The Xpert™ HemosIL® Factor II & Factor V Assay is a qualitative in vitro diagnostic genotyping test for the rapid detection of Factor II and Factor V alleles from sodium citrate or EDTA anticoagulated whole blood. The test is performed on the Cepheid GeneXpert® Dx System. This test is intended to provide rapid results for Factor II (G20210A) and Factor V (Leiden) mutations as an aid in the diagnosis in individuals with suspected thrombophilia.

Device Description

The Cepheid Xpert® HemosIL® Factor II & Factor V Assay is an automated DNA test for detecting Factor II and Factor V normal and mutant alleles directly from sodium citrate or EDTA anticoagulated whole blood specimens. Blood specimens are drawn into either sodium citrate or EDTA anticoagulant tubes. Following brief mixing of the sample, the blood sample and two single-use reagents (Reagent 1 and Reagent 2) that are provided with the assay are transferred to different, uniquely-labeled chambers of the disposable fluidic cartridge (the Xpert HemosIL Factor V cartridge). The user initiates a test from the system user interface and places the cartridge into the GeneXpert® Dx System instrument platform, which performs hands-off real-time, multiplex polymerase chain reaction (PCR) for detection of DNA. In this platform, sample preparation, amplification, and real-time detection are all fully-automated and completely integrated.

The GeneXpert Dx System consists of a GeneXpert instrument, personal computer, a barcode scanner and the multi-chambered fluidic cartridges that are designed to complete sample preparation and real-time PCR for detection of Factor II and Factor V normal and mutant alleles in approximately 30 minutes. Each system has 1 to 16 randomly accessible modules that are each capable of performing separate sample preparation and real-time PCR tests. Each module contains a syringe drive for dispensing fluids, an ultrasonic horn for lysing nuclei, and a proprietary I-CORE® thermocycler for performing real-time PCR and detection.

The Xpert HemosIL Factor II & Factor V Assay includes reagents for the detection of Factor II and Factor V normal and mutant alleles. The primers and probes in the Xpert HemosIL Factor II & Factor V Assay determine the genotype of the Factor II gene (at position 20210) and the Factor V gene (at position 1691).

The test includes a Probe Check Control (PCC) that verifies reagent rehydration, PCR tube filling in the cartridge, probe integrity, and dye stability and an instrument control verifies the instrument is performing properly. Additionally, the sample functions as its own internal control since both normal and mutant gene sequences are detected, and each person tested is expected to have one of these sequence signatures.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study that proves the device meets them, based on the provided text:

Cepheid Xpert® HemosIL® FII & FV: Acceptance Criteria and Performance Study

The Cepheid Xpert® HemosIL® Factor II & Factor V Assay is a qualitative in vitro diagnostic genotyping test designed to detect Factor II (G20210A) and Factor V Leiden (G1691A) mutations in whole blood, aiding in the diagnosis of individuals with suspected thrombophilia. The primary study presented demonstrates the device's accuracy compared to bi-directional sequencing, which serves as the gold standard.

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly define "acceptance criteria" through numerical thresholds but presents performance metrics that implicitly indicate the successful validation of the device. Based on the clinical comparison study, the implicit acceptance criterion is a high agreement with the gold standard (bi-directional sequencing).

Acceptance Criteria (Implicit)	Reported Device Performance
Overall Accuracy for Factor II (G20210A) relative to bi-directional sequencing	99.3%
Overall Accuracy for Factor V (G1691A) relative to bi-directional sequencing	99.3%
Reproducibility (Inter-site, Inter-operator, Inter-lot) for Factor II and Factor V genotypes	Generally 98.3% - 100% agreement, with a few indeterminate results on first run. Overall reproducibility rates are very high (e.g., 99.7% overall across sites/operators).
Analytical Specificity (correct genotyping with SNPs)	Correct genotyping call, or invalid result in case of SNP in probe binding region.
Interference with common blood components/treatments	No inhibition from heparin, bilirubin, cholesterol, triglycerides, or one freeze-thaw cycle (hemolyzed blood).

