(102 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 patients for serological evidence of previous infection by CMV using manual and semiautomated methods, NEO Iris® and Galileo NEO®.
Capture-CMV® is a Solid Phase Red Cell Adherence System for the detection of IgG and lgM antibodies to Cytomegalovirus (CMV).
The CMV assay is to be used with NEO Iris® and the Galileo NEO® instruments. The NEO Iris®/Galileo NEO® is a microprocessor-controlled instrument that fully automates test processing, result interpretation and data management functions for the associated assays. The instrument is designed to automate, in addition to the CMV assay, standard immunohematology assays using a microplate-based platform. The originally cleared Galileo NEO® (BK100033) was updated with the following modifications in the current submission:
- The Digi CCD camera module was replaced with an IDS CMOS camera module
- Galileo NEO® software was replaced with NEO Iris® Install Set 3.0.1.0 U software and configuration files
- Galileo NEO® versions of the files OiBxEngl.dll and GalileoLogo.bmp were installed to preserve Galileo NEO® branding in the User Interface and on Reports
The provided text describes the regulatory clearance of the Immucor Capture-CMV® assay for use on an upgraded Galileo NEO® instrument. The core of the submission is to demonstrate that the upgraded Galileo NEO® is functionally identical to the NEO Iris® instrument, on which the Capture-CMV® assay was previously cleared. Therefore, no new primary studies were conducted for this specific submission; instead, data from the previous K183571 clearance for the NEO Iris® were presented.
Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided text:
1. Acceptance Criteria and Reported Device Performance
The acceptance criteria are implicitly defined by the reported performance metrics comparing the NEO Iris® (the predicate for the current submission and the reference for the data) to the original Galileo NEO® or the "FDA cleared assay." The key performance metrics are Sensitivity and Specificity.
| Acceptance Criteria (Implied) | Reported Device Performance (NEO Iris® vs. Galileo NEO® / FDA cleared assay) |
|---|---|
| Sensitivity: High sensitivity expected for detecting CMV antibodies. | 100.0% (95% 2-sided LCI: 98.7%) |
| Specificity: High specificity expected for correctly identifying negative samples. | 97.8% (95% 2-sided LCI: 95.0%) |
| Reproducibility: Consistent results across different sites, operators, and runs. | Positive Concordance: 100.0% (95% LCI: 98.5%) for 600 positive tests across 3 sites. |
| Negative Concordance: 99.8% (95% LCI: 99.2%) for 599 out of 600 negative tests across 3 sites (one site had 99.5% concordance for negative). | |
| Cross-reactivity: Minimal cross-reactivity with other common viral antibodies or autoimmune markers. | No cross-reactivity observed with: EBV, HSV (Type I & II, IgM), Parvovirus B19, RF, VZ, Rubella, Toxoplasma gondii. |
| Limited cross-reactivity observed with: Hepatitis A (1 positive out of 5), ANA (1 positive out of 11). |
2. Sample Size Used for the Test Set and Data Provenance
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Test Set for Method Comparison (Clinical Performance):
- Patient Specimens: N=501 total.
- Breakdown by type: Not fully specified if all 501 were unique patients or if it includes serum/plasma duplicates. The table shows 26, 0, 195, and 280 patient specimens collected across 4 sites, summing to 501.
- Breakdown by specimen type: Of the 501, 300 were serum and 201 were plasma.
- Data Provenance: The studies were performed at "four clinical sites, three external sites and internally at Immucor, Inc. for donor specimens and at two external sites and internally at Immucor, Inc. for patient specimens." The specific country of origin is not explicitly stated, but Immucor Inc. is based in Norcross, Georgia, implying US-based studies. The studies are retrospective as the data was from a previously cleared device (K183571).
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Test Set for Reproducibility:
- Panel of Coded Samples: 10 samples (5 CMV antibody positive, 5 CMV antibody negative).
- Total Tests: 1200 (10 samples * 3 sites * 2 operators * 2 runs * 5 days = 1200 total tests). This implies each sample was run multiple times.
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Test Set for Specificity and Cross-reactivity:
- Various numbers of samples for each category of lgG antibodies. For example, 16 for EBV, 23 for HSV, 5 for Hepatitis A, 11 for ANA, etc. The total number of unique samples for this section is the sum of these values.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
The document does not specify the number or qualifications of experts used to establish the ground truth for the test set. For the method comparison study, discordant specimens were further tested with a "commercially available particle agglutination assay for total antibody (IgG+IgM) to CMV" which served as the reference method or "ground truth resolver" for discordant results.
4. Adjudication Method for the Test Set
For the method comparison study, the adjudication method for discordant results was further testing with a "commercially available particle agglutination assay for total antibody (IgG+IgM) to CMV." This acts as a reference standard to resolve differences between the two systems being compared (NEO Iris® and original Galileo NEO®). This is a form of "tie-breaker" or "ground truth resolution" rather than expert consensus adjudication.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, and Effect Size
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not performed. This device is an in vitro diagnostic (IVD) assay system and does not involve human readers interpreting images, so the concept of human readers improving with AI assistance is not applicable. The study focuses on the agreement between two automated instrument platforms (NEO Iris® and Galileo NEO®) and their performance against a reference assay.
6. If a Standalone (algorithm only without human-in-the-loop performance) was done
Yes, this is essentially a standalone performance study. The Capture-CMV® assay, run on the NEO Iris® (and thus, by extension, the upgraded Galileo NEO®), provides a qualitative result (positive or negative) without human intervention in the interpretation of the primary result. The comparison is between two automated systems (NEO Iris® and Galileo NEO®).
7. The Type of Ground Truth Used
The ground truth for the clinical performance assessment (sensitivity and specificity) was established using:
- The results from the original Galileo NEO® instrument as a comparator, specifically for concordance.
- For discordant specimens, a "commercially available particle agglutination assay for total antibody (IgG+IgM) to CMV" was used as the reference standard or "FDA cleared assay." This implies a laboratory-based reference standard or established diagnostic assay as the ground truth.
8. The Sample Size for the Training Set
The document does not explicitly mention a "training set" in the context of an AI/ML device. The Capture-CMV® assay is an in vitro diagnostic test system based on a solid phase red cell adherence principle, not an AI/ML algorithm that requires training data in the conventional sense. The "development" and "verification" activities referenced are typical for IVD device development, not AI model training. Therefore, a sample size for a training set (as understood for AI/ML) is not applicable or provided.
9. How the Ground Truth for the Training Set was Established
As this is not an AI/ML device, the concept of a training set and its ground truth establishment does not apply in the same way. The development and verification process for IVD assays involves establishing performance characteristics against known positive and negative samples, and the consistency of these characteristics across manufacturing lots and instrument platforms.
§ 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).