(494 days)
IMMULITE Herpes I & II IgG is designed for the qualitative detection of IgG antibodies to herpes simplex virus (HSV) type I & II in human serum. It is intended strictly for in vitro diagnostic use as an aid in the determination of serological status to HSV I & II.
IMMULITE® Herpes I & II IgG is a solid-phase, two-step, chemiluminescent enzyme immunoassay. The solid phase, a polystyrene bead enclosed within an IMMULITE® Test Unit, is coated with a partially purified HSV I and II viral antigen.
Here's an analysis of the provided text regarding the acceptance criteria and the study proving the device meets them:
1. A table of acceptance criteria and the reported device performance
The document does not explicitly state pre-defined acceptance criteria values for agreement, sensitivity, or specificity. Instead, it presents the performance of the IMMULITE Herpes I & II IgG assay and implicitly suggests a level of performance comparable to the predicate device and CDC results as acceptable.
Here's a table summarizing the reported performance, compared to what the document implies as acceptable by demonstrating substantial equivalence:
| Performance Metric | Implied Acceptance Criterion (e.g., comparable to predicate/CDC) | Reported Device Performance (IMMULITE Herpes I & II IgG) | Study Context |
|---|---|---|---|
| Total Agreement | N/A (compared to CDC results) | 97% | CDC Panel |
| Positive Agreement | N/A (compared to CDC results) | 99% | CDC Panel |
| Negative Agreement | N/A (compared to CDC results) | 93% | CDC Panel |
| Agreement | Comparable to BioWhittaker HSV ELISA II IgG | 99.0% (Site 1), 96.0% (Site 2) | Method Comparison with Predicate |
| Relative Sensitivity | Comparable to BioWhittaker HSV ELISA II IgG | 100.0% (Site 1), 96.2% (Site 2) | Method Comparison with Predicate |
| Relative Specificity | Comparable to BioWhittaker HSV ELISA II IgG | 96.6% (Site 1), 94.9% (Site 2) | Method Comparison with Predicate |
2. Sample sized used for the test set and the data provenance
-
CDC Panel Study:
- Sample Size: Not explicitly stated as a number, but the panel consisted of "72% positive and 28% negative samples." To infer the total size, we would need the absolute number of positive or negative samples. However, the exact sample size for this specific test set is not provided in numerical terms.
- Data Provenance: United States Centers for Disease Control and Prevention (CDC), retrospective.
-
Method Comparison Study (with BioWhittaker):
- Sample Size:
- Site 1: n = 200
- Site 2: n = 202
- Data Provenance: "two independent sites," but the country of origin is not specified. The study was "nonconcurrently" conducted at these sites. The nature of the samples (e.g., patient samples, banked samples) is not detailed, but it tested the performance against the predicate device.
- Sample Size:
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
The document does not provide information on the number of experts used or their qualifications for establishing ground truth, for either the CDC panel or the method comparison studies.
For the CDC panel, it states the results were "obtained by IMMULITE" (which implies the DPC device) and then "sending the results to the CDC for unmasking." This suggests the CDC had their own "characterized" panel, but how that characterization (ground truth) was established, or by whom, is not detailed.
For the method comparison, the "ground truth" for the comparison was the results of the predicate device (BioWhittaker HSV ELISA II IgG).
4. Adjudication method for the test set
The document does not specify any adjudication method (e.g., 2+1, 3+1). For the CDC panel, it seems the ground truth was pre-established (a "masked, characterized serum panel") by the CDC. For the method comparison, the predicate device's results served as the reference for "relative" sensitivity and specificity, so no human adjudication method for disagreement is described.
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
- No, an MRMC comparative effectiveness study was not done. This device is an automated immunoassay analyzer for detecting antibodies, not an AI-assisted diagnostic imaging or interpretation tool that would involve human readers.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
- Yes, a standalone study was done. The IMMULITE Herpes I & II IgG is an automated immunoassay system. The reported performance metrics (agreement, sensitivity, specificity) reflect the performance of the device itself (the "algorithm" in the context of an automated analyzer) without human interpretive intervention. The process involves introducing samples and buffers, incubation, and then the luminometer measures the photon output, which is then quantitatively compared to a cutoff to yield a qualitative result.
7. The type of ground truth used
- CDC Panel Study: The ground truth was provided by the CDC as a "masked, characterized serum panel." The specific method of characterization (e.g., expert consensus, other established assays, clinical outcomes) is not detailed, beyond stating it was "characterized."
- Method Comparison Study: The ground truth for calculating "relative sensitivity" and "relative specificity" was the results obtained from the predicate device, BioWhittaker HSV ELISA II IgG kit. This means the IMMULITE device's performance was compared against the predicate device, not necessarily against a definitive gold standard.
8. The sample size for the training set
The document does not mention or provide information about a specific "training set" or its size for the IMMULITE Herpes I & II IgG assay. This is typical for such diagnostic assays, where assay development and optimization (often referred to as "training" in AI contexts) are part of the manufacturer's internal process and not usually reported as a separate "training set" in regulatory submissions. The studies described are performance validation studies.
9. How the ground truth for the training set was established
Since no "training set" is described in the context of this regulatory submission, there is no information on how its ground truth was established. Assay development usually involves internal validation against known positive and negative samples, often characterized through reference methods or clinical diagnosis, but these details are not provided here.
§ 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).