(90 days)
ETEST® is a manual, quantitative technique for the determination of antimicrobial susceptibility of non fastidious Gram negative and Gram positive aerobic bacteria and fastidious bacteria. The system comprises a predefined antibiotic gradient which is used to determine the Minimum Inhibitory Concentration (MIC, in μg/mL) of different antimicrobial agents against microorganisms tested on agar media after overnight incubation.
Testing with ETEST Imipenem/Relebactam P. aeruginosa (IRPA) (0.008/4-128/4 µg/mL) is indicated for Pseudomonas aeruginosa, as recognized by the FDA Susceptibility Test Interpretive Criteria (STIC).
The ETEST Imipenem/Relebactam P. aeruginosa (IRPA) (0.008/4-128/4 µg/mL) demonstrated acceptable performance with the following microorganism:
• Pseudomonas aeruginosa
ETEST® is a thin, inert and non-porous plastic strip carrying the MIC reading scale in μg/mL on one side and a predefined antibiotic gradient on the other side.
When the strip is applied to an inoculated agar surface, the preformed antibiotic gradient immediately transfers into the agar matrix, then forming a stable, continuous and exponential gradient of antibiotic concentrations directly underneath the strip. Bacterial growth becomes visible during incubation, and a symmetrical inhibition ellipse centered along the strip appears. The MIC value is read from the scale in terms of μg/mL at complete inhibition of bacterial growth, where the pointed end of the ellipse intersects the strip.
ETEST Imipenem/Relebactam P. aeruginosa (IRPA) with a concentration range of 0.008/4-128/4 µg/mL is specially designed and formulated for testing P. aeruginosa.
This document describes the regulatory clearance for the ETEST® Imipenem/Relebactam P. aeruginosa (IRPA) device, which is an antimicrobial susceptibility test. Here's a breakdown of the acceptance criteria and the study that proves the device meets them, based on the provided text:
Acceptance Criteria and Reported Device Performance
The acceptance criteria for this device are defined by established performance metrics in antimicrobial susceptibility testing, specifically Essential Agreement (EA) and Category Agreement (CA), compared to a reference method. The reported performance demonstrates the device meets these criteria.
| Metric | Acceptance Criteria (Implicit) | Reported Device Performance (Pseudomonas aeruginosa) |
|---|---|---|
| Essential Agreement (EA) | Not explicitly stated, but generally expected to be high (e.g., typically >90% or 95% for AST devices). | 97.7% |
| Category Agreement (CA) | Not explicitly stated, but generally expected to be high (e.g., typically >90% or 95% for AST devices). | 91.1% |
| Reproducibility | Best case: >95% (as per predicate device) | Best case: 99.6% |
| Reproducibility | Worst case: >95% (as per predicate device) | Worst case: 99.6% |
| Quality Control | Results within range >95% (as per predicate device) | Results within range >95% of the times tested |
| Meets Guidance Document Performance Requirements | Yes (explicitly stated) | Yes |
Study Details Proving Device Meets Acceptance Criteria
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Sample Size Used for the Test Set and Data Provenance:
- Sample Size: 437 strains of Pseudomonas aeruginosa.
- Data Provenance: The study involved external evaluations conducted with fresh and stock clinical isolates, as well as a set of challenge strains. The specific country of origin is not mentioned, but "external evaluations" imply samples from clinical settings. The nature of "fresh" and "stock clinical isolates" suggests a mix of retrospective and prospective data, where fresh isolates would be prospective and stock isolates could be retrospective.
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Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts:
- This information is not explicitly provided in the document. Antimicrobial Susceptibility Testing (AST) generally relies on established laboratory methods rather than expert consensus for ground truth, but the personnel performing the reference method would be trained laboratory technicians.
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Adjudication Method for the Test Set:
- None explicitly stated as it's a comparison to a reference laboratory method (CLSI M07-11th Ed broth microdilution). Discrepancy resolution (adjudication) is typically less relevant for quantitative laboratory assays where results are directly compared to a gold standard.
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If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done:
- No, a MRMC study was not done. This is an automated/manual laboratory test for determining Minimum Inhibitory Concentration (MIC), not an imaging device requiring human reader interpretation in a diagnostic workflow. The "human-in-the-loop" aspect for this device is the application of the strip and reading the MIC, which is part of the validation for the device's accuracy against a gold standard method.
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If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- This concept does not directly apply to this type of device. The ETEST device itself is a "standalone" test. The performance reported (EA and CA) is the performance of the ETEST system (strip + reading methodology) compared to the reference broth microdilution method. It inherently involves a human reading the result by interpreting the inhibition ellipse on the strip. The note "b) In the ETEST® Imipenem/Relebactam clinical studies, swabs were used for plate inoculation/streaking and forceps were used for ETEST® strip application. Testing with the optional Inoculator RETRO C80™, Vacuum Pen NEMA C88™ and Applicator SIMPLEX C76™ was not evaluated during the clinical studies" suggests that human manual steps were involved in the performance evaluation.
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The Type of Ground Truth Used:
- Reference Method: The ground truth was established by the CLSI M07-11th Ed (January 2018) broth microdilution reference method, following specifications as defined in CLSI M100 34th Ed. (February 2024). This is considered the gold standard for antimicrobial susceptibility testing. Outcomes data or pathology are not relevant for this type of in vitro diagnostic device.
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The Sample Size for the Training Set:
- The document does not mention a training set in the context of machine learning or AI models. This device is a manual, quantitative laboratory test (an ETEST strip system) and not an AI/ML-driven diagnostic. Therefore, there's no "training set" in the typical sense of AI development. The "strains" mentioned are for the performance evaluation against the reference method.
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How the Ground Truth for the Training Set was Established:
- As there is no mention of a training set for an AI/ML model, this question is not applicable. The device's performance is validated against a well-established reference laboratory method using a test set of clinical isolates and challenge strains.
§ 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).