(206 days)
The Test Kit provides the cells and reagents necessary for detection and identification of HSV in patient specimens.
The subject device consists of a mixed cell monolayer comprised of MRC-5 (Human Fetal Lung) and genetically modified Baby Hamster Kidney Cells (ELVIS™ HSV cells) which, when infected with HSV-1 or -2, are activated to produce and accumulate intracellularly the bacterial enzyme, beta-galactosidase. As in standard tube culture procedures, inoculated monolayers are examined daily for CPE. When CPE is observed, the monolayers are fixed and stained for the presence of beta-galactosidase. If blue cells are detected, indicating the presence of the enzyme which was induced by HSV, then the specimen is confirmed as being positive for HSV. If CPE is not detected by day 7 after inoculation, the monolayers are stained for the presence of pre-CPE, blue, HSV-infected cells. If none are found, the specimens are negative for HSV.
Acceptance Criteria and Study Details for ELVIS™ HSV GOLD
1. Acceptance Criteria and Reported Device Performance
The acceptance criteria for the ELVIS™ HSV GOLD device were implicitly established through a non-inferiority comparison to existing "Gold Standard" tube culture methods. While explicit numerical thresholds for acceptance were not stated, the study aimed to demonstrate "substantial equivalence" in terms of clinical sensitivity and specificity.
| Performance Metric | Acceptance Criteria (Implicit - Substantial Equivalence to "Gold Standard") | Reported Device Performance (ELVIS™ HSV GOLD) |
|---|---|---|
| Clinical Sensitivity | Comparable to standard tube culture methods | 98.1% |
| Clinical Specificity | Comparable to standard tube culture methods | 98.7% |
2. Sample Size and Data Provenance
- Sample Size (Test Set): Over 670 specimens.
- Data Provenance: The specimens were "normally submitted to the respective institution for HSV testing," implying they were clinical samples from human patients. The study was conducted in 4 different laboratories, suggesting a multi-center study. The information does not explicitly state the country of origin but given the 510(k) submission to the FDA, it is highly likely the data originated from the United States. The statement "ELVIS™ HSV GOLD testing was performed on those specimens for which there was sufficient residual sample" suggests a prospective collection of data for the ELVIS™ HSV GOLD testing, using samples that were also tested with the predicate methods.
3. Number of Experts and Qualifications for Ground Truth
The provided text does not specify the number of experts used or their qualifications for establishing the ground truth for the test set.
4. Adjudication Method for the Test Set
The provided text does not specify an adjudication method. The ground truth was established by "predicate tests" which are "Classical 'Gold' standard tube culture methods... Confirmation, where used, is by fluorescent antibodies directed against HSV antigens." This implies the results of these predicate methods served as the ground truth.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
A multi-reader multi-case (MRMC) comparative effectiveness study was not conducted as the device is a diagnostic test kit and not an AI-based system assisting human readers. Therefore, there is no effect size reported for human readers in conjunction with AI.
6. Standalone Performance
Yes, a standalone study was performed. The reported clinical sensitivity of 98.1% and clinical specificity of 98.7% for the ELVIS™ HSV GOLD test are measures of its performance as a standalone diagnostic device.
7. Type of Ground Truth Used
The ground truth used was expert consensus / predicate method. Specifically, the "Classical 'Gold' standard tube culture methods commonly used by many clinical laboratories for isolation and identification of HSV." This includes confirmation by fluorescent antibodies where necessary.
8. Sample Size for the Training Set
The provided text does not specify a training set size. This is a diagnostic test kit based on biological assays, not a machine learning algorithm, so a "training set" in the computational sense is not applicable. The development of the device likely involved internal optimization and validation, but this is distinct from a machine learning training set.
9. How Ground Truth for the Training Set was Established
As there is no "training set" in the context of a machine learning algorithm, the concept of establishing ground truth for a training set is not applicable here. The inherent biological mechanisms of the ELVIS™ HSV GOLD system (genetically modified cells, beta-galactosidase induction) were developed and optimized based on known characteristics of HSV infection and cellular responses, rather than being "trained" on a dataset in the AI sense.
§ 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).