2. Sample Size Used for the Test Set and Data Provenance

Sample Size for Clinical Comparison Study:
- Factor II: 1018 samples (plus 6 human genomic DNA samples homozygous for Factor II to supplement homozygous sample size).
- Factor V: 1014 samples (plus 5 human genomic DNA samples homozygous for Factor V to supplement homozygous sample size).
Data Provenance: The samples were collected in a multi-site investigational study at seven U.S. institutions.
- The study involved prospective collection of aliquots from routine clinical whole blood specimens (intended for Factor II and/or Factor V testing).
- Excess DNA from these samples was sent to a contract laboratory for bi-directional sequencing.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications

The ground truth was established by bi-directional sequencing, which is a laboratory technique rather than expert interpretation. Therefore, the concept of "experts" to establish ground truth in the traditional sense (e.g., radiologists reviewing images) does not directly apply here. The expertise lies in the laboratory personnel performing and interpreting the sequencing results, but specific numbers or qualifications of these individuals are not detailed in the summary.

4. Adjudication Method for the Test Set

The document primarily describes a direct comparison of the device's results against bi-directional sequencing.
No explicit adjudication method (e.g., 2+1, 3+1) is mentioned beyond the direct comparison with the gold standard.
Invalid results are noted. For Factor II, there were 43 invalid results on the first run, reduced to 7 after repeat runs. For Factor V, there were 42 invalid results on the first run, reduced to 7 after repeat runs. These "invalid results" are referred to as "indeterminate" results, meaning they could not be called by the device, but there were no discordant results (where the device definitively called a genotype incorrectly compared to sequencing). This implies that if the device did make a call, it was correct relative to the gold standard.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No MRMC comparative effectiveness study was done. This is a diagnostic test where the device directly provides a result, not an assistive AI tool for human readers.

6. Standalone Performance

Yes, a standalone (algorithm only without human-in-the-loop performance) study was conducted. The clinical comparison study directly assessed the performance of the Xpert HemosIL Factor II & Factor V Assay (the device) against bi-directional sequencing. The device automatically performs sample preparation, amplification, and real-time detection without human interpretation of the final genotype call. The results in Table 5.2 (Agreement after Repeat Run) represent the standalone performance of the device after initial run and any necessary repeat testing for "indeterminate" results.

7. The Type of Ground Truth Used

The ground truth used was bi-directional sequencing results, which is considered the gold standard for genetic sequencing.

8. The Sample Size for the Training Set

The document does not report the sample size for a training set. For an in-vitro diagnostic (IVD) PCR-based assay like this, "training set" doesn't typically apply in the same way it would for machine learning algorithms. The device's primers and probes are designed based on known genetic sequences, and its performance is validated through analytical and clinical studies, not typically through a distinct machine learning training phase on patient data.

9. How the Ground Truth for the Training Set Was Established

As there's no explicitly mentioned "training set" in the context of the device's development as a machine learning model, the method for establishing ground truth for a training set is not applicable. The device's underlying principles are molecular biology and biochemistry (PCR and hybridization probes) rather than learned patterns from a large dataset. The specificity of the probes for Factor II and Factor V mutations defines the "ground truth" the assay is designed to detect.

Summary

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Cepheid.

SFP 1 8 2009

510(k) Summary

As required by 21 CFR Section 807.92(c).

Submitted by:

Cepheid® 904 Caribbean Drive Sunnyvale, CA 90489 Phone number: (408) 400-8230 Fax number: (408) 541-6439

Xpert® HemosIL® FII & FV

Factor II and Factor V Genotyping Assay.

