(74 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 Penicillin to Pasco panels at concentrations of 8-0.03 mcg/ml for use in determining the susceptibility of non-pneumococcal streptococci.
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 an analysis of the provided text, outlining the acceptance criteria and study details for the Pasco MIC and MIC/ID Panels for Penicillin susceptibility testing:
Acceptance Criteria and Device Performance for Pasco MIC and MIC/ID Panels (Penicillin)
1. Table of Acceptance Criteria and Reported Device Performance
| Parameter | Acceptance Criteria (Implied by FDA & NCCLS) | Reported Device Performance (Penicillin) |
|---|---|---|
| S. pneumoniae | ||
| Essential Agreement (EA) | Acceptable | 99.4% (initial), 100% (retesting) |
| Major (M) Errors | None expected / Acceptable low rate | 0 |
| Very Major (VM) Errors | None expected / Acceptable low rate | 0 |
| Minor Errors | Acceptable low rate | 1 (initial, resolved on retesting) |
| Category Agreement (CA) | 100% | 100% |
| Non-pneumococcal streptococci | ||
| Essential Agreement (EA) | Acceptable | 99.3% |
| Major (M) Errors | None expected / Acceptable low rate | 0 |
| Very Major (VM) Errors | None expected / Acceptable low rate | 0 |
| Minor Errors | Acceptable low rate | 0 (random minor errors noted, but all within EA) |
| Category Agreement (CA) | 100% | 100% |
| Reproducibility | +/- 1 dilution | 100% within +/- 1 dilution |
| QC Endpoints (S. pneumoniae ATCC 49619) | Within recommended NCCLS acceptable range | Within recommended NCCLS acceptable range |
Note: The document states that the results support "Substantial Equivalence as outlined in the FDA draft document 'Review Criteria For Assessment Of Antimicrobial Susceptibility Devices' (May 1991)." This FDA draft likely defines the specific numerical thresholds for "acceptable" EA, M, VM, and minor errors, which are not explicitly provided in the summary but are considered met by the reported performance.
2. Sample Size Used for the Test Set and Data Provenance
- S. pneumoniae: 101 strains
- Non-pneumococcal streptococci: 130 strains
- Reproducibility testing: 12 organisms at each of two sites. (7 organisms had on-scale endpoints).
- Data Provenance:
- Clinical Isolates: Used for comparative testing.
- CDC Challenge Strains: Used for comparative testing.
- The document implies a prospective study design for the comparative testing at two sites, as new test panels were prepared for this purpose. The country of origin is not explicitly stated, but Pasco Laboratories is based in Wheat Ridge, Colorado, USA, suggesting the data is likely from the United States.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document does not explicitly state the number or qualifications of experts used to establish the ground truth. However, the ground truth was established using a "reference panel" and "NCCLS acceptable range" for QC organisms. This implies that the ground truth was based on established microbiological methods and standards, likely interpreted and validated by trained microbiology laboratory personnel.
4. Adjudication Method for the Test Set
The document does not explicitly describe an adjudication method for disagreements in results. The term "Essential Agreement" itself implies a comparison to a reference standard, and errors (major, very major, minor) are noted based on this comparison. For the one minor error in S. pneumoniae, it states "which resolved on retesting," suggesting re-evaluation or confirmation was performed for discrepancy resolution rather than a formal adjudication panel.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, an MRMC comparative effectiveness study was not done. This study is for an antimicrobial susceptibility test panel, which provides quantitative or qualitative measurements directly, rather than relying on human interpretation of images or other subjective data. Therefore, the concept of "human readers improve with AI vs without AI assistance" is not applicable here.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
The device itself is designed as a standalone test. The "observed for visible growth or color changes" and "recorded as the minimum inhibitory concentration (MIC)" sections describe the direct output of the device. While human observation is involved in reading the results, the performance metrics (EA, CA, error rates, reproducibility) are based on the device's ability to produce those results accurately compared to a reference standard, effectively assessing its "standalone" performance.
7. The Type of Ground Truth Used
The primary ground truth used was a reference panel for antimicrobial susceptibility testing. This reference panel would have established MIC values for the tested organisms and antimicrobials using a validated, gold-standard method (e.g., broth microdilution or agar dilution as per NCCLS guidelines). Additionally, CDC challenge strains and QC organism S. pneumoniae ATCC 49619 with known, accepted MIC ranges (NCCLS acceptable range) were used to confirm accuracy and consistency.
8. The Sample Size for the Training Set
The document does not explicitly mention a separate "training set" or its size for the Penicillin component. Since this is an in-vitro diagnostic device for susceptibility testing, the development typically involves extensive work with various strains and antimicrobial concentrations during product formulation and optimization (analogous to training). However, the specific data used to "train" a statistical or machine learning model is not applicable here as it is a panel-based chemical/biological assay. The document focuses on the validation and verification of the panel's performance against established standards.
9. How the Ground Truth for the Training Set Was Established
As noted in point 8, a formal "training set" in the context of AI/ML is not described. The "ground truth" used throughout the product development and validation would have been established by:
- Internal laboratory testing: Using well-characterized strains and standard reference methods (e.g., broth microdilution).
- Adherence to recognized standards: Such as those from the NCCLS (National Committee for Clinical Laboratory Standards), which prescribe methodologies and expected results for quality control organisms.
- Expert microbiological knowledge: To define appropriate concentrations, incubation conditions, and interpretation criteria for the panel.
§ 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).