(57 days)
To determine bacterial antimicrobial agent susceptibility. The MicroScan® MICroSTREP plus™ Panel is used to determine quantitative and/or qualitative antimicrobial agent susceptibility of colonies grown on solid media of aerobic streptococci, including Streptococcus pneumoniae. After inoculation, panels are incubated for 20 - 24 hours at 35℃ +/- 1℃ in a non-CO2 incubator, and read visually according to the Package Insert. This particular submission is for the addition of the antimicrobial Cefuroxime at concentrations of 0.12 to 8 mcg/ml to the test panel. The organisms which may be used for Cefuroxime susceptibility testing in this panel are: Streptococcus pneumoniae.
The MicroScan® MICroSTREP plus™ Panel is used to determine quantitative and/or qualitative antimicrobial agent susceptibility of colonies grown on solid media of aerobic streptococci, including Streptococcus pneumoniae. After inoculation, panels are incubated for 20 - 24 hours at 35°C +/- 1°C in a non-CO2 incubator, and read visually according to the Package Insert. The antimicrobial susceptibility tests are miniaturizations of the broth dilution susceptibility test. 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 115 ul Mueller-Hinton broth supplemented with 2-5% lysed horse blood (LHB) and buffered with 50 mM HEPES, after inoculation of the broth with a standardized suspension of the organism in saline. After incubation in a non-CO2 incubator for 20-24 hours, the minimum inhibitory concentration (MIC) for the test organism is manually read by observing the lowest antimicrobial concentration showing inhibition of growth.
Here's an analysis of the acceptance criteria and study detailed in the provided document:
Acceptance Criteria and Device Performance Study
The MicroScan® MICroSTREP plus™ Panel with Cefuroxime is designed to determine the minimum inhibitory concentration (MIC) of Cefuroxime for Streptococcus pneumoniae. The primary study to demonstrate substantial equivalence compared the device's performance to an NCCLS frozen Reference Panel.
1. Table of Acceptance Criteria and Reported Device Performance
| Criteria Category | Acceptance Criteria (from FDA DRAFT "Guidance on Review Criteria for Assessment of Antimicrobial Susceptibility Devices") | Reported Device Performance (MicroScan® MICroSTREP plus™ Panel with Cefuroxime) |
|---|---|---|
| Overall Essential Agreement | Not explicitly stated in the provided text but implied to be high for substantial equivalence. | >99% for Cefuroxime when compared with the frozen Reference panel. |
| Reproducibility | Acceptable reproducibility and precision | Demonstrated acceptable reproducibility and precision with Cefuroxime. |
| Quality Control Testing | Acceptable results | Demonstrated acceptable results for Cefuroxime. |
Note: The specific numerical acceptance criteria for essential agreement, reproducibility, and quality control are not detailed in the provided text. The document states "acceptable performance" and "acceptable reproducibility/results" without numerical thresholds other than the Essential Agreement percentage.
2. Sample Size and Data Provenance
- Test Set Sample Size:
- The document refers to "fresh and stock Efficacy isolates and stock Challenge strains" for the external evaluation. However, the specific number of isolates/strains used is not provided in the summary.
- Data Provenance: The document does not explicitly state the country of origin. The test isolates included "fresh and stock Efficacy isolates and stock Challenge strains." It is implied that these were clinical isolates and standardized challenge strains, respectively. The study design was a prospective comparison against a reference standard.
3. Number of Experts and Qualifications for Ground Truth
- The document does not specify the number or qualifications of experts used to establish the ground truth. The ground truth (reference MIC values) was established using an NCCLS frozen Reference Panel. This implies that the reference panel itself underwent rigorous characterization, likely involving expert consensus and standardized protocols, but the details are not described in this submission. The device is read "visually" by a human, but this is the device's output, not the ground truth establishment.
4. Adjudication Method
- The document does not describe an adjudication method (e.g., 2+1, 3+1). The performance was compared directly to an NCCLS frozen Reference Panel, which serves as the established ground truth. Discrepancies between the device and the reference panel would traditionally be analyzed, but no specific adjudication process for these discrepancies is mentioned.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No MRMC comparative effectiveness study was done comparing human reader performance with and without AI assistance (or device assistance in this context). This device is a diagnostic panel that is read visually by a human. The study focuses on the accuracy of the panel itself in providing the MIC value compared to a reference method, not on the improvement of a human reader's diagnostic accuracy with the panel's assistance.
6. Standalone Performance Study
- Yes, a standalone (algorithm only without human-in-the-loop performance) study was effectively done. The "MicroScan® MICroSTREP plus™ Panel" itself, when read visually according to instructions, constitutes the "device" whose performance was evaluated in comparison to the NCCLS frozen Reference Panel. While a human performs the visual reading, the performance evaluation is centered on the panel's ability to accurately present the MIC, not on the human's interpretation skills in isolation or with assistance. The comparison of the panel's results to a reference standard is a standalone assessment of the device's diagnostic output.
7. Type of Ground Truth Used
- The ground truth used was comparison to an NCCLS frozen Reference Panel. This type of ground truth represents a highly standardized and recognized reference method for antimicrobial susceptibility testing, considered the "gold standard" in the field at the time.
8. Sample Size for the Training Set
- The document does not explicitly describe a separate "training set" for the MicroScan® MICroSTREP plus™ Panel. As a diagnostic device for antimicrobial susceptibility, it is typically developed through extensive R&D and internal testing with various isolates. The provided submission describes the validation/testing of the market-ready device. Therefore, a specific "training set" sample size for an AI/algorithm context is not applicable or provided.
9. How the Ground Truth for the Training Set was Established
- Since a separate "training set" is not explicitly mentioned in the context of an AI/algorithm development and validation, the method for establishing its ground truth is not applicable or detailed. The device's underlying principles are based on established broth dilution susceptibility testing. Any internal development or calibration would have used similar laboratory reference methods to establish the 'true' MIC values for those internal isolates.
§ 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).