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idK172287_s2000_e4000

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conclusion

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

for ET specimens and Table 3 for PMF specimens. Table 2. Concordance table between ipsogen JAK2 RGQ PCR Kit and Sanger Bidirectional Sequencing in ET population Sanger bi-directional sequencing JAK2 V617F positive JAK2 V617F negative Total ipsogen JAK2 RGQ PCR Kit JAK2 V617F positive 43 9 52 JAK2 V617F negative 0 46 46 Total 43 55 98 The overall agreement is 90.8% (89/98 subjects; 95% CI: [83.3% – 95.7%]), the positive agreement is 100% (43/43 subjects; 95% CI: [91.8% – 100%]), and the negative agreement is 83.6% (46/55 subjects; 95% CI: [71.2% – 92.2%]). 7 Table 3. Concordance table between ipsogen JAK2 RGQ PCR Kit and Sanger Bidirectional Sequencing in PMF population Sanger Bi-directional sequencing JAK2 V617F positive JAK2 V617F negative Total ipsogen JAK2 RGQ PCR Kit JAK2 V617F positive 51 5 56 JAK2 V617F negative 0 43 43 Total 51 48 99 The overall agreement is 94.9% (94/99 subjects; 95% CI: [88.6% – 98.3%]), the positive agreement is 100% (51/51 subjects; 95% CI: [93.0% – 100%]), and the negative agreement is 89.6% (43/48 subjects; 95% CI: [77.3% – 96.5%]). Previously in DEN160028, a clinical study was conducted in which 276 PV samples were evaluated with the ipsogen JAK2 RGQ PCR Kit and the results were compared to results obtained with BDS. One PV sample was found JAK2 V617F positive with the ipsogen JAK2 RGQ PCR Kit and negative with BDS. Concordance between the two methods is shown in Table 4 for PV specimens. The overall agreement is 99.6% (275/276 subjects; 95% CI: [98.0% – 100%]), the positive agreement is 100% (71/71 subjects; 95% CI: [94.9% – 100%]), and the negative agreement is 99.5% (204/205 subjects; 95% CI: [97.3% – 100%]). Table 4. Concordance table between ipsogen JAK2 RGQ PCR Kit and Sanger Bidirectional Sequencing in PV population Sanger Bi-directional sequencing JAK2 V617F positive JAK2 V617F negative Total ipsogen JAK2 RGQ PCR Kit JAK2 V617F positive 71 1 72 JAK2 V617F negative 0 204 204 Total 71 205 276 Accuracy with all MPN specimens evaluated combined The overall accuracy of the test in MPN specimens was assessed by combining the 8 data obtained from each specimen cohort. A total of 473 MPN specimens were evaluated and a total of 15 samples were discordant. The overall agreement is 96.8% (458/473 subjects; 95% CI: [94.8%; 98.2%]). The positive agreement was 100% (165/165 subjects; 95%CI: [97.8%; 100%] and the negative agreement was 95.1 % (293/308 subjects; 95% CI: [92.1%; 97.2 %]). The results are shown in Table 5. Table 5. Concordance table between ipsogen JAK2 RGQ PCR Kit and Sanger Bidirectional Sequencing in MPN population (combined ET, PMF and PV populations) Sanger bi-directional sequencing JAK2 V617F positive JAK2 V617F negative Total ipsogen JAK2 RGQ PCR Kit JAK2 V617F positive 165 15 180 JAK2 V617F negative 0 293 293 Total 165 308 473 The specimens yielding discordant results appeared to have mutation levels below the BDS detection capability (around 10%). Because Sanger sequencing is not as sensitive as the JAK2 assay, and the JAK2 assay sensitivity is 1%, a separate study was conducted using a validated next generation sequencing (NGS) method to detect JAK2 V617F allele in the 15 discordant samples (9 ET, 5 PMF, and 1 PV), as well as a randomly selected set of 22 JAK2 V617F concordant specimens (11 positive and 11 negative specimens). All 15 discordants tested positive by NGS, agreeing with the ipsogen JAK2 RGQ PCR Kit. All concordant samples tested the same with NGS. b. Whole blood stability A specimen stability was conducted with 6 PV specimens (3 JAK2 V617F positive and 3 JAK2 V617F negative samples in K2-EDTA tubes) collected and stored at 4°C or room temperature (RT) before proceeding to gDNA extraction. Specimen stability was tested by assessing the agreement between qualitative results, and separately, for trends in changes in the percent mutation measured with the JAK2 Kit at each time point (i.e., baseline, day 2, 3, 4 and day 4 + 2h) and storage condition (RT or 2-8°C). At each extraction, 3 aliquots per sample were extracted using QIAsymphony. The results passed acceptance criteria and support the claim that whole blood can be stored at RT and 2-8°C for 96 hours before being processed for gDNA extraction to assess the JAK2 V617F status with the JAK2 Kit. 9 2. Comparison studies: a. Method comparison with predicate device: Not applicable. b. Matrix comparison: Not applicable. 3. Clinical studies: Not applicable. 4. Clinical cut-off: Specimens < 1% are considered negative and no value is generated. Specimens ≥1% are considered positive. The assay reports the JAK2 percentage because the additional information on potential mutant allele burden enhances diagnostic evaluation, however the assay is not intended for quantitative use. There is currently no consensus on the clinical value of extremely low JAK2 V617F loads, however a 1% mutation load is considered by experts and literature (Tefferi, 2011 and Martinaud, 2010) as a meaningful cut-off for reporting JAK2 V617F positivity. 5. Expected values/Reference range: The assay is not intended for quantitative use. Low JAK2 allele has been detected in subjects without MPNs. . N. Instrument Name: QIAGEN Rotor-Gene Q MDx platform using Rotor-Gene AssayManager software version 2.1. The instrument was cleared by FDA under K113319 on February 06, 2012. 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_____ 10 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: Whole blood. 4. Specimen Sampling and Handling: 4C or RT for 96 hours. 5. Calibration and Quality Control: Installation and calibration are performed by the manufacturer. The assay uses standards for generation of a curve by which the % mutation is assessed. The Instrument and assay employ both in-process QC checks and array QC metrics to assist in identifying problems in the assay and instances in which the assay has failed. P. Other Supportive Instrument Performance Characteristics Data Not Covered In The “Performance Characteristics” Section above: None. Q. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Parts 801 and 809 and the special controls for this device type. R. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Conclusion:

