount of fluorescence detected is directly related to bacterial growth. The MIC is determined by observing the lowest dilution of antimicrobial agent that inhibits growth of the organism. The substrate can be added to the inoculum broth which is dispensed into the test plate at the same time as the test organism, or, the plates can be prepared with the substrate already added to each micro-well. V Substantial Equivalence Information: A Predicate Device Name(s): Sensititre 20-24 hour Haemophilus influenzae/Streptococcus pneumoniae MIC or Breakpoint Susceptibility System with Omadacycline in the dilution range of 0.008 - 32 ug/mL B Predicate 510(k) Number(s): K183324 K193024 - Page 4 of 11 C Comparison with Predicate(s): Table 1: Comparison with the Predicate Device & Predicate Device(s): Device K193024 Predicate K183324 Device Trade Name Sensititre Haemophilus/Streptococcus pneumoniae (HP) MIC Plates with Lefamulin Sensititre Haemophilus/Streptococcus pneumoniae (HP) MIC Plates with Omadacycline General Device Characteristic Similarities Intended Use/Indications For Use The Sensititre Haemophilus influenzae/Streptococcus pneumoniae plates are in vitro diagnostic products for clinical susceptibility testing of Haemophilus influenzae, Streptococcus pneumoniae, and Streptococcus species. Same Test Panel 96 well plate is dosed with selected antimicrobial agents and substrate for the fluorescent reads, then dried. The bacterial suspension in the appropriate broth is used to rehydrate the plate. Same Test Organism Haemophilus influenzae, Streptococcus pneumoniae, and Streptococcus spp. Same Reading Methods for Streptococcus spp. Results can be read using the following methods: 1) Automatically with the OptiRead (fluorescent substrate technology) 2) On the VIZION (digital viewing device) Same Reading Methods for Haemophilus Results can be read using the VIZION (digital viewing device) only Same Incubation 20-24 hours, 35 ± 1° C Same Inoculation Media CAMHBT + LHB (Streptococcus spp.), HTM broth (H. influenzae) Same General Device Characteristic Differences Antimicrobial Agent Lefamulin Omadacycline K193024 - Page 5 of 11 Concentration Range 0.008 – 16 µg/mL 0.008 – 32 µg/mL VI Standards/Guidance Documents Referenced: Guidance for Industry and FDA - Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems – August 28, 2009. CLSI. Performance Standards for Antimicrobial Susceptibility Testing. 29th ed. CLSI supplement M100. Wayne, PA: Clinical and Laboratory Standards Institute; 2019. CLSI. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically. 11th ed. CLSI standard M07. Wayne, PA: Clinical and Laboratory Standards Institute; 2018. VII Performance Characteristics (if/when applicable): A Analytical Performance: 1. Precision/Reproducibility: A reproducibility study was performed at four sites using a panel comprised of 10 isolates of Streptococcus spp.: S. pneumoniae (three isolates), S. pyogenes (one isolate), S. agalactiae (two isolates), S. anginosus (two isolates), S. mitis (one isolate), Applicant:

idK193024_s0_e2000

K193024.txt

regulation section

21 CFR 866.1640 - Antimicrobial Susceptibility Test Powder

03 New Hampshire Avenue Silver Spring, MD 20993-0002 www.fda.gov 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY I Background Information: A 510(k) Number K193024 B Applicant Thermo Fisher Scientific C Proprietary and Established Names Sensititre 20-24 hour Haemophilus influenzae/Streptococcus pneumoniae MIC or Breakpoint, Susceptibility System with Lefamulin in the dilution range of 0.008-16 µg/mL D Regulatory Information Product Code(s) Classification Regulation Section Panel JWY, LRG, LTT Class II 21 CFR 866.1640 - Antimicrobial Susceptibility Test Powder MI - Microbiology II Submission/Device Overview: A Purpose for Submission: To obtain a substantial equivalence determination for the addition of Lefamulin to the Sensititre 20-24 hour Haemophilus influenzae/Streptococcus pneumoniae MIC or Breakpoint, Susceptibility System with Lefamulin in the dilution range of 0.008 – 16 ug/mL B Measurand: Lefamulin in the dilution range of 0.008 – 16 μg/mL C Type of Test: Quantitative Antimicrobial Susceptibility Test (AST), growth-based detection III Intended Use/Indications for Use: K193024 - Page 2 of 11 A Intended Use(s): See Indications for Use below. B Indication(s) for Use: The Sensititre 20 - 24 hour Haemophilus influenzae/Streptococcus pneumoniae MIC or Breakpoint Susceptibility System is an in vitro diagnostic product for clinical susceptibility testing of H. influenzae, Streptococcus pneumoniae, and Streptococcus spp. This 510(k) is for Lefamulin in the dilution range of 0.008 - 16 ug/mL for testing Streptococcus spp. and Haemophilus influenzae on the Sensititre 20 - 24 hour MIC panel. Lefamulin has been shown to be active both clinically and in vitro against the following organisms according to the FDA drug label: Streptococcus pneumoniae Haemophilus influenzae C Special Conditions for Use Statement(s): Rx - For Prescription Use Only The performance of lefamulin with Haemophilus influenzae and Streptococcus pneumoniae was evaluated using the AIM autoinoculator only. The use of an alternative inoculation system when testing lefamulin has not been evaluated. The reading of lefamulin results for S. pneumoniae was performed using the AutoReader (OptiRead) and VIZION reading methods. The reading of lefamulin results for Haemophilus influenzae was only performed by VIZION method. The use of alternative reading methods when testing lefamulin has not been evaluated. The ability of the Sensititre system to detect resistance to Lefamulin in the following species is unknown because non-susceptible strains were not available at the time of comparative testing: S. pneumoniae and H. influenzae. Isolates yielding Lefamulin MIC results suggestive of a non- susceptible interpretive category should be submitted to a reference laboratory. Due to the lack of an intermediate category and observed trending towards higher dilutions for Lefamulin, testing of H. influenzae have resulted in major discrepancies for isolates that are otherwise within essential agreement for the reference method. Testing should be repeated using an alternative testing/reference method prior to reporting results for H. influenzae when the Sensititre with the VIZION is 4 μg/mL. D Special Instrument Requirements: Sensititre AIM for device inoculation K193024 - Page 3 of 11 Sensititre VIZION or OptiRead for plate reading (results for Haemophilus influenzae are interpreted using VIZION only) IV Device/System Characteristics: A Device Description: Sensititre MIC Susceptibility MIC panels are multi-well microtiter plates, dosed with dried, stabilized antimicrobials. It is a miniaturized version of the classic broth dilution method and can provide both qualitative and quantitative susceptibility results. After inoculation, plates are sealed with an adhesive seal, incubated at 34 – 36 °C for 20 – 24 hours and examined for bacterial growth. Antimicrobial susceptibility test results can be determined by reading growth using the digital viewing device (VIZION) or automatically on an autoreader (OptiRead) using fluorescence. B Principle of Operation: The Sensititre 20 - 24 hour Haemophilus influenzae/Streptococcus pneumoniae system includes multi-well plastic microtiter plates that contain doubled dilutions of antibacterial agents. Each plate includes antimicrobial agents at appropriate dilutions. Results can be read by the digital device, VIZION, or by use of an automated reader, OptiRead (Streptococcus spp. only). The VIZION allows the panel image to be displayed on a touch screen directly from a video camera and allows the user to visually determine MIC results. The Sensititre OptiRead utilizes fluorescence technology to read the microbroth dilution plates after 20 to 24 hours incubation. The technology involves the detection of bacterial growth by monitoring the activity of specific surface enzymes produced by the test organism. Growth is determined by generating a fluorescent product from a fluorogenic substrate. The substrate is prepared by conjugating a fluorescent compound to the specific enzyme substrates with a bond which prevents fluorescence. The enzymatic action of the bacterial surface enzymes on the substrate cleaves the bond releasing fluorescence. The amount of fluorescence detected is directly related to bacterial growth. The MIC is determined by observing the lowest dilution of antimicrobial agent that inhibits growth of the organism. The substrate can be added to the inoculum broth which is dispensed into the test plate at the same time as the test organism, or, the plates can be prepared with the substrate already added to each micro-well. V Substantial Equivalence Information: A Predicate Device Name(s): Sensititre 20-24 hour Haemophilus influenzae/Streptococcus pneumoniae MIC or Breakpoint Susceptibility System with Omadacycline in the dilution range of 0.008 - 32 ug/mL B Predicate 510(k) Number(s): K183324 K193024 - Page 4 of 11 C Comparison with Predicate(s): Table 1: Comparison with the Predicate Device & Predicate Device(s): Device K193024 Predicate K183324 Device Trade Name Sensititre Haemophilus/Streptococcus pneumoniae (HP) MIC Plates with Lefamulin Sensititre Haemophilus/Streptococcus pneumoniae (HP) MIC Plates with Omadacycline General Device Characteristic Similarities Intended Use/Indications For Use The Sensititre Haemophilus influenzae/Streptococcus pneumoniae plates are in vitro diagnostic products for clinical susceptibility testing of Haemophilus influenzae, Streptococcus pneumoniae, and Streptococcus species. Same Test Panel 96 well plate is dosed with selected antimicrobial agents and substrate for the fluorescent reads, then dried. The bacterial suspension in the appropriate broth is used to rehydrate the plate. Same Test Organism Haemophilus influenzae, Streptococcus pneumoniae, and Streptococcus spp. Same Reading Methods for Streptococcus spp. Results can be read using the following methods: 1) Automatically with the OptiRead (fluorescent substrate technology) 2) On the VIZION (digital viewing device) Same Reading Methods for Haemophilus Results can be read using the VIZION (digital viewing device) only Same Incubation 20-24 hours, 35 ± 1° C Same Inoculation Media CAMHBT + LHB (Streptococcus spp.), HTM broth (H. influenzae) Same General Device Characteristic Differences Antimicrobial Agent Lefamulin Omadacycline K193024 - Page 5 of 11 Concentration Range 0.008 – 16 µg/mL 0.008 – 32 µg/mL VI Standards/Guidance Documents Referenced: Guidance for Industry and FDA - Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems – August 28, 2009. CLSI. Performance Standards for Antimicrobial Susceptibility Testing. 29th ed. CLSI supplement M100. Wayne, PA: Clinical and Laboratory Standards Institute; 2019. CLSI. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically. 11th ed. CLSI standard M07. Wayne, PA: Clinical and Laboratory Standards Institute; 2018. VII Performance Characteristics (if/when applicable): A Analytical Performance: 1. Precision/Reproducibility: A reproducibility study was performed at four sites using a panel comprised of 10 isolates of Streptococcus spp.: S. pneumoniae (three isolates), S. pyogenes (one isolate), S. agalactiae (two isolates), S. anginosus (two isolates), S. mitis (one isolate), Regulation section:

idK193024_s4000_e6000

K193024.txt

proposed labeling

The labeling supports the finding of substantial equivalence for this device.

N EA % Eval Tot Eval EA N Eval EA % CA Tot CA % No. NS No. S min maj vmj S. pneumoniae Clinical 200 197 98.5 200 197 98.5 198 99.0 4 196 NA 0 2 Challenge 50 50 100 50 50 100 49 98.0 1 49 NA 0 1 Total 250 247 98.8 250 247 98.8 247 98.8 5 245 NA 0 3 1Adjusted very major error rate is 0%. EA – Essential agreement maj – Major errors CA – Category agreement vmj – Very major errors Eval – Evaluable isolates min – Minor errors NS – Non-susceptible isolates S - Susceptible NA – Not Applicable due to lack of intermediate category To address the testing and reporting of non-indicated species the following comment was added to the Precautions section of the device labeling: The safety and efficacy of antimicrobial drugs for which antimicrobial susceptibility is tested by this AST device, may or may not have been established in adequate and well- K193024 - Page 9 of 11 controlled clinical trials for treating clinical infections due to microorganisms outside of those found in the indications and usage in the drug label. The clinical significance of susceptibility information in those instances is unknown. The approved labelling for specific antimicrobial drugs provides the uses for which the antimicrobial drug is approved. Due to the lack of intermediate or resistant categories and availability of insufficient number of non-susceptible isolates tested in the comparison study, the sponsor also included the following to instruct users to use an alternative method of testing when non-susceptible isolates of S. pneumoniae and H. influenzae are encountered: The ability of the Sensititre system to detect resistance to Lefamulin in the following species is unknown because non-susceptible strains were not available at the time of comparative testing: S. pneumoniae and H. influenzae. Isolates yielding Lefamulin MIC results suggestive of a non-susceptible interpretive category should be submitted to a reference laboratory. MIC Trending An analysis of trending was calculated using the combined clinical and challenge data for each organism group. This trending calculation takes into account MIC values that are determined to be one or more doubling dilutions lower or higher compared to the reference method irrespective of whether the device MIC values are on-scale or not. Trending results are shown in Table 5. Results for S. pneumoniae were stratified by both reading methods and H. influenzae was evaluated using the VIZION only to determine if particular trends were observed. The acceptable percent difference between higher and lower dilution readings is <30%. Based on the results observed, a trend was identified for H. influenzae when interpreted by the VIZION which trended towards higher dilutions when compared to the reference method. Given this, the following was included in the package insert as a footnote: Lefamulin MIC values tended to be in exact agreement or at least one doubling dilution higher when testing H. influenzae with the VIZION reading method compared to the CLSI reference broth microdilution. Table 5: Lefamulin Trending Analysis for S. pneumoniae and H. influenzae, Read by VIZION and OptiRead (S. pneumoniae only) Organism (Read Method) Total Evaluable for Trending ≥ 1 Dilution lower No. (%) Exact No. (%) ≥ 1 Dilution Higher No. (%) Percent Difference (CI) Trending Noted S. pneumoniae (VIZION) 250 67 (26.8) 157 (62.8) 26 (10.4) -16.4 (-23.0 to -9.7) No S. pneumoniae (OptiRead) 250 80 (32.0) 154 (61.6) 16 (6.4) -25.6 (-32.1 to -19.0) No H. influenzae (VIZION) 438 10 (2.3) 191 (43.6) 237 (54.1) 51.8 (46.8 – 56.6) Yes K193024 - Page 10 of 11 2. Matrix Comparison: Not applicable C Clinical Studies: 1. Clinical Sensitivity: Not applicable 2. Clinical Specificity: Not applicable 3. Other Clinical Supportive Data (When 1. and 2. Are Not Applicable): Not applicable D Clinical Cut-Off: Not applicable E Expected Values/Reference Range: The FDA-identified susceptibility interpretive criteria for lefamulin are as listed in Table 6. Table 6: FDA-Recognized Interpretive Criteriaa for Lefamulin (μg/mL) Susceptible (S) Intermediate (I) Resistant (R) Streptococcus pneumoniae ≤0.5 - - Haemophilus influenzae ≤2 - - a FDA STIC Webpage VIII Proposed Labeling: The labeling supports the finding of substantial equivalence for this device. IX Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. To support the implementation of changes to FDA-recognized susceptibility test interpretive criteria (i.e., breakpoints), this submission included a breakpoint change protocol that was reviewed and accepted by FDA. This protocol addresses future revisions to device labeling in response to breakpoint changes that are recognized on the FDA STIC webpage (https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/ucm410971. htm). The protocol outlined the specific procedures and acceptance criteria that ThermoFisher intends to use to evaluate the Sensititre 20-24 hour Haemophilus influenzae/Streptococcus K193024 - Page 11 of 11 pneumoniae MIC or Breakpoint, Susceptibility System with Lefamulin in the dilution range of 0.008-16 ug/ml when revised breakpoints for lefamulin are published on the FDA STIC webpage. The breakpoint change protocol included with the submission indicated that if specific criteria are met, ThermoFisher will update the lefamulin device label to include (1) the new breakpoints, (2) an updated performance section after re-evaluation of data in this premarket notification with the new breakpoints, and (3) any new limitations as determined by their evaluation. Proposed labeling:

idK170293_s0_e2000

K170293.txt

purpose for submission

Adding a previously cleared test (Emit II Plus Cocaine Metabolite Assay) to the Beckman Coulter DxC 700 AU Clinical Chemistry Analyzer

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: k170293 B. Purpose for Submission: Adding a previously cleared test (Emit II Plus Cocaine Metabolite Assay) to the Beckman Coulter DxC 700 AU Clinical Chemistry Analyzer C. Measurand: Benzoylecgonine D. Type of Test: Qualitative and semi-quantative homogenous enzyme immunoassay E. Applicant: Siemens Healthcare Diagnostics, Inc. F. Proprietary and Established Names: Emit II Plus Cocaine Metabolite Assay G. Regulatory Information: Product Code Classification Regulation Section Panel DIO – Cocaine and cocaine metabolic test system Class II 21 CFR 862.3250 91 - Toxicology H. Intended Use: 1. Intended use(s): See indication(s) for use below. 2 2. Indication(s) for use: The Emit II Plus Cocaine Metabolite Assay is a homogeneous enzyme immunoassay with a 150 ng/mL or 300 ng/mL cutoff. The assay is intended for use in the qualitative and semiquantitative analyses of benzoylecgonine (cocaine metabolite) in human urine. Emit II Plus assays are designed for use with a number of chemistry analyzers. The Emit II Plus Cocaine Metabolite Assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used to obtain a confirmed analytical result. Gas chromatography/mass spectrometry (GC/MS) is the preferred confirmatory method. Other chemical confirmation methods are available. Clinical consideration and professional judgment should be applied to any drug-of-abuse test result, particularly when preliminary positive results are used. 3. Special conditions for use statement(s): For Prescription use only. 4. Special instrument requirements: Performance data was obtained using Beckman Coulter DxC 700 AU Clinical Chemistry Analyzer I. Device Description: The Emit II Plus Cocaine Metabolite Assay consists of two ready-to-use reagents: Antibody/Substrate Reagent 1 consists of sheep polyclonal antibodies to benzoylecgonine (2.2 μg/mL), bovine serum albumin, G6P (15 mM), NAD (12 mM), preservatives, and stabilizers. Enzyme Reagent 2 consists of Benzoylecgonine labeled with bacterial G6PDH (0.46 U/mL), HEPES buffer, bovine serum albumin, preservatives, and stabilizers. Materials that are required but thar are sold separately include the following: · Emit Calibrators/Controls with concentrations of (0, 150, 300, 500 and 1000 ng/mL). · Commercial controls two levels with concentrations of (0 and 1000 ng/mL) J. Substantial Equivalence Information: 1. Predicate device name(s): Emit II Plus Cocaine Metabolite Assay 3 2. Predicate 510(k) number(s): k993988 3. Comparison with predicate: Similarities Item Emit II Plus Cocaine Metabolite Assay (Candidate) Emit II Plus Cocaine Metabolite Assay Predicate k993988 Intended Use Same For the qualitative and semiquantitative determination of the presence of benzoylecgonine in human urine Measurant Same Benzoylecgonine Type of Test Same Qualitative and semi-quantitative homogeneous enzyme immunoassay Antibody Same Sheep polyclonal Reagent Form Same Liquid, ready to use Reagent Composition Same Antibody/Substrate Reagent 1 Sheep polyclonal antibodies to benzoylecgonine (2.2 μg/mL), bovine serum albumin, G6P (15 mM), NAD (12 mM), preservatives, and stabilizers Enzyme Reagent 2 Benzoylecgonine labeled with bacterial G6PDH (0.46 U/mL), HEPES buffer, bovine serum albumin, preservatives, and stabilizers Cutoff/controls Same 150ng/mL (±25%) 300 ng/mL (±25%) Sample Matrix Same Human Urine Difference Item Emit II Plus Cocaine Metabolite Assay Candidate Emit II Plus Cocaine Metabolite Assay k993988 Predicate Instrument Beckman Coulter DxC 700 AU Clinical Chemistry Analyzer SYVA 30R Biochemical System 4 K. Standard/Guidance Document Referenced (if applicable): · CLSI EP05-A3, Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline – Third Edition · CLSI EP06-A, Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline · CLSI EP07-A2, Interference Testing in Clinical Chemistry; Approved Guideline – Second Edition · CLSI EP09-A3, Measurement Procedure Comparison and Bias Estimation Using Patient Samples; Approved Guideline – Third Edition · CLSI EP12-A2, User Protocol for Evaluation of Qualitative Test Performance; Approved Guideline – Second Edition · CLSI EP25-A Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline L. Test Principle: The Emit II Plus Cocaine Metabolite Assayis is based on competition between free drug in the specimen and drug labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH), for antibody binding sites. G6PDH enzyme activity decreases upon binding to the antibody, so the drug concentration in the specimen is proportional to G6PDH activity. The G6PDH enzyme converts nicotinamide adenine dinucleotide (NAD) to NADH, which can be measured as an absorbance change spectrophotometrically at 340 nm. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Precision studies were conducted in accordance with CLSI EP05-A3. Testing was performed for twenty (20) days with two (2) runs per day, two (2) replicates per run for a total of n = 80 sample replicates per test concentration. Nine (9) drug-free negative urine samples were spiked with benzolecogonine to concentrations of ±25%, ±50% , ±75% , and ±100 of each cutoff, as well as a zero drug concentration sample. The results are provided below, as determined in qualitative and semi-quantitative modes using each of the 150 ng/mL and 300 ng/mL cutoffs: 5 Qualitative Analysis (for 150 ng/mL cutoff) Concentration (ng/mL) % of cutoff # of determinations Results 0 -100% 80 80 Neg / 0 Pos 38 -75% 80 80 Neg / 0 Pos 75 -50% 80 80 Neg / 0 Pos 113 -25% 80 80 Neg / 0 Pos 150 Cutoff 80 9 Neg / 71 Pos 188 +25% 80 80 Pos / 0 Neg 225 +50% 80 80 Pos / 0 Neg 263 +75% 80 80 Pos / 0 Neg 300 +100% 80 80 Pos / 0 Neg Semi-Quantitative Analysis (for 150 ng/mL cutoff) Concentration (ng/mL) % of cutoff # of determinations Results 0 -100% 80 80 Neg / 0 Pos 38 -75% 80 80 Neg / 0 Pos 75 -50% 80 80 Neg / 0 Pos 113 -25% 80 80 Neg / 0 Pos 150 Cutoff 80 9 Neg / 71 Pos 188 +25% 80 80 Pos / 0 Neg 225 +50% 80 80 Pos / 0 Neg 263 +75% 80 80 Pos / 0 Neg 300 +100% 80 80 Pos / 0 Neg Qualitative Analysis (for 300 ng/mL cutoff) Concentration (ng/mL) % of cutoff # of determinations Results 0 -100 80 80 Neg / 0 Pos 75 -75 80 80 Neg / 0 Pos 150 -50 80 80 Neg / 0 Pos 225 -25 80 80 Neg / 0 Pos 300 Cutoff 80 54 Neg / 26 Pos 375 +25 80 80 Pos / 0 Neg 450 +50 80 80 Pos / 0 Neg 525 +75 80 80 Pos / 0 Neg 600 +100 80 80 Pos / 0 Neg 6 Semi-Quantitative Analysis (for 300ng/mL cutoff) Concentration (ng/mL) % of cutoff # of determinations Results 0 -100 80 80 Neg / 0 Pos 75 -75 80 80 Neg / 0 Pos 150 -50 80 80 Neg / 0 Pos 225 -25 80 80 Neg / 0 Pos 300 Cutoff 80 54 Neg / 26 Pos 375 +25 80 80 Pos / 0 Neg 450 +50 80 80 Pos / 0 Neg 525 +75 80 80 Pos / 0 Neg 600 +100 80 80 Pos / 0 Neg b. Linearity/assay reportable range: Recovery studies were conducted in accordance with CLSI EP 6-A in the semi- quantitative mode using spiked drug-free urine sample pools with known concentrations of benzoylecgonine to generate eleven (11) dilutions to achieve concentrations ranging from 50 ng/mL to 1000 ng/mL. Each concentration was tested in five replicates and Purpose for submission:

idK170293_s0_e2000

K170293.txt

measurand

Benzoylecgonine

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: k170293 B. Purpose for Submission: Adding a previously cleared test (Emit II Plus Cocaine Metabolite Assay) to the Beckman Coulter DxC 700 AU Clinical Chemistry Analyzer C. Measurand: Benzoylecgonine D. Type of Test: Qualitative and semi-quantative homogenous enzyme immunoassay E. Applicant: Siemens Healthcare Diagnostics, Inc. F. Proprietary and Established Names: Emit II Plus Cocaine Metabolite Assay G. Regulatory Information: Product Code Classification Regulation Section Panel DIO – Cocaine and cocaine metabolic test system Class II 21 CFR 862.3250 91 - Toxicology H. Intended Use: 1. Intended use(s): See indication(s) for use below. 2 2. Indication(s) for use: The Emit II Plus Cocaine Metabolite Assay is a homogeneous enzyme immunoassay with a 150 ng/mL or 300 ng/mL cutoff. The assay is intended for use in the qualitative and semiquantitative analyses of benzoylecgonine (cocaine metabolite) in human urine. Emit II Plus assays are designed for use with a number of chemistry analyzers. The Emit II Plus Cocaine Metabolite Assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used to obtain a confirmed analytical result. Gas chromatography/mass spectrometry (GC/MS) is the preferred confirmatory method. Other chemical confirmation methods are available. Clinical consideration and professional judgment should be applied to any drug-of-abuse test result, particularly when preliminary positive results are used. 3. Special conditions for use statement(s): For Prescription use only. 4. Special instrument requirements: Performance data was obtained using Beckman Coulter DxC 700 AU Clinical Chemistry Analyzer I. Device Description: The Emit II Plus Cocaine Metabolite Assay consists of two ready-to-use reagents: Antibody/Substrate Reagent 1 consists of sheep polyclonal antibodies to benzoylecgonine (2.2 μg/mL), bovine serum albumin, G6P (15 mM), NAD (12 mM), preservatives, and stabilizers. Enzyme Reagent 2 consists of Benzoylecgonine labeled with bacterial G6PDH (0.46 U/mL), HEPES buffer, bovine serum albumin, preservatives, and stabilizers. Materials that are required but thar are sold separately include the following: · Emit Calibrators/Controls with concentrations of (0, 150, 300, 500 and 1000 ng/mL). · Commercial controls two levels with concentrations of (0 and 1000 ng/mL) J. Substantial Equivalence Information: 1. Predicate device name(s): Emit II Plus Cocaine Metabolite Assay 3 2. Predicate 510(k) number(s): k993988 3. Comparison with predicate: Similarities Item Emit II Plus Cocaine Metabolite Assay (Candidate) Emit II Plus Cocaine Metabolite Assay Predicate k993988 Intended Use Same For the qualitative and semiquantitative determination of the presence of benzoylecgonine in human urine Measurant Same Benzoylecgonine Type of Test Same Qualitative and semi-quantitative homogeneous enzyme immunoassay Antibody Same Sheep polyclonal Reagent Form Same Liquid, ready to use Reagent Composition Same Antibody/Substrate Reagent 1 Sheep polyclonal antibodies to benzoylecgonine (2.2 μg/mL), bovine serum albumin, G6P (15 mM), NAD (12 mM), preservatives, and stabilizers Enzyme Reagent 2 Benzoylecgonine labeled with bacterial G6PDH (0.46 U/mL), HEPES buffer, bovine serum albumin, preservatives, and stabilizers Cutoff/controls Same 150ng/mL (±25%) 300 ng/mL (±25%) Sample Matrix Same Human Urine Difference Item Emit II Plus Cocaine Metabolite Assay Candidate Emit II Plus Cocaine Metabolite Assay k993988 Predicate Instrument Beckman Coulter DxC 700 AU Clinical Chemistry Analyzer SYVA 30R Biochemical System 4 K. Standard/Guidance Document Referenced (if applicable): · CLSI EP05-A3, Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline – Third Edition · CLSI EP06-A, Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline · CLSI EP07-A2, Interference Testing in Clinical Chemistry; Approved Guideline – Second Edition · CLSI EP09-A3, Measurement Procedure Comparison and Bias Estimation Using Patient Samples; Approved Guideline – Third Edition · CLSI EP12-A2, User Protocol for Evaluation of Qualitative Test Performance; Approved Guideline – Second Edition · CLSI EP25-A Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline L. Test Principle: The Emit II Plus Cocaine Metabolite Assayis is based on competition between free drug in the specimen and drug labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH), for antibody binding sites. G6PDH enzyme activity decreases upon binding to the antibody, so the drug concentration in the specimen is proportional to G6PDH activity. The G6PDH enzyme converts nicotinamide adenine dinucleotide (NAD) to NADH, which can be measured as an absorbance change spectrophotometrically at 340 nm. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Precision studies were conducted in accordance with CLSI EP05-A3. Testing was performed for twenty (20) days with two (2) runs per day, two (2) replicates per run for a total of n = 80 sample replicates per test concentration. Nine (9) drug-free negative urine samples were spiked with benzolecogonine to concentrations of ±25%, ±50% , ±75% , and ±100 of each cutoff, as well as a zero drug concentration sample. The results are provided below, as determined in qualitative and semi-quantitative modes using each of the 150 ng/mL and 300 ng/mL cutoffs: 5 Qualitative Analysis (for 150 ng/mL cutoff) Concentration (ng/mL) % of cutoff # of determinations Results 0 -100% 80 80 Neg / 0 Pos 38 -75% 80 80 Neg / 0 Pos 75 -50% 80 80 Neg / 0 Pos 113 -25% 80 80 Neg / 0 Pos 150 Cutoff 80 9 Neg / 71 Pos 188 +25% 80 80 Pos / 0 Neg 225 +50% 80 80 Pos / 0 Neg 263 +75% 80 80 Pos / 0 Neg 300 +100% 80 80 Pos / 0 Neg Semi-Quantitative Analysis (for 150 ng/mL cutoff) Concentration (ng/mL) % of cutoff # of determinations Results 0 -100% 80 80 Neg / 0 Pos 38 -75% 80 80 Neg / 0 Pos 75 -50% 80 80 Neg / 0 Pos 113 -25% 80 80 Neg / 0 Pos 150 Cutoff 80 9 Neg / 71 Pos 188 +25% 80 80 Pos / 0 Neg 225 +50% 80 80 Pos / 0 Neg 263 +75% 80 80 Pos / 0 Neg 300 +100% 80 80 Pos / 0 Neg Qualitative Analysis (for 300 ng/mL cutoff) Concentration (ng/mL) % of cutoff # of determinations Results 0 -100 80 80 Neg / 0 Pos 75 -75 80 80 Neg / 0 Pos 150 -50 80 80 Neg / 0 Pos 225 -25 80 80 Neg / 0 Pos 300 Cutoff 80 54 Neg / 26 Pos 375 +25 80 80 Pos / 0 Neg 450 +50 80 80 Pos / 0 Neg 525 +75 80 80 Pos / 0 Neg 600 +100 80 80 Pos / 0 Neg 6 Semi-Quantitative Analysis (for 300ng/mL cutoff) Concentration (ng/mL) % of cutoff # of determinations Results 0 -100 80 80 Neg / 0 Pos 75 -75 80 80 Neg / 0 Pos 150 -50 80 80 Neg / 0 Pos 225 -25 80 80 Neg / 0 Pos 300 Cutoff 80 54 Neg / 26 Pos 375 +25 80 80 Pos / 0 Neg 450 +50 80 80 Pos / 0 Neg 525 +75 80 80 Pos / 0 Neg 600 +100 80 80 Pos / 0 Neg b. Linearity/assay reportable range: Recovery studies were conducted in accordance with CLSI EP 6-A in the semi- quantitative mode using spiked drug-free urine sample pools with known concentrations of benzoylecgonine to generate eleven (11) dilutions to achieve concentrations ranging from 50 ng/mL to 1000 ng/mL. Each concentration was tested in five replicates and Measurand:

idK170293_s0_e2000

K170293.txt

type of test

Qualitative and semi-quantative homogenous enzyme immunoassay

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: k170293 B. Purpose for Submission: Adding a previously cleared test (Emit II Plus Cocaine Metabolite Assay) to the Beckman Coulter DxC 700 AU Clinical Chemistry Analyzer C. Measurand: Benzoylecgonine D. Type of Test: Qualitative and semi-quantative homogenous enzyme immunoassay E. Applicant: Siemens Healthcare Diagnostics, Inc. F. Proprietary and Established Names: Emit II Plus Cocaine Metabolite Assay G. Regulatory Information: Product Code Classification Regulation Section Panel DIO – Cocaine and cocaine metabolic test system Class II 21 CFR 862.3250 91 - Toxicology H. Intended Use: 1. Intended use(s): See indication(s) for use below. 2 2. Indication(s) for use: The Emit II Plus Cocaine Metabolite Assay is a homogeneous enzyme immunoassay with a 150 ng/mL or 300 ng/mL cutoff. The assay is intended for use in the qualitative and semiquantitative analyses of benzoylecgonine (cocaine metabolite) in human urine. Emit II Plus assays are designed for use with a number of chemistry analyzers. The Emit II Plus Cocaine Metabolite Assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used to obtain a confirmed analytical result. Gas chromatography/mass spectrometry (GC/MS) is the preferred confirmatory method. Other chemical confirmation methods are available. Clinical consideration and professional judgment should be applied to any drug-of-abuse test result, particularly when preliminary positive results are used. 3. Special conditions for use statement(s): For Prescription use only. 4. Special instrument requirements: Performance data was obtained using Beckman Coulter DxC 700 AU Clinical Chemistry Analyzer I. Device Description: The Emit II Plus Cocaine Metabolite Assay consists of two ready-to-use reagents: Antibody/Substrate Reagent 1 consists of sheep polyclonal antibodies to benzoylecgonine (2.2 μg/mL), bovine serum albumin, G6P (15 mM), NAD (12 mM), preservatives, and stabilizers. Enzyme Reagent 2 consists of Benzoylecgonine labeled with bacterial G6PDH (0.46 U/mL), HEPES buffer, bovine serum albumin, preservatives, and stabilizers. Materials that are required but thar are sold separately include the following: · Emit Calibrators/Controls with concentrations of (0, 150, 300, 500 and 1000 ng/mL). · Commercial controls two levels with concentrations of (0 and 1000 ng/mL) J. Substantial Equivalence Information: 1. Predicate device name(s): Emit II Plus Cocaine Metabolite Assay 3 2. Predicate 510(k) number(s): k993988 3. Comparison with predicate: Similarities Item Emit II Plus Cocaine Metabolite Assay (Candidate) Emit II Plus Cocaine Metabolite Assay Predicate k993988 Intended Use Same For the qualitative and semiquantitative determination of the presence of benzoylecgonine in human urine Measurant Same Benzoylecgonine Type of Test Same Qualitative and semi-quantitative homogeneous enzyme immunoassay Antibody Same Sheep polyclonal Reagent Form Same Liquid, ready to use Reagent Composition Same Antibody/Substrate Reagent 1 Sheep polyclonal antibodies to benzoylecgonine (2.2 μg/mL), bovine serum albumin, G6P (15 mM), NAD (12 mM), preservatives, and stabilizers Enzyme Reagent 2 Benzoylecgonine labeled with bacterial G6PDH (0.46 U/mL), HEPES buffer, bovine serum albumin, preservatives, and stabilizers Cutoff/controls Same 150ng/mL (±25%) 300 ng/mL (±25%) Sample Matrix Same Human Urine Difference Item Emit II Plus Cocaine Metabolite Assay Candidate Emit II Plus Cocaine Metabolite Assay k993988 Predicate Instrument Beckman Coulter DxC 700 AU Clinical Chemistry Analyzer SYVA 30R Biochemical System 4 K. Standard/Guidance Document Referenced (if applicable): · CLSI EP05-A3, Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline – Third Edition · CLSI EP06-A, Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline · CLSI EP07-A2, Interference Testing in Clinical Chemistry; Approved Guideline – Second Edition · CLSI EP09-A3, Measurement Procedure Comparison and Bias Estimation Using Patient Samples; Approved Guideline – Third Edition · CLSI EP12-A2, User Protocol for Evaluation of Qualitative Test Performance; Approved Guideline – Second Edition · CLSI EP25-A Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline L. Test Principle: The Emit II Plus Cocaine Metabolite Assayis is based on competition between free drug in the specimen and drug labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH), for antibody binding sites. G6PDH enzyme activity decreases upon binding to the antibody, so the drug concentration in the specimen is proportional to G6PDH activity. The G6PDH enzyme converts nicotinamide adenine dinucleotide (NAD) to NADH, which can be measured as an absorbance change spectrophotometrically at 340 nm. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Precision studies were conducted in accordance with CLSI EP05-A3. Testing was performed for twenty (20) days with two (2) runs per day, two (2) replicates per run for a total of n = 80 sample replicates per test concentration. Nine (9) drug-free negative urine samples were spiked with benzolecogonine to concentrations of ±25%, ±50% , ±75% , and ±100 of each cutoff, as well as a zero drug concentration sample. The results are provided below, as determined in qualitative and semi-quantitative modes using each of the 150 ng/mL and 300 ng/mL cutoffs: 5 Qualitative Analysis (for 150 ng/mL cutoff) Concentration (ng/mL) % of cutoff # of determinations Results 0 -100% 80 80 Neg / 0 Pos 38 -75% 80 80 Neg / 0 Pos 75 -50% 80 80 Neg / 0 Pos 113 -25% 80 80 Neg / 0 Pos 150 Cutoff 80 9 Neg / 71 Pos 188 +25% 80 80 Pos / 0 Neg 225 +50% 80 80 Pos / 0 Neg 263 +75% 80 80 Pos / 0 Neg 300 +100% 80 80 Pos / 0 Neg Semi-Quantitative Analysis (for 150 ng/mL cutoff) Concentration (ng/mL) % of cutoff # of determinations Results 0 -100% 80 80 Neg / 0 Pos 38 -75% 80 80 Neg / 0 Pos 75 -50% 80 80 Neg / 0 Pos 113 -25% 80 80 Neg / 0 Pos 150 Cutoff 80 9 Neg / 71 Pos 188 +25% 80 80 Pos / 0 Neg 225 +50% 80 80 Pos / 0 Neg 263 +75% 80 80 Pos / 0 Neg 300 +100% 80 80 Pos / 0 Neg Qualitative Analysis (for 300 ng/mL cutoff) Concentration (ng/mL) % of cutoff # of determinations Results 0 -100 80 80 Neg / 0 Pos 75 -75 80 80 Neg / 0 Pos 150 -50 80 80 Neg / 0 Pos 225 -25 80 80 Neg / 0 Pos 300 Cutoff 80 54 Neg / 26 Pos 375 +25 80 80 Pos / 0 Neg 450 +50 80 80 Pos / 0 Neg 525 +75 80 80 Pos / 0 Neg 600 +100 80 80 Pos / 0 Neg 6 Semi-Quantitative Analysis (for 300ng/mL cutoff) Concentration (ng/mL) % of cutoff # of determinations Results 0 -100 80 80 Neg / 0 Pos 75 -75 80 80 Neg / 0 Pos 150 -50 80 80 Neg / 0 Pos 225 -25 80 80 Neg / 0 Pos 300 Cutoff 80 54 Neg / 26 Pos 375 +25 80 80 Pos / 0 Neg 450 +50 80 80 Pos / 0 Neg 525 +75 80 80 Pos / 0 Neg 600 +100 80 80 Pos / 0 Neg b. Linearity/assay reportable range: Recovery studies were conducted in accordance with CLSI EP 6-A in the semi- quantitative mode using spiked drug-free urine sample pools with known concentrations of benzoylecgonine to generate eleven (11) dilutions to achieve concentrations ranging from 50 ng/mL to 1000 ng/mL. Each concentration was tested in five replicates and Type of test:

