(286 days)
For the qualitative and semi-quantitative determination of IgG antibodies to Epstein-Barr Virus (recombinant) Viral Capsid Antigen (EBV-VCA IgG) in human serum by indirect enzyme immunoassay. The Is-EBV-VCA IgG Test Kit may be used in combination with other Epstein-Barr serologies (Viral Capsid Antigen (VCA) IgM , Epstein-Barr Nuclear Antigen-1 (EBNA-1) IgG and IgM, Early Antigen-Diffuse (EA-D) IgG and IgM and heterophile antibody as an aid in the diagnosis of infectious mononucleosis (IM). The evaluation of paired sera, to determine a significant increase in VCA IgG antibody titer, can also aid in the diagnosis of acute infection. These reagents can be used either manually or in conjunction with the MAGO® Plus Automated Processor.
The EBV-VCA IgG ELISA Kit is an enzyme-linked immunosorbent assay (ELISA) for the detection of IgG to Epstein Barr viral capsid antigen in human serum. Recombinant VCA antigen is bound to microwells. Diluted patient sera, Cut-Off Calibrator and controls are placed in the microwells and incubated. Anti-VCA IgG antibodes, if present, will bind to the antigen forming, antigen-antibody complexes. Residual sample is eliminated by aspirating and washing. Conjugate (horseradish peroxidase-labeled anti-human IgG) is added and will bind to these complexes. Unbound conjugate is removed by aspiration and washing. Substrate is then added and incubated. In the presence of bound enzyme the substrate is converted to an end product. The absorbance of this end product can be read spectrophotometrically at 450 nm (reference 600-630 nm) and is directly proportional to the concentration of IgG antibodies to VCA present in the sample.
Here's a breakdown of the acceptance criteria and the study that proves the device meets them, based on the provided text:
Acceptance Criteria and Device Performance
1. Table of Acceptance Criteria and Reported Device Performance:
The document doesn't explicitly state "acceptance criteria" as a separate, pre-defined set of thresholds that the device must meet. Instead, it presents the "Performance Characteristics" of the proposed device and implicitly compares them to the predicate device. For this table, I will infer "acceptance criteria" from the performance characteristics of the predicate device (Wampole EBV-VCA IgG ELISA) and the general expectation for such tests, and then show the proposed device's performance against them.
| Performance Metric | Acceptance Criteria (Inferred from Predicate/Industry Standard) | Reported Device Performance (Diamedix Is-EBV-VCA IgG ELISA Kit) |
|---|---|---|
| Relative Sensitivity | Likely 100% (as per predicate) | 100% (for past infection sera) |
| Relative Sensitivity (Current Infection) | Not explicitly stated for predicate, but high sensitivity expected | 84.8% |
| Relative Specificity (Seronegative) | 100% (as per predicate) | 93.8% |
| Overall Agreement | 100% (as per predicate) | 95.7% |
| Intra-assay Precision (CV%) | Below 10.0% for positive samples (typical for ELISA) | Manual: 1.56-9.30% |
| MAGO Plus: 2.48-12.03% | ||
| Inter-assay Precision (CV%) | Below 15.0% for positive samples (typical for ELISA) | Manual: 4.28-10.50% |
| MAGO Plus: 6.99-9.21% | ||
| Cross-reactivity | No significant cross-reactivity expected | No cross-reactivity with VZV, CMV, HSV IgG antibodies |
| Manual/Automated Correlation (Pearson Correlation Coefficient) | Strong positive correlation (e.g., >0.90) expected | 0.986 |
Notes on Acceptance Criteria:
- The document frames the study as demonstrating "substantial equivalence" to the predicate device, the Wampole VCA IgG ELISA. Therefore, the predicate device's performance characteristics serve as the primary benchmark.
- "Relative Sensitivity" is given for "Current Infection" specifically for the proposed device, while the predicate only lists "Relative Sensitivity" generally. This indicates a more nuanced evaluation of the proposed device.
- Precision results from Site #2 for MAGO Plus show one value (12.03%) for a positive sample (Serum C, Run 3) that is slightly higher than a typical 10% threshold, but overall the ranges are within acceptable limits for diagnostic assays. The negative sample precision can be higher.
2. Sample size used for the test set and the data provenance:
- Sample Size: 175 frozen retrospective sera.
- 102 convalescent sera
- 34 seronegative sera
- 39 current (recent) infection sera
- Data Provenance: The document states "Frozen retrospective sera from one hundred and seventy-five patients were characterized using commercially available kits..." It does not specify the country of origin of the data. It explicitly states the data is retrospective.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
The ground truth for the test set was established using commercially available kits for VCA IgG, VCA IgM, EBNA IgG and heterophile antibodies, rather than human expert consensus. Therefore, no information is provided on the number or qualifications of experts.
4. Adjudication method (e.g., 2+1, 3+1, none) for the test set:
Not applicable. The ground truth was established by laboratory testing with commercially available kits, not through human adjudication of interpretations.
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, a multi-reader multi-case comparative effectiveness study was not performed. This device is an ELISA kit, which is a laboratory test for determining antibody presence, not an imaging or diagnostic AI tool that assists human readers.
6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
Yes, a standalone performance study was done. The "Clinical Sensitivity and Specificity Using Characterized Sera" section directly assesses the performance of the Is-EBV-VCA IgG Test Kit (the algorithm/device) against the established serological status of patient samples. The device yielded quantitative results (index values) that were interpreted as positive, negative, or equivocal based on predetermined cut-offs.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
The ground truth was established by serological characterization using commercially available diagnostic kits. Specifically, sera were categorized as convalescent, seronegative, or current infection based on their reactivity patterns to VCA IgG, VCA IgM, EBNA IgG, and heterophile antibodies using reference kits. This is a form of reference standard testing (laboratory test results).
8. The sample size for the training set:
The document does not mention a training set. This type of device (ELISA kit) typically does not involve machine learning or AI models that require a separate training set. Its manufacturing and calibration are based on established biochemical principles and quality control, not iterative learning from data.
9. How the ground truth for the training set was established:
Not applicable, as no training set is mentioned or implied for this type of diagnostic kit.
§ 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).