(20 days)
The Xpert® vanA test performed on the GeneXpert® Instrument Systems is a qualitative in vitro diagnostic test designed for detection of the vanA gene sequence associated with vancomycin resistance in bacteria obtained from rectal swab specimens from patients at risk for intestinal colonization with vancomycin-resistant bacteria. The test utilizes automated real-time polymerase chain reaction (PCR) to detect the vanA gene that is frequently associated with vancomycin-resistant enterococci (VRE). The Xpert vanA test is intended to aid in the recognition, prevention, and control of vancomycin-resistant organisms that colonize patients in healthcare settings. The Xpert vanA test is not intended to diagnose infections caused by vancomycin-resistant bacteria nor to guide or monitor treatment for vancomycin-resistant bacterial infections. Concomitant cultures are necessary to recover organisms for identification of vancomycin-resistant bacteria, antimicrobial susceptibility testing, and for epidemiological typing.
The Xpert van4 test is an automated in vitro diagnostic test for the qualitative detection of the vanA gene sequence associated with vancomycin resistance in bacteria obtained directly from rectal swab specimens. The specimen is collected on a double swab, one of which is placed in a tube containing sample reagent. Following brief vortexing, the content of the sample reagent is transferred to the uniquely labeled Sample Chamber of a disposable fluidic cartridge (the Xpert vanA cartridge). The user initiates a test from the user interface of the GeneXpert® instrument system platform and places the cartridge with sample into the GeneXpert® instrument system which performs hands-off real-time, multiplex polymerase chain reaction (PCR) for the detection of vanA DNA.
In the GeneXpert® Instrument Systems (comprised of the GeneXpert® Dx System, GeneXpert® System with Touchscreen, and GeneXpert® Infinity System), sample preparation, amplification, and real-time detection are all fully automated and completely integrated. The platform requires the use of single-use disposable cartridges that hold the PCR reagents and host the PCR process. Because the cartridges are self-contained, cross-contamination between samples is minimized.
Depending on the specific instrument, a GeneXpert® instrument system may contain 1-80 modules, each of which are randomly accessible and 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 van4 test includes reagents for the detection of the gene for vancomycin resistance (van4) as well as an internal sample processing control (SPC) to control for adequate processing of the target bacteria and to monitor the presence of inhibitor(s) in the PCR assay. The SPC also ensures that the PCR conditions (temperature and time) are appropriate for the amplification reaction and that the PCR reagents are functional. The Probe Check Control (PCC) verifies reagent rehydration, PCR tube filling in the cartridge, probe integrity, and dye stability.
The Xpert van 4 test performed on the GeneXpert® Instrument Systems provides results in less than 45 minutes.
Each instrument in the GeneXpert® instrument family is equipped with a Windows OS-based personal computer that is preloaded with software applications for running the tests and viewing the results, as described in Table 1.
The provided text describes a 510(k) premarket notification for the Cepheid Xpert vanA test. This submission is for a modification to an already cleared device (Xpert vanA, K092953) to include the GeneXpert Infinity System instruments. As such, the document primarily focuses on demonstrating that the performance of the modified device is equivalent to the predicate device and does not present a full de novo study with a comprehensive set of acceptance criteria and performance statistics like sensitivity and specificity against a clinical ground truth.
Here's an analysis of the available information:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state formal acceptance criteria with numerical targets for the verification studies. Instead, it describes "verification studies" aiming to show equivalence to the predicate device. The performance is reported qualitatively as "100% agreement of reportable results" and "no statistically significant differences in Ct values."
| Acceptance Criteria (Implied) | Reported Device Performance (Xpert vanA on GeneXpert Infinity System) |
|---|---|
| Cartridge hold time: Maximum acceptable duration between sample addition and test initiation | Verified as 4 hours |
| Functional testing: Agreement of reportable results between predicate and modified device for contrived positive and negative samples | 100% agreement of reportable results |
| Functional testing: No statistically significant difference in Ct values between predicate and modified device for contrived positive samples | No statistically significant differences in Ct values observed between assay runs |
| Overall performance: Equivalent to predicate device (Xpert vanA, K092953) | Demonstrated equivalent performance |
2. Sample Size Used for the Test Set and Data Provenance
The document mentions "both contrived positive (vancomycin-resistant (vanA) Enterococcus faecalis cells added to negative matrix) and negative matrix only) samples" for functional testing. However, it does not specify the sample size for these contrived samples.
The data provenance is from verification studies conducted by the manufacturer (Cepheid) to demonstrate the performance of the Xpert vanA test on the GeneXpert Infinity System instruments. The samples are contrived, meaning they were prepared in a laboratory setting, rather than derived from a patient population (i.e., not prospective or retrospective clinical data in the traditional sense).
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
Given that the test set consisted of "contrived positive" and "negative matrix only" samples, the ground truth was established by the known composition of these laboratory-prepared samples. There is no mention of external experts or clinical adjudication for these ground truths, as the samples were artificially created with a defined vanA status.
4. Adjudication Method for the Test Set
No explicit adjudication method is mentioned. For contrived samples with a known composition, formal adjudication by a panel of experts is typically not performed or necessary. The "ground truth" is inherent in the preparation of the samples.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, If So, What Was the Effect Size of How Much Human Readers Improve with AI vs Without AI Assistance
This question is not applicable to this submission. The Xpert vanA test is a qualitative in vitro diagnostic test that uses automated real-time PCR to detect the vanA gene sequence. It is a fully automated system, and human interpretation of results is minimal (typically reading a "detected" or "not detected" output). There is no "AI" or "human reader" component in the diagnostic process that would warrant an MRMC study or an assessment of human reader improvement with AI assistance.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, the performance evaluated here is essentially standalone (algorithm only). The Xpert vanA test is an automated system where sample preparation, amplification, and real-time detection are fully integrated. The "device performance" refers to the automated output of the system.
7. The Type of Ground Truth Used
The ground truth for the verification studies was based on known, contrived samples. For the "contrived positive" samples, the ground truth was the presence of vanA positive Enterococcus faecalis cells. For "negative matrix only" samples, the ground truth was the absence of vanA.
8. The Sample Size for the Training Set
This document does not provide information about a "training set." This submission focuses on verification studies for a modification to a previously cleared device. Diagnostic devices like this typically undergo extensive development and validation, but the details of the initial development (including training sets for algorithms, if any) are not part of this specific 510(k) summary for a modification. The test is based on PCR, not machine learning that would require a distinct "training set."
9. How the Ground Truth for the Training Set Was Established
Since no training set is mentioned or applicable in the context of this PCR-based diagnostic device and modification, how its ground truth was established is not provided in the document.
§ 866.1640 Antimicrobial susceptibility test powder.
(a)
Identification. An antimicrobial susceptibility test powder is a device that consists of an antimicrobial drug powder packaged in vials in specified amounts and intended for use in clinical laboratories for determining in vitro susceptibility of bacterial pathogens to these therapeutic agents. Test results are used to determine the antimicrobial agent of choice in the treatment of bacterial diseases.(b)
Classification. Class II (performance standards).