Xpert® HemosIL® Factor II & Factor V

Xpert® HemosIL® Factor II & Factor V Assay

Nucleic Acid Amplification Test, DNA, Factor II Prothrombin G20210A and Factor V G1691A (Leiden)

Factor II Prothrombin and Factor V Leiden DNA Mutation

Russel K. Enns, Ph.D.

qualitative, genotyping

July 31, 2009

Contact: Date of Preparation:

Device:

Trade name:

Common names:

Type of Test:

Classification name:

Advisory Committee:

Detection Systems

Regulation number: 864.7280

NPR

Classification Hematology

Predicate Devices:

Procode:

Roche Factor II (Prothrombin) G20210A Kit (510(k) #K033612) and Roche Factor V Leiden Kit (510(k) #K033607)

Device Description:

Xpert HemosIL Factor II & Factor V Assay 510(k) Summary

Page 1 of 10

K682118

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sample preparation, amplification, and real-time detection are all fully-automated and completely integrated.

The test includes a Probe Check Control (PCC) that verifies reagent rehydration, PCR tube filling in the cartridge, probe integrity, and dye stability and an instrument control verifies the instrument is performing properly. Additionally, the sample functions as its own internal control since both normal and mutant gene sequences are detected, and each person.tested is expected to have one of these sequence signatures.

Device Intended Use:

The Xpert™ HemosIL® Factor II & Factor V Assay is a qualitative in vitro diagnostic genotyping test for the detection of Factor II and Factor V alleles from sodium citrate or EDTA anticoagulated whole blood. The assay is performed on the Cepheid GeneXpert® Dx System. This test is intended to provide results for Factor II (G20210A) and Factor V Leiden (G1691A) mutations as an aid in the diagnosis in individuals with suspected thrombophilia.

Substantial Equivalence:

The Xpert HemosIL Factor II & Factor V Assay is substantially equivalent to two predicate devices. Roche Factor II (Prothrombin) G20210A Kit (510(k) #K033612) and Roche Factor V Leiden Kit (510(k) #K033607). The Xpert HemosIL Factor II & Factor V Assay and Roche Factor II (Prothrombin) G20210A Kit and Factor V Leiden Kit determine the Factor II and Factor V genotypes through real-time PCR amplification and fluorogenic target-specific hybridization detection.

Table 5.1 shows the similarities and differences between the Xpert HemosIL Factor II & Factor V Assay and the two predicate devices. The GeneXpert Dx System, used with the Xpert HemosIL Factor II & Factor V Assay, is also used to perform the Cepheid Xpert GBS Assay, the Xpert EV Assay and the Xpert MRSA Assay. The predicate devices are performed on the Roche LightCycler® system.

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In a multi-center clinical comparison study, performance of the Xpert HemosIL Factor II & Factor V Assay and the Roche Factor II and Factor V Assays were each calculated relative to the gold standard, bi-directional sequencing results, and were shown to be substantially equivalent.

Table 5.1

Similarities and Differences Between the Xpert HemosIL Factor II & Factor V Assay and the Predicate Devices

Similarities (Assay)
Item	Device	Predicates
	Xpert HemosIL Factor II &Factor V Assay	Roche Factor II(Prothrombin)G20210A(510(k) #K033612)	Roche FactorV Leiden Kit(510(k) #K033607)
Intended Use	Rapid detection of Factor IIand Factor V alleles fromsodium citrate and EDTAanticoagulated whole blood	Same exceptdetection ofFactor II onlyfrom EDTAanticoagulatedblood only	Same exceptdetection ofFactor V onlyfrom EDTAanticoagulatedblood only
Indication for Use	Aid in the diagnosis inindividuals with suspectedthrombophilia	Same	Same
TechnologicalDetectionPrinciples	Amplification and detectionsystem for nucleic acids usingfluorescence detection.	Same	Same

Differences (Assay)
Item	Device	Predicates
	Xpert HemosIL Factor II &Factor V Assay	Roche Factor II(Prothrombin)G20210A(510(k) #K033612)	Roche FactorV Leiden Kit(510(k) #K033607)
Specimen Type	Anticoagulated Whole Blood	Purified DNAfrom humanblood samples	Purified DNAfrom humanblood samples
SamplePreparation	Automated On-line	Performed off-line	Performed off-line
Test Cartridge	Disposable single-use, multi-chambered fluidic cartridge.	Disposablesingle-use PCRcapillary	Disposablesingle-use PCRcapillary

