(43 days)
The MicroScan® Synergies plus™ Gram-Positive MIC/Combo Panel is used to determine quantitative and/or qualitative antimicrobial agent susceptibility of colonies grown on solid media of rapidly growing aerobic and facultative anaerobic gram-positive staphylococci and enterococci. After inoculation, panels are incubated for 4.5 - 18 hours at 35℃ +/- 1℃, in a WalkAway® SI, or equivalent, and read by the MicroScan® Instrumentation. Additionally, the panels may be incubated in a non-CO, incubator and the Antimicrobial Susceptibility Testing (AST) portions can be read visually, according to the Package Insert.
This particular submission is for the addition of the antimicrobial vancomycin, at concentrations of 0.25 to 64 µg/ml, to the test panel.
The gram-positive organisms which may be used for vancomycin susceptibility testing in this panel are:
- Enterococcus spp. (e.g., Enterococcus faecalis)
- Staphylococcus spp.
- Staphylococcus aureus (including methicillin-resistant strains)
- Staphylococcus epidermidis (including methicillin-resistant strains)
MicroScan® Synergies plus Gram-Positive MIC/Combo Panels, utilizing both the MicroScan® Rapid Fluorogenic Identification and Dried Overnight Antimicrobial Susceptibility Testing (AST) technologies, are designed for use in determining quantitative and/or qualitative antimicrobial agent susceptibility of colonies grown on solid media of rapidly growing aerobic and facultative anaerobic gram-positive staphylococci and enterococci.
The antimicrobial susceptibility tests are miniaturizations of the broth dilution susceptibility test that have been diluted in water and dehydrated. Various antimicrobial agents are diluted in water, buffer, or minute concentrations of broth, to concentrations bridging the range of clinical interest. Panels are rehydrated with Synergies plus™ Pos Broth, after inoculation with a standardized suspension of the organism. After incubation in the WalkAway® SJ System, or equivalent, for 4.5 - 18 hours, the minimum inhibitory concentration (MIC) for the test organism is read by determining the lowest antimicrobial concentration showing inhibition of growth.
Here's a breakdown of the acceptance criteria and study details for the MicroScan® Synergies plus™ Gram-Positive MIC/Combo Panels with vancomycin:
Description of the Acceptance Criteria and Study to Prove Device Meets Acceptance Criteria
The MicroScan® Synergies plus™ Gram-Positive MIC/Combo Panels with vancomycin are designed to determine the antimicrobial agent susceptibility of gram-positive staphylococci and enterococci using a microdilution minimum inhibitory concentration (MIC) method. The device's performance was evaluated against a frozen Reference Panel, as per FDA's "Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems."
1. Table of Acceptance Criteria and the Reported Device Performance
| Acceptance Criteria Category | Specific Metric | Acceptance Criterion | Reported Device Performance |
|---|---|---|---|
| Overall Performance | Essential Agreement | >97% | >97% for vancomycin |
| Reproducibility | Reproducibility & Precision | Acceptable | Acceptable |
| Quality Control | QC Results | Acceptable | Acceptable |
Note: The document explicitly states the overall Essential Agreement, reproducibility, and quality control. Specific numerical thresholds for "acceptable" reproducibility and QC are not provided in this summary but are generally defined in the referenced FDA guidance document.
2. Sample Size Used for the Test Set and the Data Provenance
- Test Set Sample Size for Efficacy (Rapid Read Method): 507 isolates.
- Provenance: The study used "fresh and stock Efficacy isolates and stock Challenge strains." The specific country of origin is not specified but it's an "external evaluation," implying data collected outside of the manufacturing site, most likely within the US given the FDA submission. The nature of "fresh" and "stock" isolates indicates a mix of prospectively collected and potentially retrospectively stored (stock) samples.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
- This information is not provided in the summary. For AST panels, the "ground truth" is typically established by comparative testing against a recognized reference method (e.g., broth microdilution or agar dilution as per CLSI guidelines), often performed by trained microbiologists. The "Expected Results" for challenge strains would have been determined using such reference methods.
4. Adjudication Method for the Test Set
- This information is not provided. In AST studies, direct adjudication of results in the traditional sense (like in image reading) is less common. Instead, the comparison is directly between the device's MIC determination and the reference method's MIC, and agreements/disagreements are categorized based on defined criteria (Essential Agreement, Categorical Agreement).
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, and the effect size of how much human readers improve with AI vs without AI assistance.
- No. This type of study (MRMC, AI assistance) is not applicable to this device. This device is an automated antimicrobial susceptibility test system, not an AI-assisted diagnostic imaging or interpretation tool for human readers.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done.
- Yes, indirectly. The "Rapid read method" describes the automated instrumental reading of the panels. The performance claims are based on this automated rapid read. While human involvement is required for initial inoculum preparation and loading, the reading and interpretation for performance claims are automated. The summary also notes that "Overnight Instrument and Manual read method(s) Essential Agreement & Categorical Agreement percentages were of equal, or greater, values than the Rapid read method," indicating other reading methods were also assessed, but the primary claims are based on the automated rapid read.
7. The Type of Ground Truth Used
- Reference Panel: The ground truth was established using a frozen Reference Panel. This reference panel serves as the gold standard for comparison, with results typically derived from established reference methods for antimicrobial susceptibility testing (e.g., broth microdilution methods conforming to CLSI standards). For "Challenge strains," the ground truth was "Expected Results determined prior to the evaluation," which would have been established by similar reference methods.
8. The Sample Size for the Training Set
- This information is not provided in the summary. For AST devices, there isn't typically a "training set" in the machine learning sense, as the device operates based on predefined biochemical reactions and algorithms rather than learning from data in a training phase. The "efficacy isolates" and "challenge strains" are primarily for validation/testing.
9. How the Ground Truth for the Training Set Was Established
- As a "training set" in the machine learning context is not applicable, the method for establishing ground truth for a training set is not relevant here. The ground truth for the evaluation was established using a frozen Reference Panel and pre-determined expected results for challenge strains, which are standard reference methods for AST.
§ 866.1645 Fully automated short-term incubation cycle antimicrobial susceptibility system.
(a)
Identification. A fully automated short-term incubation cycle antimicrobial susceptibility system is a device that incorporates concentrations of antimicrobial agents into a system for the purpose of determining in vitro susceptibility of bacterial pathogens isolated from clinical specimens. Test results obtained from short-term (less than 16 hours) incubation are used to determine the antimicrobial agent of choice to treat bacterial diseases.(b)
Classification. Class II (special controls). The special control for this device is FDA's guidance document entitled “Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA.”