The Xpert® FII & FV test 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 test is performed on the Cepheid GeneXpert® Instrument Systems. 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.

Device Description

The Cepheid Xpert® FII & FV is a rapid, automated DNA test for detecting FII and FV 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, 50 uL of the blood sample is transferred to the bottom wall of the Sample opening of the Xpert FII & FV test cartridge. The user initiates a test from the system user interface and places the cartridge into the GeneXpert® Instrument system instrument platform (comprised of the GeneXpert Dx Systems and GeneXpert Infinity Systems), which performs hands-off real-time, multiplex polymerase chain reaction (PCR) for detection of DNA. In the GeneXpert Instrument Systems platform, sample preparation, amplification, and real-time detection are all fully-automated and completely integrated.

The GeneXpert Instrument Systems have 1 to 80 randomly accessible modules, depending upon the instrument, that are each capable of performing separate sample preparation and real- time PCR tests. Each module contains a syringe drive for dispensing fluids (i.e., the syringe drive activates the plunger that works in concert with the rotary valve in the cartridge to move fluids between chambers), an ultrasonic horn for lysing cells or spores, and a proprietary I-CORE® thermocycler for performing real-time PCR and detection.

The Xpert FII & FV test includes reagents for the detection of Factor II and Factor V normal and mutant alleles. The primers and probes in the Xpert FII & FV test determine the genotype of the Factor II gene (at position 20210) and the Factor V gene (at position 1691). The test includes a Sample Processing Control to confirm adequate processing of the target bacteria and to monitor the presence of inhibitor(s) in the PCR assay. The Probe Check Control (PCC) verifies reagent rehydration, PCR tube filling in the cartridge, probe integrity, and dye stability.

The test is performed on the Cepheid GeneXpert Instrument Systems, which automate and integrate sample purification, nucleic acid amplification of the target sequences in simple or complex samples using real-time PCR. The systems consist of an instrument, personal computer, and preloaded software for running the tests and viewing the results. The GeneXpert Instrument Systems require the use of single-use disposable cartridges that hold the PCR reagents and host the PCR process. Because the cartridges are self-contained, crosscontamination between samples is minimized. In this platform, additional sample preparation, amplification, and real-time detection are all fully- automated and completely integrated. The Xpert FII & FV test performed on the GeneXpert Instrument Systems provides results in approximately 30 minutes.

AI/ML Overview

The FDA 510(k) summary for the Cepheid Xpert® FII & FV device outlines its performance and validation, primarily focusing on demonstrating substantial equivalence to a predicate device when used with new instrument systems (GeneXpert Infinity Systems).

Here's an analysis of the provided information against your requested criteria:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not provide a formal table of quantitative acceptance criteria with corresponding performance metrics like sensitivity, specificity, accuracy, etc. This is typical for a Special 510(k) submission where the primary objective is to demonstrate that a change (new instrument compatibility) does not negatively impact the existing, previously cleared performance.

Instead, the "Performance Data" section states:

Acceptance Criteria (Implicit): That the performance claims of the Xpert FII & FV test were not impacted by the use of the GeneXpert Infinity Systems.
Reported Device Performance: This was assessed through verification studies, including a "Cartridge Hold Time study" and a "Functional Testing study." The document explicitly states that the results "determined that the performance claims of the Xpert FII & FV test were not impacted."

Therefore, the performance is essentially stated as "comparable to the predicate device and original claims," rather than providing new specific rates (e.g., "99% sensitivity," "98% specificity").

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

The document does not explicitly state the sample sizes for the "Cartridge Hold Time study" and "Functional Testing study." It only mentions that these were "verification studies."

Data Provenance: Not specified in terms of country of origin.
Retrospective or Prospective: Not explicitly stated, but typically, verification studies like these for in vitro diagnostic devices would involve prospective testing of samples under controlled conditions to assess functionality and stability on the new instrument.

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

This type of information is not applicable to this device and study. The Xpert® FII & FV test is a qualitative in vitro diagnostic genotyping test for detecting specific DNA mutations (Factor II and Factor V alleles). The "ground truth" for such a device is established by the known genetic status of the samples used in the studies (e.g., confirmed Factor II or Factor V mutation presence/absence via reference methods or defined synthetic constructs), not by expert human interpretation of images or other subjective data. No human experts are used to establish ground truth for this kind of molecular diagnostic test performance.

4. Adjudication Method for the Test Set

Not applicable. As explained above, the "ground truth" for a genotyping test is based on direct molecular confirmation, not on subjective interpretations requiring adjudication.

