(37 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 the antimicrobial Moxifloxacin at concentrations of 0.015 - 8 mcg/ml to Pasco Panels. Moxifloxacin has been shown to be active in vitro against most strains of microorganisms listed below, as described in the FDA-approved package insert for this antimicrobic.
Active In Vitro and in Clinical Infectious Against:
Aerobic Gram-positive microorganisms Staphylococcus aureus (methicillin-susceptible strains only)
Aerobic Gram-negative microorganisms Klebsiella pneumoniae
Active In Vitro but their clinical significance is unknown
Aerobic Gram-positive microorganisms Staphylococcus epidermidis (methicillin-susceptible strains only)
Aerobic Gram-negative microorganisms Citrobacter freundii Enterobacter cloacae Escherichia coli Klebsiella oxytoca Proteus mirabilis
Pasco Panels are used for quantitatively measuring the susceptibility of rapidly growing aerobic and facultative anaerobic bacterial pathogens to a batterv of antimicrobial agents and determining the biochemical identification of those organisms. Varying concentrations of antimicrobial agents (usually in two-fold dilutions) are dispensed into the Pasco microdilution 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 for the Pasco MIC and MIC/ID Panels based on the provided 510(k) summary:
1. Table of Acceptance Criteria and Reported Device Performance
| Acceptance Criteria Category | Specific Criteria | Reported Device Performance |
|---|---|---|
| Essential Agreement (EA) | Staphylococci spp.: Not explicitly stated, but inferred to be a high percentage, typically >90% for AST devices. | |
| Enterobacteriaceae: Not explicitly stated, but inferred to be a high percentage, typically >90% for AST devices. | Staphylococci spp.: 100% EA. | |
| Enterobacteriaceae: 99.8% EA. | ||
| Major (M) Errors | Staphylococci spp.: No major errors. | |
| Enterobacteriaceae: No major errors. | Staphylococci spp.: No major (M) errors observed. | |
| Enterobacteriaceae: No major (M) errors observed. | ||
| Very Major (VM) Errors | Staphylococci spp.: No very major errors. | |
| Enterobacteriaceae: No very major errors. | Staphylococci spp.: No very major (VM) errors observed. | |
| Enterobacteriaceae: No very major (VM) errors observed. | ||
| Category Agreement (CA) | Staphylococci spp.: Acceptable (typically >90-95% for AST devices). | |
| Enterobacteriaceae: Acceptable (typically >90-95% for AST devices). | Staphylococci spp.: 98.2% CA. | |
| Enterobacteriaceae: 98.6% CA. | ||
| Minor Discrepancies | Defined as not impacting EA. | Staphylococci spp.: 11 minor discrepancies noted, all within EA. |
| Enterobacteriaceae: 12 random minor discrepancies, all within EA. | ||
| QC Endpoints | Acceptable for NCCLS recommended QC organisms (S. aureus ATCC 29213, E. faecalis ATCC 29212, E. coli ATCC 25922, P. aeruginosa ATCC 27853) using both reference and test methodology. | Acceptable for all tested QC organisms (S. aureus ATCC 29213, E. faecalis ATCC 29212, E. coli ATCC 25922 and P. aeruginosa ATCC 27853) from panels using both the reference and test methodology. |
| Inter-site Reproducibility | High percentage, inferred to be close to 100%. | 99%. |
| Intra-site Reproducibility | High percentage, inferred to be close to 100%. | 100% for 1 site, 99% for another, and 98% for the third site. |
2. Sample Size and Data Provenance
- Test Set Sample Size:
- Staphylococci spp.: 410 (challenge and clinical isolates)
- Enterobacteriaceae: 574 (challenge and clinical isolates)
- Reproducibility testing: 10 organisms at each of the three sites, tested on three separate days in triplicate.
- QC organisms: S. aureus ATCC 29213, E. faecalis ATCC 29212, E. coli ATCC 25922, and P. aeruginosa ATCC 27853.
- Data Provenance: The document states "Challenge strains, fresh clinical isolates, stock clinical isolates and QC strains were tested concurrently." It does not specify the country of origin, but given the FDA 510(k) submission, it's highly likely to be U.S.-based or from regions with comparable clinical practices. It implies a mix of prospective (fresh clinical isolates) and retrospective (stock clinical isolates, challenge strains) data for the performance evaluation.
3. Number of Experts and Qualifications for Ground Truth
The document does not explicitly state the number of experts or their qualifications used to establish the ground truth. For Antimicrobial Susceptibility Testing (AST) devices, the "reference methodology" (e.g., broth microdilution or agar dilution as defined by CLSI/NCCLS standards) is typically considered the ground truth, and its results are interpreted by trained laboratory personnel, not necessarily "experts" in the context of a panel review.
4. Adjudication Method for the Test Set
No explicit adjudication method (like 2+1, 3+1) is mentioned. For AST devices, the ground truth is established by the reference method, and the test device's results are compared directly to this reference. Discrepancies are categorized (major, very major, minor) based on established criteria for AST performance studies.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No MRMC comparative effectiveness study was done, nor is it applicable in this context. This device is an automated or semi-automated diagnostic test (Antimicrobial Susceptibility Test panel), not an imaging or interpretation aid for human readers. Therefore, the concept of "how much human readers improve with AI vs without AI assistance" does not apply.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study
Yes, a standalone performance study was clearly done. The Pasco MIC and MIC/ID Panels are designed to provide quantitative or qualitative antimicrobial susceptibility results directly. The "Pasco methodology" results were compared directly against "reference methodology," demonstrating its performance in isolation, without human intervention for result interpretation beyond reading the panel itself.
7. Type of Ground Truth Used
The ground truth was established using reference methodology, specifically comparing results from the Pasco panels with those obtained through a recognized "reference methodology" for antimicrobial susceptibility testing. This reference method is the accepted standard against which new AST devices are evaluated.
8. Sample Size for the Training Set
The document does not specify a separate "training set" or its size. In the context of a 510(k) for an AST panel, manufacturers develop the panel and its interpretation criteria. The provided data (challenge, clinical, and QC strains) is the "test set" used to demonstrate performance against the reference method for regulatory clearance. It's not a machine learning model that requires a distinct training and testing set in the same way an AI algorithm would.
9. How the Ground Truth for the Training Set Was Established
As there's no explicitly defined "training set" for an AI model, this question is not fully applicable. However, the methods used to establish ground truth for the performance evaluation were "reference methodology," meaning established, standard laboratory procedures for determining antimicrobial susceptibility, such as broth microdilution, which yield the Minimum Inhibitory Concentration (MIC) values considered the gold standard.
§ 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).