(201 days)
The CopalisTM CMV Total Antibody Assay uses Coupled Particle Light Scattering (Copalis™) technology in a microparticle agglutinationbased immunoassay for the qualitative and semi-quantitative detection of total antibodies (IgG and IgM) to cytomegalovirus (CMV) in human serum using the CopalisTM One Immunoassay System. The presence of antibodies is indicative of current or prior infection with the suspected organism. The results of this assay on a single serum specimen are used to indicate presence of antibody to CMV. When evaluating properly paired sera, the results of this assay are used to demonstrate seroconversion or a significant increase in antibody level as evidence of recent infection. Both specimens should be tested simultaneously (see Interpretation of Results). This assay has not been FDA cleared or approved for the screening of blood or plasma donors.
The Copalis CMV Total Antibody Assay is based on the principle of antibodydependent particle aggregation as detected by measurement of changes in light scattering. Latex particles coated with inactivated CMV antigens aggregate in the presence of antibodies to CMV. After 10 minutes of agitation, the level of aggregation is determined by measurement of the number of reacted and unreacted particles as they flow past a detector. The number of reacted particles is related to the level of CMV antibodies present in the test specimen. Without prior infection, antibody levels are absent or low. After infection, antibody levels rise and usually remain stable (but declining in titer) for years. Reactivity is assessed by the level of aggregation relative to a cutoff value. The Copalis CMV Assay detects the presence of both IgM and IgG antibodies. Two levels of controls are used to monitor proficiency.
Here's a breakdown of the acceptance criteria and study details for the Copalis™ CMV Total Antibody Assay, based on the provided text:
Acceptance Criteria and Reported Device Performance
| Acceptance Criteria | Reported Device Performance |
|---|---|
| Clinical Performance: | Relative Sensitivity: 97.6% |
| Relative Sensitivity (compared to predicate device) | Relative Specificity: 97.8% |
| Relative Specificity (compared to predicate device) | Relative Agreement: 97.7% |
| Reproducibility (Overall %CV): | |
| Reproducibility - Level 1 (RP1) | Site #1: 2.2% (within assay), 0.0% (between assay) |
| Site #2: 2.0% (within assay), 0.6% (between assay) | |
| Site #3: 1.6% (within assay), 0.4% (between assay) | |
| Reproducibility - Level 2 (RP2) | Site #1: 2.8% (within assay), 0.0% (between assay) |
| Site #2: 3.0% (within assay), 1.5% (between assay) | |
| Site #3: 4.5% (within assay), 1.0% (between assay) | |
| Reproducibility - Level 3 (RP3) | Site #1: 3.5% (within assay), 0.0% (between assay) |
| Site #2: 4.4% (within assay), 0.8% (between assay) | |
| Site #3: 5.1% (within assay), 3.9% (between assay) | |
| Reproducibility - Level 4 (RP4) | Site #1: 5.3% (within assay), 1.7% (between assay) |
| Site #2: 6.3% (within assay), 2.0% (between assay) | |
| Site #3: 8.8% (within assay), 3.2% (between assay) | |
| Low Positive Control Total Precision (%CV): | |
| Site #1 Low Positive Control Total Precision | 4.4% |
| Site #2 Low Positive Control Total Precision | 4.1% |
| Site #3 Low Positive Control Total Precision | 4.0% |
| Seroconversion Reproducibility (% agreement with criterion >50% rise): | |
| Site #1 Seroconversion Reproducibility | 100% |
| Site #2 Seroconversion Reproducibility | 63% |
| Site #3 Seroconversion Reproducibility | 97% |
| CDC CMV Serum Panel Agreement: | 100% total agreement |
| Interfering Substances: | No interference from Rheumatoid Factor (RF), Antinuclear Antibodies (ANA), HSV, EBV, VZV, and rubella antibodies. |
Study Details
1. Sample Size Used for the Test Set and Data Provenance:
- Clinical Comparison: 689 patient sera samples.
- Provenance: Samples represented the mid-Atlantic and Gulf Coast regions of the U.S. (likely retrospective, as they are "patient sera samples" and not explicitly stated as prospectively collected for this study, though it's not definitively stated. The context of "tested at 2 clinical laboratories" implies existing samples).
- Reproducibility: 4 samples for general reproducibility (likely internal reference samples, not human patient samples). 30 sets of simulated acute and convalescent pairs for seroconversion reproducibility.
- CDC CMV Serum Panel: 1 panel, composition not specified but mentioned as "66% positive and 34% negative samples" (implies a total size for the panel, but not the exact number of individual samples within it).
2. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications:
- Clinical Comparison: The ground truth for relative sensitivity and specificity was established by the Becton Dickinson and Co. CMVscan Test (the predicate device). No information is provided about human expert involvement in establishing ground truth for the 689 patient samples, as the comparison is against an existing diagnostic test.
- CDC CMV Serum Panel: The panel was "characterized" by the CDC. No information on the number or qualifications of experts involved in the CDC's characterization or ground truth establishment.
3. Adjudication Method for the Test Set:
- Clinical Comparison: Not explicitly stated. The comparison is directly between the Copalis assay and the predicate device. There is no mention of a third adjudicator for discordant results.
- Reproducibility & CDC Panel: Not applicable, as these studies focused on agreement with known values or reproducibility, not a diagnostic decision requiring adjudication.
4. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done:
- No, a multi-reader multi-case (MRMC) comparative effectiveness study was not conducted. This device is an in-vitro diagnostic assay for antibody detection, not an imaging or diagnostic aid that involves human readers interpreting output.
5. If a Standalone (algorithm only without human-in-the-loop performance) was done:
- Yes, this is a standalone device. The Copalis™ CMV Total Antibody Assay is an automated immunoassay system. Its performance (sensitivity, specificity, reproducibility) is measured directly without human interpretation of the assay's output. The "human-in-the-loop" would be the laboratory technician running the assay and interpreting the quantitative results per the device's cutoff values, but the performance metrics provided reflect the device's analytical capability.
6. The Type of Ground Truth Used:
- Clinical Comparison: The ground truth was established by the results of the Becton Dickinson and Co. CMVscan Test (predicate device).
- Reproducibility: The ground truth was based on pre-defined reference standards (e.g., control samples with expected reactivity levels, simulated acute/convalescent pairs with known seroconversion status).
- CDC CMV Serum Panel: The ground truth was the "characterized" results from the CDC CMV Serum Panel.
7. The Sample Size for the Training Set:
- The document does not report information about a training set. This is common for traditional immunoassay development, where performance is optimized through assay formulation and component selection, rather than through machine learning models that require distinct training and testing datasets.
8. How the Ground Truth for the Training Set Was Established:
- Since no training set is reported, this information is not applicable.
§ 866.3175 Cytomegalovirus serological reagents.
(a)
Identification. Cytomegalovirus serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to cytomegalovirus in serum. The identification aids in the diagnosis of diseases caused by cytomegaloviruses (principally cytomegalic inclusion disease) and provides epidemiological information on these diseases. Cytomegalic inclusion disease is a generalized infection of infants and is caused by intrauterine or early postnatal infection with the virus. The disease may cause severe congenital abnormalities, such as microcephaly (abnormal smallness of the head), motor disability, and mental retardation. Cytomegalovirus infection has also been associated with acquired hemolytic anemia, acute and chronic hepatitis, and an infectious mononucleosis-like syndrome.(b)
Classification. Class II (performance standards).