(113 days)
The MicroScan® Dried Gram-Negative 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-negative bacilli. After inoculation, panels are incubated for 16 - 20 hours at 35°C +/- 1°C in a non-CO2 incubator, and read either visually or with MicroScan instrumentation, according to the Package Insert.
This particular submission is for the addition of the antimicrobial Doripenem at concentrations of 0.008 to 32 mcg/ml to the test panel.
The gram-negative organisms which may be used for Doripenem susceptibility testing in this panel are:
Acinetobacter baumanii Escherichia coli Klebsiella pneumoniae Proteus mirabilis Pseudomonas aeruginosa
MicroScan Dried Gram-Negative MIC/Combo Panels 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-negative bacilli.
The antimicrobial susceptibility tests are miniaturizations of the broth dilution susceptibility test that have been diluted in broth and dehydrated. Various antimicrobial agents are diluted in broth to concentrations bridging the range of clinical interest. Panels are rehydrated with water after inoculation with a standardized suspension of the organism. After incubation in a non-CO2 incubator for 16-20 hours, the minimum inhibitory concentration (MIC) for the test organism is read by determining the lowest antimicrobial concentration showing inhibition of growth.
The acceptance criteria related to the performance of the MicroScan Dried Gram-Negative MIC/Combo Panels with Doripenem, as described in the provided text, is primarily focused on Essential Agreement with a CLSI frozen Reference Panel.
Here's a breakdown of the requested information:
1. Table of Acceptance Criteria and Reported Device Performance
| Acceptance Criteria (Reference Panel Comparison) | Reported Device Performance (Doripenem) |
|---|---|
| Essential Agreement with CLSI frozen Reference Panel | 97.0% (Overall) |
| Reproducibility of Inoculum Method (Turbidity and Prompt™) | Acceptable |
| Reproducibility of Instrument (autoSCAN® -4 and WalkAway®) | Acceptable |
| Quality Control Testing for Doripenem | Acceptable |
Note: The document implicitly suggests that "acceptable" reproducibility and quality control are also part of the acceptance criteria, as their successful demonstration is highlighted.
2. Sample Size Used for the Test Set and the Data Provenance
- The document states: "The external evaluation was conducted with fresh and stock Efficacy isolates and stock Challenge strains."
- It does not specify the exact total sample size for the test set (number of isolates or tests).
- The data provenance is not explicitly stated in terms of country of origin. Given Siemens Healthcare Diagnostics is the manufacturer and the FDA is the regulatory body, it is likely the study was conducted to meet US regulatory requirements, potentially using data gathered in the US or under US-standardized conditions.
- The study appears to be retrospective for the challenge strains (compared to "Expected Results determined prior to the evaluation"), and could be a mix for efficacy isolates (fresh isolates might involve prospective collection, while stock isolates are typically retrospective).
3. Number of Experts Used to Establish the Ground Truth for the Test Set and the Qualifications of Those Experts
- The document does not provide any information on the number of experts used or their qualifications for establishing the ground truth.
4. Adjudication Method for the Test Set
- The document does not describe any adjudication method. It states that challenge strains were "compared to Expected Results determined prior to the evaluation," and the Dried Gram-Negative Panel's performance was compared with a CLSI frozen Reference panel. This suggests the reference panel results or pre-determined expected results served as the "ground truth" rather than an adjudicated expert consensus.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
- No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This study is focused on the performance of the automated AST system (MicroScan panels) against a reference method, not on human readers' improvement with or without AI assistance. The device is for automated antimicrobial susceptibility testing, not assistive AI for human interpretation.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
- Yes, a standalone performance evaluation was done. The study directly compares the MicroScan Dried Gram-Negative MIC/Combo Panel's results to a CLSI frozen Reference panel. This is an evaluation of the device's (algorithm's) performance independent of human interpretation or intervention, except for initial setup and reading of the MICs, which can be automated (via autoSCAN® -4 and WalkAway® instruments) or visual.
7. The Type of Ground Truth Used
- The ground truth used was a CLSI frozen Reference Panel. For challenge strains, "Expected Results determined prior to the evaluation" also served as a form of ground truth. This is a standardized, recognized reference method for antimicrobial susceptibility testing.
8. The Sample Size for the Training Set
- The document does not provide any information about a separate training set or its sample size. The focus is on the performance of the device against a reference standard in an external evaluation. This is typical for AST device validations, where the system is "trained" during its development phase using various isolates, but the submission documentation primarily describes the validation (test set) performance.
9. How the Ground Truth for the Training Set Was Established
- As no information about a training set is provided, there is no information on how its ground truth was established.
§ 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).