(245 days)
The INCSTAR Herpes Simplex Virus I/II IgG "fast" ELISA kit contains instructions and materials for the qualitative and/or semi-quantitative detection of IgG antibodies to herpes simplex virus type 1 and/or type 2 in human serum by indirect enzyme-linked immunosorbent assay (ELISA) technique. When performed according to instructions, the INCSTAR Herpes Simplex Virus I/II IgG "fast" ELISA test is of value in the determination of immunological response to infection with HSV. The evaluation of paired sera, acute and convalescent, by demonstrating seroconversion or a significant rise in antibody can aid in the diagnosis of primary infection with herpes simplex virus.
The method for the determination of specific anti-HSV type 1 and/or type 2 IgG utilizes the enzyme-linked immunosorbent assay (ELISA) technique. Polystyrene microtiter wells are coated with purified HSV type 1 and type 2 antigens. Diluted patient serum is incubated with the purified HSV antigens bound to the solid surface of the microtiter well. The HSV type 1 and/or type 2 IgG antibodies present in a patient's serum will be captured by the solid phase. After washing, affinity purified polyclonal goat anti-human IgG (Fc) antibodies conjugated to horseradish peroxidase are added to the well. After this incubation, chromogen containing tetramethylbenzidine is added. Enzyme action on the chromogen results in a color reaction. The color can be detected with a photometer at a wavelength of 450 nm. The measured enzyme activity is directly proportional to the concentration of specific anti-HSV IgG bound to the solid phase.
The provided text describes the INCSTAR HSV I/II IgG "fast" ELISA Kit, which is intended for the qualitative and/or semi-quantitative detection of IgG antibodies to herpes simplex virus type 1 and/or type 2 in human serum.
Here's an analysis of the acceptance criteria and the study that proves the device meets them:
1. Table of Acceptance Criteria and Reported Device Performance
Strict acceptance criteria are not explicitly stated as numerical targets in the provided text. Instead, the device's performance is presented relative to a predicate device. The general "acceptance criteria" can be inferred as achieving comparable or superior performance to the predicate devices.
| Metric | Acceptance Criteria (Inferred from predicate equivalent) | Reported Device Performance (INCSTAR HSV I/II IgG "fast" ELISA Kit) |
|---|---|---|
| Relative Sensitivity | Comparable to predicate devices (Herpes 1 IgG Clin-ELISA, Herpes 2 IgG Clin-ELISA) | 94% to 99% (using 95% confidence intervals) |
| Relative Specificity | Comparable to predicate devices (Herpes 1 IgG Clin-ELISA, Herpes 2 IgG Clin-ELISA) | 85% to 95% (using 95% confidence intervals) |
| Overall Agreement | Comparable to predicate devices (Herpes 1 IgG Clin-ELISA, Herpes 2 IgG Clin-ELISA) | 90% to 100% (using 95% confidence intervals) |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size: 305 serum samples, representing 305 individuals.
- Data Provenance: Not explicitly stated regarding country of origin. The samples represented "a mixed population of healthy individuals, transplant patients, and patients with various illnesses." The study appears to be a retrospective comparison study, as the INCSTAR kit results were compared to "results generated from the Herpes 1 IgG Clin-ELISA and Herpes 2 IgG Clin-ELISA kits," implying these results were already established or run in parallel.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The concept of "experts" establishing ground truth in the traditional sense for a diagnostic test like an ELISA is not directly applicable here. The "ground truth" for the performance study was established by comparison to existing, cleared predicate devices (Herpes 1 IgG Clin-ELISA and Herpes 2 IgG Clin-ELISA kits).
For discrepant results, a "commercial HSV IgG IFA" (Immunofluorescence Assay) was used for further resolution. The expertise of those who performed or interpreted the IFA is not specified.
4. Adjudication Method for the Test Set
The primary comparison was against the predicate ELISA assays. For discrepant results (samples where the INCSTAR assay disagreed with the predicate assays), "further resolution of discrepant results by a commercial HSV IgG IFA" was performed. This implies a form of adjudication by a third, presumably more definitive, method (IFA). There's no mention of multiple human readers or a specific consensus method for interpreting the IFA results.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, an MRMC comparative effectiveness study was not done. This type of study typically involves multiple human readers interpreting cases with and without AI assistance to measure improvement in human performance. The INCSTAR device is a laboratory diagnostic kit, not an AI-assisted diagnostic tool for human interpretation.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, the performance study describes the standalone performance of the INCSTAR HSV I/II IgG "fast" ELISA Kit. This means the device's results were generated independently and then compared to the predicate devices. ELISA kits inherently operate as standalone systems, providing a result without requiring continuous human-in-the-loop interpretation once the assay is run and read by a photometer.
7. The Type of Ground Truth Used
The primary "ground truth" for the initial performance metrics (relative sensitivity, specificity, and overall agreement) was established by comparison against predicate ELISA devices that were already cleared by the FDA. For discrepant samples, a commercial HSV IgG IFA served as a higher-level "ground truth" for resolution.
8. The Sample Size for the Training Set
The document does not mention a training set or any machine learning/AI components. This is a traditional in-vitro diagnostic (IVD) kit. Therefore, the concept of a "training set" for an algorithm is not applicable.
9. How the Ground Truth for the Training Set Was Established
As no training set is mentioned or applicable to this type of device, this question is not relevant.
§ 864.4010 General purpose reagent.
(a) A general purpose reagent is a chemical reagent that has general laboratory application, that is used to collect, prepare, and examine specimens from the human body for diagnostic purposes, and that is not labeled or otherwise intended for a specific diagnostic application. It may be either an individual substance, or multiple substances reformulated, which, when combined with or used in conjunction with an appropriate analyte specific reagent (ASR) and other general purpose reagents, is part of a diagnostic test procedure or system constituting a finished in vitro diagnostic (IVD) test. General purpose reagents are appropriate for combining with one or more than one ASR in producing such systems and include labware or disposable constituents of tests; but they do not include laboratory machinery, automated or powered systems. General purpose reagents include cytological preservatives, decalcifying reagents, fixative and adhesives, tissue processing reagents, isotonic solutions and pH buffers. Reagents used in tests for more than one individual chemical substance or ligand are general purpose reagents (e.g.,
Thermus aquaticus (TAQ) polymerase, substrates for enzyme immunoassay (EIA)).(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 864.9. If the device is not labeled or otherwise represented as sterile, it is exempt from the current good manufacturing practice requirements of the quality system regulation in part 820 of this chapter, with the exception of § 820.180, with respect to general requirements concerning records, and § 820.198, with respect to complaint files.