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Differences (Assay)
Item	Device	Predicates
	Xpert HemosIL Factor II &Factor V Assay	Roche Factor II(Prothrombin)G20210A(510(k) #K033612)	Roche FactorV Leiden Kit(510(k) #K033607)
Instrument System	Cepheid GeneXpert® DxSystem	RocheLightCycler	RocheLightCycler
DetectionChemistry	Paired hybridization probesusing Scorpions	Pairedhybridizationprobes usingfluorescenceenergy transfer(FRET)	Pairedhybridizationprobes usingfluorescenceenergy transfer(FRET)
Fluidics/SamplePreparation	Self-contained and automatedafter two single-dose reagentadditions.	Manual	Manual
Probes	Scorpion Probes	HybProbe	HybProbe
Controls	Internal Probe check control(PCC).	External positiveand negativecontrols requiredper run	External positiveand negativecontrols requiredper run
Rapid test results	Approximately 30 minutes toresults.	<1 hour (notincluding sampleprep & set-uptime)	<1 hour (notincluding sampleprep & set-uptime)
Users	Operators with no clinical labexperience to experiencedclinical laboratorytechnologists	CLIA HighComplexityLaboratory Users	CLIA HighComplexityLaboratory Users

. .

, 、

・

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Non-Clinical Studies:

Analytical Sensitivity

Studies were performed to determine the minimum and maximum amount of input patient specimen for both EDTA and sodium citrate anticoagulated whole blood, needed to obtain a correct genotype, such that the lower bound of the 95% confidence interval for the estimated "correct call" fraction is greater than 95%.

EDTA and sodium citrate anticoagulated blood samples were tested (n=20) at 8 volumes varying from 5 uL to 250 uL.

Although the assay can tolerate varying volumes from 15 uL - 100 uL, 50 uL is the recommended sample volume to minimize the risk of errors associated with limited and excess sample.

Analytical Specificity

To evaluate the analytical specificity of the Xpert HemosIL Factor V Assay, normal gene sequences containing silent single nucleotide polymorphisms (SNPs) in the probe binding region as well as outside the probe binding region were synthesized. The presence of the additional SNP in the probe binding region, in most cases, resulted in an invalid result. When a valid result was obtained, it gave the correct genotype.

The presence of an additional SNP outside the probe binding region resulted in the correct genotyping call.

Interfering Substances

Patients on heparin therapy and blood transfusion patients may have blood specimens that potentially interfere with the PCR results and lead to invalid or erroneous results.

Studies of potentially interfering substances showed no inhibition from up to 14.3 USP units/mL heparin, 16 mg/dL bilirubin, 250 mg/dL added cholesterol, or 1932 mg/dL total triglycerides (lipids). No inhibition was observed using whole blood samples which had gone through one freeze-thaw cycle (hemolyzed blood). No statistical significance was observed between matched specimens drawn into EDTA or sodium citrate.

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Clinical Studies

Clinical Comparison Study

Performance characteristics of the Xpert HemosIL Factor V & Factor V Assay were determined in a multi-site investigational study at seven U.S. institutions by the Xpert HemosIL Factor II & Factor V Assay relative to bi-directional sequencing.

Specimens included those whose routine care called for collection of whole blood for Factor II and/or Factor V testing. Samples were first tested by routine methods used in each participating laboratory and then aliquots collected for study testing by Xpert HemosIL Factor II & Factor V Assay on the GeneXpert. Excess DNA was sent to a contract laboratory for bi-directional sequencing.

Performance of the Xpert HemosIL Factor II & Factor V Assay was calculated relative to bi-directional sequencing results.