idK170293_s0_e2000

K170293.txt

classification

Class II

k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: k170293 B. Purpose for Submission: Adding a previously cleared test (Emit II Plus Cocaine Metabolite Assay) to the Beckman Coulter DxC 700 AU Clinical Chemistry Analyzer C. Measurand: Benzoylecgonine D. Type of Test: Qualitative and semi-quantative homogenous enzyme immunoassay E. Applicant: Siemens Healthcare Diagnostics, Inc. F. Proprietary and Established Names: Emit II Plus Cocaine Metabolite Assay G. Regulatory Information: Product Code Classification Regulation Section Panel DIO – Cocaine and cocaine metabolic test system Class II 21 CFR 862.3250 91 - Toxicology H. Intended Use: 1. Intended use(s): See indication(s) for use below. 2 2. Indication(s) for use: The Emit II Plus Cocaine Metabolite Assay is a homogeneous enzyme immunoassay with a 150 ng/mL or 300 ng/mL cutoff. The assay is intended for use in the qualitative and semiquantitative analyses of benzoylecgonine (cocaine metabolite) in human urine. Emit II Plus assays are designed for use with a number of chemistry analyzers. The Emit II Plus Cocaine Metabolite Assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used to obtain a confirmed analytical result. Gas chromatography/mass spectrometry (GC/MS) is the preferred confirmatory method. Other chemical confirmation methods are available. Clinical consideration and professional judgment should be applied to any drug-of-abuse test result, particularly when preliminary positive results are used. 3. Special conditions for use statement(s): For Prescription use only. 4. Special instrument requirements: Performance data was obtained using Beckman Coulter DxC 700 AU Clinical Chemistry Analyzer I. Device Description: The Emit II Plus Cocaine Metabolite Assay consists of two ready-to-use reagents: Antibody/Substrate Reagent 1 consists of sheep polyclonal antibodies to benzoylecgonine (2.2 μg/mL), bovine serum albumin, G6P (15 mM), NAD (12 mM), preservatives, and stabilizers. Enzyme Reagent 2 consists of Benzoylecgonine labeled with bacterial G6PDH (0.46 U/mL), HEPES buffer, bovine serum albumin, preservatives, and stabilizers. Materials that are required but thar are sold separately include the following: · Emit Calibrators/Controls with concentrations of (0, 150, 300, 500 and 1000 ng/mL). · Commercial controls two levels with concentrations of (0 and 1000 ng/mL) J. Substantial Equivalence Information: 1. Predicate device name(s): Emit II Plus Cocaine Metabolite Assay 3 2. Predicate 510(k) number(s): k993988 3. Comparison with predicate: Similarities Item Emit II Plus Cocaine Metabolite Assay (Candidate) Emit II Plus Cocaine Metabolite Assay Predicate k993988 Intended Use Same For the qualitative and semiquantitative determination of the presence of benzoylecgonine in human urine Measurant Same Benzoylecgonine Type of Test Same Qualitative and semi-quantitative homogeneous enzyme immunoassay Antibody Same Sheep polyclonal Reagent Form Same Liquid, ready to use Reagent Composition Same Antibody/Substrate Reagent 1 Sheep polyclonal antibodies to benzoylecgonine (2.2 μg/mL), bovine serum albumin, G6P (15 mM), NAD (12 mM), preservatives, and stabilizers Enzyme Reagent 2 Benzoylecgonine labeled with bacterial G6PDH (0.46 U/mL), HEPES buffer, bovine serum albumin, preservatives, and stabilizers Cutoff/controls Same 150ng/mL (±25%) 300 ng/mL (±25%) Sample Matrix Same Human Urine Difference Item Emit II Plus Cocaine Metabolite Assay Candidate Emit II Plus Cocaine Metabolite Assay k993988 Predicate Instrument Beckman Coulter DxC 700 AU Clinical Chemistry Analyzer SYVA 30R Biochemical System 4 K. Standard/Guidance Document Referenced (if applicable): · CLSI EP05-A3, Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline – Third Edition · CLSI EP06-A, Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline · CLSI EP07-A2, Interference Testing in Clinical Chemistry; Approved Guideline – Second Edition · CLSI EP09-A3, Measurement Procedure Comparison and Bias Estimation Using Patient Samples; Approved Guideline – Third Edition · CLSI EP12-A2, User Protocol for Evaluation of Qualitative Test Performance; Approved Guideline – Second Edition · CLSI EP25-A Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline L. Test Principle: The Emit II Plus Cocaine Metabolite Assayis is based on competition between free drug in the specimen and drug labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH), for antibody binding sites. G6PDH enzyme activity decreases upon binding to the antibody, so the drug concentration in the specimen is proportional to G6PDH activity. The G6PDH enzyme converts nicotinamide adenine dinucleotide (NAD) to NADH, which can be measured as an absorbance change spectrophotometrically at 340 nm. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Precision studies were conducted in accordance with CLSI EP05-A3. Testing was performed for twenty (20) days with two (2) runs per day, two (2) replicates per run for a total of n = 80 sample replicates per test concentration. Nine (9) drug-free negative urine samples were spiked with benzolecogonine to concentrations of ±25%, ±50% , ±75% , and ±100 of each cutoff, as well as a zero drug concentration sample. The results are provided below, as determined in qualitative and semi-quantitative modes using each of the 150 ng/mL and 300 ng/mL cutoffs: 5 Qualitative Analysis (for 150 ng/mL cutoff) Concentration (ng/mL) % of cutoff # of determinations Results 0 -100% 80 80 Neg / 0 Pos 38 -75% 80 80 Neg / 0 Pos 75 -50% 80 80 Neg / 0 Pos 113 -25% 80 80 Neg / 0 Pos 150 Cutoff 80 9 Neg / 71 Pos 188 +25% 80 80 Pos / 0 Neg 225 +50% 80 80 Pos / 0 Neg 263 +75% 80 80 Pos / 0 Neg 300 +100% 80 80 Pos / 0 Neg Semi-Quantitative Analysis (for 150 ng/mL cutoff) Concentration (ng/mL) % of cutoff # of determinations Results 0 -100% 80 80 Neg / 0 Pos 38 -75% 80 80 Neg / 0 Pos 75 -50% 80 80 Neg / 0 Pos 113 -25% 80 80 Neg / 0 Pos 150 Cutoff 80 9 Neg / 71 Pos 188 +25% 80 80 Pos / 0 Neg 225 +50% 80 80 Pos / 0 Neg 263 +75% 80 80 Pos / 0 Neg 300 +100% 80 80 Pos / 0 Neg Qualitative Analysis (for 300 ng/mL cutoff) Concentration (ng/mL) % of cutoff # of determinations Results 0 -100 80 80 Neg / 0 Pos 75 -75 80 80 Neg / 0 Pos 150 -50 80 80 Neg / 0 Pos 225 -25 80 80 Neg / 0 Pos 300 Cutoff 80 54 Neg / 26 Pos 375 +25 80 80 Pos / 0 Neg 450 +50 80 80 Pos / 0 Neg 525 +75 80 80 Pos / 0 Neg 600 +100 80 80 Pos / 0 Neg 6 Semi-Quantitative Analysis (for 300ng/mL cutoff) Concentration (ng/mL) % of cutoff # of determinations Results 0 -100 80 80 Neg / 0 Pos 75 -75 80 80 Neg / 0 Pos 150 -50 80 80 Neg / 0 Pos 225 -25 80 80 Neg / 0 Pos 300 Cutoff 80 54 Neg / 26 Pos 375 +25 80 80 Pos / 0 Neg 450 +50 80 80 Pos / 0 Neg 525 +75 80 80 Pos / 0 Neg 600 +100 80 80 Pos / 0 Neg b. Linearity/assay reportable range: Recovery studies were conducted in accordance with CLSI EP 6-A in the semi- quantitative mode using spiked drug-free urine sample pools with known concentrations of benzoylecgonine to generate eleven (11) dilutions to achieve concentrations ranging from 50 ng/mL to 1000 ng/mL. Each concentration was tested in five replicates and Classification:

idK170293_s0_e2000

K170293.txt

product code

DIO – Cocaine and cocaine

k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: k170293 B. Purpose for Submission: Adding a previously cleared test (Emit II Plus Cocaine Metabolite Assay) to the Beckman Coulter DxC 700 AU Clinical Chemistry Analyzer C. Measurand: Benzoylecgonine D. Type of Test: Qualitative and semi-quantative homogenous enzyme immunoassay E. Applicant: Siemens Healthcare Diagnostics, Inc. F. Proprietary and Established Names: Emit II Plus Cocaine Metabolite Assay G. Regulatory Information: Product Code Classification Regulation Section Panel DIO – Cocaine and cocaine metabolic test system Class II 21 CFR 862.3250 91 - Toxicology H. Intended Use: 1. Intended use(s): See indication(s) for use below. 2 2. Indication(s) for use: The Emit II Plus Cocaine Metabolite Assay is a homogeneous enzyme immunoassay with a 150 ng/mL or 300 ng/mL cutoff. The assay is intended for use in the qualitative and semiquantitative analyses of benzoylecgonine (cocaine metabolite) in human urine. Emit II Plus assays are designed for use with a number of chemistry analyzers. The Emit II Plus Cocaine Metabolite Assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used to obtain a confirmed analytical result. Gas chromatography/mass spectrometry (GC/MS) is the preferred confirmatory method. Other chemical confirmation methods are available. Clinical consideration and professional judgment should be applied to any drug-of-abuse test result, particularly when preliminary positive results are used. 3. Special conditions for use statement(s): For Prescription use only. 4. Special instrument requirements: Performance data was obtained using Beckman Coulter DxC 700 AU Clinical Chemistry Analyzer I. Device Description: The Emit II Plus Cocaine Metabolite Assay consists of two ready-to-use reagents: Antibody/Substrate Reagent 1 consists of sheep polyclonal antibodies to benzoylecgonine (2.2 μg/mL), bovine serum albumin, G6P (15 mM), NAD (12 mM), preservatives, and stabilizers. Enzyme Reagent 2 consists of Benzoylecgonine labeled with bacterial G6PDH (0.46 U/mL), HEPES buffer, bovine serum albumin, preservatives, and stabilizers. Materials that are required but thar are sold separately include the following: · Emit Calibrators/Controls with concentrations of (0, 150, 300, 500 and 1000 ng/mL). · Commercial controls two levels with concentrations of (0 and 1000 ng/mL) J. Substantial Equivalence Information: 1. Predicate device name(s): Emit II Plus Cocaine Metabolite Assay 3 2. Predicate 510(k) number(s): k993988 3. Comparison with predicate: Similarities Item Emit II Plus Cocaine Metabolite Assay (Candidate) Emit II Plus Cocaine Metabolite Assay Predicate k993988 Intended Use Same For the qualitative and semiquantitative determination of the presence of benzoylecgonine in human urine Measurant Same Benzoylecgonine Type of Test Same Qualitative and semi-quantitative homogeneous enzyme immunoassay Antibody Same Sheep polyclonal Reagent Form Same Liquid, ready to use Reagent Composition Same Antibody/Substrate Reagent 1 Sheep polyclonal antibodies to benzoylecgonine (2.2 μg/mL), bovine serum albumin, G6P (15 mM), NAD (12 mM), preservatives, and stabilizers Enzyme Reagent 2 Benzoylecgonine labeled with bacterial G6PDH (0.46 U/mL), HEPES buffer, bovine serum albumin, preservatives, and stabilizers Cutoff/controls Same 150ng/mL (±25%) 300 ng/mL (±25%) Sample Matrix Same Human Urine Difference Item Emit II Plus Cocaine Metabolite Assay Candidate Emit II Plus Cocaine Metabolite Assay k993988 Predicate Instrument Beckman Coulter DxC 700 AU Clinical Chemistry Analyzer SYVA 30R Biochemical System 4 K. Standard/Guidance Document Referenced (if applicable): · CLSI EP05-A3, Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline – Third Edition · CLSI EP06-A, Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline · CLSI EP07-A2, Interference Testing in Clinical Chemistry; Approved Guideline – Second Edition · CLSI EP09-A3, Measurement Procedure Comparison and Bias Estimation Using Patient Samples; Approved Guideline – Third Edition · CLSI EP12-A2, User Protocol for Evaluation of Qualitative Test Performance; Approved Guideline – Second Edition · CLSI EP25-A Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline L. Test Principle: The Emit II Plus Cocaine Metabolite Assayis is based on competition between free drug in the specimen and drug labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH), for antibody binding sites. G6PDH enzyme activity decreases upon binding to the antibody, so the drug concentration in the specimen is proportional to G6PDH activity. The G6PDH enzyme converts nicotinamide adenine dinucleotide (NAD) to NADH, which can be measured as an absorbance change spectrophotometrically at 340 nm. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Precision studies were conducted in accordance with CLSI EP05-A3. Testing was performed for twenty (20) days with two (2) runs per day, two (2) replicates per run for a total of n = 80 sample replicates per test concentration. Nine (9) drug-free negative urine samples were spiked with benzolecogonine to concentrations of ±25%, ±50% , ±75% , and ±100 of each cutoff, as well as a zero drug concentration sample. The results are provided below, as determined in qualitative and semi-quantitative modes using each of the 150 ng/mL and 300 ng/mL cutoffs: 5 Qualitative Analysis (for 150 ng/mL cutoff) Concentration (ng/mL) % of cutoff # of determinations Results 0 -100% 80 80 Neg / 0 Pos 38 -75% 80 80 Neg / 0 Pos 75 -50% 80 80 Neg / 0 Pos 113 -25% 80 80 Neg / 0 Pos 150 Cutoff 80 9 Neg / 71 Pos 188 +25% 80 80 Pos / 0 Neg 225 +50% 80 80 Pos / 0 Neg 263 +75% 80 80 Pos / 0 Neg 300 +100% 80 80 Pos / 0 Neg Semi-Quantitative Analysis (for 150 ng/mL cutoff) Concentration (ng/mL) % of cutoff # of determinations Results 0 -100% 80 80 Neg / 0 Pos 38 -75% 80 80 Neg / 0 Pos 75 -50% 80 80 Neg / 0 Pos 113 -25% 80 80 Neg / 0 Pos 150 Cutoff 80 9 Neg / 71 Pos 188 +25% 80 80 Pos / 0 Neg 225 +50% 80 80 Pos / 0 Neg 263 +75% 80 80 Pos / 0 Neg 300 +100% 80 80 Pos / 0 Neg Qualitative Analysis (for 300 ng/mL cutoff) Concentration (ng/mL) % of cutoff # of determinations Results 0 -100 80 80 Neg / 0 Pos 75 -75 80 80 Neg / 0 Pos 150 -50 80 80 Neg / 0 Pos 225 -25 80 80 Neg / 0 Pos 300 Cutoff 80 54 Neg / 26 Pos 375 +25 80 80 Pos / 0 Neg 450 +50 80 80 Pos / 0 Neg 525 +75 80 80 Pos / 0 Neg 600 +100 80 80 Pos / 0 Neg 6 Semi-Quantitative Analysis (for 300ng/mL cutoff) Concentration (ng/mL) % of cutoff # of determinations Results 0 -100 80 80 Neg / 0 Pos 75 -75 80 80 Neg / 0 Pos 150 -50 80 80 Neg / 0 Pos 225 -25 80 80 Neg / 0 Pos 300 Cutoff 80 54 Neg / 26 Pos 375 +25 80 80 Pos / 0 Neg 450 +50 80 80 Pos / 0 Neg 525 +75 80 80 Pos / 0 Neg 600 +100 80 80 Pos / 0 Neg b. Linearity/assay reportable range: Recovery studies were conducted in accordance with CLSI EP 6-A in the semi- quantitative mode using spiked drug-free urine sample pools with known concentrations of benzoylecgonine to generate eleven (11) dilutions to achieve concentrations ranging from 50 ng/mL to 1000 ng/mL. Each concentration was tested in five replicates and Product code:

idK170293_s0_e2000

K170293.txt

panel

91 - Toxicology

(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: k170293 B. Purpose for Submission: Adding a previously cleared test (Emit II Plus Cocaine Metabolite Assay) to the Beckman Coulter DxC 700 AU Clinical Chemistry Analyzer C. Measurand: Benzoylecgonine D. Type of Test: Qualitative and semi-quantative homogenous enzyme immunoassay E. Applicant: Siemens Healthcare Diagnostics, Inc. F. Proprietary and Established Names: Emit II Plus Cocaine Metabolite Assay G. Regulatory Information: Product Code Classification Regulation Section Panel DIO – Cocaine and cocaine metabolic test system Class II 21 CFR 862.3250 91 - Toxicology H. Intended Use: 1. Intended use(s): See indication(s) for use below. 2 2. Indication(s) for use: The Emit II Plus Cocaine Metabolite Assay is a homogeneous enzyme immunoassay with a 150 ng/mL or 300 ng/mL cutoff. The assay is intended for use in the qualitative and semiquantitative analyses of benzoylecgonine (cocaine metabolite) in human urine. Emit II Plus assays are designed for use with a number of chemistry analyzers. The Emit II Plus Cocaine Metabolite Assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used to obtain a confirmed analytical result. Gas chromatography/mass spectrometry (GC/MS) is the preferred confirmatory method. Other chemical confirmation methods are available. Clinical consideration and professional judgment should be applied to any drug-of-abuse test result, particularly when preliminary positive results are used. 3. Special conditions for use statement(s): For Prescription use only. 4. Special instrument requirements: Performance data was obtained using Beckman Coulter DxC 700 AU Clinical Chemistry Analyzer I. Device Description: The Emit II Plus Cocaine Metabolite Assay consists of two ready-to-use reagents: Antibody/Substrate Reagent 1 consists of sheep polyclonal antibodies to benzoylecgonine (2.2 μg/mL), bovine serum albumin, G6P (15 mM), NAD (12 mM), preservatives, and stabilizers. Enzyme Reagent 2 consists of Benzoylecgonine labeled with bacterial G6PDH (0.46 U/mL), HEPES buffer, bovine serum albumin, preservatives, and stabilizers. Materials that are required but thar are sold separately include the following: · Emit Calibrators/Controls with concentrations of (0, 150, 300, 500 and 1000 ng/mL). · Commercial controls two levels with concentrations of (0 and 1000 ng/mL) J. Substantial Equivalence Information: 1. Predicate device name(s): Emit II Plus Cocaine Metabolite Assay 3 2. Predicate 510(k) number(s): k993988 3. Comparison with predicate: Similarities Item Emit II Plus Cocaine Metabolite Assay (Candidate) Emit II Plus Cocaine Metabolite Assay Predicate k993988 Intended Use Same For the qualitative and semiquantitative determination of the presence of benzoylecgonine in human urine Measurant Same Benzoylecgonine Type of Test Same Qualitative and semi-quantitative homogeneous enzyme immunoassay Antibody Same Sheep polyclonal Reagent Form Same Liquid, ready to use Reagent Composition Same Antibody/Substrate Reagent 1 Sheep polyclonal antibodies to benzoylecgonine (2.2 μg/mL), bovine serum albumin, G6P (15 mM), NAD (12 mM), preservatives, and stabilizers Enzyme Reagent 2 Benzoylecgonine labeled with bacterial G6PDH (0.46 U/mL), HEPES buffer, bovine serum albumin, preservatives, and stabilizers Cutoff/controls Same 150ng/mL (±25%) 300 ng/mL (±25%) Sample Matrix Same Human Urine Difference Item Emit II Plus Cocaine Metabolite Assay Candidate Emit II Plus Cocaine Metabolite Assay k993988 Predicate Instrument Beckman Coulter DxC 700 AU Clinical Chemistry Analyzer SYVA 30R Biochemical System 4 K. Standard/Guidance Document Referenced (if applicable): · CLSI EP05-A3, Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline – Third Edition · CLSI EP06-A, Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline · CLSI EP07-A2, Interference Testing in Clinical Chemistry; Approved Guideline – Second Edition · CLSI EP09-A3, Measurement Procedure Comparison and Bias Estimation Using Patient Samples; Approved Guideline – Third Edition · CLSI EP12-A2, User Protocol for Evaluation of Qualitative Test Performance; Approved Guideline – Second Edition · CLSI EP25-A Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline L. Test Principle: The Emit II Plus Cocaine Metabolite Assayis is based on competition between free drug in the specimen and drug labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH), for antibody binding sites. G6PDH enzyme activity decreases upon binding to the antibody, so the drug concentration in the specimen is proportional to G6PDH activity. The G6PDH enzyme converts nicotinamide adenine dinucleotide (NAD) to NADH, which can be measured as an absorbance change spectrophotometrically at 340 nm. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Precision studies were conducted in accordance with CLSI EP05-A3. Testing was performed for twenty (20) days with two (2) runs per day, two (2) replicates per run for a total of n = 80 sample replicates per test concentration. Nine (9) drug-free negative urine samples were spiked with benzolecogonine to concentrations of ±25%, ±50% , ±75% , and ±100 of each cutoff, as well as a zero drug concentration sample. The results are provided below, as determined in qualitative and semi-quantitative modes using each of the 150 ng/mL and 300 ng/mL cutoffs: 5 Qualitative Analysis (for 150 ng/mL cutoff) Concentration (ng/mL) % of cutoff # of determinations Results 0 -100% 80 80 Neg / 0 Pos 38 -75% 80 80 Neg / 0 Pos 75 -50% 80 80 Neg / 0 Pos 113 -25% 80 80 Neg / 0 Pos 150 Cutoff 80 9 Neg / 71 Pos 188 +25% 80 80 Pos / 0 Neg 225 +50% 80 80 Pos / 0 Neg 263 +75% 80 80 Pos / 0 Neg 300 +100% 80 80 Pos / 0 Neg Semi-Quantitative Analysis (for 150 ng/mL cutoff) Concentration (ng/mL) % of cutoff # of determinations Results 0 -100% 80 80 Neg / 0 Pos 38 -75% 80 80 Neg / 0 Pos 75 -50% 80 80 Neg / 0 Pos 113 -25% 80 80 Neg / 0 Pos 150 Cutoff 80 9 Neg / 71 Pos 188 +25% 80 80 Pos / 0 Neg 225 +50% 80 80 Pos / 0 Neg 263 +75% 80 80 Pos / 0 Neg 300 +100% 80 80 Pos / 0 Neg Qualitative Analysis (for 300 ng/mL cutoff) Concentration (ng/mL) % of cutoff # of determinations Results 0 -100 80 80 Neg / 0 Pos 75 -75 80 80 Neg / 0 Pos 150 -50 80 80 Neg / 0 Pos 225 -25 80 80 Neg / 0 Pos 300 Cutoff 80 54 Neg / 26 Pos 375 +25 80 80 Pos / 0 Neg 450 +50 80 80 Pos / 0 Neg 525 +75 80 80 Pos / 0 Neg 600 +100 80 80 Pos / 0 Neg 6 Semi-Quantitative Analysis (for 300ng/mL cutoff) Concentration (ng/mL) % of cutoff # of determinations Results 0 -100 80 80 Neg / 0 Pos 75 -75 80 80 Neg / 0 Pos 150 -50 80 80 Neg / 0 Pos 225 -25 80 80 Neg / 0 Pos 300 Cutoff 80 54 Neg / 26 Pos 375 +25 80 80 Pos / 0 Neg 450 +50 80 80 Pos / 0 Neg 525 +75 80 80 Pos / 0 Neg 600 +100 80 80 Pos / 0 Neg b. Linearity/assay reportable range: Recovery studies were conducted in accordance with CLSI EP 6-A in the semi- quantitative mode using spiked drug-free urine sample pools with known concentrations of benzoylecgonine to generate eleven (11) dilutions to achieve concentrations ranging from 50 ng/mL to 1000 ng/mL. Each concentration was tested in five replicates and Panel:

idK170293_s0_e2000

K170293.txt

intended use

See indication(s) for use below.

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: k170293 B. Purpose for Submission: Adding a previously cleared test (Emit II Plus Cocaine Metabolite Assay) to the Beckman Coulter DxC 700 AU Clinical Chemistry Analyzer C. Measurand: Benzoylecgonine D. Type of Test: Qualitative and semi-quantative homogenous enzyme immunoassay E. Applicant: Siemens Healthcare Diagnostics, Inc. F. Proprietary and Established Names: Emit II Plus Cocaine Metabolite Assay G. Regulatory Information: Product Code Classification Regulation Section Panel DIO – Cocaine and cocaine metabolic test system Class II 21 CFR 862.3250 91 - Toxicology H. Intended Use: 1. Intended use(s): See indication(s) for use below. 2 2. Indication(s) for use: The Emit II Plus Cocaine Metabolite Assay is a homogeneous enzyme immunoassay with a 150 ng/mL or 300 ng/mL cutoff. The assay is intended for use in the qualitative and semiquantitative analyses of benzoylecgonine (cocaine metabolite) in human urine. Emit II Plus assays are designed for use with a number of chemistry analyzers. The Emit II Plus Cocaine Metabolite Assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used to obtain a confirmed analytical result. Gas chromatography/mass spectrometry (GC/MS) is the preferred confirmatory method. Other chemical confirmation methods are available. Clinical consideration and professional judgment should be applied to any drug-of-abuse test result, particularly when preliminary positive results are used. 3. Special conditions for use statement(s): For Prescription use only. 4. Special instrument requirements: Performance data was obtained using Beckman Coulter DxC 700 AU Clinical Chemistry Analyzer I. Device Description: The Emit II Plus Cocaine Metabolite Assay consists of two ready-to-use reagents: Antibody/Substrate Reagent 1 consists of sheep polyclonal antibodies to benzoylecgonine (2.2 μg/mL), bovine serum albumin, G6P (15 mM), NAD (12 mM), preservatives, and stabilizers. Enzyme Reagent 2 consists of Benzoylecgonine labeled with bacterial G6PDH (0.46 U/mL), HEPES buffer, bovine serum albumin, preservatives, and stabilizers. Materials that are required but thar are sold separately include the following: · Emit Calibrators/Controls with concentrations of (0, 150, 300, 500 and 1000 ng/mL). · Commercial controls two levels with concentrations of (0 and 1000 ng/mL) J. Substantial Equivalence Information: 1. Predicate device name(s): Emit II Plus Cocaine Metabolite Assay 3 2. Predicate 510(k) number(s): k993988 3. Comparison with predicate: Similarities Item Emit II Plus Cocaine Metabolite Assay (Candidate) Emit II Plus Cocaine Metabolite Assay Predicate k993988 Intended Use Same For the qualitative and semiquantitative determination of the presence of benzoylecgonine in human urine Measurant Same Benzoylecgonine Type of Test Same Qualitative and semi-quantitative homogeneous enzyme immunoassay Antibody Same Sheep polyclonal Reagent Form Same Liquid, ready to use Reagent Composition Same Antibody/Substrate Reagent 1 Sheep polyclonal antibodies to benzoylecgonine (2.2 μg/mL), bovine serum albumin, G6P (15 mM), NAD (12 mM), preservatives, and stabilizers Enzyme Reagent 2 Benzoylecgonine labeled with bacterial G6PDH (0.46 U/mL), HEPES buffer, bovine serum albumin, preservatives, and stabilizers Cutoff/controls Same 150ng/mL (±25%) 300 ng/mL (±25%) Sample Matrix Same Human Urine Difference Item Emit II Plus Cocaine Metabolite Assay Candidate Emit II Plus Cocaine Metabolite Assay k993988 Predicate Instrument Beckman Coulter DxC 700 AU Clinical Chemistry Analyzer SYVA 30R Biochemical System 4 K. Standard/Guidance Document Referenced (if applicable): · CLSI EP05-A3, Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline – Third Edition · CLSI EP06-A, Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline · CLSI EP07-A2, Interference Testing in Clinical Chemistry; Approved Guideline – Second Edition · CLSI EP09-A3, Measurement Procedure Comparison and Bias Estimation Using Patient Samples; Approved Guideline – Third Edition · CLSI EP12-A2, User Protocol for Evaluation of Qualitative Test Performance; Approved Guideline – Second Edition · CLSI EP25-A Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline L. Test Principle: The Emit II Plus Cocaine Metabolite Assayis is based on competition between free drug in the specimen and drug labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH), for antibody binding sites. G6PDH enzyme activity decreases upon binding to the antibody, so the drug concentration in the specimen is proportional to G6PDH activity. The G6PDH enzyme converts nicotinamide adenine dinucleotide (NAD) to NADH, which can be measured as an absorbance change spectrophotometrically at 340 nm. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Precision studies were conducted in accordance with CLSI EP05-A3. Testing was performed for twenty (20) days with two (2) runs per day, two (2) replicates per run for a total of n = 80 sample replicates per test concentration. Nine (9) drug-free negative urine samples were spiked with benzolecogonine to concentrations of ±25%, ±50% , ±75% , and ±100 of each cutoff, as well as a zero drug concentration sample. The results are provided below, as determined in qualitative and semi-quantitative modes using each of the 150 ng/mL and 300 ng/mL cutoffs: 5 Qualitative Analysis (for 150 ng/mL cutoff) Concentration (ng/mL) % of cutoff # of determinations Results 0 -100% 80 80 Neg / 0 Pos 38 -75% 80 80 Neg / 0 Pos 75 -50% 80 80 Neg / 0 Pos 113 -25% 80 80 Neg / 0 Pos 150 Cutoff 80 9 Neg / 71 Pos 188 +25% 80 80 Pos / 0 Neg 225 +50% 80 80 Pos / 0 Neg 263 +75% 80 80 Pos / 0 Neg 300 +100% 80 80 Pos / 0 Neg Semi-Quantitative Analysis (for 150 ng/mL cutoff) Concentration (ng/mL) % of cutoff # of determinations Results 0 -100% 80 80 Neg / 0 Pos 38 -75% 80 80 Neg / 0 Pos 75 -50% 80 80 Neg / 0 Pos 113 -25% 80 80 Neg / 0 Pos 150 Cutoff 80 9 Neg / 71 Pos 188 +25% 80 80 Pos / 0 Neg 225 +50% 80 80 Pos / 0 Neg 263 +75% 80 80 Pos / 0 Neg 300 +100% 80 80 Pos / 0 Neg Qualitative Analysis (for 300 ng/mL cutoff) Concentration (ng/mL) % of cutoff # of determinations Results 0 -100 80 80 Neg / 0 Pos 75 -75 80 80 Neg / 0 Pos 150 -50 80 80 Neg / 0 Pos 225 -25 80 80 Neg / 0 Pos 300 Cutoff 80 54 Neg / 26 Pos 375 +25 80 80 Pos / 0 Neg 450 +50 80 80 Pos / 0 Neg 525 +75 80 80 Pos / 0 Neg 600 +100 80 80 Pos / 0 Neg 6 Semi-Quantitative Analysis (for 300ng/mL cutoff) Concentration (ng/mL) % of cutoff # of determinations Results 0 -100 80 80 Neg / 0 Pos 75 -75 80 80 Neg / 0 Pos 150 -50 80 80 Neg / 0 Pos 225 -25 80 80 Neg / 0 Pos 300 Cutoff 80 54 Neg / 26 Pos 375 +25 80 80 Pos / 0 Neg 450 +50 80 80 Pos / 0 Neg 525 +75 80 80 Pos / 0 Neg 600 +100 80 80 Pos / 0 Neg b. Linearity/assay reportable range: Recovery studies were conducted in accordance with CLSI EP 6-A in the semi- quantitative mode using spiked drug-free urine sample pools with known concentrations of benzoylecgonine to generate eleven (11) dilutions to achieve concentrations ranging from 50 ng/mL to 1000 ng/mL. Each concentration was tested in five replicates and Intended use:

idK170293_s0_e2000

K170293.txt

predicate device name

Emit II Plus Cocaine Metabolite Assay

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: k170293 B. Purpose for Submission: Adding a previously cleared test (Emit II Plus Cocaine Metabolite Assay) to the Beckman Coulter DxC 700 AU Clinical Chemistry Analyzer C. Measurand: Benzoylecgonine D. Type of Test: Qualitative and semi-quantative homogenous enzyme immunoassay E. Applicant: Siemens Healthcare Diagnostics, Inc. F. Proprietary and Established Names: Emit II Plus Cocaine Metabolite Assay G. Regulatory Information: Product Code Classification Regulation Section Panel DIO – Cocaine and cocaine metabolic test system Class II 21 CFR 862.3250 91 - Toxicology H. Intended Use: 1. Intended use(s): See indication(s) for use below. 2 2. Indication(s) for use: The Emit II Plus Cocaine Metabolite Assay is a homogeneous enzyme immunoassay with a 150 ng/mL or 300 ng/mL cutoff. The assay is intended for use in the qualitative and semiquantitative analyses of benzoylecgonine (cocaine metabolite) in human urine. Emit II Plus assays are designed for use with a number of chemistry analyzers. The Emit II Plus Cocaine Metabolite Assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used to obtain a confirmed analytical result. Gas chromatography/mass spectrometry (GC/MS) is the preferred confirmatory method. Other chemical confirmation methods are available. Clinical consideration and professional judgment should be applied to any drug-of-abuse test result, particularly when preliminary positive results are used. 3. Special conditions for use statement(s): For Prescription use only. 4. Special instrument requirements: Performance data was obtained using Beckman Coulter DxC 700 AU Clinical Chemistry Analyzer I. Device Description: The Emit II Plus Cocaine Metabolite Assay consists of two ready-to-use reagents: Antibody/Substrate Reagent 1 consists of sheep polyclonal antibodies to benzoylecgonine (2.2 μg/mL), bovine serum albumin, G6P (15 mM), NAD (12 mM), preservatives, and stabilizers. Enzyme Reagent 2 consists of Benzoylecgonine labeled with bacterial G6PDH (0.46 U/mL), HEPES buffer, bovine serum albumin, preservatives, and stabilizers. Materials that are required but thar are sold separately include the following: · Emit Calibrators/Controls with concentrations of (0, 150, 300, 500 and 1000 ng/mL). · Commercial controls two levels with concentrations of (0 and 1000 ng/mL) J. Substantial Equivalence Information: 1. Predicate device name(s): Emit II Plus Cocaine Metabolite Assay 3 2. Predicate 510(k) number(s): k993988 3. Comparison with predicate: Similarities Item Emit II Plus Cocaine Metabolite Assay (Candidate) Emit II Plus Cocaine Metabolite Assay Predicate k993988 Intended Use Same For the qualitative and semiquantitative determination of the presence of benzoylecgonine in human urine Measurant Same Benzoylecgonine Type of Test Same Qualitative and semi-quantitative homogeneous enzyme immunoassay Antibody Same Sheep polyclonal Reagent Form Same Liquid, ready to use Reagent Composition Same Antibody/Substrate Reagent 1 Sheep polyclonal antibodies to benzoylecgonine (2.2 μg/mL), bovine serum albumin, G6P (15 mM), NAD (12 mM), preservatives, and stabilizers Enzyme Reagent 2 Benzoylecgonine labeled with bacterial G6PDH (0.46 U/mL), HEPES buffer, bovine serum albumin, preservatives, and stabilizers Cutoff/controls Same 150ng/mL (±25%) 300 ng/mL (±25%) Sample Matrix Same Human Urine Difference Item Emit II Plus Cocaine Metabolite Assay Candidate Emit II Plus Cocaine Metabolite Assay k993988 Predicate Instrument Beckman Coulter DxC 700 AU Clinical Chemistry Analyzer SYVA 30R Biochemical System 4 K. Standard/Guidance Document Referenced (if applicable): · CLSI EP05-A3, Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline – Third Edition · CLSI EP06-A, Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline · CLSI EP07-A2, Interference Testing in Clinical Chemistry; Approved Guideline – Second Edition · CLSI EP09-A3, Measurement Procedure Comparison and Bias Estimation Using Patient Samples; Approved Guideline – Third Edition · CLSI EP12-A2, User Protocol for Evaluation of Qualitative Test Performance; Approved Guideline – Second Edition · CLSI EP25-A Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline L. Test Principle: The Emit II Plus Cocaine Metabolite Assayis is based on competition between free drug in the specimen and drug labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH), for antibody binding sites. G6PDH enzyme activity decreases upon binding to the antibody, so the drug concentration in the specimen is proportional to G6PDH activity. The G6PDH enzyme converts nicotinamide adenine dinucleotide (NAD) to NADH, which can be measured as an absorbance change spectrophotometrically at 340 nm. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Precision studies were conducted in accordance with CLSI EP05-A3. Testing was performed for twenty (20) days with two (2) runs per day, two (2) replicates per run for a total of n = 80 sample replicates per test concentration. Nine (9) drug-free negative urine samples were spiked with benzolecogonine to concentrations of ±25%, ±50% , ±75% , and ±100 of each cutoff, as well as a zero drug concentration sample. The results are provided below, as determined in qualitative and semi-quantitative modes using each of the 150 ng/mL and 300 ng/mL cutoffs: 5 Qualitative Analysis (for 150 ng/mL cutoff) Concentration (ng/mL) % of cutoff # of determinations Results 0 -100% 80 80 Neg / 0 Pos 38 -75% 80 80 Neg / 0 Pos 75 -50% 80 80 Neg / 0 Pos 113 -25% 80 80 Neg / 0 Pos 150 Cutoff 80 9 Neg / 71 Pos 188 +25% 80 80 Pos / 0 Neg 225 +50% 80 80 Pos / 0 Neg 263 +75% 80 80 Pos / 0 Neg 300 +100% 80 80 Pos / 0 Neg Semi-Quantitative Analysis (for 150 ng/mL cutoff) Concentration (ng/mL) % of cutoff # of determinations Results 0 -100% 80 80 Neg / 0 Pos 38 -75% 80 80 Neg / 0 Pos 75 -50% 80 80 Neg / 0 Pos 113 -25% 80 80 Neg / 0 Pos 150 Cutoff 80 9 Neg / 71 Pos 188 +25% 80 80 Pos / 0 Neg 225 +50% 80 80 Pos / 0 Neg 263 +75% 80 80 Pos / 0 Neg 300 +100% 80 80 Pos / 0 Neg Qualitative Analysis (for 300 ng/mL cutoff) Concentration (ng/mL) % of cutoff # of determinations Results 0 -100 80 80 Neg / 0 Pos 75 -75 80 80 Neg / 0 Pos 150 -50 80 80 Neg / 0 Pos 225 -25 80 80 Neg / 0 Pos 300 Cutoff 80 54 Neg / 26 Pos 375 +25 80 80 Pos / 0 Neg 450 +50 80 80 Pos / 0 Neg 525 +75 80 80 Pos / 0 Neg 600 +100 80 80 Pos / 0 Neg 6 Semi-Quantitative Analysis (for 300ng/mL cutoff) Concentration (ng/mL) % of cutoff # of determinations Results 0 -100 80 80 Neg / 0 Pos 75 -75 80 80 Neg / 0 Pos 150 -50 80 80 Neg / 0 Pos 225 -25 80 80 Neg / 0 Pos 300 Cutoff 80 54 Neg / 26 Pos 375 +25 80 80 Pos / 0 Neg 450 +50 80 80 Pos / 0 Neg 525 +75 80 80 Pos / 0 Neg 600 +100 80 80 Pos / 0 Neg b. Linearity/assay reportable range: Recovery studies were conducted in accordance with CLSI EP 6-A in the semi- quantitative mode using spiked drug-free urine sample pools with known concentrations of benzoylecgonine to generate eleven (11) dilutions to achieve concentrations ranging from 50 ng/mL to 1000 ng/mL. Each concentration was tested in five replicates and Predicate device name:

idK170293_s0_e2000

K170293.txt

applicant

Siemens Healthcare Diagnostics, Inc.

k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: k170293 B. Purpose for Submission: Adding a previously cleared test (Emit II Plus Cocaine Metabolite Assay) to the Beckman Coulter DxC 700 AU Clinical Chemistry Analyzer C. Measurand: Benzoylecgonine D. Type of Test: Qualitative and semi-quantative homogenous enzyme immunoassay E. Applicant: Siemens Healthcare Diagnostics, Inc. F. Proprietary and Established Names: Emit II Plus Cocaine Metabolite Assay G. Regulatory Information: Product Code Classification Regulation Section Panel DIO – Cocaine and cocaine metabolic test system Class II 21 CFR 862.3250 91 - Toxicology H. Intended Use: 1. Intended use(s): See indication(s) for use below. 2 2. Indication(s) for use: The Emit II Plus Cocaine Metabolite Assay is a homogeneous enzyme immunoassay with a 150 ng/mL or 300 ng/mL cutoff. The assay is intended for use in the qualitative and semiquantitative analyses of benzoylecgonine (cocaine metabolite) in human urine. Emit II Plus assays are designed for use with a number of chemistry analyzers. The Emit II Plus Cocaine Metabolite Assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used to obtain a confirmed analytical result. Gas chromatography/mass spectrometry (GC/MS) is the preferred confirmatory method. Other chemical confirmation methods are available. Clinical consideration and professional judgment should be applied to any drug-of-abuse test result, particularly when preliminary positive results are used. 3. Special conditions for use statement(s): For Prescription use only. 4. Special instrument requirements: Performance data was obtained using Beckman Coulter DxC 700 AU Clinical Chemistry Analyzer I. Device Description: The Emit II Plus Cocaine Metabolite Assay consists of two ready-to-use reagents: Antibody/Substrate Reagent 1 consists of sheep polyclonal antibodies to benzoylecgonine (2.2 μg/mL), bovine serum albumin, G6P (15 mM), NAD (12 mM), preservatives, and stabilizers. Enzyme Reagent 2 consists of Benzoylecgonine labeled with bacterial G6PDH (0.46 U/mL), HEPES buffer, bovine serum albumin, preservatives, and stabilizers. Materials that are required but thar are sold separately include the following: · Emit Calibrators/Controls with concentrations of (0, 150, 300, 500 and 1000 ng/mL). · Commercial controls two levels with concentrations of (0 and 1000 ng/mL) J. Substantial Equivalence Information: 1. Predicate device name(s): Emit II Plus Cocaine Metabolite Assay 3 2. Predicate 510(k) number(s): k993988 3. Comparison with predicate: Similarities Item Emit II Plus Cocaine Metabolite Assay (Candidate) Emit II Plus Cocaine Metabolite Assay Predicate k993988 Intended Use Same For the qualitative and semiquantitative determination of the presence of benzoylecgonine in human urine Measurant Same Benzoylecgonine Type of Test Same Qualitative and semi-quantitative homogeneous enzyme immunoassay Antibody Same Sheep polyclonal Reagent Form Same Liquid, ready to use Reagent Composition Same Antibody/Substrate Reagent 1 Sheep polyclonal antibodies to benzoylecgonine (2.2 μg/mL), bovine serum albumin, G6P (15 mM), NAD (12 mM), preservatives, and stabilizers Enzyme Reagent 2 Benzoylecgonine labeled with bacterial G6PDH (0.46 U/mL), HEPES buffer, bovine serum albumin, preservatives, and stabilizers Cutoff/controls Same 150ng/mL (±25%) 300 ng/mL (±25%) Sample Matrix Same Human Urine Difference Item Emit II Plus Cocaine Metabolite Assay Candidate Emit II Plus Cocaine Metabolite Assay k993988 Predicate Instrument Beckman Coulter DxC 700 AU Clinical Chemistry Analyzer SYVA 30R Biochemical System 4 K. Standard/Guidance Document Referenced (if applicable): · CLSI EP05-A3, Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline – Third Edition · CLSI EP06-A, Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline · CLSI EP07-A2, Interference Testing in Clinical Chemistry; Approved Guideline – Second Edition · CLSI EP09-A3, Measurement Procedure Comparison and Bias Estimation Using Patient Samples; Approved Guideline – Third Edition · CLSI EP12-A2, User Protocol for Evaluation of Qualitative Test Performance; Approved Guideline – Second Edition · CLSI EP25-A Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline L. Test Principle: The Emit II Plus Cocaine Metabolite Assayis is based on competition between free drug in the specimen and drug labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH), for antibody binding sites. G6PDH enzyme activity decreases upon binding to the antibody, so the drug concentration in the specimen is proportional to G6PDH activity. The G6PDH enzyme converts nicotinamide adenine dinucleotide (NAD) to NADH, which can be measured as an absorbance change spectrophotometrically at 340 nm. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Precision studies were conducted in accordance with CLSI EP05-A3. Testing was performed for twenty (20) days with two (2) runs per day, two (2) replicates per run for a total of n = 80 sample replicates per test concentration. Nine (9) drug-free negative urine samples were spiked with benzolecogonine to concentrations of ±25%, ±50% , ±75% , and ±100 of each cutoff, as well as a zero drug concentration sample. The results are provided below, as determined in qualitative and semi-quantitative modes using each of the 150 ng/mL and 300 ng/mL cutoffs: 5 Qualitative Analysis (for 150 ng/mL cutoff) Concentration (ng/mL) % of cutoff # of determinations Results 0 -100% 80 80 Neg / 0 Pos 38 -75% 80 80 Neg / 0 Pos 75 -50% 80 80 Neg / 0 Pos 113 -25% 80 80 Neg / 0 Pos 150 Cutoff 80 9 Neg / 71 Pos 188 +25% 80 80 Pos / 0 Neg 225 +50% 80 80 Pos / 0 Neg 263 +75% 80 80 Pos / 0 Neg 300 +100% 80 80 Pos / 0 Neg Semi-Quantitative Analysis (for 150 ng/mL cutoff) Concentration (ng/mL) % of cutoff # of determinations Results 0 -100% 80 80 Neg / 0 Pos 38 -75% 80 80 Neg / 0 Pos 75 -50% 80 80 Neg / 0 Pos 113 -25% 80 80 Neg / 0 Pos 150 Cutoff 80 9 Neg / 71 Pos 188 +25% 80 80 Pos / 0 Neg 225 +50% 80 80 Pos / 0 Neg 263 +75% 80 80 Pos / 0 Neg 300 +100% 80 80 Pos / 0 Neg Qualitative Analysis (for 300 ng/mL cutoff) Concentration (ng/mL) % of cutoff # of determinations Results 0 -100 80 80 Neg / 0 Pos 75 -75 80 80 Neg / 0 Pos 150 -50 80 80 Neg / 0 Pos 225 -25 80 80 Neg / 0 Pos 300 Cutoff 80 54 Neg / 26 Pos 375 +25 80 80 Pos / 0 Neg 450 +50 80 80 Pos / 0 Neg 525 +75 80 80 Pos / 0 Neg 600 +100 80 80 Pos / 0 Neg 6 Semi-Quantitative Analysis (for 300ng/mL cutoff) Concentration (ng/mL) % of cutoff # of determinations Results 0 -100 80 80 Neg / 0 Pos 75 -75 80 80 Neg / 0 Pos 150 -50 80 80 Neg / 0 Pos 225 -25 80 80 Neg / 0 Pos 300 Cutoff 80 54 Neg / 26 Pos 375 +25 80 80 Pos / 0 Neg 450 +50 80 80 Pos / 0 Neg 525 +75 80 80 Pos / 0 Neg 600 +100 80 80 Pos / 0 Neg b. Linearity/assay reportable range: Recovery studies were conducted in accordance with CLSI EP 6-A in the semi- quantitative mode using spiked drug-free urine sample pools with known concentrations of benzoylecgonine to generate eleven (11) dilutions to achieve concentrations ranging from 50 ng/mL to 1000 ng/mL. Each concentration was tested in five replicates and Applicant:

