The Xpert® FII & FV test is a qualitative in vitro diagnostic genotyping test for the detection of Factor V alleles from sodium citrate or EDTA anticoagulated whole blood. The test is performed on the 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

Xpert FII & FV is an automated genotyping 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. 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.

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/or the Factor V gene (at position 1691). The test includes a Sample Processing Control (SPC) to confirm adequate processing 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 GeneXpert Instrument Systems family is comprised of GeneXpert Dx System, GeneXpert Infinity System, and GeneXpert System with Touchscreen. The GeneXpert Instrument Systems automate and integrate sample processing, nucleic acid amplification and detection of the target sequences in simple or complex samples using real-time polymerase chain reaction (PCR). The systems consist of an instrument, computer or touchscreen, and preloaded software for running the tests and viewing the results. The GeneXpert Instrument Systems require the use of singleuse disposable cartridges that hold the PCR reagents and host the PCR process. Because the cartridges are self-contained, cross-contamination between samples is minimized.

The GeneXpert Instrument Systems have 1 to 80 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 performed on the GeneXpert Instrument Systems provides results in approximately 30 minutes.

AI/ML Overview

This document is a 510(k) summary for the Xpert FII & FV diagnostic test, seeking to remove a limitation statement and make minor branding/catalog number changes. It does not contain a study explicitly detailing acceptance criteria and performance against those criteria for the current submission. Instead, it refers to prior clearance (K082118) for the clinical validation supporting the removal of the limitation statement, and asserts that the current changes do not impact performance.

Therefore, the following information is extracted or inferred based on the provided document:

1. Table of Acceptance Criteria and Reported Device Performance:

The document explicitly states: "No new performance data were provided in this submission." The basis for substantial equivalence relies on the device being identical to its predicate (K223046) in all technological characteristics relevant to performance. The one significant change (removal of the pediatric patient limitation) is supported by prior clinical validation data (K082118). Since no new performance data or acceptance criteria are presented for this specific submission, this table cannot be fully completed from the provided text.

However, based on the nature of a genetic mutation detection system, typical acceptance criteria would involve analytical sensitivity, analytical specificity, and clinical performance (e.g., concordance with a gold standard). Without the original K082118 submission, specific numerical criteria are not available.

Acceptance Criteria Category	Specific Acceptance Criteria (Inferred/Generic for Genetic Tests)	Reported Device Performance (Implied from Substantial Equivalence and Prior Clearance)
Analytical Performance	Precision (reproducibility across runs, lots)	Not explicitly stated in this document; implied to meet prior clearance standards.
	Reproducibility (inter-site, inter-operator)	Not explicitly stated in this document; implied to meet prior clearance standards.
	Genotyping Accuracy (Concordance with reference method)	Not explicitly stated in this document; implied to meet prior clearance standards, as the test is based on PCR.
	Limit of Detection	Not explicitly stated in this document; implied to meet prior clearance standards.
	Interference	Not explicitly stated in this document; implied to meet prior clearance standards.
Clinical Performance	Clinical Sensitivity (ability to detect mutation when present)	Not explicitly stated in this document; implied to meet prior clearance standards with sufficient accuracy for diagnosis.
	Clinical Specificity (ability to correctly identify absence of mutation)	Not explicitly stated in this document; implied to meet prior clearance standards with sufficient accuracy for diagnosis.
	Overall Concordance with Gold Standard	The performance was previously validated in clinical studies (K082118) and deemed acceptable to aid in diagnosis.
Robustness/System Performance	SPC/PCC performance	SPC confirms adequate processing and monitors inhibitors; PCC verifies reagent integrity. Performance implicitly meets design requirements.

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

Sample Size: Not explicitly stated in this document. The document refers to "clinical validation data that was submitted and reviewed as part of the original device clearance (K082118)" as the basis for removing the pediatric limitation. The sample size for that original study is not provided here.
Data Provenance: Not explicitly stated in this document. Given it's a 510(k) for a US market device, it is likely the original clinical validation (K082118) included US data, but this is not confirmed. It refers to "clinical validation data," which typically implies prospective collection of patient samples.

