(267 days)
Intended Use: For In Vitro Diagnostic Use Only. The SeraQuest HSV Type 2 Specific IgG assay is an enzyme-linked immunosorbent assay (ELISA) intended for the qualitative detection of human IgG antibodies to type 2 herpes simplex virus (HSV) in human serum. The test is indicated for sexually active individuals and expectant mothers as an aid in the presumptive diagnosis of HSV-2 infection. The predictive value of a positive or negative result depends on the prevalence of HSV-2 infection in the population and the pre-test likelihood of HSV-2 infection.
The test is not FDA cleared for screening blood or plasma donors. The performance of this assay has not been established for immunocompromised patients, pediatric patients or matrices other than human serum.
The SeraQuest® HSV Type 2 Specific IgG test is a solid-phase enzyme-linked immunoassay (ELISA) , which is performed in microwells, at room temperature, and in three thirty minute incubations The test detects IgG antibodies which are directed against HSV 2 type-specific antigens in human serum. The Calibrator in the SeraQuest® HSV Type 2 Specific IgG test set has been assigned Index values based on an in-house standard. Test results are reported as Index values.
Here's a breakdown of the acceptance criteria and study details for the SeraQuest HSV Type 2 Specific IgG device, based on the provided document:
Acceptance Criteria and Device Performance
| Acceptance Criterion | Reported Device Performance (SeraQuest HSV Type 2 Specific IgG) |
|---|---|
| Precision | Intra-assay CV% for positive control: 9.9% |
| Inter-assay CV% for positive control: 13.7% | |
| Inter-laboratory CV% for positive control: 15.4% | |
| Total CV% for positive control: 13.0% | |
| (Similar data provided for negative control and 6 samples) | |
| Specificity (Cross-reactivity) | No false positives for HSV 1 IgG, CMV IgG, VZV EBNA/VCA/IgG, Measles IgG, Rubella IgG, Toxoplasma IgG, Syphilis IgG, Human Papilloma Virus, Neisseria gonorrhea. |
| One false positive out of 8 for Chlamydia trachomitis. | |
| Interference | No significant interference observed with elevated levels of hemoglobin, glucose, cholesterol, globulin, unconjugated bilirubin, conjugated bilirubin, human albumin, and ascorbic acid. |
| Relative Sensitivity & Specificity (Sexually Active Adults vs. Immunoblot) | Sensitivity: 91.8% (95% CI: 82.2 to 96.5) |
| Specificity: 94.2% (95% CI: 87.9 to 97.3) | |
| Relative Sensitivity & Specificity (Expectant Mothers vs. Immunoblot) | Sensitivity: 98.9% (95% CI: 93.8 to 99.8) |
| Specificity: 99.4% (95% CI: 96.4 to 99.9) | |
| Agreement with CDC Panel | Total Agreement: 100% (30/30 positive, 70/70 negative) |
Study Details
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Sample Size used for the test set and data provenance:
- Precision Testing: 6 serum specimens (2 negative, 4 positive) and the SeraQuest Positive and Negative Controls. Each sample/control was assayed in triplicate, on three separate occasions, at three different laboratories (Quest International and two external independent laboratories). This results in a total of 27 data points per sample/control (3 triplicates * 3 occasions * 3 labs).
- Specificity Testing:
- HSV 1 IgG: 9 samples
- CMV IgG: 11 samples
- VZV EBNA IgG: 14 samples
- VZV VCA IgG: 17 samples
- VZV IgG: 21 samples
- Measles IgG: 19 samples
- Rubella IgG: 18 samples
- Toxoplasma IgG: 6 samples
- Syphilis IgG: 4 samples
- Human Papilloma Virus: 7 samples
- Chlamydia trachomitis: 8 samples
- Neisseria gonorrhea: 7 samples
- Provenance: Samples positive for various related pathogens/antibodies but negative for Type 2 HSV by another legally marketed device. Human Papilloma Virus, Chlamydia trachomitis, and Neisseria gonorrhea samples were from individual patients with confirmed sexually transmitted infections.
- Interference Testing: Samples that were negative, weakly positive, and moderately positive for antibodies to Type 2 HSV were tested with and without the addition of elevated levels of specific interfering substances. (No specific number of samples provided for this test).