Overall Results

Xpert HemosIL Factor II & Factor V Assay

A total of 1018 samples were tested for Factor II by both the Xpert HemosIL Factor II & Factor. V Assay, and bi-directional sequencing. A total of 1014 samples were tested for Factor V by both the Xpert HemosIL Factor II & Factor V Assay and bi-directional sequencing. To supplement the homozygous sample size, six human genomic DNA samples homozygous for Factor II and five homozygous for Factor V were also tested by the Xpert HemosIL Factor II & Factor V Assay and bi-directional sequencing. The results are presented in Table 5.2.

The Xpert HemosIL Factor II & Factor V Assay demonstrated a 99.3% overall accuracy relative to bi-directional sequencing for both Factor II and Factor V.

Genotype	Number Tested	Number of Correct Calls on First Run	Number of Invalida Calls on First Run	Agreement on First Run	Number of Correct Calls Including Repeat Run	Number of Invalida Calls on Repeat Run	Agreement After Repeat Run
Factor II G20210A
WT	968	927	41	95.8%	963	5	99.5%
HET	50	48	2	96.0%	48	2	96.0%
HOM	7	7	0	100.0%	7	0	100%
Overall	1025b	982	43	95.8%	1018	7	99.3%
Factor V G1691A
WT	895	860	35	96.1%	889	6	99.3%
HET	114	108	6	94.7%	113	1	99.1%
HOM	12	11	1	91.7%	12	0	100.0%
Overall	1021c	979	42	95.9%	1014	7	99.3%

Table 5.2 - Xpert HemosIL Performance vs. Bi-directional Sequencing

ªNo discordant results. Invalid results refer to "indeterminate" results.

b Bi-directional sequencing results for Factor II were not available for 4 specimens.

·Bi-directional sequencing results for Factor V were not available for 8 specimens.

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Reproducibility Study

A panel of 5 specimens, consisting of one of each specimen type listed below were tested in duplicate by two different operators on 5 different days at each of three sites (3 specimens x 2 times/day x 2 operators per site x 5 days x 3 sites). One lot of Xpert HemosIL Factor II & Factor V Assay kit was used at each of the 3 testing sites. Xpert HemosIL Factor II & Factor V assays were performed according to the Xpert HemosIL Factor II & Factor V procedure. Results are summarized in Tables 5.3 - 5.6.

Study panel:

1. a sample with normal (wildtype) alleles for both Factor II & Factor V;
1. a sample heterozygous for Factor II mutation (i.e., one mutant and one wildtype allele for Factor II gene) and with normal (wildtype) alleles for Factor V;
1. a sample homozygous for Factor II mutation (i.e., two mutant alleles for Factor II gene) and with normal (wildtype) alleles for Factor V;
1. a sample with normal (wildtype) alleles for Factor II and homozygous for Factor V mutation (i.e., two mutant alleles for Factor V gene);
1. a sample with normal (wildtype) alleles for Factor II and heterozygous for Factor V mutation (i.e., one mutant and one wildtype allele for Factor V gene)..

Specimen ID	Site 1	Site 2	Site 3	% TotalAgreement bySample
NOR	100%(20/20)	100%(20/20)	100%(20/20)	100% (60/60)
Factor II HET/Factor V NOR	100%(20/20)	100%(20/20)	100%(20/20)	100% (60/60)
Factor II HOM/Factor V NOR	100%(20/20)	100%(20/20)	100%(20/20)	100% (60/60)
Factor II NOR/Factor V HOM	100%(20/20)	100%(20/20)	100%(20/20)	100% (60/60)
Factor II NOR/Factor V HET	100%(20/20)	100%(20/20)	95.0%(19/20)a	98.3% (59/60)a
% Total Agreement by Site	100%(60/60)	100%(60/60)	98.3%(59/60)a	99.7%(299/300)a

of Dannaduaibility Dasulta by Cit

®No discordant results. One sample was indeterminate after retest.

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Specimen ID	Site 1	Site 2	Site 3	% TotalAgreement bySample
NOR	100%(20/20)	100%(20/20)	100%(20/20)	100% (60/60)
Factor II HET/Factor V NOR	100%(20/20)	100%(20/20)	100%(20/20)	100% (60/60)
Factor II HOM/Factor V NOR	100%(20/20)	100%(20/20)	100%(20/20)	100% (60/60)
Factor II NOR/Factor V HOM	100%(20/20)	100%(20/20)	100%(20/20)	100% (60/60)
Factor II NOR/Factor V HET	100%(20/20)	100%(20/20)	95.0%(19/20)a	98.3% (59/60)a
% Total Agreement by Site	100%(60/60)	100%(60/60)	98.3%(59/60)a	99.7%(299/300)a

Table 5.4 - Summary of Reproducibility Results by Site - Factor V

®No discordant results. One sample was indeterminate after retest.

Specimen ID	Site 1		Site 2		Site 3		% TotalAgreementby Sample
	Op 1	Op 2	Op 1	Op 2	Op 1	Op 2
NOR	100%(10/10)	100%(10/10)	100%(10/10)	100%(10/10)	100%(10/10)	100%(10/10)	100%(60/60)
Factor IIHET/Factor V NOR	100%(10/10)	100%(10/10)	100%(10/10)	100%(10/10)	100%(10/10)	100%(10/10)	100%(60/60)
Factor IIHOM/Factor V NOR	100%(10/10)	100%(10/10)	100%(10/10)	100%(10/10)	100%(10/10)	100%(10/10)	100%(60/60)
Factor IINOR/Factor V HOM	100%(10/10)	100%(10/10)	100%(10/10)	100%(10/10)	100%(10/10)	100%(10/10)	100%(60/60)
Factor IINOR/Factor V HET	100%(10/10)	100%(10/10)	100%(10/10)	100%(10/10)	100%(10/10)	90.0%(9/10)a	98.3%(59/60)a
% Total Agreementby Operator	100%(50/50)	100%(50/50)	100%(50/50)	100%(50/50)	100%(50/50)	98.0%(49/50)a	99.7%(299/300)a

Table 5.5 - Summary of Reproducibility Results by Operator - Factor II

"No discordant results. One sample was indeterminate after retest.

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Specimen ID	Site 1		Site 2		Site 3		% TotalAgreementby Sample
	Op 1	Op 2	Op 1	Op 2	Op 1	Op 2
NOR	100%	100%	100%	100%	100%	100%	100%
	(10/10)	(10/10)	(10/10)	(10/10)	(10/10)	(10/10)	(60/60)
Factor IIHET/Factor V NOR	100%	100%	100%	100%	100%	100%	100%
	(10/10)	(10/10)	(10/10)	(10/10)	(10/10)	(10/10)	(60/60)
Factor IIHOM/Factor V NOR	100%	100%	100%	100%	100%	100%	100%
	(10/10)	(10/10)	(10/10)	(10/10)	(10/10)	(10/10)	(60/60)
Factor IINOR/Factor V HOM	100%	100%	100%	100%	100%	100%	100%
	(10/10)	(10/10)	(10/10)	(10/10)	(10/10)	(10/10)	(60/60)
Factor IINOR/Factor V HET	100%	100%	100%	100%	100%	90.0%	98.3%
	(10/10)	(10/10)	(10/10)	(10/10)	(10/10)	(9/10)a	(59/60)a
% Total Agreementby Operator	100%	100%	100%	100%	100%	98.0%	99.7%
	(50/50)	(50/50)	(50/50)	(50/50)	(50/50)	(49/50)a	(299/300)a

Table 5.6 - Summary of Reproducibility Results by Operator - Factor V

*No discordant results. One sample was indeterminate after retest.

To assess the between lot reproducibility, the 5-specimen panel described above was analyzed two times per day over 5 testing days using each of three assay lots, at a single testing site (5 specimens x 2 runs per day x 3 lots x 5 days). A summary of the results by lot is shown in Tàble 5.7 & 5.8.

Table 5.7 - Summary of Reproducibility Results by Lot - Factor II
Specimen ID	Lot 1	Lot 2	Lot 3	% TotalAgreement bySample
NOR	100%(10/10)	100%(10/10)	100%(10/10)	100% (30/30)
Factor II HET/Factor V NOR	100%(10/10)	100%(10/10)	100%(10/10)	100% (30/30)
Factor II HOM/Factor V NOR	100%(10/10)	100%(10/10)	100%(10/10)	100% (30/30)
Factor II NOR/Factor V HOM	100%(10/10)	100%(10/10)	100%(10/10)	100% (30/30)
Factor II NOR/Factor V HET	100%(10/10)	100%(10/10)	100%(10/10)	100% (30/30)
% Total Agreement by Lot	100%(50/50)	100%(50/50)	100%(50/50)	100% (150/150)

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Specimen ID	Lot 1	Lot 2	Lot 3	% TotalAgreement bySample
NOR	100%(10/10)	100%(10/10)	100%(10/10)	100% (30/30)
Factor II HET/Factor V NOR	100%(10/10)	100%(10/10)	100%(10/10)	100% (30/30)
Factor II HOM/Factor V NOR	100%(10/10)	100%(10/10)	100%(10/10)	100% (30/30)
Factor II NOR/Factor V HOM	100%(10/10)	100%(10/10)	100%(10/10)	100% (30/30)
Factor II NOR/Factor V HET	100%(10/10)	100%(10/10)	100%(10/10)	100% (30/30)
% Total Agreement by Lot	100%(50/50)	100%(50/50)	100%(50/50)	100% (150/150)

Table 5.8 - Summary of Reproducibility Results by Lot -- Factor V

Conclusions

The results of the rionclinical analytical and clinical performance studies summarized above demonstrate that the Xpert HemosIL Factor V Assay is substantially equivalent to the gold standard (bi-directional sequencing) and the predicate devices.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/10/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is an abstract image of an eagle.

Food and Drug Administration 10903 New Hampshire Avenue Document Mail Center - WO66-G609 Silver Spring, MD 20993-0002

Cepheid c/o Russel K. Enns, PhD Senior Vice President Regulatory, Clinical & Government Affairs 904 Caribbean Drive Sunnyvale, CA 94089-1189

Re: K082118

Trade/Device Name: Xpert® HemosIL® Factor II & Factor V Assay Regulation Number: 21 CFR 864.7280 Regulation Name: Factor V Leiden DNA mutation detection system Regulatory Class: Class II Product Code: NPO. NPR. OOI Dated: August 6, 2009 Received: August 7, 2009

Dear Dr. Enns:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.

SEP 1 8 2009

If your device is classified (see above) into class II (Special Controls), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter will allow you to begin marketing your device as described in your Section 510(k) premarket

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Page 2 - Russel K. Enns. PhD

notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Parts 801 and 809), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely vours.

-1

m chan

Maria M. Chan, PhD Director Division of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indications for Use Statement 4.0 510(k) Number (if known):

Device Name: Xpert™ HemosIL® Factor II & Factor V Assay

Indications for Use:

Prescription Use _ X (Part 21 CFR 801 Subpart D)

Over-The-Counter Use _ AND/OR (21 CFR 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE OF NEEDED)

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

5100(4) K082118

Xpert HemosIL Factor II & Factor V Assay 510(k) July 2008

Volume l Page 15

Regulation Number and Section

§ 864.7280 Factor V Leiden DNA mutation detection systems.

(a)
Identification. Factor V Leiden deoxyribonucleic acid (DNA) mutation detection systems are devices that consist of different reagents and instruments which include polymerase chain reaction (PCR) primers, hybridization matrices, thermal cyclers, imagers, and software packages. The detection of the Factor V Leiden mutation aids in the diagnosis of patients with suspected thrombophilia.(b)
Classification. Class II (special controls). The special control is FDA's guidance entitled “Class II Special Controls Guidance Document: Factor V Leiden DNA Mutation Detection Systems.” (See § 864.1(d) for the availability of this guidance document.)