idK172287_s2000_e4000

K172287.txt

applicant

QIAGEN

ET specimens and Table 3 for PMF specimens. Table 2. Concordance table between ipsogen JAK2 RGQ PCR Kit and Sanger Bidirectional Sequencing in ET population Sanger bi-directional sequencing JAK2 V617F positive JAK2 V617F negative Total ipsogen JAK2 RGQ PCR Kit JAK2 V617F positive 43 9 52 JAK2 V617F negative 0 46 46 Total 43 55 98 The overall agreement is 90.8% (89/98 subjects; 95% CI: [83.3% – 95.7%]), the positive agreement is 100% (43/43 subjects; 95% CI: [91.8% – 100%]), and the negative agreement is 83.6% (46/55 subjects; 95% CI: [71.2% – 92.2%]). 7 Table 3. Concordance table between ipsogen JAK2 RGQ PCR Kit and Sanger Bidirectional Sequencing in PMF population Sanger Bi-directional sequencing JAK2 V617F positive JAK2 V617F negative Total ipsogen JAK2 RGQ PCR Kit JAK2 V617F positive 51 5 56 JAK2 V617F negative 0 43 43 Total 51 48 99 The overall agreement is 94.9% (94/99 subjects; 95% CI: [88.6% – 98.3%]), the positive agreement is 100% (51/51 subjects; 95% CI: [93.0% – 100%]), and the negative agreement is 89.6% (43/48 subjects; 95% CI: [77.3% – 96.5%]). Previously in DEN160028, a clinical study was conducted in which 276 PV samples were evaluated with the ipsogen JAK2 RGQ PCR Kit and the results were compared to results obtained with BDS. One PV sample was found JAK2 V617F positive with the ipsogen JAK2 RGQ PCR Kit and negative with BDS. Concordance between the two methods is shown in Table 4 for PV specimens. The overall agreement is 99.6% (275/276 subjects; 95% CI: [98.0% – 100%]), the positive agreement is 100% (71/71 subjects; 95% CI: [94.9% – 100%]), and the negative agreement is 99.5% (204/205 subjects; 95% CI: [97.3% – 100%]). Table 4. Concordance table between ipsogen JAK2 RGQ PCR Kit and Sanger Bidirectional Sequencing in PV population Sanger Bi-directional sequencing JAK2 V617F positive JAK2 V617F negative Total ipsogen JAK2 RGQ PCR Kit JAK2 V617F positive 71 1 72 JAK2 V617F negative 0 204 204 Total 71 205 276 Accuracy with all MPN specimens evaluated combined The overall accuracy of the test in MPN specimens was assessed by combining the 8 data obtained from each specimen cohort. A total of 473 MPN specimens were evaluated and a total of 15 samples were discordant. The overall agreement is 96.8% (458/473 subjects; 95% CI: [94.8%; 98.2%]). The positive agreement was 100% (165/165 subjects; 95%CI: [97.8%; 100%] and the negative agreement was 95.1 % (293/308 subjects; 95% CI: [92.1%; 97.2 %]). The results are shown in Table 5. Table 5. Concordance table between ipsogen JAK2 RGQ PCR Kit and Sanger Bidirectional Sequencing in MPN population (combined ET, PMF and PV populations) Sanger bi-directional sequencing JAK2 V617F positive JAK2 V617F negative Total ipsogen JAK2 RGQ PCR Kit JAK2 V617F positive 165 15 180 JAK2 V617F negative 0 293 293 Total 165 308 473 The specimens yielding discordant results appeared to have mutation levels below the BDS detection capability (around 10%). Because Sanger sequencing is not as sensitive as the JAK2 assay, and the JAK2 assay sensitivity is 1%, a separate study was conducted