- Comparison with Predicate Device:
- Sexually Active Adults: 164 serum samples. Provenance: Prospectively collected, masked, archived, and tested at Quest International, Inc. from a clinical laboratory in the Southeastern United States.
- Expectant Mothers: 242 serum samples. Provenance: Prospectively collected, masked, archived, and tested at Quest International, Inc. from clinical laboratories in the Northeastern and Southeastern United States. 82% from first trimester, 8% second, 10% third.
- CDC Panel: 100 sera (30 HSV-2 IgG positive and 70 HSV-2 IgG negative samples). Provenance: Centers for Disease Control and Prevention (CDC) serum panel.
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Number of experts used to establish the ground truth for the test set and the qualifications of those experts: Not explicitly stated for most studies.
- For the cross-reactivity study, the samples were determined positive for various related pathogens "by other legally marketed devices" and confirmed negative for Type 2 HSV by a legally marketed device. This implies a standard diagnostic process, but no specific human experts or qualifications are mentioned for this initial determination.
- For the comparative studies with the predicate device (Immunoblot), the ground truth was established by the predicate device itself. While the predicate device is a "legally marketed" test, it doesn't specify human expert interpretation or qualifications.
- For the CDC Panel, the ground truth is "CDC consensus results" and the panel samples are described as "well characterized," implying established expert consensus or reference methods. No specific number of experts or their qualifications are detailed.
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Adjudication method (e.g., 2+1, 3+1, none) for the test set: Not explicitly stated. The ground truth seems to be established by reference methods or legally marketed devices rather than direct human adjudication of results in most cases. For the CDC panel, it's "CDC consensus results," which implies an agreed-upon truth, but the adjudication method isn't described.
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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:
- No MRMC comparative effectiveness study involving human readers or AI assistance was conducted or reported for this device. This is an IVD (In Vitro Diagnostic) assay, not an imaging AI device.
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If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- Yes, the performance characteristics (sensitivity, specificity, precision, etc.) of the SeraQuest HSV Type 2 Specific IgG assay were evaluated as a standalone device. Its results are compared to a predicate device (Immunoblot) or a "well characterized serum panel" (CDC panel). There is no "human-in-the-loop" component described for this specific device in the context of its performance evaluation.
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The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- Precision: Internal controls and reference samples.
- Specificity: Samples characterized by other legally marketed devices (positive for related pathogens, negative for HSV-2) and confirmed sexually transmitted infections.
- Interference: Artificially spiked samples.
- Comparison Studies: A "commercial HSV 2 Immunoblot test" (predicate device) was used as the reference standard for both sexually active adults and expectant mothers. This is a type of reference test ground truth.
- CDC Panel: "CDC consensus results" from a "well characterized serum panel." This implies expert consensus or a gold standard determination for each sample in the panel.
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The sample size for the training set: Not applicable and not mentioned. This document describes the performance evaluation of a medical device (an ELISA assay), not a machine learning or AI model that requires a "training set."
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How the ground truth for the training set was established: Not applicable, as there is no training set for this type of device.
§ 866.3305 Herpes simplex virus serological assays.
(a)
Identification. Herpes simplex virus serological assays are devices that consist of antigens and antisera used in various serological tests to identify antibodies to herpes simplex virus in serum. Additionally, some of the assays consist of herpes simplex virus antisera conjugated with a fluorescent dye (immunofluorescent assays) used to identify herpes simplex virus directly from clinical specimens or tissue culture isolates derived from clinical specimens. The identification aids in the diagnosis of diseases caused by herpes simplex viruses and provides epidemiological information on these diseases. Herpes simplex viral infections range from common and mild lesions of the skin and mucous membranes to a severe form of encephalitis (inflammation of the brain). Neonatal herpes virus infections range from a mild infection to a severe generalized disease with a fatal outcome.(b)
Classification. Class II (special controls). The device is classified as class II (special controls). The special control for the device is FDA's revised guidance document entitled “Class II Special Controls Guidance Document: Herpes Simplex Virus Types 1 and 2 Serological Assays.” For availability of the guidance revised document, see § 866.1(e).