idK170293_s0_e2000

K170293.txt

proprietary and established names

Emit II Plus Cocaine Metabolite Assay

ANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: k170293 B. Purpose for Submission: Adding a previously cleared test (Emit II Plus Cocaine Metabolite Assay) to the Beckman Coulter DxC 700 AU Clinical Chemistry Analyzer C. Measurand: Benzoylecgonine D. Type of Test: Qualitative and semi-quantative homogenous enzyme immunoassay E. Applicant: Siemens Healthcare Diagnostics, Inc. F. Proprietary and Established Names: Emit II Plus Cocaine Metabolite Assay G. Regulatory Information: Product Code Classification Regulation Section Panel DIO – Cocaine and cocaine metabolic test system Class II 21 CFR 862.3250 91 - Toxicology H. Intended Use: 1. Intended use(s): See indication(s) for use below. 2 2. Indication(s) for use: The Emit II Plus Cocaine Metabolite Assay is a homogeneous enzyme immunoassay with a 150 ng/mL or 300 ng/mL cutoff. The assay is intended for use in the qualitative and semiquantitative analyses of benzoylecgonine (cocaine metabolite) in human urine. Emit II Plus assays are designed for use with a number of chemistry analyzers. The Emit II Plus Cocaine Metabolite Assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used to obtain a confirmed analytical result. Gas chromatography/mass spectrometry (GC/MS) is the preferred confirmatory method. Other chemical confirmation methods are available. Clinical consideration and professional judgment should be applied to any drug-of-abuse test result, particularly when preliminary positive results are used. 3. Special conditions for use statement(s): For Prescription use only. 4. Special instrument requirements: Performance data was obtained using Beckman Coulter DxC 700 AU Clinical Chemistry Analyzer I. Device Description: The Emit II Plus Cocaine Metabolite Assay consists of two ready-to-use reagents: Antibody/Substrate Reagent 1 consists of sheep polyclonal antibodies to benzoylecgonine (2.2 μg/mL), bovine serum albumin, G6P (15 mM), NAD (12 mM), preservatives, and stabilizers. Enzyme Reagent 2 consists of Benzoylecgonine labeled with bacterial G6PDH (0.46 U/mL), HEPES buffer, bovine serum albumin, preservatives, and stabilizers. Materials that are required but thar are sold separately include the following: · Emit Calibrators/Controls with concentrations of (0, 150, 300, 500 and 1000 ng/mL). · Commercial controls two levels with concentrations of (0 and 1000 ng/mL) J. Substantial Equivalence Information: 1. Predicate device name(s): Emit II Plus Cocaine Metabolite Assay 3 2. Predicate 510(k) number(s): k993988 3. Comparison with predicate: Similarities Item Emit II Plus Cocaine Metabolite Assay (Candidate) Emit II Plus Cocaine Metabolite Assay Predicate k993988 Intended Use Same For the qualitative and semiquantitative determination of the presence of benzoylecgonine in human urine Measurant Same Benzoylecgonine Type of Test Same Qualitative and semi-quantitative homogeneous enzyme immunoassay Antibody Same Sheep polyclonal Reagent Form Same Liquid, ready to use Reagent Composition Same Antibody/Substrate Reagent 1 Sheep polyclonal antibodies to benzoylecgonine (2.2 μg/mL), bovine serum albumin, G6P (15 mM), NAD (12 mM), preservatives, and stabilizers Enzyme Reagent 2 Benzoylecgonine labeled with bacterial G6PDH (0.46 U/mL), HEPES buffer, bovine serum albumin, preservatives, and stabilizers Cutoff/controls Same 150ng/mL (±25%) 300 ng/mL (±25%) Sample Matrix Same Human Urine Difference Item Emit II Plus Cocaine Metabolite Assay Candidate Emit II Plus Cocaine Metabolite Assay k993988 Predicate Instrument Beckman Coulter DxC 700 AU Clinical Chemistry Analyzer SYVA 30R Biochemical System 4 K. Standard/Guidance Document Referenced (if applicable): · CLSI EP05-A3, Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline – Third Edition · CLSI EP06-A, Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline · CLSI EP07-A2, Interference Testing in Clinical Chemistry; Approved Guideline – Second Edition · CLSI EP09-A3, Measurement Procedure Comparison and Bias Estimation Using Patient Samples; Approved Guideline – Third Edition · CLSI EP12-A2, User Protocol for Evaluation of Qualitative Test Performance; Approved Guideline – Second Edition · CLSI EP25-A Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline L. Test Principle: The Emit II Plus Cocaine Metabolite Assayis is based on competition between free drug in the specimen and drug labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH), for antibody binding sites. G6PDH enzyme activity decreases upon binding to the antibody, so the drug concentration in the specimen is proportional to G6PDH activity. The G6PDH enzyme converts nicotinamide adenine dinucleotide (NAD) to NADH, which can be measured as an absorbance change spectrophotometrically at 340 nm. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Precision studies were conducted in accordance with CLSI EP05-A3. Testing was performed for twenty (20) days with two (2) runs per day, two (2) replicates per run for a total of n = 80 sample replicates per test concentration. Nine (9) drug-free negative urine samples were spiked with benzolecogonine to concentrations of ±25%, ±50% , ±75% , and ±100 of each cutoff, as well as a zero drug concentration sample. The results are provided below, as determined in qualitative and semi-quantitative modes using each of the 150 ng/mL and 300 ng/mL cutoffs: 5 Qualitative Analysis (for 150 ng/mL cutoff) Concentration (ng/mL) % of cutoff # of determinations Results 0 -100% 80 80 Neg / 0 Pos 38 -75% 80 80 Neg / 0 Pos 75 -50% 80 80 Neg / 0 Pos 113 -25% 80 80 Neg / 0 Pos 150 Cutoff 80 9 Neg / 71 Pos 188 +25% 80 80 Pos / 0 Neg 225 +50% 80 80 Pos / 0 Neg 263 +75% 80 80 Pos / 0 Neg 300 +100% 80 80 Pos / 0 Neg Semi-Quantitative Analysis (for 150 ng/mL cutoff) Concentration (ng/mL) % of cutoff # of determinations Results 0 -100% 80 80 Neg / 0 Pos 38 -75% 80 80 Neg / 0 Pos 75 -50% 80 80 Neg / 0 Pos 113 -25% 80 80 Neg / 0 Pos 150 Cutoff 80 9 Neg / 71 Pos 188 +25% 80 80 Pos / 0 Neg 225 +50% 80 80 Pos / 0 Neg 263 +75% 80 80 Pos / 0 Neg 300 +100% 80 80 Pos / 0 Neg Qualitative Analysis (for 300 ng/mL cutoff) Concentration (ng/mL) % of cutoff # of determinations Results 0 -100 80 80 Neg / 0 Pos 75 -75 80 80 Neg / 0 Pos 150 -50 80 80 Neg / 0 Pos 225 -25 80 80 Neg / 0 Pos 300 Cutoff 80 54 Neg / 26 Pos 375 +25 80 80 Pos / 0 Neg 450 +50 80 80 Pos / 0 Neg 525 +75 80 80 Pos / 0 Neg 600 +100 80 80 Pos / 0 Neg 6 Semi-Quantitative Analysis (for 300ng/mL cutoff) Concentration (ng/mL) % of cutoff # of determinations Results 0 -100 80 80 Neg / 0 Pos 75 -75 80 80 Neg / 0 Pos 150 -50 80 80 Neg / 0 Pos 225 -25 80 80 Neg / 0 Pos 300 Cutoff 80 54 Neg / 26 Pos 375 +25 80 80 Pos / 0 Neg 450 +50 80 80 Pos / 0 Neg 525 +75 80 80 Pos / 0 Neg 600 +100 80 80 Pos / 0 Neg b. Linearity/assay reportable range: Recovery studies were conducted in accordance with CLSI EP 6-A in the semi- quantitative mode using spiked drug-free urine sample pools with known concentrations of benzoylecgonine to generate eleven (11) dilutions to achieve concentrations ranging from 50 ng/mL to 1000 ng/mL. Each concentration was tested in five replicates and Proprietary and established names:

idK170293_s2000_e4000

K170293.txt

proposed labeling

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

the mean concentration of the five replicates. The results are summarized below: Linearity/Recovery Expected Concentration (ng/mL) Mean Concentration (ng/mL) Mean Recovery (%) 0 6 N/A 50 53 106.1% 100 103 103.1% 150 150 100.2% 225 235 104.3% 300 298 99.3% 375 380 100.4% 500 543 108.6% 750 792 105.6% 900 906 100.6% 1000 1029 102.9% c. Traceability, Stability, Expected values (controls, calibrators, or methods): The Emit II Plus Cocaine Metabolite Assay Calibrators and Controls were previously cleared in k993755. d. Detection limit: Not Applicable 7 e. Analytical specificity: For analytical specificity please reference k993988. Additional structurally related compounds were evaluated by spiking each of the drugs indicated in the tables below into drug free urine, and determining the lowest concentration that produces a response equivalent to benzoylecgonine at each device cutoff. Structurally Related Compounds, 150 ng/mL cutoff Compound Concentration (ng/mL) that generates response approximately equivalent to the cutoff % Cross-Reactivity Ecgonine* 5,000 3% Cocaine* 29,000 0.5% Norcocaine 100,000 <0.01% Cocaethylene 100,000 <0.01% Ecgonine methyl ester Not Detected <0.01% Structurally Related Compounds, 300 ng/mL cutoff Compound Concentration (ng/mL) that generates response approximately equivalent to the cutoff % Cross-Reactivity Ecgonine* 15,000 2% Cocaine* 61,000 0.5% Norcocaine 100,000 <0.01% Cocaethylene 100,000 <0.01% Ecgonine methyl ester 100,000 <0.01% *Ecgonine and cocaine tested at the concentrations above produced a result approximately equivalent to the cutoff. Benzoylecgonine glucuronide, a metabolite of benzoylecgonine, shares structural similarities to benzoylecgonine has significant cross reactivity to the Emit II Plus Cocaine Metabolite Assay. This cross reactivity was observed in the method comparison study, where the presence of Benzoylecgonine-glucuronide produced a positive result when insufficient levels of benzoylecgonine were present to produce a positive result. Laboratories who use this assay should use caution when confirming positive results. Confirmatory methods that do not detect benzoylecgonine glucuronide may not match the initial screening assay results (see method comparison results below). 8 f. Assay cut-off: Characterization of how the device performs analytically around the claimed cutoff concentrations of 150 ng/mL and 300 ng/mL is described in the precision section, M.1.a. above 2. Comparison studies: a. Method comparison with predicate device: Method comparison was conducted in accordance with CLSI EP09-A3 and CLSI EP12-A2. Benzoylecgonine values of native patient urine samples were determined and were compared to the results obtained by a comparator Gas Chromatography/Mass Spectrometry (GC/MS) method. Results were obtained in both qualitative and semi-quantitative modes, and are summarized below: Method Comparison Results for the 150 ng/mL Cutoff (n = 102) GC/MS Negative (<75 ng/mL) Negative (75-149 ng/mL) Positive (150 - 225ng/mL) Positive (> 225 ng/mL) Qualitative DxC700 AU Positive 2 7 10 51 Negative 28 4 0 0 Semi-Quantitative DxC 700 AU Positive 2 7 10 51 Negative 28 4 0 0 Discordant Results, 150ng/mL Cutoff, Qualitative and Semi-quantitative mode Emit II Plus Cocaine Metabolite Assay (Pos/Neg) GC/MS concentration (ng/mL) *Positive 124 *Positive 34 *Positive 73 *Positive 83 *Positive 102 *Positive 80 *Positive 105 *Positive 101 *Positive 75 *All samples are found to contain conjugated Benzolecgnine glucuronide molecule which shares structural similarities to Benzolecgonine and positive interference to the Emit II Plus Cocaine Metabolite Assay. Benzoylecgonine glucuronide, a metabolite of benzoylecgonine, shares structural similarities to benzoylecgonine and has significant 9 cross reactivity to the Emit II Plus Cocaine Metabolite Assay. This cross reactivity produced a positive result when insufficient levels of benzoylecgonine were present to produce a positive result. When specimens were treated with glucuronidase, the concentraton of benzoylecgonine in the sample was within +/- 50% of the cutoff. Method Comparison Results for the 300 ng/mL Cutoff (n = 95) GC/MS Negative ( <150 ng/mL) Negative (150-299 ng/mL) Positive (300-450 ng/mL) Positive (> 450 ng/mL) Qualitative DxC 700 AU Positive 1 10 18 25 Negative 40 1 0 0 Semi-Quantitative DxC700 AU Positive 1 8 20 25 Negative 40 1 0 0 Discordant Results, 300ng/mL Cutoff, Qualitative and Semi-quantitative mode Emit II Plus Cocaine Metabolite Assay (Pos/Neg) GC/MS concentration (ng/mL) *Positive 217 *Positive 240 *Positive 173 *Positive 207 *Positive 233 *Positive 143 *Positive 217 *Positive 173 *Positive 232 *Positive 157 *Positive 234 *All samples are found to contain conjugated Benzolecgnine glucuronide molecule which shares structural similarities to Benzolecgonine and positive interference to the Emit II Plus Cocaine Metabolite Assay. Benzoylecgonine glucuronide, a metabolite of benzoylecgonine, shares structural similarities to benzoylecgonine and has significant cross reactivity to the Emit II Plus Cocaine Metabolite Assay. This cross reactivity produced a positive result when insufficient levels of benzoylecgonine were present to produce a positive result. When specimens were treated with glucuronidase, the concentraton of benzoylecgonine in the sample was within +/- 50% of the cutoff. b. Matrix comparison: Only Urine samples are recommended for use with this assay. 10 3. Clinical studies: a. Clinical Sensitivity: Not Applicable b. Clinical specificity: Not Apllicable c. Other clinical supportive data (when a. and b. are not applicable): Not Applicable 4. Clinical cut-off: Not Applicable 5. Expected values/Reference range: Not Applicable N. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. O. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Proposed labeling:

idK170293_s2000_e4000

K170293.txt

conclusion

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

calculated using the mean concentration of the five replicates. The results are summarized below: Linearity/Recovery Expected Concentration (ng/mL) Mean Concentration (ng/mL) Mean Recovery (%) 0 6 N/A 50 53 106.1% 100 103 103.1% 150 150 100.2% 225 235 104.3% 300 298 99.3% 375 380 100.4% 500 543 108.6% 750 792 105.6% 900 906 100.6% 1000 1029 102.9% c. Traceability, Stability, Expected values (controls, calibrators, or methods): The Emit II Plus Cocaine Metabolite Assay Calibrators and Controls were previously cleared in k993755. d. Detection limit: Not Applicable 7 e. Analytical specificity: For analytical specificity please reference k993988. Additional structurally related compounds were evaluated by spiking each of the drugs indicated in the tables below into drug free urine, and determining the lowest concentration that produces a response equivalent to benzoylecgonine at each device cutoff. Structurally Related Compounds, 150 ng/mL cutoff Compound Concentration (ng/mL) that generates response approximately equivalent to the cutoff % Cross-Reactivity Ecgonine* 5,000 3% Cocaine* 29,000 0.5% Norcocaine 100,000 <0.01% Cocaethylene 100,000 <0.01% Ecgonine methyl ester Not Detected <0.01% Structurally Related Compounds, 300 ng/mL cutoff Compound Concentration (ng/mL) that generates response approximately equivalent to the cutoff % Cross-Reactivity Ecgonine* 15,000 2% Cocaine* 61,000 0.5% Norcocaine 100,000 <0.01% Cocaethylene 100,000 <0.01% Ecgonine methyl ester 100,000 <0.01% *Ecgonine and cocaine tested at the concentrations above produced a result approximately equivalent to the cutoff. Benzoylecgonine glucuronide, a metabolite of benzoylecgonine, shares structural similarities to benzoylecgonine has significant cross reactivity to the Emit II Plus Cocaine Metabolite Assay. This cross reactivity was observed in the method comparison study, where the presence of Benzoylecgonine-glucuronide produced a positive result when insufficient levels of benzoylecgonine were present to produce a positive result. Laboratories who use this assay should use caution when confirming positive results. Confirmatory methods that do not detect benzoylecgonine glucuronide may not match the initial screening assay results (see method comparison results below). 8 f. Assay cut-off: Characterization of how the device performs analytically around the claimed cutoff concentrations of 150 ng/mL and 300 ng/mL is described in the precision section, M.1.a. above 2. Comparison studies: a. Method comparison with predicate device: Method comparison was conducted in accordance with CLSI EP09-A3 and CLSI EP12-A2. Benzoylecgonine values of native patient urine samples were determined and were compared to the results obtained by a comparator Gas Chromatography/Mass Spectrometry (GC/MS) method. Results were obtained in both qualitative and semi-quantitative modes, and are summarized below: Method Comparison Results for the 150 ng/mL Cutoff (n = 102) GC/MS Negative (<75 ng/mL) Negative (75-149 ng/mL) Positive (150 - 225ng/mL) Positive (> 225 ng/mL) Qualitative DxC700 AU Positive 2 7 10 51 Negative 28 4 0 0 Semi-Quantitative DxC 700 AU Positive 2 7 10 51 Negative 28 4 0 0 Discordant Results, 150ng/mL Cutoff, Qualitative and Semi-quantitative mode Emit II Plus Cocaine Metabolite Assay (Pos/Neg) GC/MS concentration (ng/mL) *Positive 124 *Positive 34 *Positive 73 *Positive 83 *Positive 102 *Positive 80 *Positive 105 *Positive 101 *Positive 75 *All samples are found to contain conjugated Benzolecgnine glucuronide molecule which shares structural similarities to Benzolecgonine and positive interference to the Emit II Plus Cocaine Metabolite Assay. Benzoylecgonine glucuronide, a metabolite of benzoylecgonine, shares structural similarities to benzoylecgonine and has significant 9 cross reactivity to the Emit II Plus Cocaine Metabolite Assay. This cross reactivity produced a positive result when insufficient levels of benzoylecgonine were present to produce a positive result. When specimens were treated with glucuronidase, the concentraton of benzoylecgonine in the sample was within +/- 50% of the cutoff. Method Comparison Results for the 300 ng/mL Cutoff (n = 95) GC/MS Negative ( <150 ng/mL) Negative (150-299 ng/mL) Positive (300-450 ng/mL) Positive (> 450 ng/mL) Qualitative DxC 700 AU Positive 1 10 18 25 Negative 40 1 0 0 Semi-Quantitative DxC700 AU Positive 1 8 20 25 Negative 40 1 0 0 Discordant Results, 300ng/mL Cutoff, Qualitative and Semi-quantitative mode Emit II Plus Cocaine Metabolite Assay (Pos/Neg) GC/MS concentration (ng/mL) *Positive 217 *Positive 240 *Positive 173 *Positive 207 *Positive 233 *Positive 143 *Positive 217 *Positive 173 *Positive 232 *Positive 157 *Positive 234 *All samples are found to contain conjugated Benzolecgnine glucuronide molecule which shares structural similarities to Benzolecgonine and positive interference to the Emit II Plus Cocaine Metabolite Assay. Benzoylecgonine glucuronide, a metabolite of benzoylecgonine, shares structural similarities to benzoylecgonine and has significant cross reactivity to the Emit II Plus Cocaine Metabolite Assay. This cross reactivity produced a positive result when insufficient levels of benzoylecgonine were present to produce a positive result. When specimens were treated with glucuronidase, the concentraton of benzoylecgonine in the sample was within +/- 50% of the cutoff. b. Matrix comparison: Only Urine samples are recommended for use with this assay. 10 3. Clinical studies: a. Clinical Sensitivity: Not Applicable b. Clinical specificity: Not Apllicable c. Other clinical supportive data (when a. and b. are not applicable): Not Applicable 4. Clinical cut-off: Not Applicable 5. Expected values/Reference range: Not Applicable N. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. O. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Conclusion:

idK173887_s0_e2000

K173887.txt

purpose for submission

To determine substantial equivalence for the cobas CT/NG assay for use on the cobas 6800/8800 Systems for detection of Chlamydia trachomatis and Neisseria gonorrhoeae DNA from self-collected vaginal swabs, clinician-collected vaginal swabs, endocervical swabs, male and female urine, and cervical specimens collected in PreservCyt solution.

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K173887 B. Purpose for Submission: To determine substantial equivalence for the cobas CT/NG assay for use on the cobas 6800/8800 Systems for detection of Chlamydia trachomatis and Neisseria gonorrhoeae DNA from self-collected vaginal swabs, clinician-collected vaginal swabs, endocervical swabs, male and female urine, and cervical specimens collected in PreservCyt solution. C. Measurand: Chlamydia trachomatis and Neisseria gonorrhoeae DNA D. Type of Test: Nucleic acid extraction, purification and amplification assay (real-time polymerase chain reaction) E. Applicant: Roche Molecular Systems, Inc. F. Proprietary and Established Names: cobas CT/NG cobas 6800/8800 Systems G. Regulatory Information: 1. Regulation section: 21 CFR 866.3390 - Neisseria spp. direct serological test reagents 2. Classification: Class II 3. Product code: LSL - DNA-Reagents, Neisseria 2 MKZ - DNA Probe, Nucleic Acid Amplification, Chlamydia OOI - Real Time Nucleic Acid Amplification System 4. Panel: Microbiology (83) H. Intended Use: 1. Intended use(s): The cobas CT/NG on the cobas 6800/8800 system is an automated, qualitative in vitro nucleic acid diagnostic test, that utilizes real-time polymerase chain reaction (PCR), for the direct detection of Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (NG) DNA in male and female urine, clinician-instructed self-collected vaginal swab specimens (collected in a clinical setting), clinician-collected vaginal swab specimens, and endocervical swab specimens, all collected in cobas PCR Media (Roche Molecular Systems, Inc.), and cervical specimens collected in PreservCyt solution. This test is intended as an aid in the diagnosis of chlamydial and gonococcal disease in both symptomatic and asymptomatic individuals. Ancillary Collection Kits: The cobas PCR Media Dual Swab Sample Kit is used to collect and transport endocervical and vaginal swab specimens. The cobas PCR Media serves as a nucleic acid stabilizing transport and storage medium for gynecological specimens. Note: This kit has been validated for use with the following tests: • cobas CT/NG v2.0 Test • cobas CT/NG for use on cobas 6800/8800 Systems The cobas PCR Media Uni Swab Sample Kit is used to collect and transport human specimens. The cobas PCR Media serves as a nucleic acid stabilizing transport and storage medium for human specimens. Note: This kit has been validated for use with the following tests: • cobas CT/NG v2.0 Test • cobas CT/NG for use on cobas 6800/8800 Systems • cobas Cdiff Test for use on the cobas 4800 System The cobas PCR Urine Sample Kit is used to collect and transport urine specimens. The cobas PCR Media serves as a nucleic acid stabilizing transport and storage medium for urine specimens. Use this collection kit only with either cobas CT/NG on cobas 6800/8800 Systems or the cobas CT/NG v2.0 Test. 2. Indication(s) for use: Same as the Intended Use 3 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: cobas 6800/8800 Systems I. Device Description: The cobas CT/NG assay is a new fully automated, qualitative real-time PCR assay performed on the cobas 6800 System and cobas 8800 System. cobas CT/NG enables the detection of CT/NG DNA in endocervical and vaginal swabs, urine, and cervical specimens from infected female patients and urine specimens from infected male patients. Target-specific primers and two probes are used to detect but not discriminate between the CT cryptic plasmid and the ompA gene. Additionally, target-specific primers and two probes are used to detect but not discriminate between two conserved sequences in the NG DR-9 region. The DNA Internal Control, used to monitor the entire sample preparation and PCR amplification process, is introduced into each specimen during sample processing. In addition, the test utilizes a low titer positive and a negative control. J. Substantial Equivalence Information: 1. Predicate device name(s): cobas CT/NG v2.0 Test 2. Predicate 510(k) number(s): K163184 3. Comparison with predicate: Similarities Item Device Predicate Regulation 866.3390 866.3390 Intended Use The cobas CT/NG on the cobas 6800/8800 system is an automated, qualitative in vitro nucleic acid diagnostic test, that utilizes real- time polymerase chain reaction (PCR), for the direct detection of Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (NG) DNA in male and female urine, clinician instructed self- collected vaginal swab specimens (collected in a clinical setting), clinician-collected vaginal swab The cobas CT/NG v2.0 Test is an automated, in vitro nucleic acid amplification test for the qualitative detection of Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (NG) DNA in urogenital specimens. The Test utilizes the Polymerase Chain Reaction (PCR) for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae DNA in male and female urine, self-collected vaginal swab specimens (collected in a clinical setting), cliniciancollected vaginal swab 4 Similarities Item Device Predicate specimens, and endocervical swab specimens, all collected in cobas PCR Media (Roche Molecular Systems, Inc.), and cervical specimens collected in PreservCyt solution. This test is intended as an aid in the diagnosis of chlamydial and gonococcal disease in both symptomatic and asymptomatic individuals. Ancillary Collection Kits: The cobas PCR Media Dual Swab Sample Kit is used to collect and transport endocervical and vaginal swab specimens. The cobas® PCR Media serves as a nucleic acid stabilizing transport and storage medium for gynecological specimens. Note: This kit has been validated for use with the following tests: cobas CT/NG v2.0 Test cobas® CT/NG for use on cobas 6800/8800 Systems. The cobas PCR Media Uni Swab Sample Kit is used to collect and transport human specimens. The cobas PCR Media serves as a nucleic acid stabilizing transport and storage medium for human specimens Note: This kit has been validated for use with the following tests: cobas CT/NG v2.0 Test cobas CT/NG for use on cobas 6800/8800 Systems cobas Cdiff Test for use on the cobas 4800 System The cobas PCR Urine Sample Kit is used to collect and transport urine specimens. The cobas PCR Media serves as a nucleic acid specimens, and endocervical swab specimens, all collected in cobas PCR Media (Roche Molecular Systems, Inc.), and cervical specimens collected in PreservCyt solution. This test is intended as an aid in the diagnosis of chlamydial and gonococcal disease in both symptomatic and asymptomatic individuals. Ancillary Collection Kits: The cobas PCR Media Dual Swab Sample Kit is used to collect and transport endocervical and vaginal swab specimens. The cobas PCR Media serves as a nucleic acid stabilizing transport and storage medium for gynecological specimens. Use this collection kit only with the cobas CT/NG v2.0 Test. The cobas PCR Media Uni Swab Sample Kit is used to collect and transport human specimens. The cobas PCR Media serves as a nucleic acid stabilizing transport and storage medium for human specimens. Use this collection kit with cobas CT/NG v2.0 Test and cobas Cdiff Tests. The cobas PCR Urine Sample Kit is used to collect and transport urine specimens. The cobas PCR Media serves as a nucleic acid stabilizing transport and storage medium for urine specimens. Use this collection kit only with the cobas CT/NG v2.0 Test. 5 Similarities Item Device Predicate stabilizing transport and storage medium for urine specimens Use this collection kit only with either cobas CT/NG on cobas 6800/8800 Systems or the cobas CT/NG v2.0 Test. Sample Types Same Male and female urine, Self- collected/clinician-collected vaginal swab specimens in cobas PCR Media, Endocervical swab specimens in cobas PCR Media, Cervical specimens in PreservCyt solution Subject Status Same Asymptomatic and symptomatic Sample Collection Devices Same cobas PCR Media Dual Swab Sample Kit cobas PCR Media Uni Swab Sample Kit cobas PCR Urine Sample Kit CT Analyte targets Same CT cryptic plasmid DNA CT o Purpose for submission:

idK173887_s0_e2000

K173887.txt

measurand

Chlamydia trachomatis and Neisseria gonorrhoeae DNA

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K173887 B. Purpose for Submission: To determine substantial equivalence for the cobas CT/NG assay for use on the cobas 6800/8800 Systems for detection of Chlamydia trachomatis and Neisseria gonorrhoeae DNA from self-collected vaginal swabs, clinician-collected vaginal swabs, endocervical swabs, male and female urine, and cervical specimens collected in PreservCyt solution. C. Measurand: Chlamydia trachomatis and Neisseria gonorrhoeae DNA D. Type of Test: Nucleic acid extraction, purification and amplification assay (real-time polymerase chain reaction) E. Applicant: Roche Molecular Systems, Inc. F. Proprietary and Established Names: cobas CT/NG cobas 6800/8800 Systems G. Regulatory Information: 1. Regulation section: 21 CFR 866.3390 - Neisseria spp. direct serological test reagents 2. Classification: Class II 3. Product code: LSL - DNA-Reagents, Neisseria 2 MKZ - DNA Probe, Nucleic Acid Amplification, Chlamydia OOI - Real Time Nucleic Acid Amplification System 4. Panel: Microbiology (83) H. Intended Use: 1. Intended use(s): The cobas CT/NG on the cobas 6800/8800 system is an automated, qualitative in vitro nucleic acid diagnostic test, that utilizes real-time polymerase chain reaction (PCR), for the direct detection of Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (NG) DNA in male and female urine, clinician-instructed self-collected vaginal swab specimens (collected in a clinical setting), clinician-collected vaginal swab specimens, and endocervical swab specimens, all collected in cobas PCR Media (Roche Molecular Systems, Inc.), and cervical specimens collected in PreservCyt solution. This test is intended as an aid in the diagnosis of chlamydial and gonococcal disease in both symptomatic and asymptomatic individuals. Ancillary Collection Kits: The cobas PCR Media Dual Swab Sample Kit is used to collect and transport endocervical and vaginal swab specimens. The cobas PCR Media serves as a nucleic acid stabilizing transport and storage medium for gynecological specimens. Note: This kit has been validated for use with the following tests: • cobas CT/NG v2.0 Test • cobas CT/NG for use on cobas 6800/8800 Systems The cobas PCR Media Uni Swab Sample Kit is used to collect and transport human specimens. The cobas PCR Media serves as a nucleic acid stabilizing transport and storage medium for human specimens. Note: This kit has been validated for use with the following tests: • cobas CT/NG v2.0 Test • cobas CT/NG for use on cobas 6800/8800 Systems • cobas Cdiff Test for use on the cobas 4800 System The cobas PCR Urine Sample Kit is used to collect and transport urine specimens. The cobas PCR Media serves as a nucleic acid stabilizing transport and storage medium for urine specimens. Use this collection kit only with either cobas CT/NG on cobas 6800/8800 Systems or the cobas CT/NG v2.0 Test. 2. Indication(s) for use: Same as the Intended Use 3 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: cobas 6800/8800 Systems I. Device Description: The cobas CT/NG assay is a new fully automated, qualitative real-time PCR assay performed on the cobas 6800 System and cobas 8800 System. cobas CT/NG enables the detection of CT/NG DNA in endocervical and vaginal swabs, urine, and cervical specimens from infected female patients and urine specimens from infected male patients. Target-specific primers and two probes are used to detect but not discriminate between the CT cryptic plasmid and the ompA gene. Additionally, target-specific primers and two probes are used to detect but not discriminate between two conserved sequences in the NG DR-9 region. The DNA Internal Control, used to monitor the entire sample preparation and PCR amplification process, is introduced into each specimen during sample processing. In addition, the test utilizes a low titer positive and a negative control. J. Substantial Equivalence Information: 1. Predicate device name(s): cobas CT/NG v2.0 Test 2. Predicate 510(k) number(s): K163184 3. Comparison with predicate: Similarities Item Device Predicate Regulation 866.3390 866.3390 Intended Use The cobas CT/NG on the cobas 6800/8800 system is an automated, qualitative in vitro nucleic acid diagnostic test, that utilizes real- time polymerase chain reaction (PCR), for the direct detection of Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (NG) DNA in male and female urine, clinician instructed self- collected vaginal swab specimens (collected in a clinical setting), clinician-collected vaginal swab The cobas CT/NG v2.0 Test is an automated, in vitro nucleic acid amplification test for the qualitative detection of Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (NG) DNA in urogenital specimens. The Test utilizes the Polymerase Chain Reaction (PCR) for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae DNA in male and female urine, self-collected vaginal swab specimens (collected in a clinical setting), cliniciancollected vaginal swab 4 Similarities Item Device Predicate specimens, and endocervical swab specimens, all collected in cobas PCR Media (Roche Molecular Systems, Inc.), and cervical specimens collected in PreservCyt solution. This test is intended as an aid in the diagnosis of chlamydial and gonococcal disease in both symptomatic and asymptomatic individuals. Ancillary Collection Kits: The cobas PCR Media Dual Swab Sample Kit is used to collect and transport endocervical and vaginal swab specimens. The cobas® PCR Media serves as a nucleic acid stabilizing transport and storage medium for gynecological specimens. Note: This kit has been validated for use with the following tests: cobas CT/NG v2.0 Test cobas® CT/NG for use on cobas 6800/8800 Systems. The cobas PCR Media Uni Swab Sample Kit is used to collect and transport human specimens. The cobas PCR Media serves as a nucleic acid stabilizing transport and storage medium for human specimens Note: This kit has been validated for use with the following tests: cobas CT/NG v2.0 Test cobas CT/NG for use on cobas 6800/8800 Systems cobas Cdiff Test for use on the cobas 4800 System The cobas PCR Urine Sample Kit is used to collect and transport urine specimens. The cobas PCR Media serves as a nucleic acid specimens, and endocervical swab specimens, all collected in cobas PCR Media (Roche Molecular Systems, Inc.), and cervical specimens collected in PreservCyt solution. This test is intended as an aid in the diagnosis of chlamydial and gonococcal disease in both symptomatic and asymptomatic individuals. Ancillary Collection Kits: The cobas PCR Media Dual Swab Sample Kit is used to collect and transport endocervical and vaginal swab specimens. The cobas PCR Media serves as a nucleic acid stabilizing transport and storage medium for gynecological specimens. Use this collection kit only with the cobas CT/NG v2.0 Test. The cobas PCR Media Uni Swab Sample Kit is used to collect and transport human specimens. The cobas PCR Media serves as a nucleic acid stabilizing transport and storage medium for human specimens. Use this collection kit with cobas CT/NG v2.0 Test and cobas Cdiff Tests. The cobas PCR Urine Sample Kit is used to collect and transport urine specimens. The cobas PCR Media serves as a nucleic acid stabilizing transport and storage medium for urine specimens. Use this collection kit only with the cobas CT/NG v2.0 Test. 5 Similarities Item Device Predicate stabilizing transport and storage medium for urine specimens Use this collection kit only with either cobas CT/NG on cobas 6800/8800 Systems or the cobas CT/NG v2.0 Test. Sample Types Same Male and female urine, Self- collected/clinician-collected vaginal swab specimens in cobas PCR Media, Endocervical swab specimens in cobas PCR Media, Cervical specimens in PreservCyt solution Subject Status Same Asymptomatic and symptomatic Sample Collection Devices Same cobas PCR Media Dual Swab Sample Kit cobas PCR Media Uni Swab Sample Kit cobas PCR Urine Sample Kit CT Analyte targets Same CT cryptic plasmid DNA CT o Measurand:

idK173887_s0_e2000

K173887.txt

type of test

Nucleic acid extraction, purification and amplification assay (real-time polymerase chain reaction)

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K173887 B. Purpose for Submission: To determine substantial equivalence for the cobas CT/NG assay for use on the cobas 6800/8800 Systems for detection of Chlamydia trachomatis and Neisseria gonorrhoeae DNA from self-collected vaginal swabs, clinician-collected vaginal swabs, endocervical swabs, male and female urine, and cervical specimens collected in PreservCyt solution. C. Measurand: Chlamydia trachomatis and Neisseria gonorrhoeae DNA D. Type of Test: Nucleic acid extraction, purification and amplification assay (real-time polymerase chain reaction) E. Applicant: Roche Molecular Systems, Inc. F. Proprietary and Established Names: cobas CT/NG cobas 6800/8800 Systems G. Regulatory Information: 1. Regulation section: 21 CFR 866.3390 - Neisseria spp. direct serological test reagents 2. Classification: Class II 3. Product code: LSL - DNA-Reagents, Neisseria 2 MKZ - DNA Probe, Nucleic Acid Amplification, Chlamydia OOI - Real Time Nucleic Acid Amplification System 4. Panel: Microbiology (83) H. Intended Use: 1. Intended use(s): The cobas CT/NG on the cobas 6800/8800 system is an automated, qualitative in vitro nucleic acid diagnostic test, that utilizes real-time polymerase chain reaction (PCR), for the direct detection of Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (NG) DNA in male and female urine, clinician-instructed self-collected vaginal swab specimens (collected in a clinical setting), clinician-collected vaginal swab specimens, and endocervical swab specimens, all collected in cobas PCR Media (Roche Molecular Systems, Inc.), and cervical specimens collected in PreservCyt solution. This test is intended as an aid in the diagnosis of chlamydial and gonococcal disease in both symptomatic and asymptomatic individuals. Ancillary Collection Kits: The cobas PCR Media Dual Swab Sample Kit is used to collect and transport endocervical and vaginal swab specimens. The cobas PCR Media serves as a nucleic acid stabilizing transport and storage medium for gynecological specimens. Note: This kit has been validated for use with the following tests: • cobas CT/NG v2.0 Test • cobas CT/NG for use on cobas 6800/8800 Systems The cobas PCR Media Uni Swab Sample Kit is used to collect and transport human specimens. The cobas PCR Media serves as a nucleic acid stabilizing transport and storage medium for human specimens. Note: This kit has been validated for use with the following tests: • cobas CT/NG v2.0 Test • cobas CT/NG for use on cobas 6800/8800 Systems • cobas Cdiff Test for use on the cobas 4800 System The cobas PCR Urine Sample Kit is used to collect and transport urine specimens. The cobas PCR Media serves as a nucleic acid stabilizing transport and storage medium for urine specimens. Use this collection kit only with either cobas CT/NG on cobas 6800/8800 Systems or the cobas CT/NG v2.0 Test. 2. Indication(s) for use: Same as the Intended Use 3 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: cobas 6800/8800 Systems I. Device Description: The cobas CT/NG assay is a new fully automated, qualitative real-time PCR assay performed on the cobas 6800 System and cobas 8800 System. cobas CT/NG enables the detection of CT/NG DNA in endocervical and vaginal swabs, urine, and cervical specimens from infected female patients and urine specimens from infected male patients. Target-specific primers and two probes are used to detect but not discriminate between the CT cryptic plasmid and the ompA gene. Additionally, target-specific primers and two probes are used to detect but not discriminate between two conserved sequences in the NG DR-9 region. The DNA Internal Control, used to monitor the entire sample preparation and PCR amplification process, is introduced into each specimen during sample processing. In addition, the test utilizes a low titer positive and a negative control. J. Substantial Equivalence Information: 1. Predicate device name(s): cobas CT/NG v2.0 Test 2. Predicate 510(k) number(s): K163184 3. Comparison with predicate: Similarities Item Device Predicate Regulation 866.3390 866.3390 Intended Use The cobas CT/NG on the cobas 6800/8800 system is an automated, qualitative in vitro nucleic acid diagnostic test, that utilizes real- time polymerase chain reaction (PCR), for the direct detection of Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (NG) DNA in male and female urine, clinician instructed self- collected vaginal swab specimens (collected in a clinical setting), clinician-collected vaginal swab The cobas CT/NG v2.0 Test is an automated, in vitro nucleic acid amplification test for the qualitative detection of Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (NG) DNA in urogenital specimens. The Test utilizes the Polymerase Chain Reaction (PCR) for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae DNA in male and female urine, self-collected vaginal swab specimens (collected in a clinical setting), cliniciancollected vaginal swab 4 Similarities Item Device Predicate specimens, and endocervical swab specimens, all collected in cobas PCR Media (Roche Molecular Systems, Inc.), and cervical specimens collected in PreservCyt solution. This test is intended as an aid in the diagnosis of chlamydial and gonococcal disease in both symptomatic and asymptomatic individuals. Ancillary Collection Kits: The cobas PCR Media Dual Swab Sample Kit is used to collect and transport endocervical and vaginal swab specimens. The cobas® PCR Media serves as a nucleic acid stabilizing transport and storage medium for gynecological specimens. Note: This kit has been validated for use with the following tests: cobas CT/NG v2.0 Test cobas® CT/NG for use on cobas 6800/8800 Systems. The cobas PCR Media Uni Swab Sample Kit is used to collect and transport human specimens. The cobas PCR Media serves as a nucleic acid stabilizing transport and storage medium for human specimens Note: This kit has been validated for use with the following tests: cobas CT/NG v2.0 Test cobas CT/NG for use on cobas 6800/8800 Systems cobas Cdiff Test for use on the cobas 4800 System The cobas PCR Urine Sample Kit is used to collect and transport urine specimens. The cobas PCR Media serves as a nucleic acid specimens, and endocervical swab specimens, all collected in cobas PCR Media (Roche Molecular Systems, Inc.), and cervical specimens collected in PreservCyt solution. This test is intended as an aid in the diagnosis of chlamydial and gonococcal disease in both symptomatic and asymptomatic individuals. Ancillary Collection Kits: The cobas PCR Media Dual Swab Sample Kit is used to collect and transport endocervical and vaginal swab specimens. The cobas PCR Media serves as a nucleic acid stabilizing transport and storage medium for gynecological specimens. Use this collection kit only with the cobas CT/NG v2.0 Test. The cobas PCR Media Uni Swab Sample Kit is used to collect and transport human specimens. The cobas PCR Media serves as a nucleic acid stabilizing transport and storage medium for human specimens. Use this collection kit with cobas CT/NG v2.0 Test and cobas Cdiff Tests. The cobas PCR Urine Sample Kit is used to collect and transport urine specimens. The cobas PCR Media serves as a nucleic acid stabilizing transport and storage medium for urine specimens. Use this collection kit only with the cobas CT/NG v2.0 Test. 5 Similarities Item Device Predicate stabilizing transport and storage medium for urine specimens Use this collection kit only with either cobas CT/NG on cobas 6800/8800 Systems or the cobas CT/NG v2.0 Test. Sample Types Same Male and female urine, Self- collected/clinician-collected vaginal swab specimens in cobas PCR Media, Endocervical swab specimens in cobas PCR Media, Cervical specimens in PreservCyt solution Subject Status Same Asymptomatic and symptomatic Sample Collection Devices Same cobas PCR Media Dual Swab Sample Kit cobas PCR Media Uni Swab Sample Kit cobas PCR Urine Sample Kit CT Analyte targets Same CT cryptic plasmid DNA CT o Type of test:

