(147 days)
The VersaTREK® MYCO PZA KIT is used as a rapid qualitative procedure for susceptibility testing of Mycobacterium tuberculosis, from culture to pyrazinamide (PZA). The VersaTREK® MYCO PZA KIT is used with the ESP Culture System II (ESP) and the VersaTREK® Microbial Detection System (VTI).
The VersaTREK® MYCO PZA susceptibility testing kit is used with the VersaTREK MYCO culture bottle and performed on the ESP Culture System II and on the VersaTREK® Microbial Detection System. The MYCO bottles are supplemented with Myco Growth Supplement and VersaTREK® MYCO PZA reagent and prepared with the appropriate dilution of pyrazinamide as the mechanism for performing the susceptibility test.
The VersaTREK® MYCO PZA susceptibility test utilizes a 3 to 15 day testing protocol. A standard suspension of Mycobacterium tuberculosis growth is prepared from a liquid (seed inoculum). 0.5 mL is inoculated into a Growth Control bottle (drug-free), and a bottle containing PZA (both bottles are referred to as an AST set). The test determination is based upon growth of the M. tuberculosis isolate in the Growth Control Bottle compared to the growth in the drug-containing bottle.
At the completion of the PZA susceptibility testing protocol, the determination of susceptible or resistant is performed manually by the user, by comparing the time to detection of the Growth Control Bottle to the PZA test bottle.
Here's an analysis of the acceptance criteria and the study proving the device meets them, based on the provided text:
Acceptance Criteria and Device Performance
| Acceptance Criteria / Performance Aspect | Reported Device Performance |
|---|---|
| Critical PZA Concentration | Set at 300 µg/mL. MIC results for susceptible strains were ≤200 µg/mL. Verification with resistant strains confirmed this cutoff. |
| Lot Reproducibility (Analytical) | 100% for seeded inoculum across 4 well-characterized strains (2 ATCC, 2 CDC), tested in triplicate on 3 separate days with 3 different reagent lots. No difference in results for susceptible strains tested at various concentrations, and all resistant strains remained resistant. 8 lots of PZA, 7 Myco broth, and 6 Myco GS showed acceptable reproducibility. |
| CDC Challenge Panel Testing | 100% overall agreement with BACTEC and expected results for 10 CDC Mycobacterium tuberculosis strains. |
| Equivalence between VersaTREK and ESP Systems | No significant difference in recovery of microorganisms, time to detection, or M. tuberculosis and PZA test results between ESP Culture System II and the VersaTREK Microbial Detection System. |
| Lot Reproducibility (Clinical) | ≥ 95% for seeded inoculum across 2 well-characterized CDC M. tuberculosis strains, using 2 lots each of Myco broth and MYCO GS, tested in triplicate on 3 separate days. |
| Challenge Testing (Clinical) | For 77 valid tests from a 30-organism CDC challenge set (tested at 3 sites), there was an overall agreement of 98.7% with expected results. |
| Clinical Isolate Testing | 88% category agreement for 96 tests performed on samples from seed bottle inoculum. |
Study Details
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A table of acceptance criteria and the reported device performance: (Provided above)
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Sample size used for the test set and the data provenance:
- Analytical Studies:
- Critical Drug Concentration: 6 susceptible wild strains and 4 resistant strains of M. tuberculosis.
- Lot Reproducibility: 4 well-characterized M. tuberculosis strains (2 ATCC, 2 CDC).
- CDC Challenge Panel Testing: 10 strains of Mycobacterium tuberculosis obtained from the Centers for Disease Control (CDC).
- Clinical Studies:
- Lot Reproducibility: 2 well-characterized M. tuberculosis strains from CDC.
- Challenge Testing: 30 organisms from a CDC challenge set, resulting in 77 valid test points.
- Clinical Isolate Testing: A total of 96 tests from seed bottle inoculum.
- Data Provenance: The strains used were from known sources like ATCC and CDC, indicating well-characterized, reference strains. Clinical isolates were collected from 5 geographically diverse clinical sites, including regional reference centers, university- and community-based laboratories, suggesting real-world clinical samples. The study appears to be prospective in nature for the clinical isolate testing as it refers to performing tests on samples.
- Analytical Studies:
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Number of experts used to establish the ground truth for the test set and the qualifications of those experts: The document does not explicitly state the number or qualifications of experts used to establish the ground truth. It refers to "expected results" and comparisons to the predicate device (BACTEC 460TB PZA Kit) and CDC-provided challenge sets, implying that the ground truth for these reference strains and challenge sets was pre-established and widely accepted in the field.
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Adjudication method (e.g. 2+1, 3+1, none) for the test set: The document does not specify an adjudication method. For the "Challenge Testing" in clinical studies, the "expected results" were used as the ground truth.
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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: Not applicable. This device is an in-vitro diagnostic (IVD) kit for antimicrobial susceptibility testing, not an AI-assisted diagnostic tool that involves human readers interpreting images or data. The "user manipulation for reading" is mentioned as "Yes" for the predicate and "No" for the new device in the comparison table, but this refers to the automation of the reading process, not human interpretation improvement.
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If a standalone (i.e. algorithm only without human-in-the-loop performance) was done: The device itself performs the susceptibility testing. The interpretation of the test "is performed manually by the user, by comparing the time to detection of the Growth Control Bottle to the PZA test bottle." This indicates a manual interpretation step. However, the device determines the growth automatically (via pressure sensor). Therefore, while the final call is human-derived, the core measurement is automated, but it's not a standalone "algorithm only" in the sense of a fully automated diagnostic decision.
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The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- For analytical studies and challenge sets, the ground truth was based on known characteristics of reference strains (ATCC, CDC) and comparisons to the established predicate device (BACTEC 460TB PZA Kit), which implicitly relies on previous expert consensus or established laboratory methods.
- For clinical isolate testing, the 'expected results' would likely be derived from a reference method or expert consensus interpretation of growth patterns.
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The sample size for the training set: Not applicable. This document describes performance studies for an IVD kit, not a machine learning model that requires a "training set."
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How the ground truth for the training set was established: Not applicable, as there is no "training set" in the context of device performance studies described here.
§ 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).