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

Not applicable. The Xpert® FII & FV is an automated diagnostic test that provides a definitive genetic result. It does not involve human readers interpreting output that would be improved with AI assistance, nor is it a diagnostic imaging device where MRMC studies are common.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study

This is the primary mode of operation for this device. The Xpert® FII & FV test is an automated system as described: "perform[s] hands-off real-time, multiplex polymerase chain reaction (PCR) for detection of DNA." The results ("Result," "Not Detected," or "Invalid") are generated by the instrument's internal algorithms based on PCR amplification signals. The human interaction is limited to sample loading and initiating the test. Therefore, the "Functional Testing study" and "Cartridge Hold Time study" effectively assess the standalone performance of the algorithm and instrument system.

7. The Type of Ground Truth Used

The ground truth for a genotyping test is based on the presence or absence of specific DNA sequences/mutations. While not explicitly stated how this truth was established for the specific "verification studies," for molecular diagnostic tests, ground truth is typically confirmed using:

Reference molecular methods: Such as Sanger sequencing or highly validated in-house PCR assays.
Characterized samples: Samples with known genetic status (e.g., from biobanks, synthetic constructs, or previously validated patient samples).
Clinical diagnosis/outcomes data: In some cases, to correlate the genetic findings with the clinical presentation, although for genotyping tests, the primary ground truth is molecular.

Given the nature of this device, it would be based on the confirmed genetic status of the samples.

8. The Sample Size for the Training Set

This information is not provided. As this is a Special 510(k) for an instrument change, the focus is on verification rather than a full re-validation involving new training sets. The underlying algorithms and core test technology (primers, probes, PCR) remain the same as the predicate device. Training sets would have been used in the original development and validation of the Xpert® FII & FV test (K082118).

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

Not provided in this document as it pertains to the original development of the predicate device (K082118), not this Special 510(k). For the original development, ground truth would have been established as described in point 7 (reference molecular methods, characterized samples).

Summary

{0}------------------------------------------------

Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food & Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

February 15, 2023

Cepheid Bobbi Ferrell Principal Regulatory Affairs Specialist 904 Caribbean Drive Sunnyvale, CA 94089

Re: K223046

Trade/Device Name: Xpert FII & FV Regulation Number: 21 CFR 864.7280 Regulation Name: Factor V Leiden DNA Mutation Detection Systems Regulatory Class: Class II Product Code: NPR, NPQ, OOI Dated: September 29, 2022 Received: September 29, 2022

Dear Bobbi Ferrell:

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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. 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

{1}------------------------------------------------

requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR

for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Image /page/1/Picture/6 description: The image shows the text "Min Wu -" in a simple, sans-serif font. The text is arranged horizontally, with a clear separation between the words. The background is plain white, which makes the text stand out. The text is written in black.

Min Wu, Ph.D. Branch Chief for Hematology Branch Division of Immunology and Hematology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

{2}------------------------------------------------

Indications for Use

510(k) Number (if known) K223046

Device Name Xpert® FII & FV

Indications for Use (Describe)

Type of Use (Select one or both, as applicable)
Prescription Use (Part 21 CFR 801 Subpart D)	Over-The-Counter Use (21 CFR 801 Subpart C)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

{3}------------------------------------------------

Image /page/3/Picture/1 description: The image contains the Cepheid company logo, which features a stylized blue wing-like design above the company name in a simple sans-serif font. Below the company name, the text "Xpert® FII & FV" is displayed, indicating a specific product or service offered by Cepheid. The text is in a smaller font size compared to the company name, and the "Xpert" is followed by a registered trademark symbol.

5. 510(k) Summary

As required by 21 CFR Section 807.92(c). The purpose of this submission is to submit documentation to support the addition of the GeneXpert Infinity systems for the use with Xpert FII & FV (GXFIIFV-10).

Submitted by:	Cepheid904 Caribbean DriveSunnyvale, CA 90489Phone number: (408) 400-8230Fax number: (408) 541-6439
Contact:	Bobbi L. Ferrell, MSRA
Date of Preparation:	September 27, 2022
Proprietary/Trade name:	Xpert® FII & FV
Common name:	Xpert® Factor II & Factor V
Type of Test:	Nucleic Acid Amplification Test, DNA, Factor IIProthrombin G20210A and Factor V G1691A (Leiden)qualitative, genotyping
Regulation number,Classification name,Product code:	21 CFR 864.7280, Factor II Prothrombin and Factor VLeiden DNA Mutation Detection Systems, NPQ, NPR21 CFR 862.2570, Real Time Nucleic Acid Amplification System, OOI;
Classification AdvisoryPanel	Pathology
Prescription Use	Yes
Predicate Device Test:	Cepheid Xpert HemosIL Factor II & Factor V (K082118)

5.1 Device Description

{4}------------------------------------------------

Image /page/4/Picture/1 description: The image contains the Cepheid company logo, which features a stylized blue wing-like design above the company name in black. Below the company name, the text "Xpert® FII & FV" is displayed, indicating a specific product or service offered by Cepheid. The text is also in black and appears to be a part of the product branding.

