(82 days)
PASCO MIC AND MIC/ID PANELS are used for quantitatively measuring (with the exception of the Breakpoint/ID panel which provides qualitative measurement or category results) the susceptibility of rapidly growing aerobic and facultative anaerobic bacterial pathogens to a battery of antimicrobial agents and determining the biochemical identification of those organisms.
This 510(k) notification is for the addition of Quinupristin/Dalfopristin to Pasco panels at concentrations of 8-0.03 mcg/ml for use in determining the susceptibility of Streptococcus pyogenes and Streptococcus agalactiae.
Varying concentrations of antimicrobial agents (usually in two-fold dilutions) are dispensed into the Pasco panels and the panels are then frozen. Panels are thawed prior to use, inoculated with the test organisms, incubated the traditional 16-24 hours and panels are then observed for visible growth or color changes as described in the package insert. The lowest concentration of each antimicrobial agent with no apparent visible growth of the test organism is recorded as the minimum inhibitory concentration (MIC). Changes in pH and production of specific metabolites from growth in biochemical substrates are interpreted as described in the package insert for conventional tubed media.
Here's a breakdown of the acceptance criteria and study details based on the provided document:
Acceptance Criteria and Reported Device Performance
| Acceptance Criteria | Reported Device Performance (S. pneumoniae, N=101) | Reported Device Performance (Non-pneumococcal, N=130) |
|---|---|---|
| Acceptable Essential Agreement (EA) | Initial: 93.6% | |
| Retesting: 94.8% | 98.5% | |
| Major (M), Very Major (VM) or Minor Errors | No major (M), very major (VM) or minor errors observed | No major (M), very major (VM) or minor errors observed |
| Category Agreement (CA) | 100% (with 1 additional random minor error) | 100% (with 16 random minor errors, all within EA) |
| QC Endpoints for S. pneumoniae ATCC 49619 | Within recommended NCCLS acceptable range (with 2 exceptions acceptable in subsequent testing) | N/A (specific to S. pneumoniae) |
| Reproducibility (within ± 1 dilution) | 100% (for 12 organisms with on-scale endpoints) | 100% (for 12 organisms with on-scale endpoints at each site) |
Note: The document explicitly states that the results "supports Substantial Equivalence as outlined in the FDA draft document 'Review Criteria For Assessment Of Antimicrobial Susceptibility Devices' (May 1991)." This implies the reported device performance met or exceeded the criteria outlined in that FDA document.
Study Details
2. Sample sizes used for the test set and the data provenance:
- Test Set (S. pneumoniae strains): 101 strains
- Test Set (Non-pneumococcal strains): 130 strains
- Data Provenance: The document states "Comparative testing of the Pasco test panel to a reference panel was performed at two sites using CDC challenge strains and clinical isolates." This indicates the data is from multiple sites, includes both CDC challenge strains (likely standardized, external controls) and clinical isolates (real-world patient samples), making it a prospective study in the sense that these specific tests were conducted for this submission. The country of origin is not explicitly stated, but given the FDA submission, it's highly probable to be the United States.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- The document does not specify the number of experts or their qualifications for establishing the ground truth. It mentions "a reference panel" for comparative testing, implying an established method or standard against which the Pasco panel was compared. This "reference panel" itself would have an established ground truth, likely based on standard microbiological techniques and expert interpretation.
4. Adjudication method for the test set:
- The document does not explicitly state an adjudication method (e.g., 2+1, 3+1). The "reference panel" comparison suggests that the standard method's results served as the reference for determining essential agreement and errors. This implies a direct comparison rather than a separate expert adjudication process for the test results.
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:
- No. This study is for an Antimicrobial Susceptibility Test (AST) panel, not an AI-assisted diagnostic imaging or interpretation device. Therefore, an MRMC comparative effectiveness study involving human readers and AI assistance is not applicable to this device type. The device provides a quantitative or qualitative measurement of susceptibility, not an image or signal for human interpretation.
6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- Yes, in essence. The Pasco MIC and MIC/ID Panels are designed to provide direct measurements of antimicrobial susceptibility. While humans observe visible growth or color changes, the interpretation rules for MIC determination and biochemical identification are predefined in the package insert. The "algorithm" here is the established protocol for interpreting the panel results (e.g., "The lowest concentration of each antimicrobial agent with no apparent visible growth of the test organism is recorded as the minimum inhibitory concentration (MIC)"). The performance metrics (EA, CA, error rates, reproducibility) are based on the panel's ability to produce these results accurately, independent of user-to-user variability in interpretation beyond following the stated protocol.
7. The type of ground truth used:
- The ground truth was established by a reference panel to which the Pasco panel was compared. This reference panel represents expert consensus on standard microbiological methods for determining minimum inhibitory concentrations and biochemical identification. These reference methods are typically well-validated and widely accepted within microbiology.
8. The sample size for the training set:
- The document does not explicitly mention a "training set" in the context of device development. This is typical for AST panels, which are wet laboratory assays rather than machine learning models. The development process involves chemical and biological optimization, not algorithm training on data in the conventional sense. The "training" would be the initial R&D and optimization of the panel's reagents and concentrations.
9. How the ground truth for the training set was established:
- As there's no explicitly defined "training set" as understood in machine learning, there's no ground truth established in that manner. The development and optimization of the Pasco panels would have relied on established microbiological principles and validated reference methods to achieve accurate and reproducible results for antimicrobial susceptibility testing.
§ 866.1620 Antimicrobial susceptibility test disc.
(a)
Identification. An antimicrobial susceptibility test disc is a device that consists of antimicrobic-impregnated paper discs used to measure by a disc-agar diffusion technique or a disc-broth elution technique the in vitro susceptibility of most clinically important bacterial pathogens to antimicrobial agents. In the disc-agar diffusion technique, bacterial susceptibility is ascertained by directly measuring the magnitude of a zone of bacterial inhibition around the disc on an agar surface. The disc-broth elution technique is associated with an automated rapid susceptibility test system and employs a fluid medium in which susceptibility is ascertained by photometrically measuring changes in bacterial growth resulting when antimicrobial material is eluted from the disc into the fluid medium. Test results are used to determine the antimicrobial agent of choice in the treatment of bacterial diseases.(b)
Classification. Class II (performance standards).