(220 days)
The Diagnostic Hybrids, Inc D3 DFA Varicella-zoster Virus Identification Kit is intended for use in the qualitative detection of varicella-zoster virus (VZV) in cell cultures by immunofluorescence using fluoresceinated monoclonal antibodies (MAbs). Negative results do not preclude an infection and should not be used as the sole basis for diagnosis, treatment or other management decision. Performance testing has not been done on direct patient specimen testing.
The Diagnostic Hybrids, Inc. D3 DFA VARICELLA-ZOSTER IDENTIFICATION KIT includes a DFA Reagent that contains a blend of two fluorescein-labeled murine monoclonal antibodies directed against VZV antigens. The kit includes the following components: VZV DFA Reagent, Mounting Fluid, VZV Antigen Control Slides, PBS Concentrate.
Here's a breakdown of the acceptance criteria and study information for the Diagnostic Hybrids, Inc. D3 DFA Varicella-zoster Virus Identification Kit, based on the provided 510(k) summary:
1. Table of Acceptance Criteria and Reported Device Performance
The 510(k) summary primarily focuses on establishing substantial equivalence to a predicate device rather than defining strict, pre-specified acceptance criteria with numerical targets. Instead, the performance is reported as agreement with the predicate device.
| Performance Metric | Acceptance Criteria (Implied by Substantial Equivalence Goal) | Reported Device Performance |
|---|---|---|
| Positive Percent Agreement (PPA) | Demonstrate high agreement with the predicate device for positive VZV detection. | 100% (95% CI: 91.6% to 100%) |
| Negative Percent Agreement (NPA) | Demonstrate high agreement with the predicate device for negative VZV detection. | 99.5% (95% CI: 97.3% to 99.9%) |
| Cross-Reactivity | No cross-reactivity with common respiratory and other relevant microorganisms/cell lines (except for Protein A producing Staphylococcus aureus, which is distinguishable by morphology). | No cross-reactivity observed for 55 virus strains, 20 host culture cell types, 26 bacterial cultures, and 1 yeast culture. Staphylococcus aureus showed small, bright dots of fluorescence, distinguishable from viral antigen binding. |
| Detection Limit (Comparison) | Comparable detection limit to the predicate device. | No "statistical difference" between the subject and predicate kits in detecting 1-TCID50 per well (average 21.8 positive wells for subject vs. 22.3 for predicate). |
2. Sample Size Used for the Test Set and Data Provenance
- Test Set Sample Size: 251 specimens (after excluding 3 specimens due to toxic cell culture monolayers from an initial 254 prospectively collected specimens).
- Data Provenance: Prospectively collected specimens. The country of origin is not explicitly stated, but it was collected at "three laboratory sites" which typically implies within the country of submission (USA for FDA approval).
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
The ground truth for the test set was established by comparison to a currently marketed Varicella-zoster virus identification kit (the predicate device) which serves as the reference method. No independent experts are mentioned as having adjudicated or established ground truth in this particular type of study (method comparison). The "experts" in this context would be the technicians and microbiologists performing and interpreting the predicate device's results. Their specific qualifications are not detailed in the summary, but it's implied they are qualified laboratory personnel accustomed to these types of assays.
4. Adjudication Method for the Test Set
The adjudication method was a direct comparison between the D3 DFA VZV Identification Kit and a predicate device, serving as the "comparison device." There is no mention of an independent expert adjudication process for discordant results. The table presented shows agreement and disagreement between the two kits.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This study is a method comparison study between two diagnostic kits, not an evaluation of human reader performance with or without AI assistance.
6. Standalone (Algorithm Only Without Human-in-the-Loop) Performance Study
Yes, a standalone performance study was done. The study evaluates the performance of the D3 DFA Varicella-zoster Virus Identification Kit itself (using immunofluorescence read by a human under a microscope) against a predicate device. This is the "algorithm only" in the context of a laboratory assay, where the "algorithm" is the entire test procedure and the interpretation criteria provided. There is no automated image analysis or AI component involved in the reading of this specific device; it relies on human observation through a fluorescence microscope.
7. Type of Ground Truth Used
The ground truth used was established by comparison to a legally marketed predicate device (Light Diagnostics Varicella-zoster (VZV) Direct Immunofluorescence Assay or Light Diagnostics Simulfluor HSV/VZV Immunofluorescence Assay) which also uses immunofluorescence for VZV detection in cell cultures. This is a form of "reference method" ground truth.
8. Sample Size for the Training Set
The 510(k) summary does not explicitly describe a separate "training set" as would be common for machine learning applications. This is a traditional diagnostic kit submission. The "training" for such a kit involves the development and optimization of the antibodies and reagents by the manufacturer. The data presented in the performance characteristics section (Analytical performance, Analytical Specificity, Comparison Studies) are primarily for validation and demonstrate the kit's performance, not for training a model.
9. How the Ground Truth for the Training Set Was Established
As noted above, a distinct "training set" and associated ground truth establishment in the context of statistical model training is not applicable to this type of device (an immunofluorescence assay kit). The development of the kit itself involves internal R&D and quality control, ensuring the antibodies correctly bind to VZV antigens. This developmental process would involve testing against known positive and negative VZV samples, where "ground truth" would be established by standard microbiological techniques (e.g., cell cultures, PCR, viral isolation) for VZV positivity. However, this is part of product development, not a separate "training set" study as described for AI/ML devices.
§ 866.3900 Varicella-zoster virus serological reagents.
(a)
Identification. Varicella-zoster virus serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to varicella-zoster in serum. The identification aids in the diagnosis of diseases caused by varicella-zoster viruses and provides epidemiological information on these diseases. Varicella (chicken pox) is a mild, highly infectious disease, chiefly of children. Zoster (shingles) is the recurrent form of the disease, occurring in adults who were previously infected with varicella-zoster viruses. Zoster is the response (characterized by a rash) of the partially immune host to a reactivation of varicella viruses present in latent form in the patient's body.(b)
Classification. Class II (performance standards).