using a validated next generation sequencing (NGS) method to detect JAK2 V617F allele in the 15 discordant samples (9 ET, 5 PMF, and 1 PV), as well as a randomly selected set of 22 JAK2 V617F concordant specimens (11 positive and 11 negative specimens). All 15 discordants tested positive by NGS, agreeing with the ipsogen JAK2 RGQ PCR Kit. All concordant samples tested the same with NGS. b. Whole blood stability A specimen stability was conducted with 6 PV specimens (3 JAK2 V617F positive and 3 JAK2 V617F negative samples in K2-EDTA tubes) collected and stored at 4°C or room temperature (RT) before proceeding to gDNA extraction. Specimen stability was tested by assessing the agreement between qualitative results, and separately, for trends in changes in the percent mutation measured with the JAK2 Kit at each time point (i.e., baseline, day 2, 3, 4 and day 4 + 2h) and storage condition (RT or 2-8°C). At each extraction, 3 aliquots per sample were extracted using QIAsymphony. The results passed acceptance criteria and support the claim that whole blood can be stored at RT and 2-8°C for 96 hours before being processed for gDNA extraction to assess the JAK2 V617F status with the JAK2 Kit. 9 2. Comparison studies: a. Method comparison with predicate device: Not applicable. b. Matrix comparison: Not applicable. 3. Clinical studies: Not applicable. 4. Clinical cut-off: Specimens < 1% are considered negative and no value is generated. Specimens ≥1% are considered positive. The assay reports the JAK2 percentage because the additional information on potential mutant allele burden enhances diagnostic evaluation, however the assay is not intended for quantitative use. There is currently no consensus on the clinical value of extremely low JAK2 V617F loads, however a 1% mutation load is considered by experts and literature (Tefferi, 2011 and Martinaud, 2010) as a meaningful cut-off for reporting JAK2 V617F positivity. 5. Expected values/Reference range: The assay is not intended for quantitative use. Low JAK2 allele has been detected in subjects without MPNs. . N. Instrument Name: QIAGEN Rotor-Gene Q MDx platform using Rotor-Gene AssayManager software version 2.1. The instrument was cleared by FDA under K113319 on February 06, 2012. 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_____ 10 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: Whole blood. 4. Specimen Sampling and Handling: 4C or RT for 96 hours. 5. Calibration and Quality Control: Installation and calibration are performed by the manufacturer. The assay uses standards for generation of a curve by which the % mutation is assessed. The Instrument and assay employ both in-process QC checks and array QC metrics to assist in identifying problems in the assay and instances in which the assay has failed. P. Other Supportive Instrument Performance Characteristics Data Not Covered In The “Performance Characteristics” Section above: None. Q. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Parts 801 and 809 and the special controls for this device type. R. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Applicant: