XPERT HEMOSIL FACTOR II & FACTOR V ASSAY
Device Facts
| Record ID | K082118 |
|---|---|
| Device Name | XPERT HEMOSIL FACTOR II & FACTOR V ASSAY |
| Applicant | Cepheid |
| Product Code | NPQ · Hematology |
| Decision Date | Sep 18, 2009 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 864.7280 |
| Device Class | Class 2 |
Intended Use
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 Story
The Xpert HemosIL Factor II & Factor V Assay is an automated, qualitative in vitro diagnostic genotyping test. It processes sodium citrate or EDTA anticoagulated whole blood samples. The user adds the sample and two reagents to a disposable, multi-chambered fluidic cartridge, which is then inserted into the GeneXpert Dx System. The system performs fully-automated, integrated sample preparation, real-time multiplex PCR, and detection. It utilizes an ultrasonic horn for cell lysis and a proprietary I-CORE thermocycler for amplification. The device identifies Factor II (G20210A) and Factor V (Leiden) genotypes. Results are provided in approximately 30 minutes, enabling rapid clinical assessment for suspected thrombophilia. The system is designed for use by a range of operators, from those without clinical lab experience to experienced technologists, in a clinical laboratory setting. The output assists clinicians in diagnosing thrombophilia, potentially guiding patient management and treatment decisions.
Clinical Evidence
Multi-site study (n=1018 for Factor II, n=1014 for Factor V) compared Xpert HemosIL assay results to bi-directional sequencing. Overall accuracy was 99.3% for both Factor II and Factor V. Reproducibility studies across three sites, two operators, and three lots showed 99.7% agreement. Analytical specificity confirmed correct genotyping in the presence of silent SNPs and common interfering substances (bilirubin, cholesterol, lipids, hemoglobin).
Technological Characteristics
Automated, cartridge-based, real-time multiplex PCR system. Uses disposable, multi-chambered fluidic cartridges. Detection via paired hybridization probes using Scorpions chemistry. Features include ultrasonic lysis, I-CORE thermocycler, and internal Probe Check Control (PCC). Operates on the GeneXpert Dx System platform.
Indications for Use
Indicated for individuals with suspected thrombophilia to detect Factor II (G20210A) and Factor V (Leiden) mutations using sodium citrate or EDTA anticoagulated whole blood.
Regulatory Classification
Identification
In vitro diagnostic test to detect the Factor V Leiden mutation in genomic DNA, as an aid to diagnosis in the evaluation of patients with suspected thrombophilia.
Special Controls
*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.)
Predicate Devices
- Roche Factor V Leiden Kit (k033607)
- Roche Factor II (Prothrombin) G20210A Kit (k033612)
Related Devices
- K223046 — Xpert® FII & FV · Cepheid® · Feb 15, 2023
- K250218 — Xpert® FII & FV · Cepheid · Feb 21, 2025
- K172913 — cobas Factor II and Factor V Test · Roche Molecular Systems, Inc. · Jan 12, 2018
Submission Summary (Full Text)
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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:
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,
Xpert HemosIL Factor II & Factor V Assay 510(k) Summary
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K682118
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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.
#### 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 &<br>Factor V Assay | Roche Factor II<br>(Prothrombin)<br>G20210A<br>(510(k) #k033612) | Roche Factor<br>V Leiden Kit<br>(510(k) #k033607) |
| Intended Use | Rapid detection of Factor II<br>and Factor V alleles from<br>sodium citrate and EDTA<br>anticoagulated whole blood | Same except<br>detection of<br>Factor II only<br>from EDTA<br>anticoagulated<br>blood only | Same except<br>detection of<br>Factor V only<br>from EDTA<br>anticoagulated<br>blood only |
| Indication for Use | Aid in the diagnosis in<br>individuals with suspected<br>thrombophilia | Same | Same |
| Technological<br>Detection<br>Principles | Amplification and detection<br>system for nucleic acids using<br>fluorescence detection. | Same | Same |
| Differences (Assay) | | | |
|-----------------------|---------------------------------------------------------------|------------------------------------------------------------------|---------------------------------------------------|
| Item | Device | Predicates | |
| | Xpert HemosIL Factor II &<br>Factor V Assay | Roche Factor II<br>(Prothrombin)<br>G20210A<br>(510(k) #k033612) | Roche Factor<br>V Leiden Kit<br>(510(k) #k033607) |
| Specimen Type | Anticoagulated Whole Blood | Purified DNA<br>from human<br>blood samples | Purified DNA<br>from human<br>blood samples |
| Sample<br>Preparation | Automated On-line | Performed off-<br>line | Performed off-<br>line |
| Test Cartridge | Disposable single-use, multi-<br>chambered fluidic cartridge. | Disposable<br>single-use PCR<br>capillary | Disposable<br>single-use PCR<br>capillary |
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| Differences (Assay) | | | |
|--------------------------------|-----------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------|
| Item | Device | Predicates | |
| | Xpert HemosIL Factor II &<br>Factor V Assay | Roche Factor II<br>(Prothrombin)<br>G20210A<br>(510(k) #k033612) | Roche Factor<br>V Leiden Kit<br>(510(k) #k033607) |
| Instrument System | Cepheid GeneXpert® Dx<br>System | Roche<br>LightCycler | Roche<br>LightCycler |
| Detection<br>Chemistry | Paired hybridization probes<br>using Scorpions | Paired<br>hybridization<br>probes using<br>fluorescence<br>energy transfer<br>(FRET) | Paired<br>hybridization<br>probes using<br>fluorescence<br>energy transfer<br>(FRET) |
| Fluidics/Sample<br>Preparation | Self-contained and automated<br>after two single-dose reagent<br>additions. | Manual | Manual |
| Probes | Scorpion Probes | HybProbe | HybProbe |
| Controls | Internal Probe check control<br>(PCC). | External positive<br>and negative<br>controls required<br>per run | External positive<br>and negative<br>controls required<br>per run |
| Rapid test results | Approximately 30 minutes to<br>results. | <1 hour (not<br>including sample<br>prep & set-up<br>time) | <1 hour (not<br>including sample<br>prep & set-up<br>time) |
| Users | Operators with no clinical lab<br>experience to experienced<br>clinical laboratory<br>technologists | CLIA High<br>Complexity<br>Laboratory Users | CLIA High<br>Complexity<br>Laboratory 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;
- 2. 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;
- 3. a sample homozygous for Factor II mutation (i.e., two mutant alleles for Factor II gene) and with normal (wildtype) alleles for Factor V;
- 4. a sample with normal (wildtype) alleles for Factor II and homozygous for Factor V mutation (i.e., two mutant alleles for Factor V gene);
- 5. 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 | % Total<br>Agreement by<br>Sample |
|----------------------------|-----------------|-----------------|-------------------|-----------------------------------|
| NOR | 100%<br>(20/20) | 100%<br>(20/20) | 100%<br>(20/20) | 100% (60/60) |
| Factor II HET/Factor V NOR | 100%<br>(20/20) | 100%<br>(20/20) | 100%<br>(20/20) | 100% (60/60) |
| Factor II HOM/Factor V NOR | 100%<br>(20/20) | 100%<br>(20/20) | 100%<br>(20/20) | 100% (60/60) |
| Factor II NOR/Factor V HOM | 100%<br>(20/20) | 100%<br>(20/20) | 100%<br>(20/20) | 100% (60/60) |
| Factor II NOR/Factor V HET | 100%<br>(20/20) | 100%<br>(20/20) | 95.0%<br>(19/20)a | 98.3% (59/60)a |
| % Total Agreement by Site | 100%<br>(60/60) | 100%<br>(60/60) | 98.3%<br>(59/60)a | 99.7%<br>(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 | % Total<br>Agreement by<br>Sample |
|----------------------------|-----------------|-----------------|-------------------|-----------------------------------|
| NOR | 100%<br>(20/20) | 100%<br>(20/20) | 100%<br>(20/20) | 100% (60/60) |
| Factor II HET/Factor V NOR | 100%<br>(20/20) | 100%<br>(20/20) | 100%<br>(20/20) | 100% (60/60) |
| Factor II HOM/Factor V NOR | 100%<br>(20/20) | 100%<br>(20/20) | 100%<br>(20/20) | 100% (60/60) |
| Factor II NOR/Factor V HOM | 100%<br>(20/20) | 100%<br>(20/20) | 100%<br>(20/20) | 100% (60/60) |
| Factor II NOR/Factor V HET | 100%<br>(20/20) | 100%<br>(20/20) | 95.0%<br>(19/20)a | 98.3% (59/60)a |
| % Total Agreement by Site | 100%<br>(60/60) | 100%<br>(60/60) | 98.3%<br>(59/60)a | 99.7%<br>(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 | | % Total<br>Agreement<br>by Sample |
|----------------------------------|-----------------|-----------------|-----------------|-----------------|-----------------|-------------------|-----------------------------------|
| | Op 1 | Op 2 | Op 1 | Op 2 | Op 1 | Op 2 | |
| NOR | 100%<br>(10/10) | 100%<br>(10/10) | 100%<br>(10/10) | 100%<br>(10/10) | 100%<br>(10/10) | 100%<br>(10/10) | 100%<br>(60/60) |
| Factor II<br>HET/Factor V NOR | 100%<br>(10/10) | 100%<br>(10/10) | 100%<br>(10/10) | 100%<br>(10/10) | 100%<br>(10/10) | 100%<br>(10/10) | 100%<br>(60/60) |
| Factor II<br>HOM/Factor V NOR | 100%<br>(10/10) | 100%<br>(10/10) | 100%<br>(10/10) | 100%<br>(10/10) | 100%<br>(10/10) | 100%<br>(10/10) | 100%<br>(60/60) |
| Factor II<br>NOR/Factor V HOM | 100%<br>(10/10) | 100%<br>(10/10) | 100%<br>(10/10) | 100%<br>(10/10) | 100%<br>(10/10) | 100%<br>(10/10) | 100%<br>(60/60) |
| Factor II<br>NOR/Factor V HET | 100%<br>(10/10) | 100%<br>(10/10) | 100%<br>(10/10) | 100%<br>(10/10) | 100%<br>(10/10) | 90.0%<br>(9/10)a | 98.3%<br>(59/60)a |
| % Total Agreement<br>by Operator | 100%<br>(50/50) | 100%<br>(50/50) | 100%<br>(50/50) | 100%<br>(50/50) | 100%<br>(50/50) | 98.0%<br>(49/50)a | 99.7%<br>(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 | | % Total<br>Agreement<br>by 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 II<br>HET/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 II<br>HOM/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 II<br>NOR/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 II<br>NOR/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 Agreement<br>by 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 | % Total<br>Agreement by<br>Sample |
| NOR | 100%<br>(10/10) | 100%<br>(10/10) | 100%<br>(10/10) | 100% (30/30) |
| Factor II HET/Factor V NOR | 100%<br>(10/10) | 100%<br>(10/10) | 100%<br>(10/10) | 100% (30/30) |
| Factor II HOM/Factor V NOR | 100%<br>(10/10) | 100%<br>(10/10) | 100%<br>(10/10) | 100% (30/30) |
| Factor II NOR/Factor V HOM | 100%<br>(10/10) | 100%<br>(10/10) | 100%<br>(10/10) | 100% (30/30) |
| Factor II NOR/Factor V HET | 100%<br>(10/10) | 100%<br>(10/10) | 100%<br>(10/10) | 100% (30/30) |
| % Total Agreement by Lot | 100%<br>(50/50) | 100%<br>(50/50) | 100%<br>(50/50) | 100% (150/150) |
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| Specimen ID | Lot 1 | Lot 2 | Lot 3 | % Total<br>Agreement by<br>Sample |
|----------------------------|-----------------|-----------------|-----------------|-----------------------------------|
| NOR | 100%<br>(10/10) | 100%<br>(10/10) | 100%<br>(10/10) | 100% (30/30) |
| Factor II HET/Factor V NOR | 100%<br>(10/10) | 100%<br>(10/10) | 100%<br>(10/10) | 100% (30/30) |
| Factor II HOM/Factor V NOR | 100%<br>(10/10) | 100%<br>(10/10) | 100%<br>(10/10) | 100% (30/30) |
| Factor II NOR/Factor V HOM | 100%<br>(10/10) | 100%<br>(10/10) | 100%<br>(10/10) | 100% (30/30) |
| Factor II NOR/Factor V HET | 100%<br>(10/10) | 100%<br>(10/10) | 100%<br>(10/10) | 100% (30/30) |
| % Total Agreement by Lot | 100%<br>(50/50) | 100%<br>(50/50) | 100%<br>(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
{12}------------------------------------------------
### Indications for Use Statement 4.0 510(k) Number (if known):
Device Name: Xpert™ HemosIL® Factor II & Factor V Assay
### Indications for Use:
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.
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