idK173887_s0_e2000

K173887.txt

classification

Class II

k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K173887 B. Purpose for Submission: To determine substantial equivalence for the cobas CT/NG assay for use on the cobas 6800/8800 Systems for detection of Chlamydia trachomatis and Neisseria gonorrhoeae DNA from self-collected vaginal swabs, clinician-collected vaginal swabs, endocervical swabs, male and female urine, and cervical specimens collected in PreservCyt solution. C. Measurand: Chlamydia trachomatis and Neisseria gonorrhoeae DNA D. Type of Test: Nucleic acid extraction, purification and amplification assay (real-time polymerase chain reaction) E. Applicant: Roche Molecular Systems, Inc. F. Proprietary and Established Names: cobas CT/NG cobas 6800/8800 Systems G. Regulatory Information: 1. Regulation section: 21 CFR 866.3390 - Neisseria spp. direct serological test reagents 2. Classification: Class II 3. Product code: LSL - DNA-Reagents, Neisseria 2 MKZ - DNA Probe, Nucleic Acid Amplification, Chlamydia OOI - Real Time Nucleic Acid Amplification System 4. Panel: Microbiology (83) H. Intended Use: 1. Intended use(s): The cobas CT/NG on the cobas 6800/8800 system is an automated, qualitative in vitro nucleic acid diagnostic test, that utilizes real-time polymerase chain reaction (PCR), for the direct detection of Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (NG) DNA in male and female urine, clinician-instructed self-collected vaginal swab specimens (collected in a clinical setting), clinician-collected vaginal swab specimens, and endocervical swab specimens, all collected in cobas PCR Media (Roche Molecular Systems, Inc.), and cervical specimens collected in PreservCyt solution. This test is intended as an aid in the diagnosis of chlamydial and gonococcal disease in both symptomatic and asymptomatic individuals. Ancillary Collection Kits: The cobas PCR Media Dual Swab Sample Kit is used to collect and transport endocervical and vaginal swab specimens. The cobas PCR Media serves as a nucleic acid stabilizing transport and storage medium for gynecological specimens. Note: This kit has been validated for use with the following tests: • cobas CT/NG v2.0 Test • cobas CT/NG for use on cobas 6800/8800 Systems The cobas PCR Media Uni Swab Sample Kit is used to collect and transport human specimens. The cobas PCR Media serves as a nucleic acid stabilizing transport and storage medium for human specimens. Note: This kit has been validated for use with the following tests: • cobas CT/NG v2.0 Test • cobas CT/NG for use on cobas 6800/8800 Systems • cobas Cdiff Test for use on the cobas 4800 System The cobas PCR Urine Sample Kit is used to collect and transport urine specimens. The cobas PCR Media serves as a nucleic acid stabilizing transport and storage medium for urine specimens. Use this collection kit only with either cobas CT/NG on cobas 6800/8800 Systems or the cobas CT/NG v2.0 Test. 2. Indication(s) for use: Same as the Intended Use 3 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: cobas 6800/8800 Systems I. Device Description: The cobas CT/NG assay is a new fully automated, qualitative real-time PCR assay performed on the cobas 6800 System and cobas 8800 System. cobas CT/NG enables the detection of CT/NG DNA in endocervical and vaginal swabs, urine, and cervical specimens from infected female patients and urine specimens from infected male patients. Target-specific primers and two probes are used to detect but not discriminate between the CT cryptic plasmid and the ompA gene. Additionally, target-specific primers and two probes are used to detect but not discriminate between two conserved sequences in the NG DR-9 region. The DNA Internal Control, used to monitor the entire sample preparation and PCR amplification process, is introduced into each specimen during sample processing. In addition, the test utilizes a low titer positive and a negative control. J. Substantial Equivalence Information: 1. Predicate device name(s): cobas CT/NG v2.0 Test 2. Predicate 510(k) number(s): K163184 3. Comparison with predicate: Similarities Item Device Predicate Regulation 866.3390 866.3390 Intended Use The cobas CT/NG on the cobas 6800/8800 system is an automated, qualitative in vitro nucleic acid diagnostic test, that utilizes real- time polymerase chain reaction (PCR), for the direct detection of Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (NG) DNA in male and female urine, clinician instructed self- collected vaginal swab specimens (collected in a clinical setting), clinician-collected vaginal swab The cobas CT/NG v2.0 Test is an automated, in vitro nucleic acid amplification test for the qualitative detection of Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (NG) DNA in urogenital specimens. The Test utilizes the Polymerase Chain Reaction (PCR) for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae DNA in male and female urine, self-collected vaginal swab specimens (collected in a clinical setting), cliniciancollected vaginal swab 4 Similarities Item Device Predicate specimens, and endocervical swab specimens, all collected in cobas PCR Media (Roche Molecular Systems, Inc.), and cervical specimens collected in PreservCyt solution. This test is intended as an aid in the diagnosis of chlamydial and gonococcal disease in both symptomatic and asymptomatic individuals. Ancillary Collection Kits: The cobas PCR Media Dual Swab Sample Kit is used to collect and transport endocervical and vaginal swab specimens. The cobas® PCR Media serves as a nucleic acid stabilizing transport and storage medium for gynecological specimens. Note: This kit has been validated for use with the following tests: cobas CT/NG v2.0 Test cobas® CT/NG for use on cobas 6800/8800 Systems. The cobas PCR Media Uni Swab Sample Kit is used to collect and transport human specimens. The cobas PCR Media serves as a nucleic acid stabilizing transport and storage medium for human specimens Note: This kit has been validated for use with the following tests: cobas CT/NG v2.0 Test cobas CT/NG for use on cobas 6800/8800 Systems cobas Cdiff Test for use on the cobas 4800 System The cobas PCR Urine Sample Kit is used to collect and transport urine specimens. The cobas PCR Media serves as a nucleic acid specimens, and endocervical swab specimens, all collected in cobas PCR Media (Roche Molecular Systems, Inc.), and cervical specimens collected in PreservCyt solution. This test is intended as an aid in the diagnosis of chlamydial and gonococcal disease in both symptomatic and asymptomatic individuals. Ancillary Collection Kits: The cobas PCR Media Dual Swab Sample Kit is used to collect and transport endocervical and vaginal swab specimens. The cobas PCR Media serves as a nucleic acid stabilizing transport and storage medium for gynecological specimens. Use this collection kit only with the cobas CT/NG v2.0 Test. The cobas PCR Media Uni Swab Sample Kit is used to collect and transport human specimens. The cobas PCR Media serves as a nucleic acid stabilizing transport and storage medium for human specimens. Use this collection kit with cobas CT/NG v2.0 Test and cobas Cdiff Tests. The cobas PCR Urine Sample Kit is used to collect and transport urine specimens. The cobas PCR Media serves as a nucleic acid stabilizing transport and storage medium for urine specimens. Use this collection kit only with the cobas CT/NG v2.0 Test. 5 Similarities Item Device Predicate stabilizing transport and storage medium for urine specimens Use this collection kit only with either cobas CT/NG on cobas 6800/8800 Systems or the cobas CT/NG v2.0 Test. Sample Types Same Male and female urine, Self- collected/clinician-collected vaginal swab specimens in cobas PCR Media, Endocervical swab specimens in cobas PCR Media, Cervical specimens in PreservCyt solution Subject Status Same Asymptomatic and symptomatic Sample Collection Devices Same cobas PCR Media Dual Swab Sample Kit cobas PCR Media Uni Swab Sample Kit cobas PCR Urine Sample Kit CT Analyte targets Same CT cryptic plasmid DNA CT o Classification:

idK173887_s0_e2000

K173887.txt

panel

Microbiology (83)

(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K173887 B. Purpose for Submission: To determine substantial equivalence for the cobas CT/NG assay for use on the cobas 6800/8800 Systems for detection of Chlamydia trachomatis and Neisseria gonorrhoeae DNA from self-collected vaginal swabs, clinician-collected vaginal swabs, endocervical swabs, male and female urine, and cervical specimens collected in PreservCyt solution. C. Measurand: Chlamydia trachomatis and Neisseria gonorrhoeae DNA D. Type of Test: Nucleic acid extraction, purification and amplification assay (real-time polymerase chain reaction) E. Applicant: Roche Molecular Systems, Inc. F. Proprietary and Established Names: cobas CT/NG cobas 6800/8800 Systems G. Regulatory Information: 1. Regulation section: 21 CFR 866.3390 - Neisseria spp. direct serological test reagents 2. Classification: Class II 3. Product code: LSL - DNA-Reagents, Neisseria 2 MKZ - DNA Probe, Nucleic Acid Amplification, Chlamydia OOI - Real Time Nucleic Acid Amplification System 4. Panel: Microbiology (83) H. Intended Use: 1. Intended use(s): The cobas CT/NG on the cobas 6800/8800 system is an automated, qualitative in vitro nucleic acid diagnostic test, that utilizes real-time polymerase chain reaction (PCR), for the direct detection of Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (NG) DNA in male and female urine, clinician-instructed self-collected vaginal swab specimens (collected in a clinical setting), clinician-collected vaginal swab specimens, and endocervical swab specimens, all collected in cobas PCR Media (Roche Molecular Systems, Inc.), and cervical specimens collected in PreservCyt solution. This test is intended as an aid in the diagnosis of chlamydial and gonococcal disease in both symptomatic and asymptomatic individuals. Ancillary Collection Kits: The cobas PCR Media Dual Swab Sample Kit is used to collect and transport endocervical and vaginal swab specimens. The cobas PCR Media serves as a nucleic acid stabilizing transport and storage medium for gynecological specimens. Note: This kit has been validated for use with the following tests: • cobas CT/NG v2.0 Test • cobas CT/NG for use on cobas 6800/8800 Systems The cobas PCR Media Uni Swab Sample Kit is used to collect and transport human specimens. The cobas PCR Media serves as a nucleic acid stabilizing transport and storage medium for human specimens. Note: This kit has been validated for use with the following tests: • cobas CT/NG v2.0 Test • cobas CT/NG for use on cobas 6800/8800 Systems • cobas Cdiff Test for use on the cobas 4800 System The cobas PCR Urine Sample Kit is used to collect and transport urine specimens. The cobas PCR Media serves as a nucleic acid stabilizing transport and storage medium for urine specimens. Use this collection kit only with either cobas CT/NG on cobas 6800/8800 Systems or the cobas CT/NG v2.0 Test. 2. Indication(s) for use: Same as the Intended Use 3 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: cobas 6800/8800 Systems I. Device Description: The cobas CT/NG assay is a new fully automated, qualitative real-time PCR assay performed on the cobas 6800 System and cobas 8800 System. cobas CT/NG enables the detection of CT/NG DNA in endocervical and vaginal swabs, urine, and cervical specimens from infected female patients and urine specimens from infected male patients. Target-specific primers and two probes are used to detect but not discriminate between the CT cryptic plasmid and the ompA gene. Additionally, target-specific primers and two probes are used to detect but not discriminate between two conserved sequences in the NG DR-9 region. The DNA Internal Control, used to monitor the entire sample preparation and PCR amplification process, is introduced into each specimen during sample processing. In addition, the test utilizes a low titer positive and a negative control. J. Substantial Equivalence Information: 1. Predicate device name(s): cobas CT/NG v2.0 Test 2. Predicate 510(k) number(s): K163184 3. Comparison with predicate: Similarities Item Device Predicate Regulation 866.3390 866.3390 Intended Use The cobas CT/NG on the cobas 6800/8800 system is an automated, qualitative in vitro nucleic acid diagnostic test, that utilizes real- time polymerase chain reaction (PCR), for the direct detection of Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (NG) DNA in male and female urine, clinician instructed self- collected vaginal swab specimens (collected in a clinical setting), clinician-collected vaginal swab The cobas CT/NG v2.0 Test is an automated, in vitro nucleic acid amplification test for the qualitative detection of Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (NG) DNA in urogenital specimens. The Test utilizes the Polymerase Chain Reaction (PCR) for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae DNA in male and female urine, self-collected vaginal swab specimens (collected in a clinical setting), cliniciancollected vaginal swab 4 Similarities Item Device Predicate specimens, and endocervical swab specimens, all collected in cobas PCR Media (Roche Molecular Systems, Inc.), and cervical specimens collected in PreservCyt solution. This test is intended as an aid in the diagnosis of chlamydial and gonococcal disease in both symptomatic and asymptomatic individuals. Ancillary Collection Kits: The cobas PCR Media Dual Swab Sample Kit is used to collect and transport endocervical and vaginal swab specimens. The cobas® PCR Media serves as a nucleic acid stabilizing transport and storage medium for gynecological specimens. Note: This kit has been validated for use with the following tests: cobas CT/NG v2.0 Test cobas® CT/NG for use on cobas 6800/8800 Systems. The cobas PCR Media Uni Swab Sample Kit is used to collect and transport human specimens. The cobas PCR Media serves as a nucleic acid stabilizing transport and storage medium for human specimens Note: This kit has been validated for use with the following tests: cobas CT/NG v2.0 Test cobas CT/NG for use on cobas 6800/8800 Systems cobas Cdiff Test for use on the cobas 4800 System The cobas PCR Urine Sample Kit is used to collect and transport urine specimens. The cobas PCR Media serves as a nucleic acid specimens, and endocervical swab specimens, all collected in cobas PCR Media (Roche Molecular Systems, Inc.), and cervical specimens collected in PreservCyt solution. This test is intended as an aid in the diagnosis of chlamydial and gonococcal disease in both symptomatic and asymptomatic individuals. Ancillary Collection Kits: The cobas PCR Media Dual Swab Sample Kit is used to collect and transport endocervical and vaginal swab specimens. The cobas PCR Media serves as a nucleic acid stabilizing transport and storage medium for gynecological specimens. Use this collection kit only with the cobas CT/NG v2.0 Test. The cobas PCR Media Uni Swab Sample Kit is used to collect and transport human specimens. The cobas PCR Media serves as a nucleic acid stabilizing transport and storage medium for human specimens. Use this collection kit with cobas CT/NG v2.0 Test and cobas Cdiff Tests. The cobas PCR Urine Sample Kit is used to collect and transport urine specimens. The cobas PCR Media serves as a nucleic acid stabilizing transport and storage medium for urine specimens. Use this collection kit only with the cobas CT/NG v2.0 Test. 5 Similarities Item Device Predicate stabilizing transport and storage medium for urine specimens Use this collection kit only with either cobas CT/NG on cobas 6800/8800 Systems or the cobas CT/NG v2.0 Test. Sample Types Same Male and female urine, Self- collected/clinician-collected vaginal swab specimens in cobas PCR Media, Endocervical swab specimens in cobas PCR Media, Cervical specimens in PreservCyt solution Subject Status Same Asymptomatic and symptomatic Sample Collection Devices Same cobas PCR Media Dual Swab Sample Kit cobas PCR Media Uni Swab Sample Kit cobas PCR Urine Sample Kit CT Analyte targets Same CT cryptic plasmid DNA CT o Panel:

idK173887_s0_e2000

K173887.txt

predicate device name

cobas CT/NG v2.0 Test

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K173887 B. Purpose for Submission: To determine substantial equivalence for the cobas CT/NG assay for use on the cobas 6800/8800 Systems for detection of Chlamydia trachomatis and Neisseria gonorrhoeae DNA from self-collected vaginal swabs, clinician-collected vaginal swabs, endocervical swabs, male and female urine, and cervical specimens collected in PreservCyt solution. C. Measurand: Chlamydia trachomatis and Neisseria gonorrhoeae DNA D. Type of Test: Nucleic acid extraction, purification and amplification assay (real-time polymerase chain reaction) E. Applicant: Roche Molecular Systems, Inc. F. Proprietary and Established Names: cobas CT/NG cobas 6800/8800 Systems G. Regulatory Information: 1. Regulation section: 21 CFR 866.3390 - Neisseria spp. direct serological test reagents 2. Classification: Class II 3. Product code: LSL - DNA-Reagents, Neisseria 2 MKZ - DNA Probe, Nucleic Acid Amplification, Chlamydia OOI - Real Time Nucleic Acid Amplification System 4. Panel: Microbiology (83) H. Intended Use: 1. Intended use(s): The cobas CT/NG on the cobas 6800/8800 system is an automated, qualitative in vitro nucleic acid diagnostic test, that utilizes real-time polymerase chain reaction (PCR), for the direct detection of Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (NG) DNA in male and female urine, clinician-instructed self-collected vaginal swab specimens (collected in a clinical setting), clinician-collected vaginal swab specimens, and endocervical swab specimens, all collected in cobas PCR Media (Roche Molecular Systems, Inc.), and cervical specimens collected in PreservCyt solution. This test is intended as an aid in the diagnosis of chlamydial and gonococcal disease in both symptomatic and asymptomatic individuals. Ancillary Collection Kits: The cobas PCR Media Dual Swab Sample Kit is used to collect and transport endocervical and vaginal swab specimens. The cobas PCR Media serves as a nucleic acid stabilizing transport and storage medium for gynecological specimens. Note: This kit has been validated for use with the following tests: • cobas CT/NG v2.0 Test • cobas CT/NG for use on cobas 6800/8800 Systems The cobas PCR Media Uni Swab Sample Kit is used to collect and transport human specimens. The cobas PCR Media serves as a nucleic acid stabilizing transport and storage medium for human specimens. Note: This kit has been validated for use with the following tests: • cobas CT/NG v2.0 Test • cobas CT/NG for use on cobas 6800/8800 Systems • cobas Cdiff Test for use on the cobas 4800 System The cobas PCR Urine Sample Kit is used to collect and transport urine specimens. The cobas PCR Media serves as a nucleic acid stabilizing transport and storage medium for urine specimens. Use this collection kit only with either cobas CT/NG on cobas 6800/8800 Systems or the cobas CT/NG v2.0 Test. 2. Indication(s) for use: Same as the Intended Use 3 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: cobas 6800/8800 Systems I. Device Description: The cobas CT/NG assay is a new fully automated, qualitative real-time PCR assay performed on the cobas 6800 System and cobas 8800 System. cobas CT/NG enables the detection of CT/NG DNA in endocervical and vaginal swabs, urine, and cervical specimens from infected female patients and urine specimens from infected male patients. Target-specific primers and two probes are used to detect but not discriminate between the CT cryptic plasmid and the ompA gene. Additionally, target-specific primers and two probes are used to detect but not discriminate between two conserved sequences in the NG DR-9 region. The DNA Internal Control, used to monitor the entire sample preparation and PCR amplification process, is introduced into each specimen during sample processing. In addition, the test utilizes a low titer positive and a negative control. J. Substantial Equivalence Information: 1. Predicate device name(s): cobas CT/NG v2.0 Test 2. Predicate 510(k) number(s): K163184 3. Comparison with predicate: Similarities Item Device Predicate Regulation 866.3390 866.3390 Intended Use The cobas CT/NG on the cobas 6800/8800 system is an automated, qualitative in vitro nucleic acid diagnostic test, that utilizes real- time polymerase chain reaction (PCR), for the direct detection of Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (NG) DNA in male and female urine, clinician instructed self- collected vaginal swab specimens (collected in a clinical setting), clinician-collected vaginal swab The cobas CT/NG v2.0 Test is an automated, in vitro nucleic acid amplification test for the qualitative detection of Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (NG) DNA in urogenital specimens. The Test utilizes the Polymerase Chain Reaction (PCR) for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae DNA in male and female urine, self-collected vaginal swab specimens (collected in a clinical setting), cliniciancollected vaginal swab 4 Similarities Item Device Predicate specimens, and endocervical swab specimens, all collected in cobas PCR Media (Roche Molecular Systems, Inc.), and cervical specimens collected in PreservCyt solution. This test is intended as an aid in the diagnosis of chlamydial and gonococcal disease in both symptomatic and asymptomatic individuals. Ancillary Collection Kits: The cobas PCR Media Dual Swab Sample Kit is used to collect and transport endocervical and vaginal swab specimens. The cobas® PCR Media serves as a nucleic acid stabilizing transport and storage medium for gynecological specimens. Note: This kit has been validated for use with the following tests: cobas CT/NG v2.0 Test cobas® CT/NG for use on cobas 6800/8800 Systems. The cobas PCR Media Uni Swab Sample Kit is used to collect and transport human specimens. The cobas PCR Media serves as a nucleic acid stabilizing transport and storage medium for human specimens Note: This kit has been validated for use with the following tests: cobas CT/NG v2.0 Test cobas CT/NG for use on cobas 6800/8800 Systems cobas Cdiff Test for use on the cobas 4800 System The cobas PCR Urine Sample Kit is used to collect and transport urine specimens. The cobas PCR Media serves as a nucleic acid specimens, and endocervical swab specimens, all collected in cobas PCR Media (Roche Molecular Systems, Inc.), and cervical specimens collected in PreservCyt solution. This test is intended as an aid in the diagnosis of chlamydial and gonococcal disease in both symptomatic and asymptomatic individuals. Ancillary Collection Kits: The cobas PCR Media Dual Swab Sample Kit is used to collect and transport endocervical and vaginal swab specimens. The cobas PCR Media serves as a nucleic acid stabilizing transport and storage medium for gynecological specimens. Use this collection kit only with the cobas CT/NG v2.0 Test. The cobas PCR Media Uni Swab Sample Kit is used to collect and transport human specimens. The cobas PCR Media serves as a nucleic acid stabilizing transport and storage medium for human specimens. Use this collection kit with cobas CT/NG v2.0 Test and cobas Cdiff Tests. The cobas PCR Urine Sample Kit is used to collect and transport urine specimens. The cobas PCR Media serves as a nucleic acid stabilizing transport and storage medium for urine specimens. Use this collection kit only with the cobas CT/NG v2.0 Test. 5 Similarities Item Device Predicate stabilizing transport and storage medium for urine specimens Use this collection kit only with either cobas CT/NG on cobas 6800/8800 Systems or the cobas CT/NG v2.0 Test. Sample Types Same Male and female urine, Self- collected/clinician-collected vaginal swab specimens in cobas PCR Media, Endocervical swab specimens in cobas PCR Media, Cervical specimens in PreservCyt solution Subject Status Same Asymptomatic and symptomatic Sample Collection Devices Same cobas PCR Media Dual Swab Sample Kit cobas PCR Media Uni Swab Sample Kit cobas PCR Urine Sample Kit CT Analyte targets Same CT cryptic plasmid DNA CT o Predicate device name:

idK173887_s0_e2000

K173887.txt

applicant

Roche Molecular Systems, Inc.

k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K173887 B. Purpose for Submission: To determine substantial equivalence for the cobas CT/NG assay for use on the cobas 6800/8800 Systems for detection of Chlamydia trachomatis and Neisseria gonorrhoeae DNA from self-collected vaginal swabs, clinician-collected vaginal swabs, endocervical swabs, male and female urine, and cervical specimens collected in PreservCyt solution. C. Measurand: Chlamydia trachomatis and Neisseria gonorrhoeae DNA D. Type of Test: Nucleic acid extraction, purification and amplification assay (real-time polymerase chain reaction) E. Applicant: Roche Molecular Systems, Inc. F. Proprietary and Established Names: cobas CT/NG cobas 6800/8800 Systems G. Regulatory Information: 1. Regulation section: 21 CFR 866.3390 - Neisseria spp. direct serological test reagents 2. Classification: Class II 3. Product code: LSL - DNA-Reagents, Neisseria 2 MKZ - DNA Probe, Nucleic Acid Amplification, Chlamydia OOI - Real Time Nucleic Acid Amplification System 4. Panel: Microbiology (83) H. Intended Use: 1. Intended use(s): The cobas CT/NG on the cobas 6800/8800 system is an automated, qualitative in vitro nucleic acid diagnostic test, that utilizes real-time polymerase chain reaction (PCR), for the direct detection of Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (NG) DNA in male and female urine, clinician-instructed self-collected vaginal swab specimens (collected in a clinical setting), clinician-collected vaginal swab specimens, and endocervical swab specimens, all collected in cobas PCR Media (Roche Molecular Systems, Inc.), and cervical specimens collected in PreservCyt solution. This test is intended as an aid in the diagnosis of chlamydial and gonococcal disease in both symptomatic and asymptomatic individuals. Ancillary Collection Kits: The cobas PCR Media Dual Swab Sample Kit is used to collect and transport endocervical and vaginal swab specimens. The cobas PCR Media serves as a nucleic acid stabilizing transport and storage medium for gynecological specimens. Note: This kit has been validated for use with the following tests: • cobas CT/NG v2.0 Test • cobas CT/NG for use on cobas 6800/8800 Systems The cobas PCR Media Uni Swab Sample Kit is used to collect and transport human specimens. The cobas PCR Media serves as a nucleic acid stabilizing transport and storage medium for human specimens. Note: This kit has been validated for use with the following tests: • cobas CT/NG v2.0 Test • cobas CT/NG for use on cobas 6800/8800 Systems • cobas Cdiff Test for use on the cobas 4800 System The cobas PCR Urine Sample Kit is used to collect and transport urine specimens. The cobas PCR Media serves as a nucleic acid stabilizing transport and storage medium for urine specimens. Use this collection kit only with either cobas CT/NG on cobas 6800/8800 Systems or the cobas CT/NG v2.0 Test. 2. Indication(s) for use: Same as the Intended Use 3 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: cobas 6800/8800 Systems I. Device Description: The cobas CT/NG assay is a new fully automated, qualitative real-time PCR assay performed on the cobas 6800 System and cobas 8800 System. cobas CT/NG enables the detection of CT/NG DNA in endocervical and vaginal swabs, urine, and cervical specimens from infected female patients and urine specimens from infected male patients. Target-specific primers and two probes are used to detect but not discriminate between the CT cryptic plasmid and the ompA gene. Additionally, target-specific primers and two probes are used to detect but not discriminate between two conserved sequences in the NG DR-9 region. The DNA Internal Control, used to monitor the entire sample preparation and PCR amplification process, is introduced into each specimen during sample processing. In addition, the test utilizes a low titer positive and a negative control. J. Substantial Equivalence Information: 1. Predicate device name(s): cobas CT/NG v2.0 Test 2. Predicate 510(k) number(s): K163184 3. Comparison with predicate: Similarities Item Device Predicate Regulation 866.3390 866.3390 Intended Use The cobas CT/NG on the cobas 6800/8800 system is an automated, qualitative in vitro nucleic acid diagnostic test, that utilizes real- time polymerase chain reaction (PCR), for the direct detection of Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (NG) DNA in male and female urine, clinician instructed self- collected vaginal swab specimens (collected in a clinical setting), clinician-collected vaginal swab The cobas CT/NG v2.0 Test is an automated, in vitro nucleic acid amplification test for the qualitative detection of Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (NG) DNA in urogenital specimens. The Test utilizes the Polymerase Chain Reaction (PCR) for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae DNA in male and female urine, self-collected vaginal swab specimens (collected in a clinical setting), cliniciancollected vaginal swab 4 Similarities Item Device Predicate specimens, and endocervical swab specimens, all collected in cobas PCR Media (Roche Molecular Systems, Inc.), and cervical specimens collected in PreservCyt solution. This test is intended as an aid in the diagnosis of chlamydial and gonococcal disease in both symptomatic and asymptomatic individuals. Ancillary Collection Kits: The cobas PCR Media Dual Swab Sample Kit is used to collect and transport endocervical and vaginal swab specimens. The cobas® PCR Media serves as a nucleic acid stabilizing transport and storage medium for gynecological specimens. Note: This kit has been validated for use with the following tests: cobas CT/NG v2.0 Test cobas® CT/NG for use on cobas 6800/8800 Systems. The cobas PCR Media Uni Swab Sample Kit is used to collect and transport human specimens. The cobas PCR Media serves as a nucleic acid stabilizing transport and storage medium for human specimens Note: This kit has been validated for use with the following tests: cobas CT/NG v2.0 Test cobas CT/NG for use on cobas 6800/8800 Systems cobas Cdiff Test for use on the cobas 4800 System The cobas PCR Urine Sample Kit is used to collect and transport urine specimens. The cobas PCR Media serves as a nucleic acid specimens, and endocervical swab specimens, all collected in cobas PCR Media (Roche Molecular Systems, Inc.), and cervical specimens collected in PreservCyt solution. This test is intended as an aid in the diagnosis of chlamydial and gonococcal disease in both symptomatic and asymptomatic individuals. Ancillary Collection Kits: The cobas PCR Media Dual Swab Sample Kit is used to collect and transport endocervical and vaginal swab specimens. The cobas PCR Media serves as a nucleic acid stabilizing transport and storage medium for gynecological specimens. Use this collection kit only with the cobas CT/NG v2.0 Test. The cobas PCR Media Uni Swab Sample Kit is used to collect and transport human specimens. The cobas PCR Media serves as a nucleic acid stabilizing transport and storage medium for human specimens. Use this collection kit with cobas CT/NG v2.0 Test and cobas Cdiff Tests. The cobas PCR Urine Sample Kit is used to collect and transport urine specimens. The cobas PCR Media serves as a nucleic acid stabilizing transport and storage medium for urine specimens. Use this collection kit only with the cobas CT/NG v2.0 Test. 5 Similarities Item Device Predicate stabilizing transport and storage medium for urine specimens Use this collection kit only with either cobas CT/NG on cobas 6800/8800 Systems or the cobas CT/NG v2.0 Test. Sample Types Same Male and female urine, Self- collected/clinician-collected vaginal swab specimens in cobas PCR Media, Endocervical swab specimens in cobas PCR Media, Cervical specimens in PreservCyt solution Subject Status Same Asymptomatic and symptomatic Sample Collection Devices Same cobas PCR Media Dual Swab Sample Kit cobas PCR Media Uni Swab Sample Kit cobas PCR Urine Sample Kit CT Analyte targets Same CT cryptic plasmid DNA CT o Applicant:

idK173887_s0_e2000

K173887.txt

regulation section

21 CFR 866.3390 - Neisseria spp. direct serological test reagents

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K173887 B. Purpose for Submission: To determine substantial equivalence for the cobas CT/NG assay for use on the cobas 6800/8800 Systems for detection of Chlamydia trachomatis and Neisseria gonorrhoeae DNA from self-collected vaginal swabs, clinician-collected vaginal swabs, endocervical swabs, male and female urine, and cervical specimens collected in PreservCyt solution. C. Measurand: Chlamydia trachomatis and Neisseria gonorrhoeae DNA D. Type of Test: Nucleic acid extraction, purification and amplification assay (real-time polymerase chain reaction) E. Applicant: Roche Molecular Systems, Inc. F. Proprietary and Established Names: cobas CT/NG cobas 6800/8800 Systems G. Regulatory Information: 1. Regulation section: 21 CFR 866.3390 - Neisseria spp. direct serological test reagents 2. Classification: Class II 3. Product code: LSL - DNA-Reagents, Neisseria 2 MKZ - DNA Probe, Nucleic Acid Amplification, Chlamydia OOI - Real Time Nucleic Acid Amplification System 4. Panel: Microbiology (83) H. Intended Use: 1. Intended use(s): The cobas CT/NG on the cobas 6800/8800 system is an automated, qualitative in vitro nucleic acid diagnostic test, that utilizes real-time polymerase chain reaction (PCR), for the direct detection of Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (NG) DNA in male and female urine, clinician-instructed self-collected vaginal swab specimens (collected in a clinical setting), clinician-collected vaginal swab specimens, and endocervical swab specimens, all collected in cobas PCR Media (Roche Molecular Systems, Inc.), and cervical specimens collected in PreservCyt solution. This test is intended as an aid in the diagnosis of chlamydial and gonococcal disease in both symptomatic and asymptomatic individuals. Ancillary Collection Kits: The cobas PCR Media Dual Swab Sample Kit is used to collect and transport endocervical and vaginal swab specimens. The cobas PCR Media serves as a nucleic acid stabilizing transport and storage medium for gynecological specimens. Note: This kit has been validated for use with the following tests: • cobas CT/NG v2.0 Test • cobas CT/NG for use on cobas 6800/8800 Systems The cobas PCR Media Uni Swab Sample Kit is used to collect and transport human specimens. The cobas PCR Media serves as a nucleic acid stabilizing transport and storage medium for human specimens. Note: This kit has been validated for use with the following tests: • cobas CT/NG v2.0 Test • cobas CT/NG for use on cobas 6800/8800 Systems • cobas Cdiff Test for use on the cobas 4800 System The cobas PCR Urine Sample Kit is used to collect and transport urine specimens. The cobas PCR Media serves as a nucleic acid stabilizing transport and storage medium for urine specimens. Use this collection kit only with either cobas CT/NG on cobas 6800/8800 Systems or the cobas CT/NG v2.0 Test. 2. Indication(s) for use: Same as the Intended Use 3 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: cobas 6800/8800 Systems I. Device Description: The cobas CT/NG assay is a new fully automated, qualitative real-time PCR assay performed on the cobas 6800 System and cobas 8800 System. cobas CT/NG enables the detection of CT/NG DNA in endocervical and vaginal swabs, urine, and cervical specimens from infected female patients and urine specimens from infected male patients. Target-specific primers and two probes are used to detect but not discriminate between the CT cryptic plasmid and the ompA gene. Additionally, target-specific primers and two probes are used to detect but not discriminate between two conserved sequences in the NG DR-9 region. The DNA Internal Control, used to monitor the entire sample preparation and PCR amplification process, is introduced into each specimen during sample processing. In addition, the test utilizes a low titer positive and a negative control. J. Substantial Equivalence Information: 1. Predicate device name(s): cobas CT/NG v2.0 Test 2. Predicate 510(k) number(s): K163184 3. Comparison with predicate: Similarities Item Device Predicate Regulation 866.3390 866.3390 Intended Use The cobas CT/NG on the cobas 6800/8800 system is an automated, qualitative in vitro nucleic acid diagnostic test, that utilizes real- time polymerase chain reaction (PCR), for the direct detection of Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (NG) DNA in male and female urine, clinician instructed self- collected vaginal swab specimens (collected in a clinical setting), clinician-collected vaginal swab The cobas CT/NG v2.0 Test is an automated, in vitro nucleic acid amplification test for the qualitative detection of Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (NG) DNA in urogenital specimens. The Test utilizes the Polymerase Chain Reaction (PCR) for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae DNA in male and female urine, self-collected vaginal swab specimens (collected in a clinical setting), cliniciancollected vaginal swab 4 Similarities Item Device Predicate specimens, and endocervical swab specimens, all collected in cobas PCR Media (Roche Molecular Systems, Inc.), and cervical specimens collected in PreservCyt solution. This test is intended as an aid in the diagnosis of chlamydial and gonococcal disease in both symptomatic and asymptomatic individuals. Ancillary Collection Kits: The cobas PCR Media Dual Swab Sample Kit is used to collect and transport endocervical and vaginal swab specimens. The cobas® PCR Media serves as a nucleic acid stabilizing transport and storage medium for gynecological specimens. Note: This kit has been validated for use with the following tests: cobas CT/NG v2.0 Test cobas® CT/NG for use on cobas 6800/8800 Systems. The cobas PCR Media Uni Swab Sample Kit is used to collect and transport human specimens. The cobas PCR Media serves as a nucleic acid stabilizing transport and storage medium for human specimens Note: This kit has been validated for use with the following tests: cobas CT/NG v2.0 Test cobas CT/NG for use on cobas 6800/8800 Systems cobas Cdiff Test for use on the cobas 4800 System The cobas PCR Urine Sample Kit is used to collect and transport urine specimens. The cobas PCR Media serves as a nucleic acid specimens, and endocervical swab specimens, all collected in cobas PCR Media (Roche Molecular Systems, Inc.), and cervical specimens collected in PreservCyt solution. This test is intended as an aid in the diagnosis of chlamydial and gonococcal disease in both symptomatic and asymptomatic individuals. Ancillary Collection Kits: The cobas PCR Media Dual Swab Sample Kit is used to collect and transport endocervical and vaginal swab specimens. The cobas PCR Media serves as a nucleic acid stabilizing transport and storage medium for gynecological specimens. Use this collection kit only with the cobas CT/NG v2.0 Test. The cobas PCR Media Uni Swab Sample Kit is used to collect and transport human specimens. The cobas PCR Media serves as a nucleic acid stabilizing transport and storage medium for human specimens. Use this collection kit with cobas CT/NG v2.0 Test and cobas Cdiff Tests. The cobas PCR Urine Sample Kit is used to collect and transport urine specimens. The cobas PCR Media serves as a nucleic acid stabilizing transport and storage medium for urine specimens. Use this collection kit only with the cobas CT/NG v2.0 Test. 5 Similarities Item Device Predicate stabilizing transport and storage medium for urine specimens Use this collection kit only with either cobas CT/NG on cobas 6800/8800 Systems or the cobas CT/NG v2.0 Test. Sample Types Same Male and female urine, Self- collected/clinician-collected vaginal swab specimens in cobas PCR Media, Endocervical swab specimens in cobas PCR Media, Cervical specimens in PreservCyt solution Subject Status Same Asymptomatic and symptomatic Sample Collection Devices Same cobas PCR Media Dual Swab Sample Kit cobas PCR Media Uni Swab Sample Kit cobas PCR Urine Sample Kit CT Analyte targets Same CT cryptic plasmid DNA CT o Regulation section:

idK173887_s28000_e30000

K173887.txt

proposed labeling

The labeling is sufficient and it satisfies the requirements of 21 CFR Parts 801 and 809, as applicable.

by comparing the cobas CT/NG Test results to patient infected status across all sample types in both female and male subjects. N. Instrument Name: Cobas 6800 and cobas 8800 Systems O. System Descriptions: 1. Modes of Operation: Does the applicant’s device contain the ability to transmit data to a computer, webserver, or mobile device? Yes _____X___ or No ________ Does the applicant’s device transmit data to a computer, webserver, or mobile device using wireless transmission? Yes ________ or No __X______ 2. Software: FDA has reviewed applicant’s Hazard Analysis and software development processes for this line of product types: Yes ____X____ or No ________ 3. Specimen Identification: Cobas 6800/8800 supports multiple types of barcodes. Loaded samples are automatically moved for barcode scanning and processing. 49 4. Specimen Sampling and Handling: Specimens are collected using the appropriate ancillary kits (cobas PCR Media Dual Swab Sample Kit, cobas PCR Media Uni Swab Sample Kit, or cobas PCR Urine Sample Kit) or PreservCyt Solution as per defined instructions. Swab specimens containing a single swab in the cobas PCR Media tube can be directly processed on the cobas 6800/8800 Systems, or the swab may be removed prior to loading onto the instrument. Urine specimens must show a liquid level between two black indicator lines on the cobas PCR Media tube to proceed to testing. Cervical specimens in PreservCyt Solution are to be aliquoted into barcoded cobas PCR Secondary tubes for processing. Only racks of uncapped tubes may be loaded into the Sample Supply Module of the cobas 6800/8800 Systems for testing. Specimen processing is fully automated. 5. Calibration: No calibration is required by the user. 6. Quality Control: Please see section M.1.c. P. Other Supportive Instrument Performance Characteristics Data Not Covered In The “Performance Characteristics” Section above: N/A Q. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Parts 801 and 809, as applicable. R. Conclusion: 1. The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Proposed labeling:

idK173887_s28000_e30000

K173887.txt

conclusion

1. The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

were estimated by comparing the cobas CT/NG Test results to patient infected status across all sample types in both female and male subjects. N. Instrument Name: Cobas 6800 and cobas 8800 Systems O. System Descriptions: 1. Modes of Operation: Does the applicant’s device contain the ability to transmit data to a computer, webserver, or mobile device? Yes _____X___ or No ________ Does the applicant’s device transmit data to a computer, webserver, or mobile device using wireless transmission? Yes ________ or No __X______ 2. Software: FDA has reviewed applicant’s Hazard Analysis and software development processes for this line of product types: Yes ____X____ or No ________ 3. Specimen Identification: Cobas 6800/8800 supports multiple types of barcodes. Loaded samples are automatically moved for barcode scanning and processing. 49 4. Specimen Sampling and Handling: Specimens are collected using the appropriate ancillary kits (cobas PCR Media Dual Swab Sample Kit, cobas PCR Media Uni Swab Sample Kit, or cobas PCR Urine Sample Kit) or PreservCyt Solution as per defined instructions. Swab specimens containing a single swab in the cobas PCR Media tube can be directly processed on the cobas 6800/8800 Systems, or the swab may be removed prior to loading onto the instrument. Urine specimens must show a liquid level between two black indicator lines on the cobas PCR Media tube to proceed to testing. Cervical specimens in PreservCyt Solution are to be aliquoted into barcoded cobas PCR Secondary tubes for processing. Only racks of uncapped tubes may be loaded into the Sample Supply Module of the cobas 6800/8800 Systems for testing. Specimen processing is fully automated. 5. Calibration: No calibration is required by the user. 6. Quality Control: Please see section M.1.c. P. Other Supportive Instrument Performance Characteristics Data Not Covered In The “Performance Characteristics” Section above: N/A Q. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Parts 801 and 809, as applicable. R. Conclusion: 1. The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Conclusion:

idK173927_s0_e2000

K173927.txt

purpose for submission

To obtain a substantial equivalence determination for the Elecsys BRAHMS PCT.