5.2 Intended Use

5.3 Technical Characteristics

The Xpert FII & FV test has the same technological characteristics as the predicate device.

5.4 Substantial Equivalence

The purpose of this Special 510(k) submission is for a modification to an existing device (Xpert® FII & FV) to incorporate its intended use on an additional instrument, the GeneXpert Infinity Systems. Table 5-1 shows the similarities and differences between the Xpert FII & FV test and predicate device. The differences between Xpert FII & FV test and the predicate device do not raise different questions of safety and effectiveness.

{5}------------------------------------------------

Image /page/5/Picture/0 description: The image contains the Cepheid company logo, which features a stylized blue wing-like design above the company name in black. Below the company name, the text "Xpert® FII & FV" is displayed, indicating a specific product or service offered by Cepheid. The logo is clean and professional, suggesting a focus on technology and innovation in the medical or diagnostic field.

	Table 5-1: Comparison of Similarities and Differences
	of Modified and Predicate Xpert FII & FV

Similarities
Item	Modified Device	Predicate Device
	Xpert Factor II & Factor V	Xpert (HemosIL) Factor II & Factor V(K082118)
Indications for Use	Same	Aid in the identification of individualssuspected with thrombophilia
Sample Preparation	Same	Self-contained and automated after mixedspecimen is added to cartridge.
Laboratory Users	Same	Trained users
Specimen Type	Same	Sodium citrate or EDTA anticoagulated wholeblood
Test Technology	Same	Fully automated nucleic acid amplification(DNA); real-time PCR
Test CartridgeTechnology	Same	Disposable single-use, multi-chamberedfluidic cartridge
Internal Controls	Same	Sample processing control (SPC) and probecheck control (PCC).
DNA Target Sequence	Same	Sequence specific to for Factor II (G20210A)and Factor V Leiden (G1691A) mutations
Time to Results	Same	Approximately 30 minutes to result
Assay Definition FileResults Algorithm	Same	Rules-based algorithms incorporating delta Ctvalues between targets within a valid Ct rangeand algorithms based on the Ct value for thetargets falling within a valid Ct range.
Differences
	Modified Device	Predicate Device
Item	Xpert FII & FV	Xpert (HemosIL) Factor II & Factor VK082118
Intended Use(Difference bolded)	The Xpert® FII & FV test is aqualitative in vitro diagnosticgenotyping test for the detection ofFactor II and Factor V alleles fromsodium citrate or EDTAanticoagulated whole blood. The testis performed on the CepheidGeneXpert® Instrument Systems.This test is intended to provide resultsfor Factor II (G20210A) and Factor VLeiden (G1691A) mutations as an aidin the diagnosis in individuals withsuspected thrombophilia.	The Xpert® Factor II & Factor V test is aqualitative in vitro diagnostic genotypingtest for the detection of Factor II andFactor V alleles from sodium citrate orEDTA anticoagulated whole blood. Thetest is performed on the CepheidGeneXpert® Dx Systems. This test isintended to provide results for Factor II(G20210A) and Factor V Leiden(G1691A) mutations as an aid in thediagnosis in individuals with suspectedthrombophilia.
Instrument System	Cepheid GeneXpert Dx Systems andGeneXpert Infinity-48s and Infinity-80 Systems	Cepheid GeneXpert Dx Systems
Software	GeneXpert Dx software version4.0 and higher, GeneXpert Infinity-48sand Infinity-80 Xpertise softwareversion 6.6 and higher	GeneXpert Dx software version2.1 or higher

{6}------------------------------------------------

Image /page/6/Picture/0 description: The image contains the Cepheid company logo, which features a stylized blue wing-like design above the company name in black. Below the company name, the text "Xpert® FII & FV" is displayed, indicating a specific product or service offered by Cepheid. The "Xpert" is followed by a registered trademark symbol.

5.5 Summary of Performance Data

The performance of the Xpert FII & FV test when used with the GeneXpert Infinity Systems was assessed through verification studies, including a Cartridge Hold Time study and Functional Testing study. The assessment of the results from these studies determined that the performance claims of the Xpert FII & FV test were not impacted.

5.6 Conclusion

The results of the verification studies demonstrate that the Xpert FII & FV test as performed on the GeneXpert Infinity Systems is substantially equivalent to the original design of the Xpert (HemosIL) Factor II & Factor V (K082118, the predicate device).

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.)