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

Not explicitly stated in this document. This level of detail would typically be found in the original clinical validation report (K082118). For genotyping, ground truth is usually established by orthogonal molecular methods, not primarily by expert consensus in the same way as imaging or pathology interpretation.

4. Adjudication Method for the Test Set:

Not applicable/Not mentioned. For genetic tests where the ground truth is often established through well-defined molecular techniques (e.g., Sanger sequencing or a validated reference method), adjudication by multiple experts in the traditional sense (like for imaging reads) is generally not performed. The ground truth is objective.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done:

No, an MRMC comparative effectiveness study was not done. This type of study is relevant for interpretive tasks (e.g., radiologists reading images) where human performance is being evaluated and compared with and without AI assistance. The Xpert FII & FV is an automated genotyping test; it does not involve human readers interpreting results in the same manner.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done:

Yes, the performance characteristics mentioned (e.g., analytical sensitivity, specificity) for a molecular diagnostic test like the Xpert FII & FV are inherently "standalone" in nature. The device itself performs the assay and provides a qualitative genotype call. The results are automated and interpreted by the diagnostic software.

7. The Type of Ground Truth Used:

Not explicitly stated in this document, but for genetic tests, the ground truth is typically established by orthogonal molecular methods, such as Sanger sequencing or another highly accurate, validated reference genotyping method. It is not based on expert consensus, pathology, or outcomes data in the way these terms are typically used for imaging or disease diagnosis.

8. The Sample Size for the Training Set:

Not explicitly stated in this document. The device uses real-time PCR for detection, and while there might be algorithm tuning within the software, the foundational "training" often refers to the design and optimization of primers and probes, and establishment of cut-offs, rather than machine learning on a large training set of clinical samples. The document refers to "clinical validation data" for performance, but not specifically to a training set size for an algorithm.

9. How the Ground Truth for the Training Set was Established:

Not explicitly stated in this document. This would be part of the original developmental studies for the device (predating K082118). For a PCR-based test, ground truth for developing and optimizing the assay would involve samples with known genotypes confirmed through reference methods.

Summary

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February 21, 2025

Cepheid Sruti Krishna Regulatory Affairs Principal, New Product Development 904 Caribbean Drive Sunnyvale, California 94089

Re: K250218

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. NPO. OOI Dated: January 24, 2025 Received: January 24, 2025

Dear Sruti Krishna:

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 (the 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 available 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.

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Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).

Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30. Design controls; 21 CFR 820.90. Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

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 Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safetyreporting-combination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.

All medical devices, including Class I and unclassified devices and combination product device constituent parts are required to be in compliance with the final Unique Device Identification System rule ("UDI Rule"). The UDI Rule requires, among other things, that a device bear a unique device identifier (UDI) on its label and package (21 CFR 801.20(a)) unless an exception or alternative applies (21 CFR 801.20(b)) and that the dates on the device label be formatted in accordance with 21 CFR 801.18. The UDI Rule (21 CFR 830.300(a) and 830.320(b)) also requires that certain information be submitted to the Global Unique Device Identification Database (GUDID) (21 CFR Part 830 Subpart E). For additional information on these requirements, please see the UDI System webpage at https://www.fda.gov/medical-device-advicecomprehensive-regulatory-assistance/unique-device-identification-system-udi-system.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 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 medical devices and radiation-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-regulatory

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assistance/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/2/Picture/3 description: The image contains the text "Min Wu-S". The text is written in a simple, sans-serif font. The background of the image is plain, with a faint watermark or design element in the lower right corner.

Min Wu, Ph.D. Branch Chief 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

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Indications for Use

510(k) Number (if known) K250218

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)

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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. 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 bold, sans-serif font, and the overall design is clean and professional.

510(k) Summary

As required by 21 CFR Section 807.92(c).

Submitted by:	Cepheid904 Caribbean DriveSunnyvale, CA 90489Phone number: (408) 541-4191
Contact :	Sruti Krishna, Ph.D.
Date of Preparation :	January 24, 2025
Device:
Trade Name:	Xpert® FII & FV
Common Name:	Xpert Factor II & Factor V
Type of Test:	Test, Factor II G20210A Mutations, Genomic DNA PCR
Regulation Number:	21 CFR 864.7280
Regulation Description:	Factor V Leiden DNA Mutation Detection Systems
Product Codes:	NPR (primary), NPQ, OOI
Classification:	Class II
Review Panel:	Pathology
Prescription Use:	Yes
Predicate Device:	Xpert FII & FV (K223046)

Device Description 1.