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K173927 B. Purpose for Submission: To obtain a substantial equivalence determination for the Elecsys BRAHMS PCT. C. Measurand: Procalcitonin (PCT) D. Type of Test: Quantitative, Electrochemiluminescence Immunoassay E. Applicant: Roche Diagnostics F. Proprietary and Established Names: Elecsys BRAHMS PCT G. Regulatory Information: 1. Regulation section: 21 CFR 866.3215; Device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis 2. Classification: Class II (Special Controls) 3. Product codes: PMT 4. Panel: 83 - (Microbiology) 2 H. Intended Use/ Indications for Use: 1. Intended Use/ Indications for Use: Immunoassay for the in vitro quantitative determination of PCT (procalcitonin) in human serum and plasma (K2 –EDTA, K3-EDTA and Li-Heparin). The electrochemiluminescence immunoassay “ECLIA” is intended for use on Elecsys and cobas e immunoassay analyzers. Used in conjunction with other laboratory findings and clinical assessments, Elecsys BRAHMS PCT is intended for use as follows: · to aid in the risk assessment of critically ill patients on their first day of ICU admission for progression to severe sepsis and septic shock, · to determine the change in PCT level over time as an aid in assessing the cumulative 28-day risk of all-cause mortality for patients diagnosed with severe sepsis or septic shock in the ICU or when obtained in the emergency department or other medical wards prior to ICU admission, · to aid in decision making on antibiotic therapy, for inpatients or patients in the emergency department with suspected or confirmed lower respiratory tract infections (LRTI) – defined as community-acquired pneumonia (CAP), acute bronchitis, and acute exacerbation of chronic obstructive pulmonary disease (AECOPD), · to aid in decision making on antibiotic discontinuation for patients with suspected or confirmed sepsis. 2. Special conditions for use statement(s): For prescription use only Warnings and Precautions: The Elecsys BRAHMS PCT assay should not be used as a sole basis for diagnosis for determining the risk of 28 day all-cause mortality. Changes in PCT should always be interpreted in the context of the clinical status of the patient and other laboratory results. There is no uniformly recognized interpretation of the change in PCT levels for the prediction of mortality, and overall mortality is strongly dependent on many factors, including pre-existing patient risk factors and clinical course. The need for continued ICU care at Day 4 and other covariates (e.g., age, sepsis-related organ failure assessment (SOFA score) are also significant predictors of 28-day cumulative mortality risk. Validation of the Elecsys BRAHMS PCT assay as an aid in predicting mortality was performed in a study population with an overall 28-day mortality of 22%. 3. Special instrument requirements: 3 The submission demonstrates performance on the cobas e411 immunoassay analyzer. I. Device Description: Reagents Materials provided in Elecsys BRAHMS PCT: The reagent working solutions include: Rackpack (kit placed on analyzer) · M: Streptavidin-coated microparticles · R1: Anti-PCT-Ab~biotin · R2: Anti-PCT – Ab~Ru (bpy) J. Substantial Equivalence Information: 1. Predicate device name(s): BRAHMS PCT sensitive KRYPTOR 2. Predicate 510(k) number(s): K171338 4. Comparison with predicate: 4 Similarities Item Candidate Device: Elecsys BRAHMS PCT (K173927) Predicate Device: BRAHMS PCT sensitive KRYPTOR (K171338) Intended Use Immunoassay for the in vitro quantitative determination of PCT (procalcitonin) in human serum and plasma (K2 –EDTA, K3- EDTA and Li-Heparin). The electrochemiluminescence immunoassay “ECLIA” is intended for use on Elecsys and cobas e immunoassay analyzers. Used in conjunction with other laboratory findings and clinical assessments, Elecsys B·R·A·H·M·S PCT is intended for use as follows: · to aid in the risk assessment of critically ill patients on their first day of ICU admission for progression to severe sepsis and septic shock, · to determine the change in PCT level over time as an aid in assessing the cumulative 28-day risk of all-cause mortality for patients diagnosed with severe sepsis or septic shock in the ICU or when obtained in the emergency department or other medical wards prior to ICU admission, · to aid in decision making on antibiotic therapy, for inpatients or patients in the emergency department with suspected or confirmed lower respiratory tract infections (LRTI) – defined as community-acquired pneumonia (CAP), acute bronchitis, and acute exacerbation of chronic obstructive pulmonary disease (AECOPD), · to aid in decision making on antibiotic discontinuation for patients with suspected or confirmed sepsis. The BRAHMS PCT sensitive KRYPTOR is an immunofluorescent assay using Time- Resolved Amplified Cryptate Emission (TRACE) technology to determine the concentration of PCT (procalcitonin) in human serum and EDTA or heparin plasma. The BRAHMS PCT sensitive KRYPTOR is intended to be performed on the BRAHMS KRYPTOR analyzer family. Used in conjunction with other laboratory findings and clinical assessments, BRAHMS PCT sensitive KRYPTOR is intended for use as follows: · to aid in the risk assessment of critically ill patients on their first day of ICU admission for progression to severe sepsis and septic shock, · to determine the change in PCT level over time as an aid in assessing the cumulative 28-day risk of all-cause mortality for patients diagnosed with severe sepsis or septic shock in the ICU or when obtained in the emergency department or other medical wards prior to ICU admission, · to aid in decision making on antibiotic therapy, for inpatients or patients in the emergency department with suspected or confirmed lower respiratory tract infections (LRTI) – defined as community-acquired pneumonia (CAP), acute bronchitis, and acute exacerbation of chronic obstructive pulmonary disease (AECOPD), · to aid in decision making on antibiotic discontinuation for patients with suspected or confirmed sepsis. 5 Differences Item Candidate Device: Elecsys BRAHMS PCT (K173927) Predicate Device: BRAHMS PCT sensitive KRYPTOR (DEN150009) Assay Protocol The Elecsys BRAHMS PCT assay is a two-step sandwich immunoassay with streptavidin microparticles and an electrochemiluminescence detection system. The test system reagents contain a biotinylated monoclonal PCT-specific antibody and a ruthenium labeled monoclonal PCT-specific antibody. The BRAHMS PCT sensitive KRYPTOR assay is a homogeneous sandwich immunoassay for detection of PCT in human serum or plasma. The measuring principle is based on Time-Resolved Amplified Cryptate Emission (TRACE) technology, which measures the signal that is emitted from an immunocomplex with time delay. Detection Protocol Electrochemiluminescent Assay Time-Resolved Amplified Cryptate Emission (TRACE) Applications 18-minute application 19-minute incubation Instrument Platform cobas e 411 analyzer BRAHMS KRYPTOR analyzer Sample Volume 30 µL 50 µL Sample Type Human serum and plasma (Li- Heparin, K2/K3 EDTA) Human serum and plasma (EDTA, heparin) Reagents · Streptavidin-coated microparticles: · Steptavidin-coated microparticles; preservative · Anti-PCT-Ab~biotin: Biotinylated monoclonal anti-PCT antibody (mouse), phosphate buffer, preservative · Anti-PCT – Ab~Ru(bpy) 2/3+ a monoclonal anti-PCT antibody (mouse) labeled with ruthenium complex, phosphate buffer, preservative · Cryptate conjugate, cryptate labeled, anti-PCT antibody (polyclonal, sheep), 3.2mL after reconstitution with KRYPTOR Solution 2 · L665 conjugate, XL665 labeled, anti- PCT antibody (monoclonal, mouse), 3.95 mL after reconstitution with KRYPTOR Solution 1 and KRYPTOR Solution 2 · Defibrinated human plasma, for diluting samples above 50 µg/L, ready for use Calibrator Elecsys PCT CalSet BRAHMS PCT sensitive KRYPTOR Calibrator Calibration Purpose for submission:

idK173927_s0_e2000

K173927.txt

measurand

Procalcitonin (PCT)

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K173927 B. Purpose for Submission: To obtain a substantial equivalence determination for the Elecsys BRAHMS PCT. C. Measurand: Procalcitonin (PCT) D. Type of Test: Quantitative, Electrochemiluminescence Immunoassay E. Applicant: Roche Diagnostics F. Proprietary and Established Names: Elecsys BRAHMS PCT G. Regulatory Information: 1. Regulation section: 21 CFR 866.3215; Device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis 2. Classification: Class II (Special Controls) 3. Product codes: PMT 4. Panel: 83 - (Microbiology) 2 H. Intended Use/ Indications for Use: 1. Intended Use/ Indications for Use: Immunoassay for the in vitro quantitative determination of PCT (procalcitonin) in human serum and plasma (K2 –EDTA, K3-EDTA and Li-Heparin). The electrochemiluminescence immunoassay “ECLIA” is intended for use on Elecsys and cobas e immunoassay analyzers. Used in conjunction with other laboratory findings and clinical assessments, Elecsys BRAHMS PCT is intended for use as follows: · to aid in the risk assessment of critically ill patients on their first day of ICU admission for progression to severe sepsis and septic shock, · to determine the change in PCT level over time as an aid in assessing the cumulative 28-day risk of all-cause mortality for patients diagnosed with severe sepsis or septic shock in the ICU or when obtained in the emergency department or other medical wards prior to ICU admission, · to aid in decision making on antibiotic therapy, for inpatients or patients in the emergency department with suspected or confirmed lower respiratory tract infections (LRTI) – defined as community-acquired pneumonia (CAP), acute bronchitis, and acute exacerbation of chronic obstructive pulmonary disease (AECOPD), · to aid in decision making on antibiotic discontinuation for patients with suspected or confirmed sepsis. 2. Special conditions for use statement(s): For prescription use only Warnings and Precautions: The Elecsys BRAHMS PCT assay should not be used as a sole basis for diagnosis for determining the risk of 28 day all-cause mortality. Changes in PCT should always be interpreted in the context of the clinical status of the patient and other laboratory results. There is no uniformly recognized interpretation of the change in PCT levels for the prediction of mortality, and overall mortality is strongly dependent on many factors, including pre-existing patient risk factors and clinical course. The need for continued ICU care at Day 4 and other covariates (e.g., age, sepsis-related organ failure assessment (SOFA score) are also significant predictors of 28-day cumulative mortality risk. Validation of the Elecsys BRAHMS PCT assay as an aid in predicting mortality was performed in a study population with an overall 28-day mortality of 22%. 3. Special instrument requirements: 3 The submission demonstrates performance on the cobas e411 immunoassay analyzer. I. Device Description: Reagents Materials provided in Elecsys BRAHMS PCT: The reagent working solutions include: Rackpack (kit placed on analyzer) · M: Streptavidin-coated microparticles · R1: Anti-PCT-Ab~biotin · R2: Anti-PCT – Ab~Ru (bpy) J. Substantial Equivalence Information: 1. Predicate device name(s): BRAHMS PCT sensitive KRYPTOR 2. Predicate 510(k) number(s): K171338 4. Comparison with predicate: 4 Similarities Item Candidate Device: Elecsys BRAHMS PCT (K173927) Predicate Device: BRAHMS PCT sensitive KRYPTOR (K171338) Intended Use Immunoassay for the in vitro quantitative determination of PCT (procalcitonin) in human serum and plasma (K2 –EDTA, K3- EDTA and Li-Heparin). The electrochemiluminescence immunoassay “ECLIA” is intended for use on Elecsys and cobas e immunoassay analyzers. Used in conjunction with other laboratory findings and clinical assessments, Elecsys B·R·A·H·M·S PCT is intended for use as follows: · to aid in the risk assessment of critically ill patients on their first day of ICU admission for progression to severe sepsis and septic shock, · to determine the change in PCT level over time as an aid in assessing the cumulative 28-day risk of all-cause mortality for patients diagnosed with severe sepsis or septic shock in the ICU or when obtained in the emergency department or other medical wards prior to ICU admission, · to aid in decision making on antibiotic therapy, for inpatients or patients in the emergency department with suspected or confirmed lower respiratory tract infections (LRTI) – defined as community-acquired pneumonia (CAP), acute bronchitis, and acute exacerbation of chronic obstructive pulmonary disease (AECOPD), · to aid in decision making on antibiotic discontinuation for patients with suspected or confirmed sepsis. The BRAHMS PCT sensitive KRYPTOR is an immunofluorescent assay using Time- Resolved Amplified Cryptate Emission (TRACE) technology to determine the concentration of PCT (procalcitonin) in human serum and EDTA or heparin plasma. The BRAHMS PCT sensitive KRYPTOR is intended to be performed on the BRAHMS KRYPTOR analyzer family. Used in conjunction with other laboratory findings and clinical assessments, BRAHMS PCT sensitive KRYPTOR is intended for use as follows: · to aid in the risk assessment of critically ill patients on their first day of ICU admission for progression to severe sepsis and septic shock, · to determine the change in PCT level over time as an aid in assessing the cumulative 28-day risk of all-cause mortality for patients diagnosed with severe sepsis or septic shock in the ICU or when obtained in the emergency department or other medical wards prior to ICU admission, · to aid in decision making on antibiotic therapy, for inpatients or patients in the emergency department with suspected or confirmed lower respiratory tract infections (LRTI) – defined as community-acquired pneumonia (CAP), acute bronchitis, and acute exacerbation of chronic obstructive pulmonary disease (AECOPD), · to aid in decision making on antibiotic discontinuation for patients with suspected or confirmed sepsis. 5 Differences Item Candidate Device: Elecsys BRAHMS PCT (K173927) Predicate Device: BRAHMS PCT sensitive KRYPTOR (DEN150009) Assay Protocol The Elecsys BRAHMS PCT assay is a two-step sandwich immunoassay with streptavidin microparticles and an electrochemiluminescence detection system. The test system reagents contain a biotinylated monoclonal PCT-specific antibody and a ruthenium labeled monoclonal PCT-specific antibody. The BRAHMS PCT sensitive KRYPTOR assay is a homogeneous sandwich immunoassay for detection of PCT in human serum or plasma. The measuring principle is based on Time-Resolved Amplified Cryptate Emission (TRACE) technology, which measures the signal that is emitted from an immunocomplex with time delay. Detection Protocol Electrochemiluminescent Assay Time-Resolved Amplified Cryptate Emission (TRACE) Applications 18-minute application 19-minute incubation Instrument Platform cobas e 411 analyzer BRAHMS KRYPTOR analyzer Sample Volume 30 µL 50 µL Sample Type Human serum and plasma (Li- Heparin, K2/K3 EDTA) Human serum and plasma (EDTA, heparin) Reagents · Streptavidin-coated microparticles: · Steptavidin-coated microparticles; preservative · Anti-PCT-Ab~biotin: Biotinylated monoclonal anti-PCT antibody (mouse), phosphate buffer, preservative · Anti-PCT – Ab~Ru(bpy) 2/3+ a monoclonal anti-PCT antibody (mouse) labeled with ruthenium complex, phosphate buffer, preservative · Cryptate conjugate, cryptate labeled, anti-PCT antibody (polyclonal, sheep), 3.2mL after reconstitution with KRYPTOR Solution 2 · L665 conjugate, XL665 labeled, anti- PCT antibody (monoclonal, mouse), 3.95 mL after reconstitution with KRYPTOR Solution 1 and KRYPTOR Solution 2 · Defibrinated human plasma, for diluting samples above 50 µg/L, ready for use Calibrator Elecsys PCT CalSet BRAHMS PCT sensitive KRYPTOR Calibrator Calibration Measurand:

idK173927_s0_e2000

K173927.txt

type of test

Quantitative, Electrochemiluminescence Immunoassay

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K173927 B. Purpose for Submission: To obtain a substantial equivalence determination for the Elecsys BRAHMS PCT. C. Measurand: Procalcitonin (PCT) D. Type of Test: Quantitative, Electrochemiluminescence Immunoassay E. Applicant: Roche Diagnostics F. Proprietary and Established Names: Elecsys BRAHMS PCT G. Regulatory Information: 1. Regulation section: 21 CFR 866.3215; Device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis 2. Classification: Class II (Special Controls) 3. Product codes: PMT 4. Panel: 83 - (Microbiology) 2 H. Intended Use/ Indications for Use: 1. Intended Use/ Indications for Use: Immunoassay for the in vitro quantitative determination of PCT (procalcitonin) in human serum and plasma (K2 –EDTA, K3-EDTA and Li-Heparin). The electrochemiluminescence immunoassay “ECLIA” is intended for use on Elecsys and cobas e immunoassay analyzers. Used in conjunction with other laboratory findings and clinical assessments, Elecsys BRAHMS PCT is intended for use as follows: · to aid in the risk assessment of critically ill patients on their first day of ICU admission for progression to severe sepsis and septic shock, · to determine the change in PCT level over time as an aid in assessing the cumulative 28-day risk of all-cause mortality for patients diagnosed with severe sepsis or septic shock in the ICU or when obtained in the emergency department or other medical wards prior to ICU admission, · to aid in decision making on antibiotic therapy, for inpatients or patients in the emergency department with suspected or confirmed lower respiratory tract infections (LRTI) – defined as community-acquired pneumonia (CAP), acute bronchitis, and acute exacerbation of chronic obstructive pulmonary disease (AECOPD), · to aid in decision making on antibiotic discontinuation for patients with suspected or confirmed sepsis. 2. Special conditions for use statement(s): For prescription use only Warnings and Precautions: The Elecsys BRAHMS PCT assay should not be used as a sole basis for diagnosis for determining the risk of 28 day all-cause mortality. Changes in PCT should always be interpreted in the context of the clinical status of the patient and other laboratory results. There is no uniformly recognized interpretation of the change in PCT levels for the prediction of mortality, and overall mortality is strongly dependent on many factors, including pre-existing patient risk factors and clinical course. The need for continued ICU care at Day 4 and other covariates (e.g., age, sepsis-related organ failure assessment (SOFA score) are also significant predictors of 28-day cumulative mortality risk. Validation of the Elecsys BRAHMS PCT assay as an aid in predicting mortality was performed in a study population with an overall 28-day mortality of 22%. 3. Special instrument requirements: 3 The submission demonstrates performance on the cobas e411 immunoassay analyzer. I. Device Description: Reagents Materials provided in Elecsys BRAHMS PCT: The reagent working solutions include: Rackpack (kit placed on analyzer) · M: Streptavidin-coated microparticles · R1: Anti-PCT-Ab~biotin · R2: Anti-PCT – Ab~Ru (bpy) J. Substantial Equivalence Information: 1. Predicate device name(s): BRAHMS PCT sensitive KRYPTOR 2. Predicate 510(k) number(s): K171338 4. Comparison with predicate: 4 Similarities Item Candidate Device: Elecsys BRAHMS PCT (K173927) Predicate Device: BRAHMS PCT sensitive KRYPTOR (K171338) Intended Use Immunoassay for the in vitro quantitative determination of PCT (procalcitonin) in human serum and plasma (K2 –EDTA, K3- EDTA and Li-Heparin). The electrochemiluminescence immunoassay “ECLIA” is intended for use on Elecsys and cobas e immunoassay analyzers. Used in conjunction with other laboratory findings and clinical assessments, Elecsys B·R·A·H·M·S PCT is intended for use as follows: · to aid in the risk assessment of critically ill patients on their first day of ICU admission for progression to severe sepsis and septic shock, · to determine the change in PCT level over time as an aid in assessing the cumulative 28-day risk of all-cause mortality for patients diagnosed with severe sepsis or septic shock in the ICU or when obtained in the emergency department or other medical wards prior to ICU admission, · to aid in decision making on antibiotic therapy, for inpatients or patients in the emergency department with suspected or confirmed lower respiratory tract infections (LRTI) – defined as community-acquired pneumonia (CAP), acute bronchitis, and acute exacerbation of chronic obstructive pulmonary disease (AECOPD), · to aid in decision making on antibiotic discontinuation for patients with suspected or confirmed sepsis. The BRAHMS PCT sensitive KRYPTOR is an immunofluorescent assay using Time- Resolved Amplified Cryptate Emission (TRACE) technology to determine the concentration of PCT (procalcitonin) in human serum and EDTA or heparin plasma. The BRAHMS PCT sensitive KRYPTOR is intended to be performed on the BRAHMS KRYPTOR analyzer family. Used in conjunction with other laboratory findings and clinical assessments, BRAHMS PCT sensitive KRYPTOR is intended for use as follows: · to aid in the risk assessment of critically ill patients on their first day of ICU admission for progression to severe sepsis and septic shock, · to determine the change in PCT level over time as an aid in assessing the cumulative 28-day risk of all-cause mortality for patients diagnosed with severe sepsis or septic shock in the ICU or when obtained in the emergency department or other medical wards prior to ICU admission, · to aid in decision making on antibiotic therapy, for inpatients or patients in the emergency department with suspected or confirmed lower respiratory tract infections (LRTI) – defined as community-acquired pneumonia (CAP), acute bronchitis, and acute exacerbation of chronic obstructive pulmonary disease (AECOPD), · to aid in decision making on antibiotic discontinuation for patients with suspected or confirmed sepsis. 5 Differences Item Candidate Device: Elecsys BRAHMS PCT (K173927) Predicate Device: BRAHMS PCT sensitive KRYPTOR (DEN150009) Assay Protocol The Elecsys BRAHMS PCT assay is a two-step sandwich immunoassay with streptavidin microparticles and an electrochemiluminescence detection system. The test system reagents contain a biotinylated monoclonal PCT-specific antibody and a ruthenium labeled monoclonal PCT-specific antibody. The BRAHMS PCT sensitive KRYPTOR assay is a homogeneous sandwich immunoassay for detection of PCT in human serum or plasma. The measuring principle is based on Time-Resolved Amplified Cryptate Emission (TRACE) technology, which measures the signal that is emitted from an immunocomplex with time delay. Detection Protocol Electrochemiluminescent Assay Time-Resolved Amplified Cryptate Emission (TRACE) Applications 18-minute application 19-minute incubation Instrument Platform cobas e 411 analyzer BRAHMS KRYPTOR analyzer Sample Volume 30 µL 50 µL Sample Type Human serum and plasma (Li- Heparin, K2/K3 EDTA) Human serum and plasma (EDTA, heparin) Reagents · Streptavidin-coated microparticles: · Steptavidin-coated microparticles; preservative · Anti-PCT-Ab~biotin: Biotinylated monoclonal anti-PCT antibody (mouse), phosphate buffer, preservative · Anti-PCT – Ab~Ru(bpy) 2/3+ a monoclonal anti-PCT antibody (mouse) labeled with ruthenium complex, phosphate buffer, preservative · Cryptate conjugate, cryptate labeled, anti-PCT antibody (polyclonal, sheep), 3.2mL after reconstitution with KRYPTOR Solution 2 · L665 conjugate, XL665 labeled, anti- PCT antibody (monoclonal, mouse), 3.95 mL after reconstitution with KRYPTOR Solution 1 and KRYPTOR Solution 2 · Defibrinated human plasma, for diluting samples above 50 µg/L, ready for use Calibrator Elecsys PCT CalSet BRAHMS PCT sensitive KRYPTOR Calibrator Calibration Type of test:

idK173927_s0_e2000

K173927.txt

classification

Class II

k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K173927 B. Purpose for Submission: To obtain a substantial equivalence determination for the Elecsys BRAHMS PCT. C. Measurand: Procalcitonin (PCT) D. Type of Test: Quantitative, Electrochemiluminescence Immunoassay E. Applicant: Roche Diagnostics F. Proprietary and Established Names: Elecsys BRAHMS PCT G. Regulatory Information: 1. Regulation section: 21 CFR 866.3215; Device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis 2. Classification: Class II (Special Controls) 3. Product codes: PMT 4. Panel: 83 - (Microbiology) 2 H. Intended Use/ Indications for Use: 1. Intended Use/ Indications for Use: Immunoassay for the in vitro quantitative determination of PCT (procalcitonin) in human serum and plasma (K2 –EDTA, K3-EDTA and Li-Heparin). The electrochemiluminescence immunoassay “ECLIA” is intended for use on Elecsys and cobas e immunoassay analyzers. Used in conjunction with other laboratory findings and clinical assessments, Elecsys BRAHMS PCT is intended for use as follows: · to aid in the risk assessment of critically ill patients on their first day of ICU admission for progression to severe sepsis and septic shock, · to determine the change in PCT level over time as an aid in assessing the cumulative 28-day risk of all-cause mortality for patients diagnosed with severe sepsis or septic shock in the ICU or when obtained in the emergency department or other medical wards prior to ICU admission, · to aid in decision making on antibiotic therapy, for inpatients or patients in the emergency department with suspected or confirmed lower respiratory tract infections (LRTI) – defined as community-acquired pneumonia (CAP), acute bronchitis, and acute exacerbation of chronic obstructive pulmonary disease (AECOPD), · to aid in decision making on antibiotic discontinuation for patients with suspected or confirmed sepsis. 2. Special conditions for use statement(s): For prescription use only Warnings and Precautions: The Elecsys BRAHMS PCT assay should not be used as a sole basis for diagnosis for determining the risk of 28 day all-cause mortality. Changes in PCT should always be interpreted in the context of the clinical status of the patient and other laboratory results. There is no uniformly recognized interpretation of the change in PCT levels for the prediction of mortality, and overall mortality is strongly dependent on many factors, including pre-existing patient risk factors and clinical course. The need for continued ICU care at Day 4 and other covariates (e.g., age, sepsis-related organ failure assessment (SOFA score) are also significant predictors of 28-day cumulative mortality risk. Validation of the Elecsys BRAHMS PCT assay as an aid in predicting mortality was performed in a study population with an overall 28-day mortality of 22%. 3. Special instrument requirements: 3 The submission demonstrates performance on the cobas e411 immunoassay analyzer. I. Device Description: Reagents Materials provided in Elecsys BRAHMS PCT: The reagent working solutions include: Rackpack (kit placed on analyzer) · M: Streptavidin-coated microparticles · R1: Anti-PCT-Ab~biotin · R2: Anti-PCT – Ab~Ru (bpy) J. Substantial Equivalence Information: 1. Predicate device name(s): BRAHMS PCT sensitive KRYPTOR 2. Predicate 510(k) number(s): K171338 4. Comparison with predicate: 4 Similarities Item Candidate Device: Elecsys BRAHMS PCT (K173927) Predicate Device: BRAHMS PCT sensitive KRYPTOR (K171338) Intended Use Immunoassay for the in vitro quantitative determination of PCT (procalcitonin) in human serum and plasma (K2 –EDTA, K3- EDTA and Li-Heparin). The electrochemiluminescence immunoassay “ECLIA” is intended for use on Elecsys and cobas e immunoassay analyzers. Used in conjunction with other laboratory findings and clinical assessments, Elecsys B·R·A·H·M·S PCT is intended for use as follows: · to aid in the risk assessment of critically ill patients on their first day of ICU admission for progression to severe sepsis and septic shock, · to determine the change in PCT level over time as an aid in assessing the cumulative 28-day risk of all-cause mortality for patients diagnosed with severe sepsis or septic shock in the ICU or when obtained in the emergency department or other medical wards prior to ICU admission, · to aid in decision making on antibiotic therapy, for inpatients or patients in the emergency department with suspected or confirmed lower respiratory tract infections (LRTI) – defined as community-acquired pneumonia (CAP), acute bronchitis, and acute exacerbation of chronic obstructive pulmonary disease (AECOPD), · to aid in decision making on antibiotic discontinuation for patients with suspected or confirmed sepsis. The BRAHMS PCT sensitive KRYPTOR is an immunofluorescent assay using Time- Resolved Amplified Cryptate Emission (TRACE) technology to determine the concentration of PCT (procalcitonin) in human serum and EDTA or heparin plasma. The BRAHMS PCT sensitive KRYPTOR is intended to be performed on the BRAHMS KRYPTOR analyzer family. Used in conjunction with other laboratory findings and clinical assessments, BRAHMS PCT sensitive KRYPTOR is intended for use as follows: · to aid in the risk assessment of critically ill patients on their first day of ICU admission for progression to severe sepsis and septic shock, · to determine the change in PCT level over time as an aid in assessing the cumulative 28-day risk of all-cause mortality for patients diagnosed with severe sepsis or septic shock in the ICU or when obtained in the emergency department or other medical wards prior to ICU admission, · to aid in decision making on antibiotic therapy, for inpatients or patients in the emergency department with suspected or confirmed lower respiratory tract infections (LRTI) – defined as community-acquired pneumonia (CAP), acute bronchitis, and acute exacerbation of chronic obstructive pulmonary disease (AECOPD), · to aid in decision making on antibiotic discontinuation for patients with suspected or confirmed sepsis. 5 Differences Item Candidate Device: Elecsys BRAHMS PCT (K173927) Predicate Device: BRAHMS PCT sensitive KRYPTOR (DEN150009) Assay Protocol The Elecsys BRAHMS PCT assay is a two-step sandwich immunoassay with streptavidin microparticles and an electrochemiluminescence detection system. The test system reagents contain a biotinylated monoclonal PCT-specific antibody and a ruthenium labeled monoclonal PCT-specific antibody. The BRAHMS PCT sensitive KRYPTOR assay is a homogeneous sandwich immunoassay for detection of PCT in human serum or plasma. The measuring principle is based on Time-Resolved Amplified Cryptate Emission (TRACE) technology, which measures the signal that is emitted from an immunocomplex with time delay. Detection Protocol Electrochemiluminescent Assay Time-Resolved Amplified Cryptate Emission (TRACE) Applications 18-minute application 19-minute incubation Instrument Platform cobas e 411 analyzer BRAHMS KRYPTOR analyzer Sample Volume 30 µL 50 µL Sample Type Human serum and plasma (Li- Heparin, K2/K3 EDTA) Human serum and plasma (EDTA, heparin) Reagents · Streptavidin-coated microparticles: · Steptavidin-coated microparticles; preservative · Anti-PCT-Ab~biotin: Biotinylated monoclonal anti-PCT antibody (mouse), phosphate buffer, preservative · Anti-PCT – Ab~Ru(bpy) 2/3+ a monoclonal anti-PCT antibody (mouse) labeled with ruthenium complex, phosphate buffer, preservative · Cryptate conjugate, cryptate labeled, anti-PCT antibody (polyclonal, sheep), 3.2mL after reconstitution with KRYPTOR Solution 2 · L665 conjugate, XL665 labeled, anti- PCT antibody (monoclonal, mouse), 3.95 mL after reconstitution with KRYPTOR Solution 1 and KRYPTOR Solution 2 · Defibrinated human plasma, for diluting samples above 50 µg/L, ready for use Calibrator Elecsys PCT CalSet BRAHMS PCT sensitive KRYPTOR Calibrator Calibration Classification:

idK173927_s0_e2000

K173927.txt

product code

PMT

k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K173927 B. Purpose for Submission: To obtain a substantial equivalence determination for the Elecsys BRAHMS PCT. C. Measurand: Procalcitonin (PCT) D. Type of Test: Quantitative, Electrochemiluminescence Immunoassay E. Applicant: Roche Diagnostics F. Proprietary and Established Names: Elecsys BRAHMS PCT G. Regulatory Information: 1. Regulation section: 21 CFR 866.3215; Device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis 2. Classification: Class II (Special Controls) 3. Product codes: PMT 4. Panel: 83 - (Microbiology) 2 H. Intended Use/ Indications for Use: 1. Intended Use/ Indications for Use: Immunoassay for the in vitro quantitative determination of PCT (procalcitonin) in human serum and plasma (K2 –EDTA, K3-EDTA and Li-Heparin). The electrochemiluminescence immunoassay “ECLIA” is intended for use on Elecsys and cobas e immunoassay analyzers. Used in conjunction with other laboratory findings and clinical assessments, Elecsys BRAHMS PCT is intended for use as follows: · to aid in the risk assessment of critically ill patients on their first day of ICU admission for progression to severe sepsis and septic shock, · to determine the change in PCT level over time as an aid in assessing the cumulative 28-day risk of all-cause mortality for patients diagnosed with severe sepsis or septic shock in the ICU or when obtained in the emergency department or other medical wards prior to ICU admission, · to aid in decision making on antibiotic therapy, for inpatients or patients in the emergency department with suspected or confirmed lower respiratory tract infections (LRTI) – defined as community-acquired pneumonia (CAP), acute bronchitis, and acute exacerbation of chronic obstructive pulmonary disease (AECOPD), · to aid in decision making on antibiotic discontinuation for patients with suspected or confirmed sepsis. 2. Special conditions for use statement(s): For prescription use only Warnings and Precautions: The Elecsys BRAHMS PCT assay should not be used as a sole basis for diagnosis for determining the risk of 28 day all-cause mortality. Changes in PCT should always be interpreted in the context of the clinical status of the patient and other laboratory results. There is no uniformly recognized interpretation of the change in PCT levels for the prediction of mortality, and overall mortality is strongly dependent on many factors, including pre-existing patient risk factors and clinical course. The need for continued ICU care at Day 4 and other covariates (e.g., age, sepsis-related organ failure assessment (SOFA score) are also significant predictors of 28-day cumulative mortality risk. Validation of the Elecsys BRAHMS PCT assay as an aid in predicting mortality was performed in a study population with an overall 28-day mortality of 22%. 3. Special instrument requirements: 3 The submission demonstrates performance on the cobas e411 immunoassay analyzer. I. Device Description: Reagents Materials provided in Elecsys BRAHMS PCT: The reagent working solutions include: Rackpack (kit placed on analyzer) · M: Streptavidin-coated microparticles · R1: Anti-PCT-Ab~biotin · R2: Anti-PCT – Ab~Ru (bpy) J. Substantial Equivalence Information: 1. Predicate device name(s): BRAHMS PCT sensitive KRYPTOR 2. Predicate 510(k) number(s): K171338 4. Comparison with predicate: 4 Similarities Item Candidate Device: Elecsys BRAHMS PCT (K173927) Predicate Device: BRAHMS PCT sensitive KRYPTOR (K171338) Intended Use Immunoassay for the in vitro quantitative determination of PCT (procalcitonin) in human serum and plasma (K2 –EDTA, K3- EDTA and Li-Heparin). The electrochemiluminescence immunoassay “ECLIA” is intended for use on Elecsys and cobas e immunoassay analyzers. Used in conjunction with other laboratory findings and clinical assessments, Elecsys B·R·A·H·M·S PCT is intended for use as follows: · to aid in the risk assessment of critically ill patients on their first day of ICU admission for progression to severe sepsis and septic shock, · to determine the change in PCT level over time as an aid in assessing the cumulative 28-day risk of all-cause mortality for patients diagnosed with severe sepsis or septic shock in the ICU or when obtained in the emergency department or other medical wards prior to ICU admission, · to aid in decision making on antibiotic therapy, for inpatients or patients in the emergency department with suspected or confirmed lower respiratory tract infections (LRTI) – defined as community-acquired pneumonia (CAP), acute bronchitis, and acute exacerbation of chronic obstructive pulmonary disease (AECOPD), · to aid in decision making on antibiotic discontinuation for patients with suspected or confirmed sepsis. The BRAHMS PCT sensitive KRYPTOR is an immunofluorescent assay using Time- Resolved Amplified Cryptate Emission (TRACE) technology to determine the concentration of PCT (procalcitonin) in human serum and EDTA or heparin plasma. The BRAHMS PCT sensitive KRYPTOR is intended to be performed on the BRAHMS KRYPTOR analyzer family. Used in conjunction with other laboratory findings and clinical assessments, BRAHMS PCT sensitive KRYPTOR is intended for use as follows: · to aid in the risk assessment of critically ill patients on their first day of ICU admission for progression to severe sepsis and septic shock, · to determine the change in PCT level over time as an aid in assessing the cumulative 28-day risk of all-cause mortality for patients diagnosed with severe sepsis or septic shock in the ICU or when obtained in the emergency department or other medical wards prior to ICU admission, · to aid in decision making on antibiotic therapy, for inpatients or patients in the emergency department with suspected or confirmed lower respiratory tract infections (LRTI) – defined as community-acquired pneumonia (CAP), acute bronchitis, and acute exacerbation of chronic obstructive pulmonary disease (AECOPD), · to aid in decision making on antibiotic discontinuation for patients with suspected or confirmed sepsis. 5 Differences Item Candidate Device: Elecsys BRAHMS PCT (K173927) Predicate Device: BRAHMS PCT sensitive KRYPTOR (DEN150009) Assay Protocol The Elecsys BRAHMS PCT assay is a two-step sandwich immunoassay with streptavidin microparticles and an electrochemiluminescence detection system. The test system reagents contain a biotinylated monoclonal PCT-specific antibody and a ruthenium labeled monoclonal PCT-specific antibody. The BRAHMS PCT sensitive KRYPTOR assay is a homogeneous sandwich immunoassay for detection of PCT in human serum or plasma. The measuring principle is based on Time-Resolved Amplified Cryptate Emission (TRACE) technology, which measures the signal that is emitted from an immunocomplex with time delay. Detection Protocol Electrochemiluminescent Assay Time-Resolved Amplified Cryptate Emission (TRACE) Applications 18-minute application 19-minute incubation Instrument Platform cobas e 411 analyzer BRAHMS KRYPTOR analyzer Sample Volume 30 µL 50 µL Sample Type Human serum and plasma (Li- Heparin, K2/K3 EDTA) Human serum and plasma (EDTA, heparin) Reagents · Streptavidin-coated microparticles: · Steptavidin-coated microparticles; preservative · Anti-PCT-Ab~biotin: Biotinylated monoclonal anti-PCT antibody (mouse), phosphate buffer, preservative · Anti-PCT – Ab~Ru(bpy) 2/3+ a monoclonal anti-PCT antibody (mouse) labeled with ruthenium complex, phosphate buffer, preservative · Cryptate conjugate, cryptate labeled, anti-PCT antibody (polyclonal, sheep), 3.2mL after reconstitution with KRYPTOR Solution 2 · L665 conjugate, XL665 labeled, anti- PCT antibody (monoclonal, mouse), 3.95 mL after reconstitution with KRYPTOR Solution 1 and KRYPTOR Solution 2 · Defibrinated human plasma, for diluting samples above 50 µg/L, ready for use Calibrator Elecsys PCT CalSet BRAHMS PCT sensitive KRYPTOR Calibrator Calibration Product code:

idK173927_s0_e2000

K173927.txt

panel

83 - (Microbiology)

(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K173927 B. Purpose for Submission: To obtain a substantial equivalence determination for the Elecsys BRAHMS PCT. C. Measurand: Procalcitonin (PCT) D. Type of Test: Quantitative, Electrochemiluminescence Immunoassay E. Applicant: Roche Diagnostics F. Proprietary and Established Names: Elecsys BRAHMS PCT G. Regulatory Information: 1. Regulation section: 21 CFR 866.3215; Device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis 2. Classification: Class II (Special Controls) 3. Product codes: PMT 4. Panel: 83 - (Microbiology) 2 H. Intended Use/ Indications for Use: 1. Intended Use/ Indications for Use: Immunoassay for the in vitro quantitative determination of PCT (procalcitonin) in human serum and plasma (K2 –EDTA, K3-EDTA and Li-Heparin). The electrochemiluminescence immunoassay “ECLIA” is intended for use on Elecsys and cobas e immunoassay analyzers. Used in conjunction with other laboratory findings and clinical assessments, Elecsys BRAHMS PCT is intended for use as follows: · to aid in the risk assessment of critically ill patients on their first day of ICU admission for progression to severe sepsis and septic shock, · to determine the change in PCT level over time as an aid in assessing the cumulative 28-day risk of all-cause mortality for patients diagnosed with severe sepsis or septic shock in the ICU or when obtained in the emergency department or other medical wards prior to ICU admission, · to aid in decision making on antibiotic therapy, for inpatients or patients in the emergency department with suspected or confirmed lower respiratory tract infections (LRTI) – defined as community-acquired pneumonia (CAP), acute bronchitis, and acute exacerbation of chronic obstructive pulmonary disease (AECOPD), · to aid in decision making on antibiotic discontinuation for patients with suspected or confirmed sepsis. 2. Special conditions for use statement(s): For prescription use only Warnings and Precautions: The Elecsys BRAHMS PCT assay should not be used as a sole basis for diagnosis for determining the risk of 28 day all-cause mortality. Changes in PCT should always be interpreted in the context of the clinical status of the patient and other laboratory results. There is no uniformly recognized interpretation of the change in PCT levels for the prediction of mortality, and overall mortality is strongly dependent on many factors, including pre-existing patient risk factors and clinical course. The need for continued ICU care at Day 4 and other covariates (e.g., age, sepsis-related organ failure assessment (SOFA score) are also significant predictors of 28-day cumulative mortality risk. Validation of the Elecsys BRAHMS PCT assay as an aid in predicting mortality was performed in a study population with an overall 28-day mortality of 22%. 3. Special instrument requirements: 3 The submission demonstrates performance on the cobas e411 immunoassay analyzer. I. Device Description: Reagents Materials provided in Elecsys BRAHMS PCT: The reagent working solutions include: Rackpack (kit placed on analyzer) · M: Streptavidin-coated microparticles · R1: Anti-PCT-Ab~biotin · R2: Anti-PCT – Ab~Ru (bpy) J. Substantial Equivalence Information: 1. Predicate device name(s): BRAHMS PCT sensitive KRYPTOR 2. Predicate 510(k) number(s): K171338 4. Comparison with predicate: 4 Similarities Item Candidate Device: Elecsys BRAHMS PCT (K173927) Predicate Device: BRAHMS PCT sensitive KRYPTOR (K171338) Intended Use Immunoassay for the in vitro quantitative determination of PCT (procalcitonin) in human serum and plasma (K2 –EDTA, K3- EDTA and Li-Heparin). The electrochemiluminescence immunoassay “ECLIA” is intended for use on Elecsys and cobas e immunoassay analyzers. Used in conjunction with other laboratory findings and clinical assessments, Elecsys B·R·A·H·M·S PCT is intended for use as follows: · to aid in the risk assessment of critically ill patients on their first day of ICU admission for progression to severe sepsis and septic shock, · to determine the change in PCT level over time as an aid in assessing the cumulative 28-day risk of all-cause mortality for patients diagnosed with severe sepsis or septic shock in the ICU or when obtained in the emergency department or other medical wards prior to ICU admission, · to aid in decision making on antibiotic therapy, for inpatients or patients in the emergency department with suspected or confirmed lower respiratory tract infections (LRTI) – defined as community-acquired pneumonia (CAP), acute bronchitis, and acute exacerbation of chronic obstructive pulmonary disease (AECOPD), · to aid in decision making on antibiotic discontinuation for patients with suspected or confirmed sepsis. The BRAHMS PCT sensitive KRYPTOR is an immunofluorescent assay using Time- Resolved Amplified Cryptate Emission (TRACE) technology to determine the concentration of PCT (procalcitonin) in human serum and EDTA or heparin plasma. The BRAHMS PCT sensitive KRYPTOR is intended to be performed on the BRAHMS KRYPTOR analyzer family. Used in conjunction with other laboratory findings and clinical assessments, BRAHMS PCT sensitive KRYPTOR is intended for use as follows: · to aid in the risk assessment of critically ill patients on their first day of ICU admission for progression to severe sepsis and septic shock, · to determine the change in PCT level over time as an aid in assessing the cumulative 28-day risk of all-cause mortality for patients diagnosed with severe sepsis or septic shock in the ICU or when obtained in the emergency department or other medical wards prior to ICU admission, · to aid in decision making on antibiotic therapy, for inpatients or patients in the emergency department with suspected or confirmed lower respiratory tract infections (LRTI) – defined as community-acquired pneumonia (CAP), acute bronchitis, and acute exacerbation of chronic obstructive pulmonary disease (AECOPD), · to aid in decision making on antibiotic discontinuation for patients with suspected or confirmed sepsis. 5 Differences Item Candidate Device: Elecsys BRAHMS PCT (K173927) Predicate Device: BRAHMS PCT sensitive KRYPTOR (DEN150009) Assay Protocol The Elecsys BRAHMS PCT assay is a two-step sandwich immunoassay with streptavidin microparticles and an electrochemiluminescence detection system. The test system reagents contain a biotinylated monoclonal PCT-specific antibody and a ruthenium labeled monoclonal PCT-specific antibody. The BRAHMS PCT sensitive KRYPTOR assay is a homogeneous sandwich immunoassay for detection of PCT in human serum or plasma. The measuring principle is based on Time-Resolved Amplified Cryptate Emission (TRACE) technology, which measures the signal that is emitted from an immunocomplex with time delay. Detection Protocol Electrochemiluminescent Assay Time-Resolved Amplified Cryptate Emission (TRACE) Applications 18-minute application 19-minute incubation Instrument Platform cobas e 411 analyzer BRAHMS KRYPTOR analyzer Sample Volume 30 µL 50 µL Sample Type Human serum and plasma (Li- Heparin, K2/K3 EDTA) Human serum and plasma (EDTA, heparin) Reagents · Streptavidin-coated microparticles: · Steptavidin-coated microparticles; preservative · Anti-PCT-Ab~biotin: Biotinylated monoclonal anti-PCT antibody (mouse), phosphate buffer, preservative · Anti-PCT – Ab~Ru(bpy) 2/3+ a monoclonal anti-PCT antibody (mouse) labeled with ruthenium complex, phosphate buffer, preservative · Cryptate conjugate, cryptate labeled, anti-PCT antibody (polyclonal, sheep), 3.2mL after reconstitution with KRYPTOR Solution 2 · L665 conjugate, XL665 labeled, anti- PCT antibody (monoclonal, mouse), 3.95 mL after reconstitution with KRYPTOR Solution 1 and KRYPTOR Solution 2 · Defibrinated human plasma, for diluting samples above 50 µg/L, ready for use Calibrator Elecsys PCT CalSet BRAHMS PCT sensitive KRYPTOR Calibrator Calibration Panel:

idK173927_s0_e2000

K173927.txt

intended use

Immunoassay for the in vitro quantitative determination of PCT (procalcitonin) in human serum and plasma (K2 –EDTA, K3-EDTA and Li-Heparin). The electrochemiluminescence immunoassay “ECLIA” is intended for use on Elecsys and cobas e immunoassay analyzers. Used in conjunction with other laboratory findings and clinical assessments, Elecsys BRAHMS PCT is intended for use as follows: · to aid in the risk assessment of critically ill patients on their first day of ICU admission for progression to severe sepsis and septic shock, · to determine the change in PCT level over time as an aid in assessing the cumulative 28-day risk of all-cause mortality for patients diagnosed with severe sepsis or septic shock in the ICU or when obtained in the emergency department or other medical wards prior to ICU admission, · to aid in decision making on antibiotic therapy, for inpatients or patients in the emergency department with suspected or confirmed lower respiratory tract infections (LRTI) – defined as community-acquired pneumonia (CAP), acute bronchitis, and acute exacerbation of chronic obstructive pulmonary disease (AECOPD), · to aid in decision making on antibiotic discontinuation for patients with suspected or confirmed sepsis.

