(70 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 Cefuroxime to Pasco panels at concentrations of 0.03-4 mcg/ml for use in determining the susceptibility of S. pneumoniae and 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.
Acceptance Criteria and Device Performance Study for Pasco MIC and MIC/ID Panels (Cefuroxime)
This document describes the acceptance criteria and the study that demonstrates the Pasco MIC and MIC/ID Panels, specifically with the addition of Cefuroxime, meet these criteria for antimicrobial susceptibility testing.
1. Table of Acceptance Criteria and Reported Device Performance
| Parameter | Acceptance Criteria (Implied) | Reported Device Performance (S. pneumoniae) | Reported Device Performance (Non-pneumococcal strains) |
|---|---|---|---|
| Essential Agreement (EA) | Acceptable Agreement | 100% | 100% |
| Major (M) Errors | No major errors observed | 0 | 0 |
| Very Major (VM) Errors | No very major errors observed | 0 | 0 |
| Minor Errors | Minimal sporadic errors | 1 random minor error | 1 random minor error |
| Category Agreement (CA) | Acceptable Agreement | 100% (within EA despite 1 minor error) | 100% (within EA despite 1 minor error) |
| QC Endpoints (S. pneumoniae ATCC 49619) | Within recommended NCCLS acceptable range | Within recommended NCCLS acceptable range | N/A (specific to S. pneumoniae) |
| Reproducibility | 100% within +/- 1 dilution | 100% within +/- 1 dilution (for 6 on-scale organisms) | 100% within +/- 1 dilution (for 6 on-scale organisms) |
Note: The acceptance criteria for essential agreement, categorical agreement, and error rates are implied by the statement "demonstrated acceptable Essential Agreement (EA)" and the reporting of specific percentages and zero errors. The reference to the "FDA draft document 'Review Criteria For Assessment Of Antimicrobial Susceptibility Devices' (May 1991)" suggests these criteria are aligned with regulatory guidance at the time.
2. Sample Size Used for the Test Set and Data Provenance
- S. pneumoniae strains: 101
- Non-pneumococcal strains: 130
- QC organism: S. pneumoniae ATCC 49619
- Reproducibility organisms: 12 organisms
- Data Provenance: The study used "CDC challenge strains and clinical isolates." This indicates a mix of well-characterized reference strains and samples collected from clinical settings. The study was conducted at "two sites." The information does not explicitly state the country of origin, but given the FDA submission, it is highly likely to be US-centric. The data is prospective as it describes the testing performed for the 510(k) submission.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
The document does not explicitly state the number of experts used to establish the ground truth or their specific qualifications (e.g., "Radiologist with 10 years of experience"). However, for antimicrobial susceptibility testing, the reference panel itself serves as the ground truth, and its results are established by trained microbiologists following standardized laboratory procedures. The "reference panel" is a recognized and validated method.
4. Adjudication Method
The document does not describe an explicit "adjudication method" in the context of resolving discrepancies between multiple readers or experts. In this type of in vitro diagnostic study, the comparison is made between the test device's results and a pre-established "reference panel" result. Discrepancies would typically be analyzed against the established reference, not through an adjudication process among multiple primary readers of the test device.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, a multi-reader multi-case (MRMC) comparative effectiveness study was not performed as described. This type of study is more common in diagnostic imaging where multiple human readers interpret cases with and without AI assistance. This study focuses on the performance of an in vitro diagnostic device (antimicrobial susceptibility panel) against a reference method.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study
Yes, a standalone study was performed. The "Pasco MIC and MIC/ID Panels" are automated or semi-automated systems that provide quantitative MIC values and/or categorical interpretations based on microbial growth. The study directly assesses the performance of these panels (the "device") against a reference standard. While human observation is required to read the results (e.g., "observed for visible growth or color changes"), the performance metrics (Essential Agreement, Category Agreement, error rates) reflect the device's ability to produce results comparable to the reference, independent of human interpretation variability once the basic reading method is followed.
7. Type of Ground Truth Used
The primary ground truth used was a reference panel. The "Comparative testing of the Pasco test panel to a reference panel was performed at two sites." This reference panel would typically be a highly standardized and validated method for determining antimicrobial susceptibility, such as broth microdilution or agar dilution as outlined by organizations like the Clinical and Laboratory Standards Institute (CLSI) or similar national/international standards. The "CDC challenge strains" further support the use of well-characterized isolates for validation.
8. Sample Size for the Training Set
The document does not explicitly mention a separate "training set" or its sample size. This is typical for a traditional in vitro diagnostic device that doesn't utilize machine learning models. The device's "training" in this context is the manufacturing process, quality control, and pre-validation efforts to ensure reliable performance across a range of antimicrobials and organisms, rather than an algorithmic training phase on a dataset.
9. How the Ground Truth for the Training Set Was Established
As there is no explicit "training set" for a machine learning algorithm as described in this submission, the concept of establishing ground truth for a training set is not directly applicable. The "ground truth" for the device's development and validation (its underlying mechanism) comes from established microbiological principles of antimicrobial susceptibility testing, which are validated through the performance studies (as described above) against recognized reference methods and established QC organisms.
§ 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).