(96 days)
MRL Diagnostics' HSV-1 ELISA IgG test is intended for qualitatively detecting the presence or absence of human IgG class antibodies to HSV-1 in human sera. In conjunction with the MRL HSV-2 ELISA IgG, the test is indicated for 1) testing sexually active adults, with or without a clinical history of herpes, for aiding in the presumptive diagnosis of HSV infection to identify persons who are at risk for transmitting or acquiring HSV so they may be counseled, and 2) testing expectant mothers for aiding in the presumptive assessment of the risk for acquiring and/or transmitting HSV to their child, so they may be counseled.
In the MRL Diagnostics HSV-1 ELISA IgG assay, the polystyrene microwells are coated with recombinant gG-1 antigen. Diluted serum samples and controls are incubated in the wells to allow specific antibody present in the samples to react with the antigen. Nonspecific reactants are removed by washing, and peroxidase-conjugated anti-human IgG is added and reacts with specific IgG. Excess conjugate is removed by washing. Enzyme substrate and chromogen are added, and the color is allowed to develop. After adding the Stop Reagent, the resultant color change is quantified by a spectrophotometric reading of optical density (OD) which is directly proportional to the amount of antigenspecific IgG present in the sample. Sample optical density readings are compared with reference cut-off OD readings to determine results.
Here's a breakdown of the acceptance criteria and study details for the MRL Diagnostics HSV-1 ELISA IgG device, based on the provided text:
Please note that the document is a 510(k) summary, which provides a high-level overview. Specific acceptance criteria values are not explicitly stated as distinct acceptance criteria but are implied by the reported performance and comparison to predicate devices.
1. Table of Acceptance Criteria and Reported Device Performance
Since explicit "acceptance criteria" values are not listed as predefined thresholds for each attribute, I will present the reported performance in the context of sensitivity and specificity, as these are key metrics for diagnostic devices and are compared against similar predicate devices. The document implies that the reported performance values are within acceptable ranges for the intended use and demonstrate substantial equivalence to predicate devices.
| Attribute | Implied Acceptance Standard (from Predicate Device performance/general diagnostic standards) | Reported Device Performance (MRL HSV-1 ELISA IgG) |
|---|---|---|
| Sensitivity (Sexually Active Adults) | High (e.g., comparable to predicate device performance) | 91.2% (125/137) with 95% CI: 85.2-95.4% |
| Specificity (Sexually Active Adults) | High (e.g., comparable to predicate device performance) | 92.3% (96/104) with 95% CI: 85.4-96.6% |
| Sensitivity (Expectant Mothers) | High (e.g., comparable to predicate device performance) | 96.0% (170/177) with 95% CI: 92.0-98.4% |
| Specificity (Expectant Mothers) | High (e.g., comparable to predicate device performance) | 95.2% (59/62) with 95% CI: 86.5-99.0% |
| Cross-reactivity (CMV) | Low/None | 100% MRL EL Neg (12/12) |
| Cross-reactivity (EBV VCA) | Low/None | 100% MRL EL Neg (24/24) |
| Cross-reactivity (HHV6) | Low/None | 100% MRL EL Neg (24/24) |
| Cross-reactivity (VZV) | Low/None | 100% MRL EL Neg (23/23) |
2. Sample Sizes Used for the Test Set and Data Provenance
- Sexually Active Adults: n = 246 (excluding 3 atypical Western blots and 2 ELISA equivocal samples), retrospective, from the Northwestern United States.
- Expectant Mothers: n = 241 (excluding 1 atypical Western blot and 1 ELISA equivocal sample), retrospective, from the Northwestern United States.
- Culture Positives: n = 38 (for sensitivity comparison with MRL EL vs. Culture) and n = 37 (for sensitivity comparison with MRL EL vs. WB). Provenance not explicitly stated beyond "culture positive patients," but the "serological 'truth'" was defined using a Western Blot from a major university in the Northwestern United States.
- Low Prevalence Population (College Students): n = not explicitly stated for the total, but 56 negative and 24 positive WB-1 samples in the analysis, retrospective, from a major university in the Northwestern United States.
- Type Specificity with HSV-2 Western Blot Positives: n = 90 (combined from expectant mothers, sexually active adults, low prevalence persons, and HSV-1 culture positives), retrospective, from the Northwestern United States.
- Cross-reactivity: n = 26 (sera from HSV sero-negative by another manufacturer's FDA cleared HSV ELISAs, and IFA IgG positive for taxonomically similar viruses), retrospective.
- CDC's HSV/CMV Serum Panel: n = 99, characterized serum panel.
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. It states that "Serological 'truth' was defined using a type specific Western blot from a major university located in the Northwestern United States." This implies that the Western Blot results, performed and interpreted at a reputable academic institution, served as the gold standard for defining HSV-1 serostatus. The expertise lies in the established and accepted methodology of the Western blot assay itself and its standard interpretation at that university.
4. Adjudication Method for the Test Set
The document does not describe an explicit adjudication method involving multiple readers. The "truth" was defined by the Western blot results, which is a laboratory test, not an interpretation by multiple human readers in an adjudication process. Discrepant results between the MRL ELISA and the Western blot were reported but not necessarily adjudicated by additional experts in the traditional sense of resolving differing opinions.
5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study was done
No, an MRMC comparative effectiveness study involving human readers with and without AI assistance was not done. This device is an in vitro diagnostic (IVD) assay, which directly measures specific analytes (antibodies in this case), and its performance is assessed against a laboratory gold standard (Western blot), not through human reader interpretation.
6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done
Yes, the studies presented are standalone performance evaluations of the MRL HSV-1 ELISA IgG device. The device's results (optical density readings interpreted as positive or negative) are compared directly against the serological "truth" established by the Western blot, without human intervention or interpretation of the device's output to reach a diagnosis.
7. The Type of Ground Truth Used
The primary type of ground truth used for serological status was type-specific Western blot (WB) results from a major university in the Northwestern United States. For certain sensitivity studies, culture positivity was also used in conjunction with Western blot.
8. The Sample Size for the Training Set
The document is a 510(k) summary for an ELISA diagnostic kit, which is a laboratory assay. There is no concept of a "training set" in the context of an immunoassay like there would be for an AI/machine learning device. The device itself is designed based on known biological principles and recombinant antigens, not "trained" on data. The studies presented are performance validations of the final device.
9. How the Ground Truth for the Training Set Was Established
As there is no "training set" in the machine learning sense for this in vitro diagnostic device, this question is not applicable. The device's design and functionality are based on established scientific principles of immunology and antigen-antibody reactions.
§ 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).