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K173927 B. Purpose for Submission: To obtain a substantial equivalence determination for the Elecsys BRAHMS PCT. C. Measurand: Procalcitonin (PCT) D. Type of Test: Quantitative, Electrochemiluminescence Immunoassay E. Applicant: Roche Diagnostics F. Proprietary and Established Names: Elecsys BRAHMS PCT G. Regulatory Information: 1. Regulation section: 21 CFR 866.3215; Device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis 2. Classification: Class II (Special Controls) 3. Product codes: PMT 4. Panel: 83 - (Microbiology) 2 H. Intended Use/ Indications for Use: 1. Intended Use/ Indications for Use: Immunoassay for the in vitro quantitative determination of PCT (procalcitonin) in human serum and plasma (K2 –EDTA, K3-EDTA and Li-Heparin). The electrochemiluminescence immunoassay “ECLIA” is intended for use on Elecsys and cobas e immunoassay analyzers. Used in conjunction with other laboratory findings and clinical assessments, Elecsys BRAHMS PCT is intended for use as follows: · to aid in the risk assessment of critically ill patients on their first day of ICU admission for progression to severe sepsis and septic shock, · to determine the change in PCT level over time as an aid in assessing the cumulative 28-day risk of all-cause mortality for patients diagnosed with severe sepsis or septic shock in the ICU or when obtained in the emergency department or other medical wards prior to ICU admission, · to aid in decision making on antibiotic therapy, for inpatients or patients in the emergency department with suspected or confirmed lower respiratory tract infections (LRTI) – defined as community-acquired pneumonia (CAP), acute bronchitis, and acute exacerbation of chronic obstructive pulmonary disease (AECOPD), · to aid in decision making on antibiotic discontinuation for patients with suspected or confirmed sepsis. 2. Special conditions for use statement(s): For prescription use only Warnings and Precautions: The Elecsys BRAHMS PCT assay should not be used as a sole basis for diagnosis for determining the risk of 28 day all-cause mortality. Changes in PCT should always be interpreted in the context of the clinical status of the patient and other laboratory results. There is no uniformly recognized interpretation of the change in PCT levels for the prediction of mortality, and overall mortality is strongly dependent on many factors, including pre-existing patient risk factors and clinical course. The need for continued ICU care at Day 4 and other covariates (e.g., age, sepsis-related organ failure assessment (SOFA score) are also significant predictors of 28-day cumulative mortality risk. Validation of the Elecsys BRAHMS PCT assay as an aid in predicting mortality was performed in a study population with an overall 28-day mortality of 22%. 3. Special instrument requirements: 3 The submission demonstrates performance on the cobas e411 immunoassay analyzer. I. Device Description: Reagents Materials provided in Elecsys BRAHMS PCT: The reagent working solutions include: Rackpack (kit placed on analyzer) · M: Streptavidin-coated microparticles · R1: Anti-PCT-Ab~biotin · R2: Anti-PCT – Ab~Ru (bpy) J. Substantial Equivalence Information: 1. Predicate device name(s): BRAHMS PCT sensitive KRYPTOR 2. Predicate 510(k) number(s): K171338 4. Comparison with predicate: 4 Similarities Item Candidate Device: Elecsys BRAHMS PCT (K173927) Predicate Device: BRAHMS PCT sensitive KRYPTOR (K171338) Intended Use Immunoassay for the in vitro quantitative determination of PCT (procalcitonin) in human serum and plasma (K2 –EDTA, K3- EDTA and Li-Heparin). The electrochemiluminescence immunoassay “ECLIA” is intended for use on Elecsys and cobas e immunoassay analyzers. Used in conjunction with other laboratory findings and clinical assessments, Elecsys B·R·A·H·M·S PCT is intended for use as follows: · to aid in the risk assessment of critically ill patients on their first day of ICU admission for progression to severe sepsis and septic shock, · to determine the change in PCT level over time as an aid in assessing the cumulative 28-day risk of all-cause mortality for patients diagnosed with severe sepsis or septic shock in the ICU or when obtained in the emergency department or other medical wards prior to ICU admission, · to aid in decision making on antibiotic therapy, for inpatients or patients in the emergency department with suspected or confirmed lower respiratory tract infections (LRTI) – defined as community-acquired pneumonia (CAP), acute bronchitis, and acute exacerbation of chronic obstructive pulmonary disease (AECOPD), · to aid in decision making on antibiotic discontinuation for patients with suspected or confirmed sepsis. The BRAHMS PCT sensitive KRYPTOR is an immunofluorescent assay using Time- Resolved Amplified Cryptate Emission (TRACE) technology to determine the concentration of PCT (procalcitonin) in human serum and EDTA or heparin plasma. The BRAHMS PCT sensitive KRYPTOR is intended to be performed on the BRAHMS KRYPTOR analyzer family. Used in conjunction with other laboratory findings and clinical assessments, BRAHMS PCT sensitive KRYPTOR is intended for use as follows: · to aid in the risk assessment of critically ill patients on their first day of ICU admission for progression to severe sepsis and septic shock, · to determine the change in PCT level over time as an aid in assessing the cumulative 28-day risk of all-cause mortality for patients diagnosed with severe sepsis or septic shock in the ICU or when obtained in the emergency department or other medical wards prior to ICU admission, · to aid in decision making on antibiotic therapy, for inpatients or patients in the emergency department with suspected or confirmed lower respiratory tract infections (LRTI) – defined as community-acquired pneumonia (CAP), acute bronchitis, and acute exacerbation of chronic obstructive pulmonary disease (AECOPD), · to aid in decision making on antibiotic discontinuation for patients with suspected or confirmed sepsis. 5 Differences Item Candidate Device: Elecsys BRAHMS PCT (K173927) Predicate Device: BRAHMS PCT sensitive KRYPTOR (DEN150009) Assay Protocol The Elecsys BRAHMS PCT assay is a two-step sandwich immunoassay with streptavidin microparticles and an electrochemiluminescence detection system. The test system reagents contain a biotinylated monoclonal PCT-specific antibody and a ruthenium labeled monoclonal PCT-specific antibody. The BRAHMS PCT sensitive KRYPTOR assay is a homogeneous sandwich immunoassay for detection of PCT in human serum or plasma. The measuring principle is based on Time-Resolved Amplified Cryptate Emission (TRACE) technology, which measures the signal that is emitted from an immunocomplex with time delay. Detection Protocol Electrochemiluminescent Assay Time-Resolved Amplified Cryptate Emission (TRACE) Applications 18-minute application 19-minute incubation Instrument Platform cobas e 411 analyzer BRAHMS KRYPTOR analyzer Sample Volume 30 µL 50 µL Sample Type Human serum and plasma (Li- Heparin, K2/K3 EDTA) Human serum and plasma (EDTA, heparin) Reagents · Streptavidin-coated microparticles: · Steptavidin-coated microparticles; preservative · Anti-PCT-Ab~biotin: Biotinylated monoclonal anti-PCT antibody (mouse), phosphate buffer, preservative · Anti-PCT – Ab~Ru(bpy) 2/3+ a monoclonal anti-PCT antibody (mouse) labeled with ruthenium complex, phosphate buffer, preservative · Cryptate conjugate, cryptate labeled, anti-PCT antibody (polyclonal, sheep), 3.2mL after reconstitution with KRYPTOR Solution 2 · L665 conjugate, XL665 labeled, anti- PCT antibody (monoclonal, mouse), 3.95 mL after reconstitution with KRYPTOR Solution 1 and KRYPTOR Solution 2 · Defibrinated human plasma, for diluting samples above 50 µg/L, ready for use Calibrator Elecsys PCT CalSet BRAHMS PCT sensitive KRYPTOR Calibrator Calibration Intended use:

idK173927_s0_e2000

K173927.txt

predicate device name

BRAHMS PCT sensitive KRYPTOR

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K173927 B. Purpose for Submission: To obtain a substantial equivalence determination for the Elecsys BRAHMS PCT. C. Measurand: Procalcitonin (PCT) D. Type of Test: Quantitative, Electrochemiluminescence Immunoassay E. Applicant: Roche Diagnostics F. Proprietary and Established Names: Elecsys BRAHMS PCT G. Regulatory Information: 1. Regulation section: 21 CFR 866.3215; Device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis 2. Classification: Class II (Special Controls) 3. Product codes: PMT 4. Panel: 83 - (Microbiology) 2 H. Intended Use/ Indications for Use: 1. Intended Use/ Indications for Use: Immunoassay for the in vitro quantitative determination of PCT (procalcitonin) in human serum and plasma (K2 –EDTA, K3-EDTA and Li-Heparin). The electrochemiluminescence immunoassay “ECLIA” is intended for use on Elecsys and cobas e immunoassay analyzers. Used in conjunction with other laboratory findings and clinical assessments, Elecsys BRAHMS PCT is intended for use as follows: · to aid in the risk assessment of critically ill patients on their first day of ICU admission for progression to severe sepsis and septic shock, · to determine the change in PCT level over time as an aid in assessing the cumulative 28-day risk of all-cause mortality for patients diagnosed with severe sepsis or septic shock in the ICU or when obtained in the emergency department or other medical wards prior to ICU admission, · to aid in decision making on antibiotic therapy, for inpatients or patients in the emergency department with suspected or confirmed lower respiratory tract infections (LRTI) – defined as community-acquired pneumonia (CAP), acute bronchitis, and acute exacerbation of chronic obstructive pulmonary disease (AECOPD), · to aid in decision making on antibiotic discontinuation for patients with suspected or confirmed sepsis. 2. Special conditions for use statement(s): For prescription use only Warnings and Precautions: The Elecsys BRAHMS PCT assay should not be used as a sole basis for diagnosis for determining the risk of 28 day all-cause mortality. Changes in PCT should always be interpreted in the context of the clinical status of the patient and other laboratory results. There is no uniformly recognized interpretation of the change in PCT levels for the prediction of mortality, and overall mortality is strongly dependent on many factors, including pre-existing patient risk factors and clinical course. The need for continued ICU care at Day 4 and other covariates (e.g., age, sepsis-related organ failure assessment (SOFA score) are also significant predictors of 28-day cumulative mortality risk. Validation of the Elecsys BRAHMS PCT assay as an aid in predicting mortality was performed in a study population with an overall 28-day mortality of 22%. 3. Special instrument requirements: 3 The submission demonstrates performance on the cobas e411 immunoassay analyzer. I. Device Description: Reagents Materials provided in Elecsys BRAHMS PCT: The reagent working solutions include: Rackpack (kit placed on analyzer) · M: Streptavidin-coated microparticles · R1: Anti-PCT-Ab~biotin · R2: Anti-PCT – Ab~Ru (bpy) J. Substantial Equivalence Information: 1. Predicate device name(s): BRAHMS PCT sensitive KRYPTOR 2. Predicate 510(k) number(s): K171338 4. Comparison with predicate: 4 Similarities Item Candidate Device: Elecsys BRAHMS PCT (K173927) Predicate Device: BRAHMS PCT sensitive KRYPTOR (K171338) Intended Use Immunoassay for the in vitro quantitative determination of PCT (procalcitonin) in human serum and plasma (K2 –EDTA, K3- EDTA and Li-Heparin). The electrochemiluminescence immunoassay “ECLIA” is intended for use on Elecsys and cobas e immunoassay analyzers. Used in conjunction with other laboratory findings and clinical assessments, Elecsys B·R·A·H·M·S PCT is intended for use as follows: · to aid in the risk assessment of critically ill patients on their first day of ICU admission for progression to severe sepsis and septic shock, · to determine the change in PCT level over time as an aid in assessing the cumulative 28-day risk of all-cause mortality for patients diagnosed with severe sepsis or septic shock in the ICU or when obtained in the emergency department or other medical wards prior to ICU admission, · to aid in decision making on antibiotic therapy, for inpatients or patients in the emergency department with suspected or confirmed lower respiratory tract infections (LRTI) – defined as community-acquired pneumonia (CAP), acute bronchitis, and acute exacerbation of chronic obstructive pulmonary disease (AECOPD), · to aid in decision making on antibiotic discontinuation for patients with suspected or confirmed sepsis. The BRAHMS PCT sensitive KRYPTOR is an immunofluorescent assay using Time- Resolved Amplified Cryptate Emission (TRACE) technology to determine the concentration of PCT (procalcitonin) in human serum and EDTA or heparin plasma. The BRAHMS PCT sensitive KRYPTOR is intended to be performed on the BRAHMS KRYPTOR analyzer family. Used in conjunction with other laboratory findings and clinical assessments, BRAHMS PCT sensitive KRYPTOR is intended for use as follows: · to aid in the risk assessment of critically ill patients on their first day of ICU admission for progression to severe sepsis and septic shock, · to determine the change in PCT level over time as an aid in assessing the cumulative 28-day risk of all-cause mortality for patients diagnosed with severe sepsis or septic shock in the ICU or when obtained in the emergency department or other medical wards prior to ICU admission, · to aid in decision making on antibiotic therapy, for inpatients or patients in the emergency department with suspected or confirmed lower respiratory tract infections (LRTI) – defined as community-acquired pneumonia (CAP), acute bronchitis, and acute exacerbation of chronic obstructive pulmonary disease (AECOPD), · to aid in decision making on antibiotic discontinuation for patients with suspected or confirmed sepsis. 5 Differences Item Candidate Device: Elecsys BRAHMS PCT (K173927) Predicate Device: BRAHMS PCT sensitive KRYPTOR (DEN150009) Assay Protocol The Elecsys BRAHMS PCT assay is a two-step sandwich immunoassay with streptavidin microparticles and an electrochemiluminescence detection system. The test system reagents contain a biotinylated monoclonal PCT-specific antibody and a ruthenium labeled monoclonal PCT-specific antibody. The BRAHMS PCT sensitive KRYPTOR assay is a homogeneous sandwich immunoassay for detection of PCT in human serum or plasma. The measuring principle is based on Time-Resolved Amplified Cryptate Emission (TRACE) technology, which measures the signal that is emitted from an immunocomplex with time delay. Detection Protocol Electrochemiluminescent Assay Time-Resolved Amplified Cryptate Emission (TRACE) Applications 18-minute application 19-minute incubation Instrument Platform cobas e 411 analyzer BRAHMS KRYPTOR analyzer Sample Volume 30 µL 50 µL Sample Type Human serum and plasma (Li- Heparin, K2/K3 EDTA) Human serum and plasma (EDTA, heparin) Reagents · Streptavidin-coated microparticles: · Steptavidin-coated microparticles; preservative · Anti-PCT-Ab~biotin: Biotinylated monoclonal anti-PCT antibody (mouse), phosphate buffer, preservative · Anti-PCT – Ab~Ru(bpy) 2/3+ a monoclonal anti-PCT antibody (mouse) labeled with ruthenium complex, phosphate buffer, preservative · Cryptate conjugate, cryptate labeled, anti-PCT antibody (polyclonal, sheep), 3.2mL after reconstitution with KRYPTOR Solution 2 · L665 conjugate, XL665 labeled, anti- PCT antibody (monoclonal, mouse), 3.95 mL after reconstitution with KRYPTOR Solution 1 and KRYPTOR Solution 2 · Defibrinated human plasma, for diluting samples above 50 µg/L, ready for use Calibrator Elecsys PCT CalSet BRAHMS PCT sensitive KRYPTOR Calibrator Calibration Predicate device name:

idK173927_s0_e2000

K173927.txt

applicant

Roche Diagnostics

k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K173927 B. Purpose for Submission: To obtain a substantial equivalence determination for the Elecsys BRAHMS PCT. C. Measurand: Procalcitonin (PCT) D. Type of Test: Quantitative, Electrochemiluminescence Immunoassay E. Applicant: Roche Diagnostics F. Proprietary and Established Names: Elecsys BRAHMS PCT G. Regulatory Information: 1. Regulation section: 21 CFR 866.3215; Device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis 2. Classification: Class II (Special Controls) 3. Product codes: PMT 4. Panel: 83 - (Microbiology) 2 H. Intended Use/ Indications for Use: 1. Intended Use/ Indications for Use: Immunoassay for the in vitro quantitative determination of PCT (procalcitonin) in human serum and plasma (K2 –EDTA, K3-EDTA and Li-Heparin). The electrochemiluminescence immunoassay “ECLIA” is intended for use on Elecsys and cobas e immunoassay analyzers. Used in conjunction with other laboratory findings and clinical assessments, Elecsys BRAHMS PCT is intended for use as follows: · to aid in the risk assessment of critically ill patients on their first day of ICU admission for progression to severe sepsis and septic shock, · to determine the change in PCT level over time as an aid in assessing the cumulative 28-day risk of all-cause mortality for patients diagnosed with severe sepsis or septic shock in the ICU or when obtained in the emergency department or other medical wards prior to ICU admission, · to aid in decision making on antibiotic therapy, for inpatients or patients in the emergency department with suspected or confirmed lower respiratory tract infections (LRTI) – defined as community-acquired pneumonia (CAP), acute bronchitis, and acute exacerbation of chronic obstructive pulmonary disease (AECOPD), · to aid in decision making on antibiotic discontinuation for patients with suspected or confirmed sepsis. 2. Special conditions for use statement(s): For prescription use only Warnings and Precautions: The Elecsys BRAHMS PCT assay should not be used as a sole basis for diagnosis for determining the risk of 28 day all-cause mortality. Changes in PCT should always be interpreted in the context of the clinical status of the patient and other laboratory results. There is no uniformly recognized interpretation of the change in PCT levels for the prediction of mortality, and overall mortality is strongly dependent on many factors, including pre-existing patient risk factors and clinical course. The need for continued ICU care at Day 4 and other covariates (e.g., age, sepsis-related organ failure assessment (SOFA score) are also significant predictors of 28-day cumulative mortality risk. Validation of the Elecsys BRAHMS PCT assay as an aid in predicting mortality was performed in a study population with an overall 28-day mortality of 22%. 3. Special instrument requirements: 3 The submission demonstrates performance on the cobas e411 immunoassay analyzer. I. Device Description: Reagents Materials provided in Elecsys BRAHMS PCT: The reagent working solutions include: Rackpack (kit placed on analyzer) · M: Streptavidin-coated microparticles · R1: Anti-PCT-Ab~biotin · R2: Anti-PCT – Ab~Ru (bpy) J. Substantial Equivalence Information: 1. Predicate device name(s): BRAHMS PCT sensitive KRYPTOR 2. Predicate 510(k) number(s): K171338 4. Comparison with predicate: 4 Similarities Item Candidate Device: Elecsys BRAHMS PCT (K173927) Predicate Device: BRAHMS PCT sensitive KRYPTOR (K171338) Intended Use Immunoassay for the in vitro quantitative determination of PCT (procalcitonin) in human serum and plasma (K2 –EDTA, K3- EDTA and Li-Heparin). The electrochemiluminescence immunoassay “ECLIA” is intended for use on Elecsys and cobas e immunoassay analyzers. Used in conjunction with other laboratory findings and clinical assessments, Elecsys B·R·A·H·M·S PCT is intended for use as follows: · to aid in the risk assessment of critically ill patients on their first day of ICU admission for progression to severe sepsis and septic shock, · to determine the change in PCT level over time as an aid in assessing the cumulative 28-day risk of all-cause mortality for patients diagnosed with severe sepsis or septic shock in the ICU or when obtained in the emergency department or other medical wards prior to ICU admission, · to aid in decision making on antibiotic therapy, for inpatients or patients in the emergency department with suspected or confirmed lower respiratory tract infections (LRTI) – defined as community-acquired pneumonia (CAP), acute bronchitis, and acute exacerbation of chronic obstructive pulmonary disease (AECOPD), · to aid in decision making on antibiotic discontinuation for patients with suspected or confirmed sepsis. The BRAHMS PCT sensitive KRYPTOR is an immunofluorescent assay using Time- Resolved Amplified Cryptate Emission (TRACE) technology to determine the concentration of PCT (procalcitonin) in human serum and EDTA or heparin plasma. The BRAHMS PCT sensitive KRYPTOR is intended to be performed on the BRAHMS KRYPTOR analyzer family. Used in conjunction with other laboratory findings and clinical assessments, BRAHMS PCT sensitive KRYPTOR is intended for use as follows: · to aid in the risk assessment of critically ill patients on their first day of ICU admission for progression to severe sepsis and septic shock, · to determine the change in PCT level over time as an aid in assessing the cumulative 28-day risk of all-cause mortality for patients diagnosed with severe sepsis or septic shock in the ICU or when obtained in the emergency department or other medical wards prior to ICU admission, · to aid in decision making on antibiotic therapy, for inpatients or patients in the emergency department with suspected or confirmed lower respiratory tract infections (LRTI) – defined as community-acquired pneumonia (CAP), acute bronchitis, and acute exacerbation of chronic obstructive pulmonary disease (AECOPD), · to aid in decision making on antibiotic discontinuation for patients with suspected or confirmed sepsis. 5 Differences Item Candidate Device: Elecsys BRAHMS PCT (K173927) Predicate Device: BRAHMS PCT sensitive KRYPTOR (DEN150009) Assay Protocol The Elecsys BRAHMS PCT assay is a two-step sandwich immunoassay with streptavidin microparticles and an electrochemiluminescence detection system. The test system reagents contain a biotinylated monoclonal PCT-specific antibody and a ruthenium labeled monoclonal PCT-specific antibody. The BRAHMS PCT sensitive KRYPTOR assay is a homogeneous sandwich immunoassay for detection of PCT in human serum or plasma. The measuring principle is based on Time-Resolved Amplified Cryptate Emission (TRACE) technology, which measures the signal that is emitted from an immunocomplex with time delay. Detection Protocol Electrochemiluminescent Assay Time-Resolved Amplified Cryptate Emission (TRACE) Applications 18-minute application 19-minute incubation Instrument Platform cobas e 411 analyzer BRAHMS KRYPTOR analyzer Sample Volume 30 µL 50 µL Sample Type Human serum and plasma (Li- Heparin, K2/K3 EDTA) Human serum and plasma (EDTA, heparin) Reagents · Streptavidin-coated microparticles: · Steptavidin-coated microparticles; preservative · Anti-PCT-Ab~biotin: Biotinylated monoclonal anti-PCT antibody (mouse), phosphate buffer, preservative · Anti-PCT – Ab~Ru(bpy) 2/3+ a monoclonal anti-PCT antibody (mouse) labeled with ruthenium complex, phosphate buffer, preservative · Cryptate conjugate, cryptate labeled, anti-PCT antibody (polyclonal, sheep), 3.2mL after reconstitution with KRYPTOR Solution 2 · L665 conjugate, XL665 labeled, anti- PCT antibody (monoclonal, mouse), 3.95 mL after reconstitution with KRYPTOR Solution 1 and KRYPTOR Solution 2 · Defibrinated human plasma, for diluting samples above 50 µg/L, ready for use Calibrator Elecsys PCT CalSet BRAHMS PCT sensitive KRYPTOR Calibrator Calibration Applicant:

idK173927_s0_e2000

K173927.txt

proprietary and established names

Elecsys BRAHMS PCT

ANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K173927 B. Purpose for Submission: To obtain a substantial equivalence determination for the Elecsys BRAHMS PCT. C. Measurand: Procalcitonin (PCT) D. Type of Test: Quantitative, Electrochemiluminescence Immunoassay E. Applicant: Roche Diagnostics F. Proprietary and Established Names: Elecsys BRAHMS PCT G. Regulatory Information: 1. Regulation section: 21 CFR 866.3215; Device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis 2. Classification: Class II (Special Controls) 3. Product codes: PMT 4. Panel: 83 - (Microbiology) 2 H. Intended Use/ Indications for Use: 1. Intended Use/ Indications for Use: Immunoassay for the in vitro quantitative determination of PCT (procalcitonin) in human serum and plasma (K2 –EDTA, K3-EDTA and Li-Heparin). The electrochemiluminescence immunoassay “ECLIA” is intended for use on Elecsys and cobas e immunoassay analyzers. Used in conjunction with other laboratory findings and clinical assessments, Elecsys BRAHMS PCT is intended for use as follows: · to aid in the risk assessment of critically ill patients on their first day of ICU admission for progression to severe sepsis and septic shock, · to determine the change in PCT level over time as an aid in assessing the cumulative 28-day risk of all-cause mortality for patients diagnosed with severe sepsis or septic shock in the ICU or when obtained in the emergency department or other medical wards prior to ICU admission, · to aid in decision making on antibiotic therapy, for inpatients or patients in the emergency department with suspected or confirmed lower respiratory tract infections (LRTI) – defined as community-acquired pneumonia (CAP), acute bronchitis, and acute exacerbation of chronic obstructive pulmonary disease (AECOPD), · to aid in decision making on antibiotic discontinuation for patients with suspected or confirmed sepsis. 2. Special conditions for use statement(s): For prescription use only Warnings and Precautions: The Elecsys BRAHMS PCT assay should not be used as a sole basis for diagnosis for determining the risk of 28 day all-cause mortality. Changes in PCT should always be interpreted in the context of the clinical status of the patient and other laboratory results. There is no uniformly recognized interpretation of the change in PCT levels for the prediction of mortality, and overall mortality is strongly dependent on many factors, including pre-existing patient risk factors and clinical course. The need for continued ICU care at Day 4 and other covariates (e.g., age, sepsis-related organ failure assessment (SOFA score) are also significant predictors of 28-day cumulative mortality risk. Validation of the Elecsys BRAHMS PCT assay as an aid in predicting mortality was performed in a study population with an overall 28-day mortality of 22%. 3. Special instrument requirements: 3 The submission demonstrates performance on the cobas e411 immunoassay analyzer. I. Device Description: Reagents Materials provided in Elecsys BRAHMS PCT: The reagent working solutions include: Rackpack (kit placed on analyzer) · M: Streptavidin-coated microparticles · R1: Anti-PCT-Ab~biotin · R2: Anti-PCT – Ab~Ru (bpy) J. Substantial Equivalence Information: 1. Predicate device name(s): BRAHMS PCT sensitive KRYPTOR 2. Predicate 510(k) number(s): K171338 4. Comparison with predicate: 4 Similarities Item Candidate Device: Elecsys BRAHMS PCT (K173927) Predicate Device: BRAHMS PCT sensitive KRYPTOR (K171338) Intended Use Immunoassay for the in vitro quantitative determination of PCT (procalcitonin) in human serum and plasma (K2 –EDTA, K3- EDTA and Li-Heparin). The electrochemiluminescence immunoassay “ECLIA” is intended for use on Elecsys and cobas e immunoassay analyzers. Used in conjunction with other laboratory findings and clinical assessments, Elecsys B·R·A·H·M·S PCT is intended for use as follows: · to aid in the risk assessment of critically ill patients on their first day of ICU admission for progression to severe sepsis and septic shock, · to determine the change in PCT level over time as an aid in assessing the cumulative 28-day risk of all-cause mortality for patients diagnosed with severe sepsis or septic shock in the ICU or when obtained in the emergency department or other medical wards prior to ICU admission, · to aid in decision making on antibiotic therapy, for inpatients or patients in the emergency department with suspected or confirmed lower respiratory tract infections (LRTI) – defined as community-acquired pneumonia (CAP), acute bronchitis, and acute exacerbation of chronic obstructive pulmonary disease (AECOPD), · to aid in decision making on antibiotic discontinuation for patients with suspected or confirmed sepsis. The BRAHMS PCT sensitive KRYPTOR is an immunofluorescent assay using Time- Resolved Amplified Cryptate Emission (TRACE) technology to determine the concentration of PCT (procalcitonin) in human serum and EDTA or heparin plasma. The BRAHMS PCT sensitive KRYPTOR is intended to be performed on the BRAHMS KRYPTOR analyzer family. Used in conjunction with other laboratory findings and clinical assessments, BRAHMS PCT sensitive KRYPTOR is intended for use as follows: · to aid in the risk assessment of critically ill patients on their first day of ICU admission for progression to severe sepsis and septic shock, · to determine the change in PCT level over time as an aid in assessing the cumulative 28-day risk of all-cause mortality for patients diagnosed with severe sepsis or septic shock in the ICU or when obtained in the emergency department or other medical wards prior to ICU admission, · to aid in decision making on antibiotic therapy, for inpatients or patients in the emergency department with suspected or confirmed lower respiratory tract infections (LRTI) – defined as community-acquired pneumonia (CAP), acute bronchitis, and acute exacerbation of chronic obstructive pulmonary disease (AECOPD), · to aid in decision making on antibiotic discontinuation for patients with suspected or confirmed sepsis. 5 Differences Item Candidate Device: Elecsys BRAHMS PCT (K173927) Predicate Device: BRAHMS PCT sensitive KRYPTOR (DEN150009) Assay Protocol The Elecsys BRAHMS PCT assay is a two-step sandwich immunoassay with streptavidin microparticles and an electrochemiluminescence detection system. The test system reagents contain a biotinylated monoclonal PCT-specific antibody and a ruthenium labeled monoclonal PCT-specific antibody. The BRAHMS PCT sensitive KRYPTOR assay is a homogeneous sandwich immunoassay for detection of PCT in human serum or plasma. The measuring principle is based on Time-Resolved Amplified Cryptate Emission (TRACE) technology, which measures the signal that is emitted from an immunocomplex with time delay. Detection Protocol Electrochemiluminescent Assay Time-Resolved Amplified Cryptate Emission (TRACE) Applications 18-minute application 19-minute incubation Instrument Platform cobas e 411 analyzer BRAHMS KRYPTOR analyzer Sample Volume 30 µL 50 µL Sample Type Human serum and plasma (Li- Heparin, K2/K3 EDTA) Human serum and plasma (EDTA, heparin) Reagents · Streptavidin-coated microparticles: · Steptavidin-coated microparticles; preservative · Anti-PCT-Ab~biotin: Biotinylated monoclonal anti-PCT antibody (mouse), phosphate buffer, preservative · Anti-PCT – Ab~Ru(bpy) 2/3+ a monoclonal anti-PCT antibody (mouse) labeled with ruthenium complex, phosphate buffer, preservative · Cryptate conjugate, cryptate labeled, anti-PCT antibody (polyclonal, sheep), 3.2mL after reconstitution with KRYPTOR Solution 2 · L665 conjugate, XL665 labeled, anti- PCT antibody (monoclonal, mouse), 3.95 mL after reconstitution with KRYPTOR Solution 1 and KRYPTOR Solution 2 · Defibrinated human plasma, for diluting samples above 50 µg/L, ready for use Calibrator Elecsys PCT CalSet BRAHMS PCT sensitive KRYPTOR Calibrator Calibration Proprietary and established names:

idK173927_s0_e2000

K173927.txt

regulation section

21 CFR 866.3215; Device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K173927 B. Purpose for Submission: To obtain a substantial equivalence determination for the Elecsys BRAHMS PCT. C. Measurand: Procalcitonin (PCT) D. Type of Test: Quantitative, Electrochemiluminescence Immunoassay E. Applicant: Roche Diagnostics F. Proprietary and Established Names: Elecsys BRAHMS PCT G. Regulatory Information: 1. Regulation section: 21 CFR 866.3215; Device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis 2. Classification: Class II (Special Controls) 3. Product codes: PMT 4. Panel: 83 - (Microbiology) 2 H. Intended Use/ Indications for Use: 1. Intended Use/ Indications for Use: Immunoassay for the in vitro quantitative determination of PCT (procalcitonin) in human serum and plasma (K2 –EDTA, K3-EDTA and Li-Heparin). The electrochemiluminescence immunoassay “ECLIA” is intended for use on Elecsys and cobas e immunoassay analyzers. Used in conjunction with other laboratory findings and clinical assessments, Elecsys BRAHMS PCT is intended for use as follows: · to aid in the risk assessment of critically ill patients on their first day of ICU admission for progression to severe sepsis and septic shock, · to determine the change in PCT level over time as an aid in assessing the cumulative 28-day risk of all-cause mortality for patients diagnosed with severe sepsis or septic shock in the ICU or when obtained in the emergency department or other medical wards prior to ICU admission, · to aid in decision making on antibiotic therapy, for inpatients or patients in the emergency department with suspected or confirmed lower respiratory tract infections (LRTI) – defined as community-acquired pneumonia (CAP), acute bronchitis, and acute exacerbation of chronic obstructive pulmonary disease (AECOPD), · to aid in decision making on antibiotic discontinuation for patients with suspected or confirmed sepsis. 2. Special conditions for use statement(s): For prescription use only Warnings and Precautions: The Elecsys BRAHMS PCT assay should not be used as a sole basis for diagnosis for determining the risk of 28 day all-cause mortality. Changes in PCT should always be interpreted in the context of the clinical status of the patient and other laboratory results. There is no uniformly recognized interpretation of the change in PCT levels for the prediction of mortality, and overall mortality is strongly dependent on many factors, including pre-existing patient risk factors and clinical course. The need for continued ICU care at Day 4 and other covariates (e.g., age, sepsis-related organ failure assessment (SOFA score) are also significant predictors of 28-day cumulative mortality risk. Validation of the Elecsys BRAHMS PCT assay as an aid in predicting mortality was performed in a study population with an overall 28-day mortality of 22%. 3. Special instrument requirements: 3 The submission demonstrates performance on the cobas e411 immunoassay analyzer. I. Device Description: Reagents Materials provided in Elecsys BRAHMS PCT: The reagent working solutions include: Rackpack (kit placed on analyzer) · M: Streptavidin-coated microparticles · R1: Anti-PCT-Ab~biotin · R2: Anti-PCT – Ab~Ru (bpy) J. Substantial Equivalence Information: 1. Predicate device name(s): BRAHMS PCT sensitive KRYPTOR 2. Predicate 510(k) number(s): K171338 4. Comparison with predicate: 4 Similarities Item Candidate Device: Elecsys BRAHMS PCT (K173927) Predicate Device: BRAHMS PCT sensitive KRYPTOR (K171338) Intended Use Immunoassay for the in vitro quantitative determination of PCT (procalcitonin) in human serum and plasma (K2 –EDTA, K3- EDTA and Li-Heparin). The electrochemiluminescence immunoassay “ECLIA” is intended for use on Elecsys and cobas e immunoassay analyzers. Used in conjunction with other laboratory findings and clinical assessments, Elecsys B·R·A·H·M·S PCT is intended for use as follows: · to aid in the risk assessment of critically ill patients on their first day of ICU admission for progression to severe sepsis and septic shock, · to determine the change in PCT level over time as an aid in assessing the cumulative 28-day risk of all-cause mortality for patients diagnosed with severe sepsis or septic shock in the ICU or when obtained in the emergency department or other medical wards prior to ICU admission, · to aid in decision making on antibiotic therapy, for inpatients or patients in the emergency department with suspected or confirmed lower respiratory tract infections (LRTI) – defined as community-acquired pneumonia (CAP), acute bronchitis, and acute exacerbation of chronic obstructive pulmonary disease (AECOPD), · to aid in decision making on antibiotic discontinuation for patients with suspected or confirmed sepsis. The BRAHMS PCT sensitive KRYPTOR is an immunofluorescent assay using Time- Resolved Amplified Cryptate Emission (TRACE) technology to determine the concentration of PCT (procalcitonin) in human serum and EDTA or heparin plasma. The BRAHMS PCT sensitive KRYPTOR is intended to be performed on the BRAHMS KRYPTOR analyzer family. Used in conjunction with other laboratory findings and clinical assessments, BRAHMS PCT sensitive KRYPTOR is intended for use as follows: · to aid in the risk assessment of critically ill patients on their first day of ICU admission for progression to severe sepsis and septic shock, · to determine the change in PCT level over time as an aid in assessing the cumulative 28-day risk of all-cause mortality for patients diagnosed with severe sepsis or septic shock in the ICU or when obtained in the emergency department or other medical wards prior to ICU admission, · to aid in decision making on antibiotic therapy, for inpatients or patients in the emergency department with suspected or confirmed lower respiratory tract infections (LRTI) – defined as community-acquired pneumonia (CAP), acute bronchitis, and acute exacerbation of chronic obstructive pulmonary disease (AECOPD), · to aid in decision making on antibiotic discontinuation for patients with suspected or confirmed sepsis. 5 Differences Item Candidate Device: Elecsys BRAHMS PCT (K173927) Predicate Device: BRAHMS PCT sensitive KRYPTOR (DEN150009) Assay Protocol The Elecsys BRAHMS PCT assay is a two-step sandwich immunoassay with streptavidin microparticles and an electrochemiluminescence detection system. The test system reagents contain a biotinylated monoclonal PCT-specific antibody and a ruthenium labeled monoclonal PCT-specific antibody. The BRAHMS PCT sensitive KRYPTOR assay is a homogeneous sandwich immunoassay for detection of PCT in human serum or plasma. The measuring principle is based on Time-Resolved Amplified Cryptate Emission (TRACE) technology, which measures the signal that is emitted from an immunocomplex with time delay. Detection Protocol Electrochemiluminescent Assay Time-Resolved Amplified Cryptate Emission (TRACE) Applications 18-minute application 19-minute incubation Instrument Platform cobas e 411 analyzer BRAHMS KRYPTOR analyzer Sample Volume 30 µL 50 µL Sample Type Human serum and plasma (Li- Heparin, K2/K3 EDTA) Human serum and plasma (EDTA, heparin) Reagents · Streptavidin-coated microparticles: · Steptavidin-coated microparticles; preservative · Anti-PCT-Ab~biotin: Biotinylated monoclonal anti-PCT antibody (mouse), phosphate buffer, preservative · Anti-PCT – Ab~Ru(bpy) 2/3+ a monoclonal anti-PCT antibody (mouse) labeled with ruthenium complex, phosphate buffer, preservative · Cryptate conjugate, cryptate labeled, anti-PCT antibody (polyclonal, sheep), 3.2mL after reconstitution with KRYPTOR Solution 2 · L665 conjugate, XL665 labeled, anti- PCT antibody (monoclonal, mouse), 3.95 mL after reconstitution with KRYPTOR Solution 1 and KRYPTOR Solution 2 · Defibrinated human plasma, for diluting samples above 50 µg/L, ready for use Calibrator Elecsys PCT CalSet BRAHMS PCT sensitive KRYPTOR Calibrator Calibration Regulation section:

idK173927_s6000_e8000

K173927.txt

proposed labeling

The labeling supports the finding of substantial equivalence for this device.