CONFIDENTIAL

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The Xpert FII & FV test performed on the GeneXpert Instrument Systems provides results in approximately 30 minutes.

2. Device Intended Use

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 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.

3. Technical Characteristics

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

4. Substantial Equivalence

The purpose of this Special 510(k) submission is to support the removal of the following erroneous limitation statement from the Instructions for Use of an on-market device (Xpert FII & FV): "The performance of the Xpert Factor II & Factor V test has not been evaluated with samples from pediatric patients." Two additional modifications to the test are: (i) an update from "Cepheid GeneXpert® Instrument Systems" to "GeneXpert® Instrument Systems" in the Intended Use Statement, from a branding simplification perspective, and (ii) the creation of a new catalog number (GXFIIFV-US-10) for the modified device that is the subject of this Special 510(k) submission.

The following tables shows the similartities and differences between the Xpert FII& FV test and the predicate device. The differences between Xpert FII & FV and the predicate device do not raise different questions of safety and effectiveness.

CONFIDENTIAL

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Image /page/6/Picture/0 description: The image contains the Cepheid company logo and the text "Xpert® FII & FV". The Cepheid logo is a stylized blue wing-like shape above the company name. The text "Xpert® FII & FV" is located below the company name and logo.

Similarities
	Subject DeviceXpert® FII & FV(Modified)	Predicate DeviceXpert® FII & FV(K223046)
Attribute
Regulation	21 CFR 864.7280Factor V Leiden DNA Mutation DetectionSystems21 CFR 862.2570Instrumentation for Clinical Multiplex Testsystems	Same
Product Code	NPRTest, Factor II G20210A Mutations, GenomicDNA PCRNPQTest, Factor V Leiden Mutations, GenomicDNA PCROOIReal Time Nucleic Acid Amplification System	Same
Device Class	Class II	Same
Indicationsfor Use	Aid in the diagnosis of FII and FV Leidenmutations in individuals with suspectedthrombophilia	Same
Technology/Detection	Fully automated nucleic acid amplification(DNA); real-time PCR	Same
TestCartridge	Disposable single-use, multi-chambered, fluidiccartridge	Same
Fluidics	Self-contained and automated after specimen isadded to the cartridge	Same
SpecimenType	Sodium citrate or EDTA anticoagulated wholeblood	Same
Probes	Scorpion® Probes	Same
InternalControls	• Sample Processing Control (SPC)• Probe Check Control (PCC)	Same
DNA TargetSequence	Sequence specific for Factor II (G20210A) andFactor V Leiden (G1691A) mutations	Same
Time toResult	Approximately 30 minutes to result	Same
Assay Format	Amplification: PCRDetection: Fluorogenic target-specifichybridization	Same
Similarities
Attribute	Subject DeviceXpert® FII & FV(Modified)	Predicate DeviceXpert® FII & FV(K223046)
Interpretation of Test Results	Automated(Diagnostic software)	Same
Users	Trained users	Same
Instrument Systems	GeneXpert Dx Systems GeneXpert Infinity-48s and Infinity-80 Systems GeneXpert Systems with Touchscreen	Same
Software	GeneXpert Dx software version 4.0 or higher GeneXpert Xpertise software version 6.6 or higher CEP OS version 2.1 or higher	Same

Table 1. Similarities between Xpert FII & FV and the Predicate Device

CONFIDENTIAL

Attachment 78 Page 5 of 7

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Image /page/7/Picture/0 description: The image shows the Cepheid logo, which is a stylized blue wing-like design above the word "Cepheid." Below the logo, there is the text "Xpert® FII & FV". The text is in a bold, sans-serif font, with the "®" symbol indicating a registered trademark.

