(23 days)
The Xpert® MRSA/SA Skin and Soft Tissue Infection test (Xpert MRSA/SA SSTI test) performed on the GeneXpert® Instrument Systems is a qualitative in vitro diagnostic test intended for the detection of Staphylococcus aureus (SA) and methicillin-resistant Staphylococcus aureus (MRSA) from skin and soft tissue infection swabs. The test utilizes automated real-time polymerase chain reaction (PCR) to detect MRSA/SA DNA. The Xpert MRSA/SA SSTI test is indicated for use in conjunction with other laboratory tests, such as microbiology culture, and clinical data available to the clinician as an aid in the detection of MRSA/SA from skin and soft tissue infections. The Xpert MRSA/SA SSTI test is not intended to monitor treatment for MRSA/SA infections. Concomitant cultures for SA and MRSA are necessary to recover organisms for susceptibility testing or epidemiological typing. In a mixed culture containing MRSA/SA and other organisms (e.g., Gram-negative bacilli, yeast), results can be false negative or variable depending on the concentration of MRSA/SA present, particularly if the concentration of MRSA/SA is close to the limit of detection (LoD) of the test.
The Xpert MRSA/SA SSTI (Xpert MRSA/SA Skin and Soft Tissue Infection) test is an automated in vitro diagnostic DNA test for the qualitative, simultaneous detection of Staphylococcus aureus (SA) and methicillin-resistant Staphylococcus aureus (MRSA) directly from skin and soft tissue specimen swabs. The specimen is collected on a double swab, one of which is placed in a tube containing elution reagent. Following brief vortexing, the eluted material is transferred to a different, uniquely labeled sample chamber of a disposable fluidic cartridge (the Xpert MRSA/SA SSTI cartridge).
The test is performed on the GeneXpert® Instrument Systems (comprised of the GeneXpert® Dx System, GeneXpert® System with Touchscreen, and GeneXpert® Infinity System). In the GeneXpert® Instrument Systems, sample preparation, amplification, and real-time detection are all fully automated and completely integrated. The platform requires 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 user initiates a test from the system user interface of the GeneXpert® Instrument Systems platform and places the cartridge with sample into a GeneXpert® instrument system which performs hands-off real-time, multiplex polymerase chain reaction (PCR) for detection of SA and MRSA DNA.
Depending upon the specific instrument, a GeneXpert® instrument system may contain 1–80 modules, each 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 ICORE® thermocycler for performing real-time PCR and detection.
The Xpert MRSA/SA SSTI test kit includes reagents for the simultaneous detection of the target organisms, SA and MRSA. The primers and probes in the Xpert MRSA/SA SSTI test detect nucleic acid sequences of the staphylococcal protein A (spa), the gene for methicillin/oxacillin resistance (mecA), and staphylococcal cassette chromosome (SCCmec) inserted in the SA chromosomal attB site.
The test includes a 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 MRSA/SA SSTI test performed on the GeneXpert® Instrument Systems provides results in approximately 62 minutes.
The provided text is a 510(k) summary for a medical device called Xpert MRSA/SA SSTI. It describes a diagnostic test for Staphylococcus aureus (SA) and methicillin-resistant Staphylococcus aureus (MRSA) from skin and soft tissue infection swabs, performed on the GeneXpert Instrument Systems.
The document does not contain information about the design of a study to prove acceptance criteria using a test set of data with expert ground truth, human reader performance, or multi-reader multi-case studies.
Instead, it details a Special 510(k) submission to modify an already cleared and legally marketed device (Xpert MRSA/SA SSTI, K080837). The specific modification is to include the GeneXpert® Infinity System instruments as a compatible platform for the test.
Therefore, the performance data presented is focused on demonstrating that the performance of the test on the new instrument platform (GeneXpert Infinity) is equivalent to its performance on previously cleared platforms (GeneXpert Dx System, GeneXpert System with Touchscreen). This is a bridging study rather than a primary clinical validation or an AI performance study as implied by many of the questions.
Given this, I cannot answer all your questions as the relevant information is not in the provided text. However, I will answer what is available and clarify what is missing.
Acceptance Criteria and Reported Device Performance
The acceptance criteria here refer to demonstrating equivalent performance of the Xpert MRSA/SA SSTI test when run on the new GeneXpert Infinity System compared to the previously cleared GeneXpert Dx System.
| Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|
| Functional Equivalence: The test should perform equivalently on the new GeneXpert Infinity System as on the predicate GeneXpert Dx System, maintaining the ability to detect MRSA/SA. | Functional Testing: Conducted using both contrived positive (MRSA cells added to negative matrix) and negative (negative matrix only) samples. Each target of the Xpert MRSA/SA SSTI test was analyzed, resulting in a reportable outcome. Study Results: Showed 100% agreement of reportable results, with no statistically significant differences in Ct values observed between assay runs in instruments of the GeneXpert® Dx System and GeneXpert® Infinity System. This demonstrated equivalent performance. |
| Operational Stability/Hold Time: The maximum acceptable hold time for a prepared cartridge should be verified on the new system. | Prepared Cartridge Hold Time Study: The maximum acceptable hold time for a prepared cartridge was verified as 4 hours. |
| No impact on performance claims: The modifications should not negatively impact the existing performance claims of the Xpert MRSA/SA SSTI test. | Overall Assessment: The assessment of the results from these studies determined that the performance claims of the Xpert MRSA/SA SSTI test were not impacted by the modifications made to the predicate device. |
Study Details (Based on available information)
-
Sample size used for the test set and the data provenance:
- The document mentions "contrived positive (MRSA cells added to negative matrix) and negative (negative matrix only) samples" for functional testing. It does not provide the specific number of samples (sample size) used in these studies.
- Data Provenance: The data appears to be prospective as it's generated from specific verification studies ("prepared cartridge hold time study and functional testing") conducted for this 510(k) submission. The country of origin is not specified but implicitly North American given the FDA submission.
-
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- This is a molecular diagnostic test, not an AI image analysis device. The "ground truth" for the functional testing would be the known concentration/presence of MRSA/SA cells in the contrived samples. This is established by the assay design and sample preparation, not by expert interpretation.
- Therefore, this question does not apply to the type of study described.
-
Adjudication method (e.g. 2+1, 3+1, none) for the test set:
- Not applicable. This relates to expert consensus in interpreting complex data, which is not the ground truth methodology for this type of molecular test. The measurements (Ct values, presence/absence of signal) are quantitative and objective.
-
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:
- No, an MRMC study was not done. This is a diagnostic device for detecting specific DNA sequences, not an AI-powered device assisting human readers.
-
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- The device itself (Xpert MRSA/SA SSTI test on the GeneXpert Instrument Systems) is a standalone automated diagnostic test. Its "performance" is the detection of specific DNA sequences. The studies assess the instrument's ability to run the test and yield equivalent results. The "functional testing" mentioned is effectively the standalone performance of the assay on the new instrument.
-
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- The ground truth for the functional testing was contrived samples with known positive and negative status (e.g., negative matrix, or MRSA cells added to negative matrix where the concentration of MRSA/SA is known). This allows for direct assessment of sensitivity and specificity against a known standard.
-
The sample size for the training set:
- This device is based on real-time PCR technology, not machine learning that requires a "training set" in the conventional sense. The test's probes and primers are designed based on biological knowledge of the target sequences.
- Therefore, this question does not apply.
-
How the ground truth for the training set was established:
- Not applicable, as there is no traditional "training set" for this type of diagnostic device.
§ 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).