(45 days)
Capture-CMV® is an in vitro qualitative solid phase red cell adherence test system for the detection of antibodies (IgG plus IgM) to cytomegalovirus (CMV) in human serum or plasma. Capture-CMV is intended to be used in screening of blood and plasma donors or patients for serological evidence of previous infection by CMV.
Capture-CMV is a solid phase red cell adherence antibody detection system based on procedures of Plapp et al. This procedure is a modification of the mixed agglutination tests for antigen and antibody detection of Coombs et al. and Hogman employing anti-IgG and IgM-coated red cells as the indicator system. Serum or plasma samples are added to the viral-coated wells. The samples are incubated for five minutes; during which antibodies specific for CMV proteins bind to immobilized viral proteins. Unbound immunoglobulins are washed from the wells and replaced with a suspension of anti-IgG plus anti-IgM-coated indicator red cells. Centrifugation brings the indicator red cells in contact with antibodies bound to the immobilized viral proteins. In the case of a positive test, the migration of the indicator cells to the bottom of the well is impeded as the anti-IgG and anti-IgM bridges are formed between the indicator red cells and the viral-bound antibodies. As a consequence, the indicator red cells adhere over the surface of the test well. In contrast, in the absence of viral antigen-antibody interactions (i.e. a negative test) the indicator red cells are not impeded during their migration, and pellet to the bottom of the well as a packed, well-defined cell button. CMV antigen from cytomegalovirus strain AS 169 grown in human foreskin fibroblast cells is inactivated and coated onto microtitration wells and dried.
Here's an analysis of the provided text to fulfill your request regarding acceptance criteria and the study proving the device meets them:
Device: Capture-CMV®
Intended Use: An in vitro qualitative solid phase red cell adherence test system for the detection of antibodies (IgG plus IgM) to cytomegalovirus (CMV) in human serum or plasma. Intended for use in screening of blood and plasma donors or patients for serological evidence of previous infection by CMV.
The document describes the performance of the Capture-CMV assay specifically when run on the NEO Iris instrument, comparing it to the predicate device (Capture-CMV on Galileo Neo). The "acceptance criteria" here are implied by the clinical performance targets for sensitivity and specificity necessary to demonstrate substantial equivalence to the predicate device and suitability for its intended use.
1. Table of Acceptance Criteria and Reported Device Performance
The document doesn't explicitly state "acceptance criteria" in a separate table with quantified thresholds before presenting the results. Instead, it presents the results of clinical performance studies (sensitivity and specificity) and reproducibility, which implicitly demonstrate that the device meets the required performance for its intended use and substantial equivalence to the predicate. The performance of the predicate device (Galileo Neo) serves as the de facto benchmark.
Based on the "CMV Resolved Results" and "Concordance by Site" tables, the performance targets appear to be very high agreement with the predicate and high sensitivity/specificity.
| Performance Metric | Implicit Acceptance Criteria (based on provided data demonstrating performance) | Reported Device Performance (Capture-CMV on NEO Iris) |
|---|---|---|
| Sensitivity | High, approaching 100% (to ensure detection of CMV antibodies) | 100.0% (98.7%, 95% 2-sided LCI) |
| Specificity | High, approaching 100% (to minimize false positives) | 97.8% (95.0%, 95% 2-sided LCI) |
| Reproducibility (Positive Samples) | 100% concordance across sites and runs | 100.0% (98.5% LCI) |
| Reproducibility (Negative Samples) | High concordance across sites and runs (minimal false positives) | 99.8% (99.2% LCI) |
2. Sample Size Used for the Test Set and Data Provenance
- Test Set Sample Size: N=501 patient samples were used for the method comparison study (sensitivity and specificity analysis). For reproducibility, 10 coded samples (5 positive, 5 negative) were tested for 400 total tests per site across 3 sites, totaling 1200 tests.
- Data Provenance: The studies were conducted at three clinical sites: two external sites and internally at Immucor, Inc. The document does not specify the country of origin but implies a US context given the FDA submission. The study appears to be retrospective as it uses existing patient samples and compares the new device to a predicate device and a commercial particle agglutination assay.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
The document does not explicitly state the number or qualifications of experts used to establish the ground truth.
However, the ground truth for discordant results was established by further testing with a commercially available particle agglutination assay for total antibody (IgG+IgM) to CMV. This implies that the accepted "gold standard" or reference method for CMV antibody detection served as the arbiter, rather than human experts reviewing raw data. For reproducibility, "Expected Positive" and "Expected Negative" values were used for the coded samples, implying a pre-established ground truth for these control samples.
4. Adjudication Method for the Test Set
- For the sensitivity and specificity comparison: Discordant results between the NEO Iris and Galileo Neo were adjudicated using a commercially available particle agglutination assay for total antibody (IgG+IgM) to CMV. This acts as an objective, third-party reference method for reconciliation.
- For reproducibility: The reproducibility study used "coded samples" with "Expected Positive" and "Expected Negative" results, implying that these samples had a predetermined ground truth. No further adjudication method is described beyond comparing the device's output to these expected results.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done
No, an MRMC comparative effectiveness study was not done. This device is an in vitro diagnostic (IVD) assay that produces a qualitative (positive/negative) result, not an imaging device requiring human interpretation. Therefore, a multi-reader study is not applicable. The comparison here is between different automated analyzer platforms run by presumably trained lab technicians.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was Done
Yes, the performance presented is inherently standalone (algorithm/device only). The Capture-CMV assay on the NEO Iris instrument is an automated system that produces a result (positive/negative for CMV antibodies). The performance metrics (sensitivity, specificity, reproducibility) reflect the device's ability to correctly classify samples based on its internal processes, without direct human intervention in the result determination beyond loading samples and running the assay.
7. The Type of Ground Truth Used
- For the method comparison (sensitivity/specificity): The initial ground truth seems to be established by the predicate device (Capture-CMV on Galileo Neo), and discordant results were then resolved using an alternative commercial reference assay (particle agglutination assay). This is a form of reference standard test result.
- For reproducibility: The ground truth was based on pre-defined "expected" results for coded positive and negative control samples.
8. The Sample Size for the Training Set
The document does not mention a training set sample size. This is typical for a traditional IVD device like this, which is validated through performance studies rather than developed using machine learning with distinct training and test sets in the same way an AI/ML algorithm would be. The "training" in this context would likely refer to the iterative development and optimization of the assay's biochemical components and the instrument's operational parameters, which is not usually quantified as a "training set" in regulatory submissions for non-AI devices.
9. How the Ground Truth for the Training Set was Established
As noted above, a distinct "training set" in the AI/ML sense is not described. The device's performance is validated against clinical samples and known control materials. Any "ground truth" during the development phase would have been established through a combination of well-characterized clinical samples, reference laboratory methods, and known concentrations of analytes, analogous to how IVD assays are traditionally developed and optimized.
§ 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).