Table 2. Differences between Xpert FII & FV and the Predicate Device

Differences
	Subject Device	Predicate Device
Attribute	Xpert® FII & FV	Xpert® FII & FV
	(Modified)	(K223046)
Intended Use	The Xpert® FII & FV test is a qualitative invitro diagnostic genotyping test for thedetection of Factor II and Factor V allelesfrom sodium citrate or EDTA anticoagulatedwhole blood. Performed on theGeneXpert® Instrument Systems, the test isintended to provide results for Factor II(G20210A) and Factor V Leiden (G1691A)mutations and indicated as an aid in thediagnosis in individuals with suspectedthrombophilia.	The Xpert® FII & FV test is a qualitative invitro diagnostic genotyping test for thedetection of Factor II and Factor V allelesfrom sodium citrate or EDTA anticoagulatedwhole blood. Performed on the CepheidGeneXpert® Instrument Systems, the test isintended to provide results for Factor II(G20210A) and Factor V Leiden (G1691A)mutations and indicated as an aid in thediagnosis in individuals with suspectedthrombophilia.
CatalogNumber	GXFIIFV-US-10	GXFIFV-10
Instructionsfor Use -Limitations ofthe ProcedureSection	· The performance of the Xpert Factor II &Factor V test was validated using theprocedures provided in this Instructionsfor Use only. Modifications to theseprocedures may alter the performance ofthe test. Results from the Xpert Factor II& Factor V test should be interpreted inconjunction with other laboratory andclinical data available to the clinician.	· The performance of the Xpert Factor II &Factor V test was validated using theprocedures provided in this Instructionsfor Use only. Modifications to theseprocedures may alter the performance ofthe test. Results from the Xpert Factor II& Factor V test should be interpreted inconjunction with other laboratory andclinical data available to the clinician.

CONFIDENTIAL

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Image /page/8/Picture/1 description: The image shows the Cepheid logo and the text "Xpert® FII & FV". The Cepheid logo is a stylized blue wing shape above the word "Cepheid" in a serif font. Below the logo is the text "Xpert® FII & FV", with the "Xpert" having a registered trademark symbol.

Differences
	Subject Device	Predicate Device
Attribute	Xpert® FII & FV	Xpert® FII & FV
	(Modified)	(K223046)
	• Rare Factor V mutations (A1696G,G1689A, and A1692C) and anyadditional SNPs in the probe bindingregion may interfere with the targetdetection and yield an INVALID result.• Other rare Factor II mutations in theprobe binding region may interfere withthe target detection and could yield anINVALID result, or a falseHOMOZYGOUS mutant result whenoccurring concordantly with the Factor IIc.*97G>A (G20210A) mutation.	• Rare Factor V mutations (A1696G,G1689A, and A1692C) and anyadditional SNPs in the probe bindingregion may interfere with the targetdetection and yield an INVALID result.• Other rare Factor II mutations in theprobe binding region may interfere withthe target detection and could yield anINVALID result, or a falseHOMOZYGOUS mutant result whenoccurring concordantly with the Factor IIc.*97G>A (G20210A) mutation.
	• Erroneous test results might occur fromimproper specimen collection, handling,or storage or sample mix-up. Carefulcompliance to the instructions in thispackage is necessary to avoid erroneousresults.	• The performance of the Xpert FactorII & Factor V test has not beenevaluated with samples from pediatricpatients.• Erroneous test results might occur fromimproper specimen collection, handling,or storage or sample mix-up. Carefulcompliance to the instructions in thispackage is necessary to avoid erroneousresults.

5. Summary of Performance Data

No new performance data were provided in this submission. Removal of the erroneous limitation statement - which states that the performance of the test has not been evaluated with samples from pediatric patients - from the Instructions for Use is supported by clinical validation data that was submitted and reviewed as part of the original device clearance (K082118). The change from "Cepheid GeneXpert® Instrument Systems" to "GeneXpert® Instrument Systems" in the intended use statement, and from GXFIIFV-10 to GXFIIFV-US-10 for the catalog number, have no impact on device performance, safety or effectiveness.

6. Conclusion

The intended use of the modified Xpert FII & FV test and the legally marketed predicate device (Xpert FII & FV; K223046) are identical other than a minor update from a branding simplification perspective. The technological characteristics of the modified Xpert FII & FV test are identical to those of the predicate device. The performance of the modified Xpert FII & FV test is acceptable for its intended use and substantially equivalent to the predicate device.

CONFIDENTIAL

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.)