(88 days)
Immunoassay for the in vitro qualitative detection of IgM antibodies to CMV in human serum, lithium-heparin plasma, K2-EDTA plasma, and K3-EDTA plasma. The test is intended as an aid in the diagnosis of recent or current CMV infection in individuals for which a CMV IgM test was ordered, including pregnant women.
Performance characteristics have not been evaluated in immunocompromised or immunosuppressed individuals. This test is not intended for use in neonatal screening or for use at point of care facilities. This test is not intended for use in screening blood and plasma donors.
The electrochemiluminescence immunoassay "ECLIA" is intended for use on cobas e immunoassay analyzers.
Elecsys CMV IgM is a qualitative assay for the detection of IgM antibodies to CMV in human serum and plasma for use on the cobas e 801 immunoassay analyzer. The cobas e 801 immunoassay analyzer is a fully automated, software controlled analyzer system for in vitro determination of analytes in human body fluids. It is part of the cobas 8000 modular analyzer series cleared under K100853. It uses electrochemiluminescent technology for signal generation and measurement.
The document describes the Elecsys CMV IgM assay on the cobas e 801 analyzer, which is a qualitative immunoassay for the detection of IgM antibodies to CMV. The submission (K163569) seeks to demonstrate substantial equivalence to a predicate device, the Elecsys CMV IgM on the cobas e 601 (K142133).
Here's an breakdown of the acceptance criteria and study information:
1. Table of Acceptance Criteria and Reported Device Performance
The document doesn't explicitly present a "table of acceptance criteria" with corresponding performance values in every section, but rather states "All results met predefined acceptance criteria" for various performance characteristics. I will compile the relevant performance data points that were provided.
| Performance Characteristic | Acceptance Criteria (Implicit: "met predefined criteria") | Reported Device Performance (Elecsys CMV IgM on cobas e 801) |
|---|---|---|
| Precision | Implicit: Predefined precision limits satisfied. | Repeatability (CV) |
- HSP 1: 1.2%
- HSP 2: 1.3%
- HSP 3: 1.6%
- HSP 4: 1.0%
- HSP 5: 1.0%
- PC CMV IgM 1: 0.9%
- PC CMV IgM 2: 1.9% |
| | | Intermediate Precision (CV) - HSP 1: 2.8%
- HSP 2: 1.8%
- HSP 3: 1.8%
- HSP 4: 1.4%
- HSP 5: 1.8%
- PC CMV IgM 1: 2.6%
- PC CMV IgM 2: 2.2% |
| Analytical Sensitivity | Implicit: LoD below cut-off. | Limit of Blank (LoB): 0.243 COI
Limit of Detection (LoD): 0.276 COI (well below cut-off of 0.7 COI) |
| High Dose Hook Effect | Implicit: No high-dose hook effect observed. | "All results met the predefined acceptance criteria demonstrating no high dose hook effect for the Elecsys CMV IgM assay." |
| Endogenous Interferences | Implicit: No significant interference from tested substances. | No interference from: - Hemoglobin up to 500 mg/dL
- Intralipid up to 1500 mg/dL
- Bilirubin up to 20 mg/dL
- Biotin up to 100 ng/mL
- Rheumatoid factor up to 899 IU/mL |
| Exogenous Interferences (Anticoagulants) | Implicit: Acceptable sample types. | Serum, serum with separating gel, Li-heparin plasma, K2EDTA plasma, K3EDTA plasma are acceptable. |
| Exogenous Interferences (Drugs) | Implicit: No significant interference from tested drugs. | No interference from 18 common drugs, Ganciclovir, and Valganciclovir. |
| Method Comparison (Platform Equivalence) | Implicit: High positive and negative agreement. | Negative Percent Agreement (NPA): 100% (142/142)
Positive Percent Agreement (PPA): 100% (73/73)
Agreement rate for Indeterminate: 75% (6/8) |
2. Sample Size Used for the Test Set and Data Provenance
The document focuses on the technical performance of the device and its equivalence to a predicate. It does not clearly define a "test set" in the context of clinical cohorts but rather describes samples used for various analytical performance studies.
- Precision Study: 84 runs for repeatability and intermediate precision for each of the 7 samples (HSP 1-5, PC CMV IgM 1-2). The samples are referred to as "serum samples." Provenance is not specified (e.g., country of origin, retrospective/prospective).