/mL 667 48 2 717 0.5 ng/mL < PCT ≤ 2.0 ng/mL 18 490 54 562 > 2.0 ng/mL 0 13 1325 1338 Total 685 551 1381 2617 15 Table 10: 5 x 5 Table Elecsys BRAHMS PCT vs Predicate Elecsys BRAHMS PCT on cobas e 411 BRAHMS PCT sensitive Kryptor Total ≤ 0.1 ng/mL 0.1 ng/mL < PCT≤ 0.25 ng/mL 0.25 ng/mL < PCT≤ 0.5 ng/mL 0.5 ng/mL < PCT ≤ 2.0 ng/mL > 2.0 ng/mL ≤ 0.1 ng/mL 97 47 1 1 1 147 0.1 ng/mL < PCT≤ 0.25 ng/mL 6 240 42 1 1 290 0.25 ng/mL < PCT≤ 0.5 ng/mL 0 16 218 46 0 280 0.5 ng/mL < PCT≤ 2.0 ng/mL 1 1 16 490 54 562 > 2.0 ng/mL 0 0 0 13 1325 1338 Total 104 304 277 551 1381 2617 Table 11: Comparison Elecsys BRAHMS PCT vs Predicate N = 2617 (104 ≤ 0.1 ng/mL, 408 ≤ 0.25 ng/mL; 685 ≤ 0.5 ng/mL; 1236 ≤ 2.0 ng/mL) Cutoff (> vs. ≤) PositiveAgreement (95% CI) NegativeAgreement(95% CI) TotalAgreement Cohen‘sKappa 0.10 ng/mL 93.3% 98.0% 97.8% 0.762 (86.6 - 97.3) (97.4 - 97.3) 0.25 ng/mL 95.6% 97.9% 97.5% 0.908 (93.1 - 97.4) (97.2 - 98.4) 0.50 ng/mL 97.4% 97.4% 97.4% 0.934 (95.9 - 98.4) (96.6 - 98.1) 2.00 ng/mL 98.9% 95.9% 97.4% 0.947 (98.2 - 99.4) (94.8 - 96.9) 16 Table 12: Weighted Deming and Passing Bablok Regression Analysis Parameter Passing Bablok Regression Weighted Deming (λ=1) Regression Analysis n 2617 2617 Slope 0.959 0.949 95% CI [0.947; 0.972] [0.937; 0.961] Intercept -0.023 -0.008 95% CI [-0.028; -0.018] [-0.013; -0.004] Pearson Correlation Coefficient (R) 0.989 0.989 Spearman Correlation Coefficient (R) 0.990 0.990 Sample Range [0.02; 662.86] [0.02; 662.86] Figure 1: Weighted Deming Regression plots of Elecsys BRAHMS PCT versus Predicate 17 Figure 2: Passing Bablok Regression plots of Elecsys BRAHMS PCT versus Predicate 3. Clinical Cut-off: See assay cut-off M.1.j above. N. Instrument Name: The cobas e411 immunoassay analyzer O. System Descriptions: 1. Modes of Operation: See Device Description (Section I) above 2. Software FDA has reviewed applicant’s Hazard Analysis and software development processes for this line of product types: Yes ____X_ __ or No ________ 4. Specimen Identification: 18 A barcode reader reads the barcodes on each tube for positive identification. 4. Specimen Sampling and Handling: See Sample Stability (M.1.k) above. 5. Calibration: Results are determined via a calibration curve which is instrument specifically generated by 2-point calibration and a master curve provided via the reagent barcode. Calibration must be performed once per reagent lot using fresh reagent (i.e. not more than 24 hours since the reagent kit was registered on the analyzer). Renewed calibration is recommended as follows: · after 8 weeks when using the same reagent lot · after 7 days (when using the same reagent kit on the analyzer) · as required: e.g. quality control findings outside the defined limits 6. Quality Control: See “Traceability, Stability, Expected Values (controls, calibrators, or methods)” Section (M.1.c) above. P. Other Supportive Instrument Performance Characteristics Data Not Covered In the “Performance Characteristics” Section above: N/A Q. Proposed Labeling: The labeling supports the finding of substantial equivalence for this device. R. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Proposed labeling:

idK173927_s6000_e8000

K173927.txt

conclusion

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

5 ng/mL 667 48 2 717 0.5 ng/mL < PCT ≤ 2.0 ng/mL 18 490 54 562 > 2.0 ng/mL 0 13 1325 1338 Total 685 551 1381 2617 15 Table 10: 5 x 5 Table Elecsys BRAHMS PCT vs Predicate Elecsys BRAHMS PCT on cobas e 411 BRAHMS PCT sensitive Kryptor Total ≤ 0.1 ng/mL 0.1 ng/mL < PCT≤ 0.25 ng/mL 0.25 ng/mL < PCT≤ 0.5 ng/mL 0.5 ng/mL < PCT ≤ 2.0 ng/mL > 2.0 ng/mL ≤ 0.1 ng/mL 97 47 1 1 1 147 0.1 ng/mL < PCT≤ 0.25 ng/mL 6 240 42 1 1 290 0.25 ng/mL < PCT≤ 0.5 ng/mL 0 16 218 46 0 280 0.5 ng/mL < PCT≤ 2.0 ng/mL 1 1 16 490 54 562 > 2.0 ng/mL 0 0 0 13 1325 1338 Total 104 304 277 551 1381 2617 Table 11: Comparison Elecsys BRAHMS PCT vs Predicate N = 2617 (104 ≤ 0.1 ng/mL, 408 ≤ 0.25 ng/mL; 685 ≤ 0.5 ng/mL; 1236 ≤ 2.0 ng/mL) Cutoff (> vs. ≤) PositiveAgreement (95% CI) NegativeAgreement(95% CI) TotalAgreement Cohen‘sKappa 0.10 ng/mL 93.3% 98.0% 97.8% 0.762 (86.6 - 97.3) (97.4 - 97.3) 0.25 ng/mL 95.6% 97.9% 97.5% 0.908 (93.1 - 97.4) (97.2 - 98.4) 0.50 ng/mL 97.4% 97.4% 97.4% 0.934 (95.9 - 98.4) (96.6 - 98.1) 2.00 ng/mL 98.9% 95.9% 97.4% 0.947 (98.2 - 99.4) (94.8 - 96.9) 16 Table 12: Weighted Deming and Passing Bablok Regression Analysis Parameter Passing Bablok Regression Weighted Deming (λ=1) Regression Analysis n 2617 2617 Slope 0.959 0.949 95% CI [0.947; 0.972] [0.937; 0.961] Intercept -0.023 -0.008 95% CI [-0.028; -0.018] [-0.013; -0.004] Pearson Correlation Coefficient (R) 0.989 0.989 Spearman Correlation Coefficient (R) 0.990 0.990 Sample Range [0.02; 662.86] [0.02; 662.86] Figure 1: Weighted Deming Regression plots of Elecsys BRAHMS PCT versus Predicate 17 Figure 2: Passing Bablok Regression plots of Elecsys BRAHMS PCT versus Predicate 3. Clinical Cut-off: See assay cut-off M.1.j above. N. Instrument Name: The cobas e411 immunoassay analyzer O. System Descriptions: 1. Modes of Operation: See Device Description (Section I) above 2. Software FDA has reviewed applicant’s Hazard Analysis and software development processes for this line of product types: Yes ____X_ __ or No ________ 4. Specimen Identification: 18 A barcode reader reads the barcodes on each tube for positive identification. 4. Specimen Sampling and Handling: See Sample Stability (M.1.k) above. 5. Calibration: Results are determined via a calibration curve which is instrument specifically generated by 2-point calibration and a master curve provided via the reagent barcode. Calibration must be performed once per reagent lot using fresh reagent (i.e. not more than 24 hours since the reagent kit was registered on the analyzer). Renewed calibration is recommended as follows: · after 8 weeks when using the same reagent lot · after 7 days (when using the same reagent kit on the analyzer) · as required: e.g. quality control findings outside the defined limits 6. Quality Control: See “Traceability, Stability, Expected Values (controls, calibrators, or methods)” Section (M.1.c) above. P. Other Supportive Instrument Performance Characteristics Data Not Covered In the “Performance Characteristics” Section above: N/A Q. Proposed Labeling: The labeling supports the finding of substantial equivalence for this device. R. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Conclusion:

idK172109_s0_e2000

K172109.txt

purpose for submission

To obtain a substantial equivalence determination for the Liofilchem MIC Test Strip (MTS) containing Erythromycin at concentrations of 0.016 -256 µg/mL for susceptibility testing of Staphylococcus aureus

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K172109 B. Purpose for Submission: To obtain a substantial equivalence determination for the Liofilchem MIC Test Strip (MTS) containing Erythromycin at concentrations of 0.016 -256 µg/mL for susceptibility testing of Staphylococcus aureus C. Measurand: Erythromycin 0.016-256 μg/mL D. Type of Test: Quantitative AST growth based detection E. Applicant: Liofilchem s.r.l. F. Proprietary and Established Names: Liofilchem MIC Test Strip (MTS), Erythromycin 0.016-256 μg/mL G. Regulatory Information: 1. Regulation section: 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: II 3. Product code: JWY - Manual Antimicrobial Test Systems 2 4. Panel: 83 – Microbiology H. Intended Use: 1. Intended use(s): The Liofilchem MIC Test Strip (MTS) is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of bacteria. MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in µg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. The Erythromycin MTS at concentrations of 0.016-256 µg/mL should be interpreted at 16-20 hours of incubation Erythromycin has been shown to be active both clinically and in vitro against the non- fastidious bacteria listed below according to the FDA label: Staphylococcus aureus 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): For prescription use 4. Special instrument requirements: Manual reading only I. Device Description: The Erythromycin MIC Test Strip (MTS) consists of specialized paper impregnated with a predefined concentration gradient of Erythromycin across 15 two-fold dilutions like those of a conventional MIC method. One side of the strip is labelled with the Erythromycin code (E) and the MIC reading scale in µg/mL. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16- 20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the MIC Test Strip. Since MTS strip generates MIC values which fall between two-fold dilutions for interpretation, the MIC value read is recorded to the next two-fold dilution value. 3 J. Substantial Equivalence Information: 1. Predicate device name(s): Liofilchem MTS, vancomycin 2. Predicate 510(k) number(s): K153687 3. Comparison with predicate: Table 1: Comparison with the Predicate Device Similarities Item Device (K172109) Predicate Liofilchem MTS, vancomycin (K153687) Intended Use Quantitative susceptibility to antimicrobial agents Same Media Mueller Hinton agar Same Inoculation Isolated colonies from culture in suspension equivalent to 0.5 McFarland. Inoculum is applied manually using the manual plate inoculation method or plate rotator for even distribution of inoculum Same Reading Manual; the point where the edge of inhibition ellipse intersects the MIC Test Strip Same Result MIC Same Differences Item Device Predicate Antibiotic Erythromycin (E) Vancomycin (VA) Incubation 35 ± 2°C for 16 – 20 hours 35 ± 2°C for 24 hours K. Standard/Guidance Document Referenced: “Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA” CLSI M07-A10 “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, Tenth Edition January 2015” 4 CLSI M100-S26 “Performance Standards for Antimicrobial Susceptibility Testing; Twenty- Fifth Informational Supplement, January 2016” L. Test Principle: MTS are made of specialized paper impregnated with a predefined concentration gradient of antibiotic, across 15 two-fold dilutions like those of a conventional MIC method. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the strip MIC Test Strip. Growth along the entire gradient (i.e., no inhibition ellipse) indicates that the MIC value is greater than or equal to (≥) the highest value on the scale. An inhibition ellipse that intersects below the lower end of the scale is read as less than (<) the lowest value. An MIC of 0.125 μg/mL is considered to be the same as 0.12 μg/mL for reporting purposes. An MTS MIC value which falls between standard two-fold dilutions must be rounded up to the next standard upper two-fold value before categorization. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Reproducibility testing was performed using ten Staphylococcus aureus isolates. These ten isolates (5 MSSA and 5 MRSA) were tested at three sites in triplicates on three days. The mode of MIC value was determined and the reproducibility was calculated based on the number of MIC values that fell within ±1 doubling dilution of the mode. The testing resulted in overall reproducibility of greater than 95%. The results were acceptable. b. Linearity/assay reportable range: Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): The recommended QC isolates were tested a sufficient number of times (i.e., at least 20/site) at all three sites with acceptable results in comparison to the reference method. All results were within the expected range greater than 95% of the time. The results are summarized in Table 2. 5 Table 2: Erythromycin MTS QC results Organism Concentration (µg/mL) Reference MTS S. aureus ATCC 29213 Expected Result 0.25- 1µg/mL 0.12 1 0.25 17 39 0.5 43 22 1 2 E. faecalis ATCC 29212 Expected Result 1- 4µg/mL 0.5 1 27 2 2 30 27 4 4 30 8 2 The inoculum was prepared to achieve a 0.5 McFarland standard turbidity. Colony counts were performed periodically at each site. Inoculum density checks were performed and the average colony counts of each QC strain were within the recommended range of approximately 1x 108 CFU/mL. d. Detection limit: Not Applicable e. Analytical specificity: Not Applicable f. Assay cut-off: Not Applicable 2. Comparison studies: a. Method comparison with predicate device: Clinical testing was conducted at three sites (two U.S. sites and one site outside the U.S). A total of 353 Staphylococcus aureus isolates were tested. There were 252 (71.4%) isolates that were tested within seven days of collection and 101 (28.6%) isolates that were tested after 7 days but within one year of collection. The 353 clinical isolates included 201 MSSA and 152 MRSA. An additional 75 challenge Staphylococcus aureus (11 MSSA and 64 MRSA) were tested, resulting in a total of 428 clinical and challenge isolates. Results obtained with Liofilchem MIC Test Strip (MTS) with Erythromycin were compared to results obtained from frozen reference MIC panels. Reference panels were prepared and interpreted as outlined in CLSI recommendations in M7-A10. 6 Isolated colonies from an overnight blood agar plate were suspended in saline to achieve a 0.5 McFarland standard turbidity (approximately 108 CFU/mL). Testing conditions consisted of incubation of the inoculated Mueller Hinton agar plates in and inverted position at 35°C ±2 for 16-20 hours. At the end of incubation, the MIC value where the edge of the inhibition ellipse intersects the strip was compared to the reference method. Erythromycin is bacteriostatic; MIC is read at 80% inhibition when trailing is seen. The performance is listed in Table 3 below. Table 3: Performance of Staphylococcus aureus isolates* Erythromycin EA Tot EA N EA % Eval. EA Tot Eval. EA N Eval. EA % CA N CA % #R min maj vm Purpose for submission:

idK172109_s0_e2000

K172109.txt

measurand

Erythromycin 0.016-256 μg/mL

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K172109 B. Purpose for Submission: To obtain a substantial equivalence determination for the Liofilchem MIC Test Strip (MTS) containing Erythromycin at concentrations of 0.016 -256 µg/mL for susceptibility testing of Staphylococcus aureus C. Measurand: Erythromycin 0.016-256 μg/mL D. Type of Test: Quantitative AST growth based detection E. Applicant: Liofilchem s.r.l. F. Proprietary and Established Names: Liofilchem MIC Test Strip (MTS), Erythromycin 0.016-256 μg/mL G. Regulatory Information: 1. Regulation section: 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: II 3. Product code: JWY - Manual Antimicrobial Test Systems 2 4. Panel: 83 – Microbiology H. Intended Use: 1. Intended use(s): The Liofilchem MIC Test Strip (MTS) is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of bacteria. MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in µg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. The Erythromycin MTS at concentrations of 0.016-256 µg/mL should be interpreted at 16-20 hours of incubation Erythromycin has been shown to be active both clinically and in vitro against the non- fastidious bacteria listed below according to the FDA label: Staphylococcus aureus 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): For prescription use 4. Special instrument requirements: Manual reading only I. Device Description: The Erythromycin MIC Test Strip (MTS) consists of specialized paper impregnated with a predefined concentration gradient of Erythromycin across 15 two-fold dilutions like those of a conventional MIC method. One side of the strip is labelled with the Erythromycin code (E) and the MIC reading scale in µg/mL. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16- 20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the MIC Test Strip. Since MTS strip generates MIC values which fall between two-fold dilutions for interpretation, the MIC value read is recorded to the next two-fold dilution value. 3 J. Substantial Equivalence Information: 1. Predicate device name(s): Liofilchem MTS, vancomycin 2. Predicate 510(k) number(s): K153687 3. Comparison with predicate: Table 1: Comparison with the Predicate Device Similarities Item Device (K172109) Predicate Liofilchem MTS, vancomycin (K153687) Intended Use Quantitative susceptibility to antimicrobial agents Same Media Mueller Hinton agar Same Inoculation Isolated colonies from culture in suspension equivalent to 0.5 McFarland. Inoculum is applied manually using the manual plate inoculation method or plate rotator for even distribution of inoculum Same Reading Manual; the point where the edge of inhibition ellipse intersects the MIC Test Strip Same Result MIC Same Differences Item Device Predicate Antibiotic Erythromycin (E) Vancomycin (VA) Incubation 35 ± 2°C for 16 – 20 hours 35 ± 2°C for 24 hours K. Standard/Guidance Document Referenced: “Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA” CLSI M07-A10 “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, Tenth Edition January 2015” 4 CLSI M100-S26 “Performance Standards for Antimicrobial Susceptibility Testing; Twenty- Fifth Informational Supplement, January 2016” L. Test Principle: MTS are made of specialized paper impregnated with a predefined concentration gradient of antibiotic, across 15 two-fold dilutions like those of a conventional MIC method. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the strip MIC Test Strip. Growth along the entire gradient (i.e., no inhibition ellipse) indicates that the MIC value is greater than or equal to (≥) the highest value on the scale. An inhibition ellipse that intersects below the lower end of the scale is read as less than (<) the lowest value. An MIC of 0.125 μg/mL is considered to be the same as 0.12 μg/mL for reporting purposes. An MTS MIC value which falls between standard two-fold dilutions must be rounded up to the next standard upper two-fold value before categorization. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Reproducibility testing was performed using ten Staphylococcus aureus isolates. These ten isolates (5 MSSA and 5 MRSA) were tested at three sites in triplicates on three days. The mode of MIC value was determined and the reproducibility was calculated based on the number of MIC values that fell within ±1 doubling dilution of the mode. The testing resulted in overall reproducibility of greater than 95%. The results were acceptable. b. Linearity/assay reportable range: Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): The recommended QC isolates were tested a sufficient number of times (i.e., at least 20/site) at all three sites with acceptable results in comparison to the reference method. All results were within the expected range greater than 95% of the time. The results are summarized in Table 2. 5 Table 2: Erythromycin MTS QC results Organism Concentration (µg/mL) Reference MTS S. aureus ATCC 29213 Expected Result 0.25- 1µg/mL 0.12 1 0.25 17 39 0.5 43 22 1 2 E. faecalis ATCC 29212 Expected Result 1- 4µg/mL 0.5 1 27 2 2 30 27 4 4 30 8 2 The inoculum was prepared to achieve a 0.5 McFarland standard turbidity. Colony counts were performed periodically at each site. Inoculum density checks were performed and the average colony counts of each QC strain were within the recommended range of approximately 1x 108 CFU/mL. d. Detection limit: Not Applicable e. Analytical specificity: Not Applicable f. Assay cut-off: Not Applicable 2. Comparison studies: a. Method comparison with predicate device: Clinical testing was conducted at three sites (two U.S. sites and one site outside the U.S). A total of 353 Staphylococcus aureus isolates were tested. There were 252 (71.4%) isolates that were tested within seven days of collection and 101 (28.6%) isolates that were tested after 7 days but within one year of collection. The 353 clinical isolates included 201 MSSA and 152 MRSA. An additional 75 challenge Staphylococcus aureus (11 MSSA and 64 MRSA) were tested, resulting in a total of 428 clinical and challenge isolates. Results obtained with Liofilchem MIC Test Strip (MTS) with Erythromycin were compared to results obtained from frozen reference MIC panels. Reference panels were prepared and interpreted as outlined in CLSI recommendations in M7-A10. 6 Isolated colonies from an overnight blood agar plate were suspended in saline to achieve a 0.5 McFarland standard turbidity (approximately 108 CFU/mL). Testing conditions consisted of incubation of the inoculated Mueller Hinton agar plates in and inverted position at 35°C ±2 for 16-20 hours. At the end of incubation, the MIC value where the edge of the inhibition ellipse intersects the strip was compared to the reference method. Erythromycin is bacteriostatic; MIC is read at 80% inhibition when trailing is seen. The performance is listed in Table 3 below. Table 3: Performance of Staphylococcus aureus isolates* Erythromycin EA Tot EA N EA % Eval. EA Tot Eval. EA N Eval. EA % CA N CA % #R min maj vm Measurand:

idK172109_s0_e2000

K172109.txt

type of test

Quantitative AST growth based detection

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K172109 B. Purpose for Submission: To obtain a substantial equivalence determination for the Liofilchem MIC Test Strip (MTS) containing Erythromycin at concentrations of 0.016 -256 µg/mL for susceptibility testing of Staphylococcus aureus C. Measurand: Erythromycin 0.016-256 μg/mL D. Type of Test: Quantitative AST growth based detection E. Applicant: Liofilchem s.r.l. F. Proprietary and Established Names: Liofilchem MIC Test Strip (MTS), Erythromycin 0.016-256 μg/mL G. Regulatory Information: 1. Regulation section: 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: II 3. Product code: JWY - Manual Antimicrobial Test Systems 2 4. Panel: 83 – Microbiology H. Intended Use: 1. Intended use(s): The Liofilchem MIC Test Strip (MTS) is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of bacteria. MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in µg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. The Erythromycin MTS at concentrations of 0.016-256 µg/mL should be interpreted at 16-20 hours of incubation Erythromycin has been shown to be active both clinically and in vitro against the non- fastidious bacteria listed below according to the FDA label: Staphylococcus aureus 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): For prescription use 4. Special instrument requirements: Manual reading only I. Device Description: The Erythromycin MIC Test Strip (MTS) consists of specialized paper impregnated with a predefined concentration gradient of Erythromycin across 15 two-fold dilutions like those of a conventional MIC method. One side of the strip is labelled with the Erythromycin code (E) and the MIC reading scale in µg/mL. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16- 20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the MIC Test Strip. Since MTS strip generates MIC values which fall between two-fold dilutions for interpretation, the MIC value read is recorded to the next two-fold dilution value. 3 J. Substantial Equivalence Information: 1. Predicate device name(s): Liofilchem MTS, vancomycin 2. Predicate 510(k) number(s): K153687 3. Comparison with predicate: Table 1: Comparison with the Predicate Device Similarities Item Device (K172109) Predicate Liofilchem MTS, vancomycin (K153687) Intended Use Quantitative susceptibility to antimicrobial agents Same Media Mueller Hinton agar Same Inoculation Isolated colonies from culture in suspension equivalent to 0.5 McFarland. Inoculum is applied manually using the manual plate inoculation method or plate rotator for even distribution of inoculum Same Reading Manual; the point where the edge of inhibition ellipse intersects the MIC Test Strip Same Result MIC Same Differences Item Device Predicate Antibiotic Erythromycin (E) Vancomycin (VA) Incubation 35 ± 2°C for 16 – 20 hours 35 ± 2°C for 24 hours K. Standard/Guidance Document Referenced: “Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA” CLSI M07-A10 “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, Tenth Edition January 2015” 4 CLSI M100-S26 “Performance Standards for Antimicrobial Susceptibility Testing; Twenty- Fifth Informational Supplement, January 2016” L. Test Principle: MTS are made of specialized paper impregnated with a predefined concentration gradient of antibiotic, across 15 two-fold dilutions like those of a conventional MIC method. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the strip MIC Test Strip. Growth along the entire gradient (i.e., no inhibition ellipse) indicates that the MIC value is greater than or equal to (≥) the highest value on the scale. An inhibition ellipse that intersects below the lower end of the scale is read as less than (<) the lowest value. An MIC of 0.125 μg/mL is considered to be the same as 0.12 μg/mL for reporting purposes. An MTS MIC value which falls between standard two-fold dilutions must be rounded up to the next standard upper two-fold value before categorization. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Reproducibility testing was performed using ten Staphylococcus aureus isolates. These ten isolates (5 MSSA and 5 MRSA) were tested at three sites in triplicates on three days. The mode of MIC value was determined and the reproducibility was calculated based on the number of MIC values that fell within ±1 doubling dilution of the mode. The testing resulted in overall reproducibility of greater than 95%. The results were acceptable. b. Linearity/assay reportable range: Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): The recommended QC isolates were tested a sufficient number of times (i.e., at least 20/site) at all three sites with acceptable results in comparison to the reference method. All results were within the expected range greater than 95% of the time. The results are summarized in Table 2. 5 Table 2: Erythromycin MTS QC results Organism Concentration (µg/mL) Reference MTS S. aureus ATCC 29213 Expected Result 0.25- 1µg/mL 0.12 1 0.25 17 39 0.5 43 22 1 2 E. faecalis ATCC 29212 Expected Result 1- 4µg/mL 0.5 1 27 2 2 30 27 4 4 30 8 2 The inoculum was prepared to achieve a 0.5 McFarland standard turbidity. Colony counts were performed periodically at each site. Inoculum density checks were performed and the average colony counts of each QC strain were within the recommended range of approximately 1x 108 CFU/mL. d. Detection limit: Not Applicable e. Analytical specificity: Not Applicable f. Assay cut-off: Not Applicable 2. Comparison studies: a. Method comparison with predicate device: Clinical testing was conducted at three sites (two U.S. sites and one site outside the U.S). A total of 353 Staphylococcus aureus isolates were tested. There were 252 (71.4%) isolates that were tested within seven days of collection and 101 (28.6%) isolates that were tested after 7 days but within one year of collection. The 353 clinical isolates included 201 MSSA and 152 MRSA. An additional 75 challenge Staphylococcus aureus (11 MSSA and 64 MRSA) were tested, resulting in a total of 428 clinical and challenge isolates. Results obtained with Liofilchem MIC Test Strip (MTS) with Erythromycin were compared to results obtained from frozen reference MIC panels. Reference panels were prepared and interpreted as outlined in CLSI recommendations in M7-A10. 6 Isolated colonies from an overnight blood agar plate were suspended in saline to achieve a 0.5 McFarland standard turbidity (approximately 108 CFU/mL). Testing conditions consisted of incubation of the inoculated Mueller Hinton agar plates in and inverted position at 35°C ±2 for 16-20 hours. At the end of incubation, the MIC value where the edge of the inhibition ellipse intersects the strip was compared to the reference method. Erythromycin is bacteriostatic; MIC is read at 80% inhibition when trailing is seen. The performance is listed in Table 3 below. Table 3: Performance of Staphylococcus aureus isolates* Erythromycin EA Tot EA N EA % Eval. EA Tot Eval. EA N Eval. EA % CA N CA % #R min maj vm Type of test:

idK172109_s0_e2000

K172109.txt

classification

Class II

k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K172109 B. Purpose for Submission: To obtain a substantial equivalence determination for the Liofilchem MIC Test Strip (MTS) containing Erythromycin at concentrations of 0.016 -256 µg/mL for susceptibility testing of Staphylococcus aureus C. Measurand: Erythromycin 0.016-256 μg/mL D. Type of Test: Quantitative AST growth based detection E. Applicant: Liofilchem s.r.l. F. Proprietary and Established Names: Liofilchem MIC Test Strip (MTS), Erythromycin 0.016-256 μg/mL G. Regulatory Information: 1. Regulation section: 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: II 3. Product code: JWY - Manual Antimicrobial Test Systems 2 4. Panel: 83 – Microbiology H. Intended Use: 1. Intended use(s): The Liofilchem MIC Test Strip (MTS) is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of bacteria. MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in µg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. The Erythromycin MTS at concentrations of 0.016-256 µg/mL should be interpreted at 16-20 hours of incubation Erythromycin has been shown to be active both clinically and in vitro against the non- fastidious bacteria listed below according to the FDA label: Staphylococcus aureus 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): For prescription use 4. Special instrument requirements: Manual reading only I. Device Description: The Erythromycin MIC Test Strip (MTS) consists of specialized paper impregnated with a predefined concentration gradient of Erythromycin across 15 two-fold dilutions like those of a conventional MIC method. One side of the strip is labelled with the Erythromycin code (E) and the MIC reading scale in µg/mL. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16- 20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the MIC Test Strip. Since MTS strip generates MIC values which fall between two-fold dilutions for interpretation, the MIC value read is recorded to the next two-fold dilution value. 3 J. Substantial Equivalence Information: 1. Predicate device name(s): Liofilchem MTS, vancomycin 2. Predicate 510(k) number(s): K153687 3. Comparison with predicate: Table 1: Comparison with the Predicate Device Similarities Item Device (K172109) Predicate Liofilchem MTS, vancomycin (K153687) Intended Use Quantitative susceptibility to antimicrobial agents Same Media Mueller Hinton agar Same Inoculation Isolated colonies from culture in suspension equivalent to 0.5 McFarland. Inoculum is applied manually using the manual plate inoculation method or plate rotator for even distribution of inoculum Same Reading Manual; the point where the edge of inhibition ellipse intersects the MIC Test Strip Same Result MIC Same Differences Item Device Predicate Antibiotic Erythromycin (E) Vancomycin (VA) Incubation 35 ± 2°C for 16 – 20 hours 35 ± 2°C for 24 hours K. Standard/Guidance Document Referenced: “Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA” CLSI M07-A10 “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, Tenth Edition January 2015” 4 CLSI M100-S26 “Performance Standards for Antimicrobial Susceptibility Testing; Twenty- Fifth Informational Supplement, January 2016” L. Test Principle: MTS are made of specialized paper impregnated with a predefined concentration gradient of antibiotic, across 15 two-fold dilutions like those of a conventional MIC method. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the strip MIC Test Strip. Growth along the entire gradient (i.e., no inhibition ellipse) indicates that the MIC value is greater than or equal to (≥) the highest value on the scale. An inhibition ellipse that intersects below the lower end of the scale is read as less than (<) the lowest value. An MIC of 0.125 μg/mL is considered to be the same as 0.12 μg/mL for reporting purposes. An MTS MIC value which falls between standard two-fold dilutions must be rounded up to the next standard upper two-fold value before categorization. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Reproducibility testing was performed using ten Staphylococcus aureus isolates. These ten isolates (5 MSSA and 5 MRSA) were tested at three sites in triplicates on three days. The mode of MIC value was determined and the reproducibility was calculated based on the number of MIC values that fell within ±1 doubling dilution of the mode. The testing resulted in overall reproducibility of greater than 95%. The results were acceptable. b. Linearity/assay reportable range: Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): The recommended QC isolates were tested a sufficient number of times (i.e., at least 20/site) at all three sites with acceptable results in comparison to the reference method. All results were within the expected range greater than 95% of the time. The results are summarized in Table 2. 5 Table 2: Erythromycin MTS QC results Organism Concentration (µg/mL) Reference MTS S. aureus ATCC 29213 Expected Result 0.25- 1µg/mL 0.12 1 0.25 17 39 0.5 43 22 1 2 E. faecalis ATCC 29212 Expected Result 1- 4µg/mL 0.5 1 27 2 2 30 27 4 4 30 8 2 The inoculum was prepared to achieve a 0.5 McFarland standard turbidity. Colony counts were performed periodically at each site. Inoculum density checks were performed and the average colony counts of each QC strain were within the recommended range of approximately 1x 108 CFU/mL. d. Detection limit: Not Applicable e. Analytical specificity: Not Applicable f. Assay cut-off: Not Applicable 2. Comparison studies: a. Method comparison with predicate device: Clinical testing was conducted at three sites (two U.S. sites and one site outside the U.S). A total of 353 Staphylococcus aureus isolates were tested. There were 252 (71.4%) isolates that were tested within seven days of collection and 101 (28.6%) isolates that were tested after 7 days but within one year of collection. The 353 clinical isolates included 201 MSSA and 152 MRSA. An additional 75 challenge Staphylococcus aureus (11 MSSA and 64 MRSA) were tested, resulting in a total of 428 clinical and challenge isolates. Results obtained with Liofilchem MIC Test Strip (MTS) with Erythromycin were compared to results obtained from frozen reference MIC panels. Reference panels were prepared and interpreted as outlined in CLSI recommendations in M7-A10. 6 Isolated colonies from an overnight blood agar plate were suspended in saline to achieve a 0.5 McFarland standard turbidity (approximately 108 CFU/mL). Testing conditions consisted of incubation of the inoculated Mueller Hinton agar plates in and inverted position at 35°C ±2 for 16-20 hours. At the end of incubation, the MIC value where the edge of the inhibition ellipse intersects the strip was compared to the reference method. Erythromycin is bacteriostatic; MIC is read at 80% inhibition when trailing is seen. The performance is listed in Table 3 below. Table 3: Performance of Staphylococcus aureus isolates* Erythromycin EA Tot EA N EA % Eval. EA Tot Eval. EA N Eval. EA % CA N CA % #R min maj vm Classification:

idK172109_s0_e2000

K172109.txt

product code

JWY - Manual Antimicrobial Test Systems

k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K172109 B. Purpose for Submission: To obtain a substantial equivalence determination for the Liofilchem MIC Test Strip (MTS) containing Erythromycin at concentrations of 0.016 -256 µg/mL for susceptibility testing of Staphylococcus aureus C. Measurand: Erythromycin 0.016-256 μg/mL D. Type of Test: Quantitative AST growth based detection E. Applicant: Liofilchem s.r.l. F. Proprietary and Established Names: Liofilchem MIC Test Strip (MTS), Erythromycin 0.016-256 μg/mL G. Regulatory Information: 1. Regulation section: 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: II 3. Product code: JWY - Manual Antimicrobial Test Systems 2 4. Panel: 83 – Microbiology H. Intended Use: 1. Intended use(s): The Liofilchem MIC Test Strip (MTS) is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of bacteria. MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in µg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. The Erythromycin MTS at concentrations of 0.016-256 µg/mL should be interpreted at 16-20 hours of incubation Erythromycin has been shown to be active both clinically and in vitro against the non- fastidious bacteria listed below according to the FDA label: Staphylococcus aureus 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): For prescription use 4. Special instrument requirements: Manual reading only I. Device Description: The Erythromycin MIC Test Strip (MTS) consists of specialized paper impregnated with a predefined concentration gradient of Erythromycin across 15 two-fold dilutions like those of a conventional MIC method. One side of the strip is labelled with the Erythromycin code (E) and the MIC reading scale in µg/mL. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16- 20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the MIC Test Strip. Since MTS strip generates MIC values which fall between two-fold dilutions for interpretation, the MIC value read is recorded to the next two-fold dilution value. 3 J. Substantial Equivalence Information: 1. Predicate device name(s): Liofilchem MTS, vancomycin 2. Predicate 510(k) number(s): K153687 3. Comparison with predicate: Table 1: Comparison with the Predicate Device Similarities Item Device (K172109) Predicate Liofilchem MTS, vancomycin (K153687) Intended Use Quantitative susceptibility to antimicrobial agents Same Media Mueller Hinton agar Same Inoculation Isolated colonies from culture in suspension equivalent to 0.5 McFarland. Inoculum is applied manually using the manual plate inoculation method or plate rotator for even distribution of inoculum Same Reading Manual; the point where the edge of inhibition ellipse intersects the MIC Test Strip Same Result MIC Same Differences Item Device Predicate Antibiotic Erythromycin (E) Vancomycin (VA) Incubation 35 ± 2°C for 16 – 20 hours 35 ± 2°C for 24 hours K. Standard/Guidance Document Referenced: “Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA” CLSI M07-A10 “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, Tenth Edition January 2015” 4 CLSI M100-S26 “Performance Standards for Antimicrobial Susceptibility Testing; Twenty- Fifth Informational Supplement, January 2016” L. Test Principle: MTS are made of specialized paper impregnated with a predefined concentration gradient of antibiotic, across 15 two-fold dilutions like those of a conventional MIC method. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the strip MIC Test Strip. Growth along the entire gradient (i.e., no inhibition ellipse) indicates that the MIC value is greater than or equal to (≥) the highest value on the scale. An inhibition ellipse that intersects below the lower end of the scale is read as less than (<) the lowest value. An MIC of 0.125 μg/mL is considered to be the same as 0.12 μg/mL for reporting purposes. An MTS MIC value which falls between standard two-fold dilutions must be rounded up to the next standard upper two-fold value before categorization. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Reproducibility testing was performed using ten Staphylococcus aureus isolates. These ten isolates (5 MSSA and 5 MRSA) were tested at three sites in triplicates on three days. The mode of MIC value was determined and the reproducibility was calculated based on the number of MIC values that fell within ±1 doubling dilution of the mode. The testing resulted in overall reproducibility of greater than 95%. The results were acceptable. b. Linearity/assay reportable range: Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): The recommended QC isolates were tested a sufficient number of times (i.e., at least 20/site) at all three sites with acceptable results in comparison to the reference method. All results were within the expected range greater than 95% of the time. The results are summarized in Table 2. 5 Table 2: Erythromycin MTS QC results Organism Concentration (µg/mL) Reference MTS S. aureus ATCC 29213 Expected Result 0.25- 1µg/mL 0.12 1 0.25 17 39 0.5 43 22 1 2 E. faecalis ATCC 29212 Expected Result 1- 4µg/mL 0.5 1 27 2 2 30 27 4 4 30 8 2 The inoculum was prepared to achieve a 0.5 McFarland standard turbidity. Colony counts were performed periodically at each site. Inoculum density checks were performed and the average colony counts of each QC strain were within the recommended range of approximately 1x 108 CFU/mL. d. Detection limit: Not Applicable e. Analytical specificity: Not Applicable f. Assay cut-off: Not Applicable 2. Comparison studies: a. Method comparison with predicate device: Clinical testing was conducted at three sites (two U.S. sites and one site outside the U.S). A total of 353 Staphylococcus aureus isolates were tested. There were 252 (71.4%) isolates that were tested within seven days of collection and 101 (28.6%) isolates that were tested after 7 days but within one year of collection. The 353 clinical isolates included 201 MSSA and 152 MRSA. An additional 75 challenge Staphylococcus aureus (11 MSSA and 64 MRSA) were tested, resulting in a total of 428 clinical and challenge isolates. Results obtained with Liofilchem MIC Test Strip (MTS) with Erythromycin were compared to results obtained from frozen reference MIC panels. Reference panels were prepared and interpreted as outlined in CLSI recommendations in M7-A10. 6 Isolated colonies from an overnight blood agar plate were suspended in saline to achieve a 0.5 McFarland standard turbidity (approximately 108 CFU/mL). Testing conditions consisted of incubation of the inoculated Mueller Hinton agar plates in and inverted position at 35°C ±2 for 16-20 hours. At the end of incubation, the MIC value where the edge of the inhibition ellipse intersects the strip was compared to the reference method. Erythromycin is bacteriostatic; MIC is read at 80% inhibition when trailing is seen. The performance is listed in Table 3 below. Table 3: Performance of Staphylococcus aureus isolates* Erythromycin EA Tot EA N EA % Eval. EA Tot Eval. EA N Eval. EA % CA N CA % #R min maj vm Product code:

idK172109_s0_e2000

K172109.txt

panel

83 – Microbiology

(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K172109 B. Purpose for Submission: To obtain a substantial equivalence determination for the Liofilchem MIC Test Strip (MTS) containing Erythromycin at concentrations of 0.016 -256 µg/mL for susceptibility testing of Staphylococcus aureus C. Measurand: Erythromycin 0.016-256 μg/mL D. Type of Test: Quantitative AST growth based detection E. Applicant: Liofilchem s.r.l. F. Proprietary and Established Names: Liofilchem MIC Test Strip (MTS), Erythromycin 0.016-256 μg/mL G. Regulatory Information: 1. Regulation section: 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: II 3. Product code: JWY - Manual Antimicrobial Test Systems 2 4. Panel: 83 – Microbiology H. Intended Use: 1. Intended use(s): The Liofilchem MIC Test Strip (MTS) is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of bacteria. MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in µg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. The Erythromycin MTS at concentrations of 0.016-256 µg/mL should be interpreted at 16-20 hours of incubation Erythromycin has been shown to be active both clinically and in vitro against the non- fastidious bacteria listed below according to the FDA label: Staphylococcus aureus 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): For prescription use 4. Special instrument requirements: Manual reading only I. Device Description: The Erythromycin MIC Test Strip (MTS) consists of specialized paper impregnated with a predefined concentration gradient of Erythromycin across 15 two-fold dilutions like those of a conventional MIC method. One side of the strip is labelled with the Erythromycin code (E) and the MIC reading scale in µg/mL. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16- 20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the MIC Test Strip. Since MTS strip generates MIC values which fall between two-fold dilutions for interpretation, the MIC value read is recorded to the next two-fold dilution value. 3 J. Substantial Equivalence Information: 1. Predicate device name(s): Liofilchem MTS, vancomycin 2. Predicate 510(k) number(s): K153687 3. Comparison with predicate: Table 1: Comparison with the Predicate Device Similarities Item Device (K172109) Predicate Liofilchem MTS, vancomycin (K153687) Intended Use Quantitative susceptibility to antimicrobial agents Same Media Mueller Hinton agar Same Inoculation Isolated colonies from culture in suspension equivalent to 0.5 McFarland. Inoculum is applied manually using the manual plate inoculation method or plate rotator for even distribution of inoculum Same Reading Manual; the point where the edge of inhibition ellipse intersects the MIC Test Strip Same Result MIC Same Differences Item Device Predicate Antibiotic Erythromycin (E) Vancomycin (VA) Incubation 35 ± 2°C for 16 – 20 hours 35 ± 2°C for 24 hours K. Standard/Guidance Document Referenced: “Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA” CLSI M07-A10 “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, Tenth Edition January 2015” 4 CLSI M100-S26 “Performance Standards for Antimicrobial Susceptibility Testing; Twenty- Fifth Informational Supplement, January 2016” L. Test Principle: MTS are made of specialized paper impregnated with a predefined concentration gradient of antibiotic, across 15 two-fold dilutions like those of a conventional MIC method. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the strip MIC Test Strip. Growth along the entire gradient (i.e., no inhibition ellipse) indicates that the MIC value is greater than or equal to (≥) the highest value on the scale. An inhibition ellipse that intersects below the lower end of the scale is read as less than (<) the lowest value. An MIC of 0.125 μg/mL is considered to be the same as 0.12 μg/mL for reporting purposes. An MTS MIC value which falls between standard two-fold dilutions must be rounded up to the next standard upper two-fold value before categorization. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Reproducibility testing was performed using ten Staphylococcus aureus isolates. These ten isolates (5 MSSA and 5 MRSA) were tested at three sites in triplicates on three days. The mode of MIC value was determined and the reproducibility was calculated based on the number of MIC values that fell within ±1 doubling dilution of the mode. The testing resulted in overall reproducibility of greater than 95%. The results were acceptable. b. Linearity/assay reportable range: Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): The recommended QC isolates were tested a sufficient number of times (i.e., at least 20/site) at all three sites with acceptable results in comparison to the reference method. All results were within the expected range greater than 95% of the time. The results are summarized in Table 2. 5 Table 2: Erythromycin MTS QC results Organism Concentration (µg/mL) Reference MTS S. aureus ATCC 29213 Expected Result 0.25- 1µg/mL 0.12 1 0.25 17 39 0.5 43 22 1 2 E. faecalis ATCC 29212 Expected Result 1- 4µg/mL 0.5 1 27 2 2 30 27 4 4 30 8 2 The inoculum was prepared to achieve a 0.5 McFarland standard turbidity. Colony counts were performed periodically at each site. Inoculum density checks were performed and the average colony counts of each QC strain were within the recommended range of approximately 1x 108 CFU/mL. d. Detection limit: Not Applicable e. Analytical specificity: Not Applicable f. Assay cut-off: Not Applicable 2. Comparison studies: a. Method comparison with predicate device: Clinical testing was conducted at three sites (two U.S. sites and one site outside the U.S). A total of 353 Staphylococcus aureus isolates were tested. There were 252 (71.4%) isolates that were tested within seven days of collection and 101 (28.6%) isolates that were tested after 7 days but within one year of collection. The 353 clinical isolates included 201 MSSA and 152 MRSA. An additional 75 challenge Staphylococcus aureus (11 MSSA and 64 MRSA) were tested, resulting in a total of 428 clinical and challenge isolates. Results obtained with Liofilchem MIC Test Strip (MTS) with Erythromycin were compared to results obtained from frozen reference MIC panels. Reference panels were prepared and interpreted as outlined in CLSI recommendations in M7-A10. 6 Isolated colonies from an overnight blood agar plate were suspended in saline to achieve a 0.5 McFarland standard turbidity (approximately 108 CFU/mL). Testing conditions consisted of incubation of the inoculated Mueller Hinton agar plates in and inverted position at 35°C ±2 for 16-20 hours. At the end of incubation, the MIC value where the edge of the inhibition ellipse intersects the strip was compared to the reference method. Erythromycin is bacteriostatic; MIC is read at 80% inhibition when trailing is seen. The performance is listed in Table 3 below. Table 3: Performance of Staphylococcus aureus isolates* Erythromycin EA Tot EA N EA % Eval. EA Tot Eval. EA N Eval. EA % CA N CA % #R min maj vm Panel:

idK172109_s0_e2000

K172109.txt

predicate device name

Liofilchem MTS, vancomycin

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K172109 B. Purpose for Submission: To obtain a substantial equivalence determination for the Liofilchem MIC Test Strip (MTS) containing Erythromycin at concentrations of 0.016 -256 µg/mL for susceptibility testing of Staphylococcus aureus C. Measurand: Erythromycin 0.016-256 μg/mL D. Type of Test: Quantitative AST growth based detection E. Applicant: Liofilchem s.r.l. F. Proprietary and Established Names: Liofilchem MIC Test Strip (MTS), Erythromycin 0.016-256 μg/mL G. Regulatory Information: 1. Regulation section: 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: II 3. Product code: JWY - Manual Antimicrobial Test Systems 2 4. Panel: 83 – Microbiology H. Intended Use: 1. Intended use(s): The Liofilchem MIC Test Strip (MTS) is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of bacteria. MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in µg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. The Erythromycin MTS at concentrations of 0.016-256 µg/mL should be interpreted at 16-20 hours of incubation Erythromycin has been shown to be active both clinically and in vitro against the non- fastidious bacteria listed below according to the FDA label: Staphylococcus aureus 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): For prescription use 4. Special instrument requirements: Manual reading only I. Device Description: The Erythromycin MIC Test Strip (MTS) consists of specialized paper impregnated with a predefined concentration gradient of Erythromycin across 15 two-fold dilutions like those of a conventional MIC method. One side of the strip is labelled with the Erythromycin code (E) and the MIC reading scale in µg/mL. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16- 20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the MIC Test Strip. Since MTS strip generates MIC values which fall between two-fold dilutions for interpretation, the MIC value read is recorded to the next two-fold dilution value. 3 J. Substantial Equivalence Information: 1. Predicate device name(s): Liofilchem MTS, vancomycin 2. Predicate 510(k) number(s): K153687 3. Comparison with predicate: Table 1: Comparison with the Predicate Device Similarities Item Device (K172109) Predicate Liofilchem MTS, vancomycin (K153687) Intended Use Quantitative susceptibility to antimicrobial agents Same Media Mueller Hinton agar Same Inoculation Isolated colonies from culture in suspension equivalent to 0.5 McFarland. Inoculum is applied manually using the manual plate inoculation method or plate rotator for even distribution of inoculum Same Reading Manual; the point where the edge of inhibition ellipse intersects the MIC Test Strip Same Result MIC Same Differences Item Device Predicate Antibiotic Erythromycin (E) Vancomycin (VA) Incubation 35 ± 2°C for 16 – 20 hours 35 ± 2°C for 24 hours K. Standard/Guidance Document Referenced: “Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA” CLSI M07-A10 “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, Tenth Edition January 2015” 4 CLSI M100-S26 “Performance Standards for Antimicrobial Susceptibility Testing; Twenty- Fifth Informational Supplement, January 2016” L. Test Principle: MTS are made of specialized paper impregnated with a predefined concentration gradient of antibiotic, across 15 two-fold dilutions like those of a conventional MIC method. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the strip MIC Test Strip. Growth along the entire gradient (i.e., no inhibition ellipse) indicates that the MIC value is greater than or equal to (≥) the highest value on the scale. An inhibition ellipse that intersects below the lower end of the scale is read as less than (<) the lowest value. An MIC of 0.125 μg/mL is considered to be the same as 0.12 μg/mL for reporting purposes. An MTS MIC value which falls between standard two-fold dilutions must be rounded up to the next standard upper two-fold value before categorization. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Reproducibility testing was performed using ten Staphylococcus aureus isolates. These ten isolates (5 MSSA and 5 MRSA) were tested at three sites in triplicates on three days. The mode of MIC value was determined and the reproducibility was calculated based on the number of MIC values that fell within ±1 doubling dilution of the mode. The testing resulted in overall reproducibility of greater than 95%. The results were acceptable. b. Linearity/assay reportable range: Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): The recommended QC isolates were tested a sufficient number of times (i.e., at least 20/site) at all three sites with acceptable results in comparison to the reference method. All results were within the expected range greater than 95% of the time. The results are summarized in Table 2. 5 Table 2: Erythromycin MTS QC results Organism Concentration (µg/mL) Reference MTS S. aureus ATCC 29213 Expected Result 0.25- 1µg/mL 0.12 1 0.25 17 39 0.5 43 22 1 2 E. faecalis ATCC 29212 Expected Result 1- 4µg/mL 0.5 1 27 2 2 30 27 4 4 30 8 2 The inoculum was prepared to achieve a 0.5 McFarland standard turbidity. Colony counts were performed periodically at each site. Inoculum density checks were performed and the average colony counts of each QC strain were within the recommended range of approximately 1x 108 CFU/mL. d. Detection limit: Not Applicable e. Analytical specificity: Not Applicable f. Assay cut-off: Not Applicable 2. Comparison studies: a. Method comparison with predicate device: Clinical testing was conducted at three sites (two U.S. sites and one site outside the U.S). A total of 353 Staphylococcus aureus isolates were tested. There were 252 (71.4%) isolates that were tested within seven days of collection and 101 (28.6%) isolates that were tested after 7 days but within one year of collection. The 353 clinical isolates included 201 MSSA and 152 MRSA. An additional 75 challenge Staphylococcus aureus (11 MSSA and 64 MRSA) were tested, resulting in a total of 428 clinical and challenge isolates. Results obtained with Liofilchem MIC Test Strip (MTS) with Erythromycin were compared to results obtained from frozen reference MIC panels. Reference panels were prepared and interpreted as outlined in CLSI recommendations in M7-A10. 6 Isolated colonies from an overnight blood agar plate were suspended in saline to achieve a 0.5 McFarland standard turbidity (approximately 108 CFU/mL). Testing conditions consisted of incubation of the inoculated Mueller Hinton agar plates in and inverted position at 35°C ±2 for 16-20 hours. At the end of incubation, the MIC value where the edge of the inhibition ellipse intersects the strip was compared to the reference method. Erythromycin is bacteriostatic; MIC is read at 80% inhibition when trailing is seen. The performance is listed in Table 3 below. Table 3: Performance of Staphylococcus aureus isolates* Erythromycin EA Tot EA N EA % Eval. EA Tot Eval. EA N Eval. EA % CA N CA % #R min maj vm Predicate device name:

idK172109_s0_e2000

K172109.txt

applicant

Liofilchem s.r.l.

