(155 days)
The Viral Capsid Antigen (VCA) IgM kit is an Enzyme-Linked Immunosorbent Assay (ELISA) for the qualitative determination of IgM antibodies in human serum to VCA antigen. The Clark anti-VCA IgM assay may be used in conjunction with other Epstein-Barr serologies (EA-D IgG, VCA IgG, EBNA-1 IgG, EBNA-1 IgM and heterophile) as an aid in the diagnosis of infectious mononucleosis in the adult population.
The Wampole Epstein-Barr Viral Capsid Antigen (VCA) IgM kit is an Enzyme-Linked Immunosorbent Assays (ELISA) for the qualitative determination of IgM antibodies in human serum to VCA antigen. The Wampole anti-VCA IgM assay may be used in conjunction with other Epstein-Barr serologies (VCA IgG, EBNA-1 IgG, EA-D IgG, EBNA-1 IgM and heterophile) as an aid in the diagnosis of infectious mononucleosis. For In Vitro Diagnostic Use Only. The VCA IgM ELISA test is an enzyme linked immunosorbent assay to detect IgM antibodies to Epstein-Barr Viral Capsid antigen. Afinity purified gp125 VCA antigen is attached to a solid phase microtiter well. Diluted test sera is added to each well. If the antibodies are present that recognize the antigen, they will bind to the antigen in the well. After incubation the wells are washed to remove unbound antibody. An enzyme labeled anti-human IgM is added to each well. If antibody is present it will bind to the antibody attached to the antigen on the well. After incubation the wells are washed to remove unbound conjugate. A substrate solution is added to each well. If enzyme is present the substrate will undergo a color change. After an incubation period the reaction is stopped and the color intensity is measured photometrically, producing an indirect measurement of specific antibody in the patient specimen.
Here's a breakdown of the acceptance criteria and the study details for the Wampole VCA IgM ELISA Test Kit, based on the provided text:
Acceptance Criteria and Device Performance
The acceptance criteria for the Wampole VCA IgM ELISA Test Kit are based on its performance in terms of sensitivity and specificity, as demonstrated by the serum characterization study.
| Acceptance Criteria Category | Acceptance Criteria (Implicit) | Reported Device Performance |
|---|---|---|
| Sensitivity | High relative sensitivity for acute EBV cases | 97.4% (95% CI: 92.2%-100%) for Acute cases |
| Specificity (Seronegative) | High relative specificity for seronegative individuals | 96.4% (95% CI: 89.4%-100%) for Seronegative cases |
| Specificity (Seropositive) | High relative specificity for seropositive individuals | 99.0% (95% CI: 97.0%-100%) for Seropositive cases |
| Overall Agreement | High overall agreement with serological characterization | 98.2% (95% CI: 96.1%-100%) |
| Cross-Reactivity | No cross-reactivity with common interfering antibodies (HSV, CMV, VZV, RF) | Demonstrated no cross-reactivity (all VCA IgM results were negative, while alternate assays were positive) |
Note: The document does not explicitly state numerical acceptance thresholds (e.g., "sensitivity must be >95%"). Instead, the reported performance metrics serve as the basis for demonstrating substantial equivalence to the predicate device.
Study Details
1. Sample Size Used for the Test Set and Data Provenance
- Test Set Sample Size: 166 selected serum samples.
- Data Provenance: The text states, "One hundred and sixty six selected serum were tested at a clinical lab." This suggests the data is retrospective, as the serum samples were "selected" and "characterized," implying they were already collected and categorized before the study. The country of origin is not specified, but the submission is to the U.S. FDA, so it's likely U.S.-based or from a region with similar clinical practices.
2. 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 or qualifications of experts used to establish the ground truth. The ground truth ("seronegative," "acute," or "seropositive" EBV infection) was established based on a panel of other Epstein-Barr serologies (VCA IgM, heterophile antibody, EBNA IgG, VCA IgG). It is implied that these serological profiles, rather than individual expert opinions, served as the basis for characterization.
3. Adjudication Method for the Test Set
The document does not detail an adjudication method. The characterization of serum samples (acute, seropositive, seronegative) was based on the presence or absence of specific markers from a panel of EBV serologies. It's an objective classification based on laboratory results, not subjective interpretation requiring adjudication.
4. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, an MRMC comparative effectiveness study was not reported. This study evaluates an in vitro diagnostic device (ELISA kit), not an AI system or imaging device where human reader performance would be a primary metric.
5. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, this study represents a standalone performance evaluation of the Wampole VCA IgM ELISA Test Kit. The test kit itself is the "algorithm" or device being evaluated, and its performance (sensitivity, specificity, precision, cross-reactivity) is assessed directly against the established ground truth of the serum samples. There is no human-in-the-loop interaction being measured for diagnostic performance, other than the standard laboratory procedures for running the assay.
6. The Type of Ground Truth Used
The ground truth used was expert serological characterization. This was based on a panel of established serological markers for Epstein-Barr Virus infection:
- Acute: VCA IgM present, EBNA IgG absent, Heterophile antibody present.
- Seropositive (Past infection): VCA IgG present, EBNA IgG present, VCA IgM absent, Heterophile antibody absent.
- Seronegative: VCA IgG absent, EBNA IgG absent, VCA IgM absent, Heterophile antibody absent.
This method relies on established clinical and laboratory diagnostic criteria to define the true state of EBV infection for each sample.
7. The Sample Size for the Training Set
The document does not report a separate training set or its sample size. This type of diagnostic device (ELISA kit) typically undergoes development and optimization before an official performance study. The data presented here is for the validation/test phase of the device.
8. How the Ground Truth for the Training Set Was Established
As no specific training set is reported, the method for establishing its ground truth is also not mentioned. For the development and optimization of such assays, manufacturers generally use well-characterized clinical samples or panels from reference laboratories.
§ 866.3235 Epstein-Barr virus serological reagents.
(a)
Identification. Epstein-Barr virus serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to Epstein-Barr virus in serum. The identification aids in the diagnosis of Epstein-Barr virus infections and provides epidemiological information on diseases caused by these viruses. Epstein-Barr viruses are thought to cause infectious mononucleosis and have been associated with Burkitt's lymphoma (a tumor of the jaw in African children and young adults) and postnasal carcinoma (cancer).(b)
Classification. Class I (general controls).