(139 days)
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.
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.
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).
§ 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.)