(69 days)
For the visual or spectrophotometric detection of the vanA and vanB genes in determining vancomycin resistance in enterococci isolated from culture.
The Velogene™ Genomic Identification Assay for VRE (Vancomycin Resistant Enterococci) is an in vitro, DNA probe based, diagnostic device that utilizes Cycling Probe™ Technology (CPT) to generate a spectrophotometric or visual result. Results can be generated 90 minutes after primary isolation. The Velogene™ Genomic Identification Assay for VRE (hereafter may be referred to as the Velogene™ assay) utilizes a fluorescein labeled, biotinylated DNA-RNA-DNA chimeric probe providing an RNase H cleavable linkage when bound to the complementary sequence of the van A or vanB gene. RNase H cleaves the RNA portion of the chimeric probe when it is hybridized to the target DNA. The uncleaved probe (vanA and vanB negative) is detected by binding of the fluoresceinated probe to a solid surface and attachment of an antifluorescein antibody conjugated with horseradish peroxidase, which converts a substrate to a colored end product. Cleavage of the probe (vanA or vanB positive) prevents binding of the probe-anti-fluorescein antibody enzyme complex, thus preventing formation of the colored end product. A vancomycin-resistant isolate (i.e. vanA or vanB gene is present) will produce a colorless result (or OD650 of ≤0.14). A vancomycin-sensitive isolate (i.e. vanA and vanB gene are absent) will produce a distinctly blue color (or OD650 of >0.14). Each Velogene™ assay kit contains supplies sufficient to process 48 samples and consists of two separate reagent kits: a VRE Lysis/Cycle Kit and a VRE Microwell Detection Kit.
Here's an analysis of the provided text regarding the acceptance criteria and the study that proves the device meets them:
1. Table of Acceptance Criteria and Reported Device Performance
The submission does not explicitly state pre-defined acceptance criteria (e.g., minimum sensitivity, specificity, or agreement metrics that needed to be met). Instead, it presents the results of a comparative study and implies that the observed agreement rate was sufficient for substantial equivalence.
| Metric | Acceptance Criteria (Implied) | Reported Device Performance | Comments |
|---|---|---|---|
| Agreement with Predicate Device (Vancomycin Screen Agar) | Sufficient for Substantial Equivalence | 94.6% agreement | This agreement rate was based on a comparative study. The submission implies that this level of agreement was acceptable for FDA clearance. |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size: 518 isolates
- Data Provenance: The study was conducted at "3 geographically distributed U.S. sites" using "routinely submitted samples for microbiological identification." This indicates the data was prospective or at least collected in a routine clinical setting.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document does not specify the number of experts or their qualifications for establishing the ground truth. The ground truth was based on the predicate device, Vancomycin Screen Agar, which is a growth-based test. Interpretation of this test would typically be performed by trained laboratory personnel, but no specifics are given regarding expert review or reconciliation.
4. Adjudication Method for the Test Set
The document does not describe any specific adjudication method (e.g., 2+1, 3+1). The "ground truth" was established by the predicate device (Vancomycin Screen Agar), and the Velogene™ assay's results were compared against this. It's implied that the results of the Vancomycin Screen Agar were considered definitive for the purpose of this comparison.
5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
A Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not applicable and therefore not performed. This device is a standalone diagnostic assay (an in vitro DNA probe test) that provides a direct result (colorless or blue, or OD650 reading). It does not involve human readers interpreting images or data where AI assistance would improve human performance.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, a standalone performance evaluation was done for the Velogene™ Genomic Identification Assay for VRE. The study compared the results of the Velogene™ assay (an "algorithm only" in the sense of a chemical/molecular assay without human interpretation of complex visuals) directly against the predicate device. The assay itself generates a direct spectrophotometric or visual result without human interpretation beyond reading the color or OD650 value.
7. The Type of Ground Truth Used
The ground truth used for the comparative study was the phenotypic result from a legally marketed predicate device: Vancomycin Screen Agar (Brain Heart Infusion (BHI) Agar with 6 ug/mL vancomycin). This is a growth-based test that identifies vancomycin resistance.
8. The Sample Size for the Training Set
The document does not provide information on a separate training set or its sample size. This type of submission (510(k)) for an IVD kit often focuses on clinical validation rather than a deep dive into the development and training of a machine learning model, which is not applicable here as it's a chemical assay. The comparison is the validation study.
9. How the Ground Truth for the Training Set Was Established
Since no separate training set is mentioned in the provided text, and the device is a molecular assay, the concept of establishing ground truth for a "training set" as it would apply to a machine learning algorithm is not relevant to this submission. The "ground truth" for the overall evaluation was the predicate device's results, against which the Velogene™ assay was compared.
§ 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).