- Method Comparison (Between Analyzer Platforms): 142 negative plasma samples, 73 positive plasma samples, and 8 indeterminate plasma samples. This totals 223 plasma samples. Provenance (e.g., country, retrospective/prospective) is not specified.
- Interference Studies: Number of samples not explicitly stated; typically involves spiking substances into a limited number of samples.
- Analytical Sensitivity (LoB/LoD): Number of runs/replicates used for determination is not specified, but the methodology (CLSI EP17-A2) implies a structured approach.
Data Provenance: The document generally lacks explicit details on the country of origin for the samples used in these performance studies or whether they were retrospective or prospective. It refers to "in-house studies" and "external clinical studies" for cutoff validation, but specifics are missing from this summary.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
This device is an in vitro diagnostic immunoassay, not an imaging device. Therefore, the concept of "experts" (like radiologists) establishing ground truth for a "test set" in the traditional sense of image interpretation is not directly applicable.
For this type of device:
- The "ground truth" for the test samples (e.g., positive, negative, indeterminate) would typically be established by known clinical status (e.g., confirmed CMV infection or absence of infection based on various clinical and laboratory parameters, potentially using a "gold standard" or reference assay).
- The document implies that the "cutoff was established with in-house studies by characterizing samples using several commercially available CMV IgG and CMV IgM assays" and "validation of the assay cutoff was performed by external clinical studies." This suggests the ground truth (or referent status) for the samples was determined by established laboratory methods, not expert consensus on qualitative interpretation.
No specific number or qualification of "experts" is mentioned for establishing the ground truth of the performance study samples.
4. Adjudication Method for the Test Set
Since this is an immunoassay and "ground truth" is established by laboratory methods rather than subjective expert interpretation, the concept of an "adjudication method" (like 2+1 or 3+1) is not applicable here. The results are quantitative (COI values) and then categorized based on predefined cut-offs.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done
No, an MRMC comparative effectiveness study was not done. This type of study is specifically designed for evaluating diagnostic aids (like AI algorithms in imaging) that assist human readers. The Elecsys CMV IgM assay is a standalone laboratory diagnostic test.
6. If a Standalone (i.e., Algorithm Only Without Human-in-the-Loop Performance) was Done
Yes, the performance data presented (precision, sensitivity, interference, method comparison) represents the standalone performance of the Elecsys CMV IgM assay on the cobas e 801 analyzer. This device does not have a human-in-the-loop component for its primary diagnostic function.
7. The Type of Ground Truth Used
The ground truth used for establishing performance characteristics and assay cut-offs appears to be:
- For Method Comparison: The results from the predicate device (Elecsys CMV IgM on cobas e 601) and potentially other established/commercial CMV IgM assays. The document states "Positive and negative agreement of the results between the two platforms were calculated."
- For Assay Cut-off: "in-house studies by characterizing samples using several commercially available CMV IgG and CMV IgM assays." Additionally, "Validation of the assay cutoff was performed by external clinical studies on the Elecsys 2010." This implies a combination of reference assay results and potentially clinical outcomes/established disease status for the samples used in those studies.
It's not explicitly stated as "pathology" or "outcomes data" in this summary, but rather defined by comparison to other commercial assays and clinical studies.
8. The Sample Size for the Training Set
This document describes the validation of a commercial in vitro diagnostic assay, not an AI/machine learning algorithm that requires a "training set" in the same way. The principles for developing diagnostic assays involve extensive research and development phases where reagents, protocols, and cutoffs are refined. The "training" in this context refers to the development and optimization studies that led to the final assay characteristics.
The specific sample sizes for these development/optimization phases are not provided in this 510(k) summary, as the summary focuses on the final analytical and comparative performance data for the substantial equivalence determination.
9. How the Ground Truth for the Training Set Was Established
Again, applying the term "training set" directly to a traditional immunoassay is not precise. However, for the establishment of the assay cut-off (which is analogous to setting decision boundaries in an algorithm), the summary states:
- "The cutoff was established with in-house studies by characterizing samples using several commercially available CMV IgG and CMV IgM assays."
- "Validation of the assay cutoff was performed by external clinical studies on the Elecsys 2010."
This indicates that the "ground truth" for determining the assay cut-offs was established through a combination of results from other established commercial CMV assays and samples from clinical studies, which would have had their CMV status determined by other means (e.g., patient history, other diagnostic tests, or clinical follow-up). The exact "how" for these broader clinical studies is referenced as being included in the predicate device's K-submission (K142133).
§ 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).