k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K172109 B. Purpose for Submission: To obtain a substantial equivalence determination for the Liofilchem MIC Test Strip (MTS) containing Erythromycin at concentrations of 0.016 -256 µg/mL for susceptibility testing of Staphylococcus aureus C. Measurand: Erythromycin 0.016-256 μg/mL D. Type of Test: Quantitative AST growth based detection E. Applicant: Liofilchem s.r.l. F. Proprietary and Established Names: Liofilchem MIC Test Strip (MTS), Erythromycin 0.016-256 μg/mL G. Regulatory Information: 1. Regulation section: 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: II 3. Product code: JWY - Manual Antimicrobial Test Systems 2 4. Panel: 83 – Microbiology H. Intended Use: 1. Intended use(s): The Liofilchem MIC Test Strip (MTS) is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of bacteria. MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in µg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. The Erythromycin MTS at concentrations of 0.016-256 µg/mL should be interpreted at 16-20 hours of incubation Erythromycin has been shown to be active both clinically and in vitro against the non- fastidious bacteria listed below according to the FDA label: Staphylococcus aureus 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): For prescription use 4. Special instrument requirements: Manual reading only I. Device Description: The Erythromycin MIC Test Strip (MTS) consists of specialized paper impregnated with a predefined concentration gradient of Erythromycin across 15 two-fold dilutions like those of a conventional MIC method. One side of the strip is labelled with the Erythromycin code (E) and the MIC reading scale in µg/mL. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16- 20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the MIC Test Strip. Since MTS strip generates MIC values which fall between two-fold dilutions for interpretation, the MIC value read is recorded to the next two-fold dilution value. 3 J. Substantial Equivalence Information: 1. Predicate device name(s): Liofilchem MTS, vancomycin 2. Predicate 510(k) number(s): K153687 3. Comparison with predicate: Table 1: Comparison with the Predicate Device Similarities Item Device (K172109) Predicate Liofilchem MTS, vancomycin (K153687) Intended Use Quantitative susceptibility to antimicrobial agents Same Media Mueller Hinton agar Same Inoculation Isolated colonies from culture in suspension equivalent to 0.5 McFarland. Inoculum is applied manually using the manual plate inoculation method or plate rotator for even distribution of inoculum Same Reading Manual; the point where the edge of inhibition ellipse intersects the MIC Test Strip Same Result MIC Same Differences Item Device Predicate Antibiotic Erythromycin (E) Vancomycin (VA) Incubation 35 ± 2°C for 16 – 20 hours 35 ± 2°C for 24 hours K. Standard/Guidance Document Referenced: “Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA” CLSI M07-A10 “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, Tenth Edition January 2015” 4 CLSI M100-S26 “Performance Standards for Antimicrobial Susceptibility Testing; Twenty- Fifth Informational Supplement, January 2016” L. Test Principle: MTS are made of specialized paper impregnated with a predefined concentration gradient of antibiotic, across 15 two-fold dilutions like those of a conventional MIC method. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the strip MIC Test Strip. Growth along the entire gradient (i.e., no inhibition ellipse) indicates that the MIC value is greater than or equal to (≥) the highest value on the scale. An inhibition ellipse that intersects below the lower end of the scale is read as less than (<) the lowest value. An MIC of 0.125 μg/mL is considered to be the same as 0.12 μg/mL for reporting purposes. An MTS MIC value which falls between standard two-fold dilutions must be rounded up to the next standard upper two-fold value before categorization. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Reproducibility testing was performed using ten Staphylococcus aureus isolates. These ten isolates (5 MSSA and 5 MRSA) were tested at three sites in triplicates on three days. The mode of MIC value was determined and the reproducibility was calculated based on the number of MIC values that fell within ±1 doubling dilution of the mode. The testing resulted in overall reproducibility of greater than 95%. The results were acceptable. b. Linearity/assay reportable range: Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): The recommended QC isolates were tested a sufficient number of times (i.e., at least 20/site) at all three sites with acceptable results in comparison to the reference method. All results were within the expected range greater than 95% of the time. The results are summarized in Table 2. 5 Table 2: Erythromycin MTS QC results Organism Concentration (µg/mL) Reference MTS S. aureus ATCC 29213 Expected Result 0.25- 1µg/mL 0.12 1 0.25 17 39 0.5 43 22 1 2 E. faecalis ATCC 29212 Expected Result 1- 4µg/mL 0.5 1 27 2 2 30 27 4 4 30 8 2 The inoculum was prepared to achieve a 0.5 McFarland standard turbidity. Colony counts were performed periodically at each site. Inoculum density checks were performed and the average colony counts of each QC strain were within the recommended range of approximately 1x 108 CFU/mL. d. Detection limit: Not Applicable e. Analytical specificity: Not Applicable f. Assay cut-off: Not Applicable 2. Comparison studies: a. Method comparison with predicate device: Clinical testing was conducted at three sites (two U.S. sites and one site outside the U.S). A total of 353 Staphylococcus aureus isolates were tested. There were 252 (71.4%) isolates that were tested within seven days of collection and 101 (28.6%) isolates that were tested after 7 days but within one year of collection. The 353 clinical isolates included 201 MSSA and 152 MRSA. An additional 75 challenge Staphylococcus aureus (11 MSSA and 64 MRSA) were tested, resulting in a total of 428 clinical and challenge isolates. Results obtained with Liofilchem MIC Test Strip (MTS) with Erythromycin were compared to results obtained from frozen reference MIC panels. Reference panels were prepared and interpreted as outlined in CLSI recommendations in M7-A10. 6 Isolated colonies from an overnight blood agar plate were suspended in saline to achieve a 0.5 McFarland standard turbidity (approximately 108 CFU/mL). Testing conditions consisted of incubation of the inoculated Mueller Hinton agar plates in and inverted position at 35°C ±2 for 16-20 hours. At the end of incubation, the MIC value where the edge of the inhibition ellipse intersects the strip was compared to the reference method. Erythromycin is bacteriostatic; MIC is read at 80% inhibition when trailing is seen. The performance is listed in Table 3 below. Table 3: Performance of Staphylococcus aureus isolates* Erythromycin EA Tot EA N EA % Eval. EA Tot Eval. EA N Eval. EA % CA N CA % #R min maj vm Applicant:

idK172109_s0_e2000

K172109.txt

proprietary and established names

Liofilchem MIC Test Strip (MTS), Erythromycin 0.016-256 μg/mL

ANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K172109 B. Purpose for Submission: To obtain a substantial equivalence determination for the Liofilchem MIC Test Strip (MTS) containing Erythromycin at concentrations of 0.016 -256 µg/mL for susceptibility testing of Staphylococcus aureus C. Measurand: Erythromycin 0.016-256 μg/mL D. Type of Test: Quantitative AST growth based detection E. Applicant: Liofilchem s.r.l. F. Proprietary and Established Names: Liofilchem MIC Test Strip (MTS), Erythromycin 0.016-256 μg/mL G. Regulatory Information: 1. Regulation section: 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: II 3. Product code: JWY - Manual Antimicrobial Test Systems 2 4. Panel: 83 – Microbiology H. Intended Use: 1. Intended use(s): The Liofilchem MIC Test Strip (MTS) is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of bacteria. MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in µg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. The Erythromycin MTS at concentrations of 0.016-256 µg/mL should be interpreted at 16-20 hours of incubation Erythromycin has been shown to be active both clinically and in vitro against the non- fastidious bacteria listed below according to the FDA label: Staphylococcus aureus 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): For prescription use 4. Special instrument requirements: Manual reading only I. Device Description: The Erythromycin MIC Test Strip (MTS) consists of specialized paper impregnated with a predefined concentration gradient of Erythromycin across 15 two-fold dilutions like those of a conventional MIC method. One side of the strip is labelled with the Erythromycin code (E) and the MIC reading scale in µg/mL. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16- 20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the MIC Test Strip. Since MTS strip generates MIC values which fall between two-fold dilutions for interpretation, the MIC value read is recorded to the next two-fold dilution value. 3 J. Substantial Equivalence Information: 1. Predicate device name(s): Liofilchem MTS, vancomycin 2. Predicate 510(k) number(s): K153687 3. Comparison with predicate: Table 1: Comparison with the Predicate Device Similarities Item Device (K172109) Predicate Liofilchem MTS, vancomycin (K153687) Intended Use Quantitative susceptibility to antimicrobial agents Same Media Mueller Hinton agar Same Inoculation Isolated colonies from culture in suspension equivalent to 0.5 McFarland. Inoculum is applied manually using the manual plate inoculation method or plate rotator for even distribution of inoculum Same Reading Manual; the point where the edge of inhibition ellipse intersects the MIC Test Strip Same Result MIC Same Differences Item Device Predicate Antibiotic Erythromycin (E) Vancomycin (VA) Incubation 35 ± 2°C for 16 – 20 hours 35 ± 2°C for 24 hours K. Standard/Guidance Document Referenced: “Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA” CLSI M07-A10 “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, Tenth Edition January 2015” 4 CLSI M100-S26 “Performance Standards for Antimicrobial Susceptibility Testing; Twenty- Fifth Informational Supplement, January 2016” L. Test Principle: MTS are made of specialized paper impregnated with a predefined concentration gradient of antibiotic, across 15 two-fold dilutions like those of a conventional MIC method. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the strip MIC Test Strip. Growth along the entire gradient (i.e., no inhibition ellipse) indicates that the MIC value is greater than or equal to (≥) the highest value on the scale. An inhibition ellipse that intersects below the lower end of the scale is read as less than (<) the lowest value. An MIC of 0.125 μg/mL is considered to be the same as 0.12 μg/mL for reporting purposes. An MTS MIC value which falls between standard two-fold dilutions must be rounded up to the next standard upper two-fold value before categorization. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Reproducibility testing was performed using ten Staphylococcus aureus isolates. These ten isolates (5 MSSA and 5 MRSA) were tested at three sites in triplicates on three days. The mode of MIC value was determined and the reproducibility was calculated based on the number of MIC values that fell within ±1 doubling dilution of the mode. The testing resulted in overall reproducibility of greater than 95%. The results were acceptable. b. Linearity/assay reportable range: Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): The recommended QC isolates were tested a sufficient number of times (i.e., at least 20/site) at all three sites with acceptable results in comparison to the reference method. All results were within the expected range greater than 95% of the time. The results are summarized in Table 2. 5 Table 2: Erythromycin MTS QC results Organism Concentration (µg/mL) Reference MTS S. aureus ATCC 29213 Expected Result 0.25- 1µg/mL 0.12 1 0.25 17 39 0.5 43 22 1 2 E. faecalis ATCC 29212 Expected Result 1- 4µg/mL 0.5 1 27 2 2 30 27 4 4 30 8 2 The inoculum was prepared to achieve a 0.5 McFarland standard turbidity. Colony counts were performed periodically at each site. Inoculum density checks were performed and the average colony counts of each QC strain were within the recommended range of approximately 1x 108 CFU/mL. d. Detection limit: Not Applicable e. Analytical specificity: Not Applicable f. Assay cut-off: Not Applicable 2. Comparison studies: a. Method comparison with predicate device: Clinical testing was conducted at three sites (two U.S. sites and one site outside the U.S). A total of 353 Staphylococcus aureus isolates were tested. There were 252 (71.4%) isolates that were tested within seven days of collection and 101 (28.6%) isolates that were tested after 7 days but within one year of collection. The 353 clinical isolates included 201 MSSA and 152 MRSA. An additional 75 challenge Staphylococcus aureus (11 MSSA and 64 MRSA) were tested, resulting in a total of 428 clinical and challenge isolates. Results obtained with Liofilchem MIC Test Strip (MTS) with Erythromycin were compared to results obtained from frozen reference MIC panels. Reference panels were prepared and interpreted as outlined in CLSI recommendations in M7-A10. 6 Isolated colonies from an overnight blood agar plate were suspended in saline to achieve a 0.5 McFarland standard turbidity (approximately 108 CFU/mL). Testing conditions consisted of incubation of the inoculated Mueller Hinton agar plates in and inverted position at 35°C ±2 for 16-20 hours. At the end of incubation, the MIC value where the edge of the inhibition ellipse intersects the strip was compared to the reference method. Erythromycin is bacteriostatic; MIC is read at 80% inhibition when trailing is seen. The performance is listed in Table 3 below. Table 3: Performance of Staphylococcus aureus isolates* Erythromycin EA Tot EA N EA % Eval. EA Tot Eval. EA N Eval. EA % CA N CA % #R min maj vm Proprietary and established names:

idK172109_s0_e2000

K172109.txt

regulation section

866.1640 Antimicrobial Susceptibility Test Powder

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K172109 B. Purpose for Submission: To obtain a substantial equivalence determination for the Liofilchem MIC Test Strip (MTS) containing Erythromycin at concentrations of 0.016 -256 µg/mL for susceptibility testing of Staphylococcus aureus C. Measurand: Erythromycin 0.016-256 μg/mL D. Type of Test: Quantitative AST growth based detection E. Applicant: Liofilchem s.r.l. F. Proprietary and Established Names: Liofilchem MIC Test Strip (MTS), Erythromycin 0.016-256 μg/mL G. Regulatory Information: 1. Regulation section: 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: II 3. Product code: JWY - Manual Antimicrobial Test Systems 2 4. Panel: 83 – Microbiology H. Intended Use: 1. Intended use(s): The Liofilchem MIC Test Strip (MTS) is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of bacteria. MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in µg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. The Erythromycin MTS at concentrations of 0.016-256 µg/mL should be interpreted at 16-20 hours of incubation Erythromycin has been shown to be active both clinically and in vitro against the non- fastidious bacteria listed below according to the FDA label: Staphylococcus aureus 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): For prescription use 4. Special instrument requirements: Manual reading only I. Device Description: The Erythromycin MIC Test Strip (MTS) consists of specialized paper impregnated with a predefined concentration gradient of Erythromycin across 15 two-fold dilutions like those of a conventional MIC method. One side of the strip is labelled with the Erythromycin code (E) and the MIC reading scale in µg/mL. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16- 20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the MIC Test Strip. Since MTS strip generates MIC values which fall between two-fold dilutions for interpretation, the MIC value read is recorded to the next two-fold dilution value. 3 J. Substantial Equivalence Information: 1. Predicate device name(s): Liofilchem MTS, vancomycin 2. Predicate 510(k) number(s): K153687 3. Comparison with predicate: Table 1: Comparison with the Predicate Device Similarities Item Device (K172109) Predicate Liofilchem MTS, vancomycin (K153687) Intended Use Quantitative susceptibility to antimicrobial agents Same Media Mueller Hinton agar Same Inoculation Isolated colonies from culture in suspension equivalent to 0.5 McFarland. Inoculum is applied manually using the manual plate inoculation method or plate rotator for even distribution of inoculum Same Reading Manual; the point where the edge of inhibition ellipse intersects the MIC Test Strip Same Result MIC Same Differences Item Device Predicate Antibiotic Erythromycin (E) Vancomycin (VA) Incubation 35 ± 2°C for 16 – 20 hours 35 ± 2°C for 24 hours K. Standard/Guidance Document Referenced: “Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA” CLSI M07-A10 “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, Tenth Edition January 2015” 4 CLSI M100-S26 “Performance Standards for Antimicrobial Susceptibility Testing; Twenty- Fifth Informational Supplement, January 2016” L. Test Principle: MTS are made of specialized paper impregnated with a predefined concentration gradient of antibiotic, across 15 two-fold dilutions like those of a conventional MIC method. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the strip MIC Test Strip. Growth along the entire gradient (i.e., no inhibition ellipse) indicates that the MIC value is greater than or equal to (≥) the highest value on the scale. An inhibition ellipse that intersects below the lower end of the scale is read as less than (<) the lowest value. An MIC of 0.125 μg/mL is considered to be the same as 0.12 μg/mL for reporting purposes. An MTS MIC value which falls between standard two-fold dilutions must be rounded up to the next standard upper two-fold value before categorization. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Reproducibility testing was performed using ten Staphylococcus aureus isolates. These ten isolates (5 MSSA and 5 MRSA) were tested at three sites in triplicates on three days. The mode of MIC value was determined and the reproducibility was calculated based on the number of MIC values that fell within ±1 doubling dilution of the mode. The testing resulted in overall reproducibility of greater than 95%. The results were acceptable. b. Linearity/assay reportable range: Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): The recommended QC isolates were tested a sufficient number of times (i.e., at least 20/site) at all three sites with acceptable results in comparison to the reference method. All results were within the expected range greater than 95% of the time. The results are summarized in Table 2. 5 Table 2: Erythromycin MTS QC results Organism Concentration (µg/mL) Reference MTS S. aureus ATCC 29213 Expected Result 0.25- 1µg/mL 0.12 1 0.25 17 39 0.5 43 22 1 2 E. faecalis ATCC 29212 Expected Result 1- 4µg/mL 0.5 1 27 2 2 30 27 4 4 30 8 2 The inoculum was prepared to achieve a 0.5 McFarland standard turbidity. Colony counts were performed periodically at each site. Inoculum density checks were performed and the average colony counts of each QC strain were within the recommended range of approximately 1x 108 CFU/mL. d. Detection limit: Not Applicable e. Analytical specificity: Not Applicable f. Assay cut-off: Not Applicable 2. Comparison studies: a. Method comparison with predicate device: Clinical testing was conducted at three sites (two U.S. sites and one site outside the U.S). A total of 353 Staphylococcus aureus isolates were tested. There were 252 (71.4%) isolates that were tested within seven days of collection and 101 (28.6%) isolates that were tested after 7 days but within one year of collection. The 353 clinical isolates included 201 MSSA and 152 MRSA. An additional 75 challenge Staphylococcus aureus (11 MSSA and 64 MRSA) were tested, resulting in a total of 428 clinical and challenge isolates. Results obtained with Liofilchem MIC Test Strip (MTS) with Erythromycin were compared to results obtained from frozen reference MIC panels. Reference panels were prepared and interpreted as outlined in CLSI recommendations in M7-A10. 6 Isolated colonies from an overnight blood agar plate were suspended in saline to achieve a 0.5 McFarland standard turbidity (approximately 108 CFU/mL). Testing conditions consisted of incubation of the inoculated Mueller Hinton agar plates in and inverted position at 35°C ±2 for 16-20 hours. At the end of incubation, the MIC value where the edge of the inhibition ellipse intersects the strip was compared to the reference method. Erythromycin is bacteriostatic; MIC is read at 80% inhibition when trailing is seen. The performance is listed in Table 3 below. Table 3: Performance of Staphylococcus aureus isolates* Erythromycin EA Tot EA N EA % Eval. EA Tot Eval. EA N Eval. EA % CA N CA % #R min maj vm Regulation section:

idK172109_s2000_e4000

K172109.txt

proposed labeling

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

cus spp. ≤0.5 (Susceptible), 1-4 (Intermediate), ≥8 (Resistant) Clinical 353 332 94.1 234 219 93.6 342 96.7 196 11 0 0 Challenge 75 74 98.7 33 32 97.0 74 98.7 61 1 0 0 Total 428 406 94.9 267 251 94.0 416 97.2 257 12 0 0 *EA - Essential Agreement maj – major discrepancies CA - Category Agreement vmj- very major discrepancies R- resistant isolates min- minor discrepancies Essential Agreement (EA) is when the Liofilchem MIC Test Strip (MTS) results agree exactly or within one doubling dilution of the reference broth microdilution results. Category Agreement (CA) is when the Liofilchem MIC Test Strip (MTS) result interpretation agrees exactly with the reference broth microdilution result interpretation. The overall performance of Staphylococcus aureus was acceptable with 94.9% EA and 97.2% CA. There were twelve minor discrepancies but no major or very major discrepancies. Growth Rate: The growth rate for the Liofilchem MIC Test Strip (MTS) with Erythromycin was 100%. Trending The analysis showed that there was no trending observed in the overall performance of Staphylococcus aureus. b. Matrix comparison: Not Applicable 3. Clinical studies: a. Clinical Sensitivity: Not Applicable b. Clinical specificity: 7 Not Applicable c. Other clinical supportive data (when a. and b. are not applicable): Not Applicable 4. Clinical cut-off: Not Applicable 5. Expected values/Reference range: Table 5: FDA Interpretive Criteria for Erythromycin (µg/mL) Organisms S I R Staphylococcus aureus ≤0.5 1-4 ≥8 N. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. O. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Proposed labeling:

idK172109_s2000_e4000

K172109.txt

conclusion

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

ylococcus spp. ≤0.5 (Susceptible), 1-4 (Intermediate), ≥8 (Resistant) Clinical 353 332 94.1 234 219 93.6 342 96.7 196 11 0 0 Challenge 75 74 98.7 33 32 97.0 74 98.7 61 1 0 0 Total 428 406 94.9 267 251 94.0 416 97.2 257 12 0 0 *EA - Essential Agreement maj – major discrepancies CA - Category Agreement vmj- very major discrepancies R- resistant isolates min- minor discrepancies Essential Agreement (EA) is when the Liofilchem MIC Test Strip (MTS) results agree exactly or within one doubling dilution of the reference broth microdilution results. Category Agreement (CA) is when the Liofilchem MIC Test Strip (MTS) result interpretation agrees exactly with the reference broth microdilution result interpretation. The overall performance of Staphylococcus aureus was acceptable with 94.9% EA and 97.2% CA. There were twelve minor discrepancies but no major or very major discrepancies. Growth Rate: The growth rate for the Liofilchem MIC Test Strip (MTS) with Erythromycin was 100%. Trending The analysis showed that there was no trending observed in the overall performance of Staphylococcus aureus. b. Matrix comparison: Not Applicable 3. Clinical studies: a. Clinical Sensitivity: Not Applicable b. Clinical specificity: 7 Not Applicable c. Other clinical supportive data (when a. and b. are not applicable): Not Applicable 4. Clinical cut-off: Not Applicable 5. Expected values/Reference range: Table 5: FDA Interpretive Criteria for Erythromycin (µg/mL) Organisms S I R Staphylococcus aureus ≤0.5 1-4 ≥8 N. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. O. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Conclusion:

idK150617_s0_e2000

K150617.txt

purpose for submission

Clearance of New Device

STANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K150617 B. Purpose for Submission: Clearance of New Device C. Measurand: Target DNA sequences from Herpes Simplex Virus type 1 (HSV-1) and Herpes Simplex Virus type 2 (HSV-2) D. Type of Test: An in vitro molecular diagnostic test for the qualitative detection and differentiation of HSV-1 and HSV-2 DNA in clinician-collected, external anogenital lesion specimens from symptomatic male and female patients. E. Applicant: Roche Molecular Systems, Inc. F. Proprietary and Established Names: cobas® HSV 1 and 2 Test G. Regulatory Information: 1. Regulation section: 21 CFR 866.3305 2. Classification: Class II 3. Product code: OQO 4. Panel: Microbiology (83) H. Intended Use: 1. Intended use(s): The cobas® HSV 1 and 2 Test on the cobas® 4800 system is an automated, qualitative in vitro diagnostic test, that utilizes real-time polymerase chain reaction (PCR), for the direct detection and differentiation of Herpes simplex virus 1 and 2 (HSV-1 and HSV-2) 2 DNA in clinician-collected, external anogenital lesion specimens from symptomatic male and female patients. The cobas® HSV 1 and 2 Test is intended for use as an aid in diagnosis of anogenital HSV-1 and HSV-2 infections in symptomatic patients. Warning: The cobas® HSV 1 and 2 Test is not FDA cleared for use with cerebrospinal fluid (CSF) and is not intended to be used for prenatal screening or for individuals under the age of 18 years. 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: cobas® 4800 System I. Device Description: The cobas® HSV 1 and 2 Test on the cobas® 4800 system is a real-time polymerase chain reaction (PCR) for the direct detection and differentiation of HSV-1 and HSV-2 DNA in clinician-collected, external anogenital lesion specimens, collected in MSwab Collection, Transport and Preservation System from symptomatic patients. The cobas® HSV 1 and HSV 2 Test is comprised of two major processes: (1) automated sample preparation to extract nucleic acids from swab specimens; (2) PCR amplification of target DNA sequences using HSV-1 and HSV-2 specific primers, and real-time detection of cleaved fluorescent-labeled HSV-1 and HSV-2 specific oligonucleotide detection probes. An internal control (IC), containing unrelated randomized DNA sequence, is added to all samples prior to automated sample preparation and is amplified and detected simultaneously with each sample to monitor the entire process. The specimens are collected and stored in the MSwab Collection, Transport and Preservation System for the cobas® HSV 1 and HSV 2 Test. The cobas® HSV 1 and HSV 2 Test is performed using the following reagent kits: 1. cobas® 4800 HSV 1 and HSV 2 Amplification/Detection Kit 2. cobas® 4800 HSV 1 and HSV 2 Controls and Cofactor Kit 3. cobas® 4800 System Wash Buffer Kit 4. cobas® 4800 System Lysis Kit 1 5. cobas® 4800 System Internal Control Kit 1 6. cobas® 4800 System Sample Preparation Kit 3 J. Substantial Equivalence Information: 1. Predicate device name(s): BD ProbeTecTM Herpes Simplex Viruses (HSV 1 & 2) Qx Amplified DNA Assays Reference Method: A composite reference method which includes a culture method, namely, the ELVIS® HSV ID/Typing Test System (Diagnostic Hybrids, Inc. (K971662)) and a validated PCR followed by bidirectional sequencing for clinical evaluation. The clinical performance of the cobas® HSV 1/2 Test was also compared to the culture method alone using the ELVIS® HSV ID/Typing Test System (Diagnostic Hybrids, Inc. (K971662)). 2. Predicate 510(k) number(s): K103798 3. Comparison with predicate: Similarities Characteristic BD ProbeTecTM Herpes Simplex Viruses (HSV 1 & 2) Qx Amplified DNA Assays on the BD Viper System in Extracted Mode, (K103798) Roche cobas® HSV 1 and 2 Test New Device (K150617) Intended use The BD ProbeTec™ Herpes Simplex Viruses (HSV 1 & 2) Qx Amplified DNA Assays (HSV Qx Assays), when tested with the BD Viper™ System in Extracted Mode, use Strand Displacement Amplification technology for the direct, qualitative detection and differentiation of Herpes Simplex virus type 1 (HSV1) and Herpes Simplex virus type 2 (HSV2) DNA in clinician-collected external anogenital lesion specimens. The assays are indicated for use with symptomatic individuals to aid in the diagnosis of anogenital HSV1 and HSV2 infections. The cobas® HSV 1 and 2 Test on the cobas® 4800 system is an automated, qualitative in vitro diagnostic test, that utilizes real-time polymerase chain reaction (PCR), for the direct detection and differentiation of Herpes simplex virus 1 and 2 (HSV-1 and HSV-2) DNA in clinician-collected anogenital lesion specimens from symptomatic male and female patients. The cobas® HSV 1 and 2 Test is intended for use as an aid in diagnosis of anogenital HSV-1 and HSV-2 infections in symptomatic patients. Warning: The cobas® HSV 1 and 2 Test is not FDA cleared for use with 4 Warning: The BD ProbeTec™ Herpes Simplex Viruses (HSV 1 & 2) Qx Amplified DNA Assays (HSV Qx Assays) are not FDA cleared for use with cerebrospinal fluid (CSF). The assays are not intended to be used for prenatal screening or for individuals under the age of 17 years. cerebrospinal fluid (CSF) and is not intended to be used for prenatal screening or for individuals under the age of 18 years. Sample Types External anogenital lesions Same Assay Results Qualitative detection and differentiation of HSV-1 and HSV-2 DNA Same Detection Chemistry Paired reporter and quencher fluorescence labeled probes using fluorescence resonance energy transfer (FRET) Same Differences Characteristic BD ProbeTecTM Herpes Simplex Viruses (HSV 1 & 2) Qx Amplified DNA Assays on the BD Viper System in Extracted Mode, (K103798) Roche cobas® HSV 1 and 2 Test New Device (K150617) Amplification Technology Strand Displacement Amplification Real-time PCR Sample Preparation Procedure Automated on BD™ Viper™ System in Extracted Mode Automated on cobas® 4800 System K. Standard/Guidance Document Referenced (if applicable): N/A 5 L. Test Principle: Target Selection The cobas® HSV 1and 2 Test utilizes real-time PCR technology to detect the conserved regions of HSV-1 Thymidine Kinase and HSV-1 DNA Polymerase as well as HSV-2 Thymidine Kinase and HSV-2 Glycoprotein B genes. Fluorogenic target-specific probes are used for the detection of the amplified HSV-1 and HSV-2 DNA as well as Internal Control. Since two HSV type targets are detected with different fluorescent dyes, the cobas® HSV 1 and 2 Test has the ability to simultaneously detect and differentiate HSV-1 and HSV-2. Primer and probe oligonucleotide sequences were designed to select HSV-1 and HSV-2 conserved sequences without cross reacting to other viruses, or other bacterial organisms commonly found in human genital areas. Sample Preparation Sample preparation for the cobas® HSV 1 and 2 Test is automated with the use of the cobas® x 480 instrument. Organisms from swab specimens collected in MSwab medium are lysed with chaotropic agent, proteinase K, and SDS reagents. Released nucleic acids, along with added Internal Control DNA, are bound by magnetic glass particles. The particles are washed and the bound nucleic acids are then eluted into a small volume of buffer. The instrument then takes an aliquot of the eluted material and sets up the PCR reaction with an activated Master Mix. PCR Amplification and TaqMan® Detection The PCR cycling steps and detection of target signal occurs in the cobas® z 480 Analyzer. The Master Mix reagent contains primer pairs and probes for HSV-1, HSV-2 and Internal Control targets. If the target nucleic acid sequences are present, amplification with the corresponding primers will occur by a thermostable DNA polymerase, generating PCR products (amplicons). These products are detected by specific TaqMan probes containing a fluorescent dye and a quencher. Normally, the quencher Purpose for submission:

idK150617_s0_e2000

K150617.txt

measurand

Target DNA sequences from Herpes Simplex Virus type 1 (HSV-1) and Herpes Simplex Virus type 2 (HSV-2)

STANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K150617 B. Purpose for Submission: Clearance of New Device C. Measurand: Target DNA sequences from Herpes Simplex Virus type 1 (HSV-1) and Herpes Simplex Virus type 2 (HSV-2) D. Type of Test: An in vitro molecular diagnostic test for the qualitative detection and differentiation of HSV-1 and HSV-2 DNA in clinician-collected, external anogenital lesion specimens from symptomatic male and female patients. E. Applicant: Roche Molecular Systems, Inc. F. Proprietary and Established Names: cobas® HSV 1 and 2 Test G. Regulatory Information: 1. Regulation section: 21 CFR 866.3305 2. Classification: Class II 3. Product code: OQO 4. Panel: Microbiology (83) H. Intended Use: 1. Intended use(s): The cobas® HSV 1 and 2 Test on the cobas® 4800 system is an automated, qualitative in vitro diagnostic test, that utilizes real-time polymerase chain reaction (PCR), for the direct detection and differentiation of Herpes simplex virus 1 and 2 (HSV-1 and HSV-2) 2 DNA in clinician-collected, external anogenital lesion specimens from symptomatic male and female patients. The cobas® HSV 1 and 2 Test is intended for use as an aid in diagnosis of anogenital HSV-1 and HSV-2 infections in symptomatic patients. Warning: The cobas® HSV 1 and 2 Test is not FDA cleared for use with cerebrospinal fluid (CSF) and is not intended to be used for prenatal screening or for individuals under the age of 18 years. 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: cobas® 4800 System I. Device Description: The cobas® HSV 1 and 2 Test on the cobas® 4800 system is a real-time polymerase chain reaction (PCR) for the direct detection and differentiation of HSV-1 and HSV-2 DNA in clinician-collected, external anogenital lesion specimens, collected in MSwab Collection, Transport and Preservation System from symptomatic patients. The cobas® HSV 1 and HSV 2 Test is comprised of two major processes: (1) automated sample preparation to extract nucleic acids from swab specimens; (2) PCR amplification of target DNA sequences using HSV-1 and HSV-2 specific primers, and real-time detection of cleaved fluorescent-labeled HSV-1 and HSV-2 specific oligonucleotide detection probes. An internal control (IC), containing unrelated randomized DNA sequence, is added to all samples prior to automated sample preparation and is amplified and detected simultaneously with each sample to monitor the entire process. The specimens are collected and stored in the MSwab Collection, Transport and Preservation System for the cobas® HSV 1 and HSV 2 Test. The cobas® HSV 1 and HSV 2 Test is performed using the following reagent kits: 1. cobas® 4800 HSV 1 and HSV 2 Amplification/Detection Kit 2. cobas® 4800 HSV 1 and HSV 2 Controls and Cofactor Kit 3. cobas® 4800 System Wash Buffer Kit 4. cobas® 4800 System Lysis Kit 1 5. cobas® 4800 System Internal Control Kit 1 6. cobas® 4800 System Sample Preparation Kit 3 J. Substantial Equivalence Information: 1. Predicate device name(s): BD ProbeTecTM Herpes Simplex Viruses (HSV 1 & 2) Qx Amplified DNA Assays Reference Method: A composite reference method which includes a culture method, namely, the ELVIS® HSV ID/Typing Test System (Diagnostic Hybrids, Inc. (K971662)) and a validated PCR followed by bidirectional sequencing for clinical evaluation. The clinical performance of the cobas® HSV 1/2 Test was also compared to the culture method alone using the ELVIS® HSV ID/Typing Test System (Diagnostic Hybrids, Inc. (K971662)). 2. Predicate 510(k) number(s): K103798 3. Comparison with predicate: Similarities Characteristic BD ProbeTecTM Herpes Simplex Viruses (HSV 1 & 2) Qx Amplified DNA Assays on the BD Viper System in Extracted Mode, (K103798) Roche cobas® HSV 1 and 2 Test New Device (K150617) Intended use The BD ProbeTec™ Herpes Simplex Viruses (HSV 1 & 2) Qx Amplified DNA Assays (HSV Qx Assays), when tested with the BD Viper™ System in Extracted Mode, use Strand Displacement Amplification technology for the direct, qualitative detection and differentiation of Herpes Simplex virus type 1 (HSV1) and Herpes Simplex virus type 2 (HSV2) DNA in clinician-collected external anogenital lesion specimens. The assays are indicated for use with symptomatic individuals to aid in the diagnosis of anogenital HSV1 and HSV2 infections. The cobas® HSV 1 and 2 Test on the cobas® 4800 system is an automated, qualitative in vitro diagnostic test, that utilizes real-time polymerase chain reaction (PCR), for the direct detection and differentiation of Herpes simplex virus 1 and 2 (HSV-1 and HSV-2) DNA in clinician-collected anogenital lesion specimens from symptomatic male and female patients. The cobas® HSV 1 and 2 Test is intended for use as an aid in diagnosis of anogenital HSV-1 and HSV-2 infections in symptomatic patients. Warning: The cobas® HSV 1 and 2 Test is not FDA cleared for use with 4 Warning: The BD ProbeTec™ Herpes Simplex Viruses (HSV 1 & 2) Qx Amplified DNA Assays (HSV Qx Assays) are not FDA cleared for use with cerebrospinal fluid (CSF). The assays are not intended to be used for prenatal screening or for individuals under the age of 17 years. cerebrospinal fluid (CSF) and is not intended to be used for prenatal screening or for individuals under the age of 18 years. Sample Types External anogenital lesions Same Assay Results Qualitative detection and differentiation of HSV-1 and HSV-2 DNA Same Detection Chemistry Paired reporter and quencher fluorescence labeled probes using fluorescence resonance energy transfer (FRET) Same Differences Characteristic BD ProbeTecTM Herpes Simplex Viruses (HSV 1 & 2) Qx Amplified DNA Assays on the BD Viper System in Extracted Mode, (K103798) Roche cobas® HSV 1 and 2 Test New Device (K150617) Amplification Technology Strand Displacement Amplification Real-time PCR Sample Preparation Procedure Automated on BD™ Viper™ System in Extracted Mode Automated on cobas® 4800 System K. Standard/Guidance Document Referenced (if applicable): N/A 5 L. Test Principle: Target Selection The cobas® HSV 1and 2 Test utilizes real-time PCR technology to detect the conserved regions of HSV-1 Thymidine Kinase and HSV-1 DNA Polymerase as well as HSV-2 Thymidine Kinase and HSV-2 Glycoprotein B genes. Fluorogenic target-specific probes are used for the detection of the amplified HSV-1 and HSV-2 DNA as well as Internal Control. Since two HSV type targets are detected with different fluorescent dyes, the cobas® HSV 1 and 2 Test has the ability to simultaneously detect and differentiate HSV-1 and HSV-2. Primer and probe oligonucleotide sequences were designed to select HSV-1 and HSV-2 conserved sequences without cross reacting to other viruses, or other bacterial organisms commonly found in human genital areas. Sample Preparation Sample preparation for the cobas® HSV 1 and 2 Test is automated with the use of the cobas® x 480 instrument. Organisms from swab specimens collected in MSwab medium are lysed with chaotropic agent, proteinase K, and SDS reagents. Released nucleic acids, along with added Internal Control DNA, are bound by magnetic glass particles. The particles are washed and the bound nucleic acids are then eluted into a small volume of buffer. The instrument then takes an aliquot of the eluted material and sets up the PCR reaction with an activated Master Mix. PCR Amplification and TaqMan® Detection The PCR cycling steps and detection of target signal occurs in the cobas® z 480 Analyzer. The Master Mix reagent contains primer pairs and probes for HSV-1, HSV-2 and Internal Control targets. If the target nucleic acid sequences are present, amplification with the corresponding primers will occur by a thermostable DNA polymerase, generating PCR products (amplicons). These products are detected by specific TaqMan probes containing a fluorescent dye and a quencher. Normally, the quencher Measurand: