(35 days)
Pasco MIC and MIC/ID panels are used for quantitatively measuring (with the exception of the Breakpoint/ID panel which provides qualitative measurement of 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 Minocycline to Pasco panels at concentrations of 0.03 to 32 mcg/ml for use in determining the susceptibility of Staphylococcus aureus, Acinetobacter spp., Enterobacter aerogenes, Escherchia coli, Klebsiella spp.and Shigella spp. "Clinical testing of S.pneumoniae with Minocycline has not been performed with the Pasco system".
Varying concentrations of antimicrobial agents (usually in twofold 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 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.
The provided 510(k) summary describes the acceptance criteria and the study conducted for the Pasco MIC and MIC/ID Panels with the inclusion of Minocycline.
Here's a breakdown of the requested information:
1. Acceptance Criteria and Reported Device Performance
| Acceptance Criteria (Target for Substantial Equivalence) | Reported Device Performance (Minocycline on Pasco Panels) |
|---|---|
| Acceptable Essential Agreement (EA) | Gram-negative strains: 99.8% (initial), 100% (retesting) |
| No Major (M) errors observed | Gram-negative strains: No Major errors |
| No Very Major (VM) errors observed | Gram-negative strains: No Very Major errors |
| Acceptable Category Agreement (CA) | Gram-negative strains: 100% (21 random minor errors noted) |
| Acceptable Essential Agreement (EA) | Gram-positive strains: 100% |
| No Major (M) errors observed | Gram-positive strains: No Major errors |
| No Very Major (VM) errors observed | Gram-positive strains: No Very Major errors |
| Acceptable Category Agreement (CA) | Gram-positive strains: 100% (6 random minor errors noted) |
| QC endpoints within recommended ranges (product info & NCCLS) | All QC endpoints within recommended ranges, except 7 within 1 dilution of the mode. |
| Reproducibility within acceptable +/- 1 dilution | 99.5% within acceptable +/- 1 dilution |
Note: The document references the "FDA draft document 'Review Criteria For Assessment Of Antimicrobial Susceptibility Devices' (May 1991)" as the basis for these acceptance criteria.
2. Sample Size and Data Provenance
- Test Set Sample Size:
- 334 gram-negative strains
- An unspecified number of gram-positive strains (the document states "Test results of the gram-positive Strains demonstrated acceptable Essential Agreement (EA) of 100%," but a specific number is not provided, though it implies a distinct set from the gram-negative strains).
- 12 organisms for reproducibility testing (at each of two sites, totaling 24 independent tests).
- Data Provenance: Not explicitly stated in terms of country of origin. The study was performed at "two sites." The data is prospective as it involves comparative testing of newly prepared Minocycline panels against a reference panel. It also used "CDC challenge strains and clinical isolates," indicating a mix of standardized and real-world samples.
3. Number of Experts and Their Qualifications for Ground Truth
- This type of study (comparative testing of antimicrobial susceptibility panels) typically does not involve human expert interpretation in the same way as, for example, image analysis. The "ground truth" here is established by the results from a "reference panel."
- Therefore, there's no mention of experts establishing ground truth in the traditional sense for the test set. The reference panel itself serves as the gold standard.
4. Adjudication Method for the Test Set
- None specified in the context of expert adjudication. The comparison is directly between the Pasco test panel and a "reference panel." Discrepancies (Minor, Major, Very Major errors) are reported based on direct comparison to the reference, not expert reconciliation.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No, an MRMC comparative effectiveness study was not conducted. This type of study is relevant for evaluating the impact of AI on human reader performance, which is not applicable to the assessment of an antimicrobial susceptibility test panel.
6. Standalone Performance
- Yes, a standalone performance evaluation was done. The entire study describes the performance of the Pasco MIC and MIC/ID panel (the device) in determining antimicrobial susceptibility on its own, compared to a reference standard. The reported Essential Agreement, Category Agreement, and error rates are measures of its standalone diagnostic accuracy. There is no human-in-the-loop component described for these performance metrics.
7. Type of Ground Truth Used
- The ground truth used was established by a "reference panel." This is a well-accepted methodology in microbiology for validating new antimicrobial susceptibility testing devices, where a validated, often manual or established automated, method serves as the gold standard. The document also mentions "CDC challenge strains," indicating the use of well-characterized reference strains with known susceptibility profiles.
8. Sample Size for the Training Set
- The document does not specify a training set sample size. This is because the device described is a physical diagnostic panel that relies on bacterial growth/inhibition and biochemical reactions, not a machine learning algorithm that requires a separate training phase. The manufacturing procedures and panel design are based on established microbiological principles, not data-driven model training.
9. How Ground Truth for the Training Set Was Established
- As there is no "training set" in the context of machine learning, this question is not applicable. The underlying principles of antimicrobial susceptibility testing (e.g., minimum inhibitory concentration definitions, biochemical reactions) are well-established "ground facts" in microbiology, upon which the device's design and interpretation rules are built. The manufacturing procedures are "routine," implying they are based on these established principles.
§ 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).