(197 days)
The Elecsys CMV IgG assay is an in vitro qualitative test for the detection of IgG 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 determination of the serological status to CMV in individuals in which a CMV IgG 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 IgG is a two-step sandwich immunoassay with streptavidin microparticles, biotinylated recombinant CMV-specific antigen labeled with a ruthenium complex and electrochemiluminescence detection. The results are determined using a calibration curve which is instrument-specifically generated by a 2-point calibration and a master curve provided via the reagent bar code. Results greater than or equal to 1.0 U/mL are considered reactive CMV IgG antibody. The test system contains the human serum-based calibrators intended for use with the system.
Elecsys PreciControl CMV lgG contains liquid control serum. The controls are used for monitoring the accuracy of the Elecsys CMV IgG immunoassay.
Note: The reagent and calibrators are packaged together in the Elecsys CMV lgG assay kit, while the associated is packaged separately.
Here's an analysis of the provided text regarding the Elecsys CMV IgG device, structured according to your requested information:
Elecsys CMV IgG Device Acceptance Criteria and Supporting Study
The provided 510(k) summary details the performance evaluation of the updated Elecsys CMV IgG assay.
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state a quantitative "acceptance criteria" table with specific thresholds (e.g., "sensitivity ≥ X%", "specificity ≥ Y%"). Instead, it describes various studies conducted and concludes that "All performance specifications were met." and "The analytical studies demonstrate that the device is as safe, as effective, and performs as well as the legally marketed predicate device with improved biotin tolerance level up to 1200 ng/mL."
However, based on the studies described, we can infer performance aspects and reported outcomes:
| Study Type | Implicit Acceptance Criteria/Goal | Reported Device Performance |
|---|---|---|
| Precision | Demonstrate acceptable repeatability and intermediate imprecision. | Repeatability and Intermediate imprecision were calculated according to CLSI EP05-A3. (No specific values provided, but stated that "All performance specifications were met.") |
| Biotin Interference | Achieve improved biotin tolerance; ensure no significant interference below a certain concentration. | Maximum value with no interference observed was 2400 ng/mL. The method sheet will be set to 1200 ng/mL. (Improvements from ≤ 100 ng/mL to ≤ 1200 ng/mL compared to the predicate.) |
| Method Comparison to Predicate | Demonstrate substantial equivalence between the updated assay and the predicate (K131605). | Positive Agreement and Negative Agreement were calculated. "The resulting data support the equivalence of the current non-biotin and biotin-updated assay." (No specific agreement percentages provided, but equivalence was concluded.) |
| Stability | Maintain performance over time under specified conditions. | "The stability data supports Roche Diagnostic's claims as reported in the package labeling." (No specific duration or performance metrics provided, but claims were supported.) |
2. Sample Size Used for the Test Set and Data Provenance
- Precision Study:
- Sample Size: "3 levels of controls and 5 human serum samples per run, 2 runs per day for 21 days." This totals (3 controls + 5 samples) * 2 runs * 21 days = 336 individual measurements (or 21 days of testing on 8 distinct samples).
- Data Provenance: The text states "human serum samples" and "native human serum pools" for interference studies, implying human origin. No specific country of origin is mentioned. The studies are described as internal performance evaluations, which are typically prospective for the device under development.
- Biotin Interference Study:
- Sample Size: "three serum samples (negative, positive close to cut-off, positive)" were used, each subjected to "11 dilution steps." This amounts to 3 samples * 11 dilutions = 33 individual sample preparations for testing.
- Data Provenance: "Native human serum pools" and "a single serum donor." No specific country of origin or retrospective/prospective nature is stated, but it's an analytical study, likely prospective.
- Method Comparison to Predicate:
- Sample Size: "A total of 280 samples."
- Data Provenance: Not specified, but likely human serum/plasma samples. The study is analytical and likely prospective.
General Note on Data Provenance: For all studies, the document does not specify the country of origin of the data or explicitly state if the studies were retrospective or prospective, though the nature of these analytical performance studies suggests they were conducted prospectively as part of the device development and validation.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The device is an in vitro diagnostic (IVD) for the detection of IgG antibodies to CMV. The "ground truth" for such assays typically relies on established reference methods, a "gold standard" laboratory test result, or classification based on a patient's clinical status (e.g., infected vs. uninfected based on a battery of tests or clinical history).
The provided text does not mention the use of experts (like radiologists) to establish ground truth for any of the studies. For IVDs, "ground truth" is usually analytical (e.g., a sample spiked with a known concentration, or a sample with a confirmed status by a highly sensitive and specific reference method).
4. Adjudication Method for the Test Set
Since the studies described are analytical performance studies for an IVD, and not clinical studies involving interpretation by multiple human readers, there is no mention of an adjudication method like 2+1 or 3+1. Ground truth for these types of studies is typically established by the analytical reference method or preparation of known samples.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study is relevant for imaging devices where human readers interpret results, sometimes with and without AI assistance, to assess the impact of AI on reader performance. The Elecsys CMV IgG is an automated immunoassay, not an imaging device requiring human interpretation of results in the same manner.
6. If a Standalone (i.e., Algorithm Only Without Human-in-the-Loop Performance) Was Done
Yes, the studies described are essentially standalone performance evaluations of the device (Elecsys CMV IgG assay). As an automated immunoassay, the "algorithm" (the assay's chemical reactions and instrument's detection/calculation) provides a result directly. The studies like precision, biotin interference, and method comparison assess the performance of the assay itself without human intervention in the result determination process. The output is a quantitative (U/mL) or qualitative (reactive/non-reactive) result.
7. The Type of Ground Truth Used
The types of "ground truth" implicitly used in the analytical studies are:
- Known Sample Status/Concentration: For the precision study, controls and samples with a certain expected concentration or qualitative status were used.
- Known Biotin Concentration: For the biotin interference study, samples were "spiked with the interfering endogenous substance" (biotin) to known concentrations.
- Predicate Device Results: For the method comparison study, the results from the legally marketed predicate device (Elecsys CMV IgG K131605) served as a comparative "ground truth" to demonstrate equivalence.
The document does not mention pathology, expert consensus, or outcomes data as ground truth, which are more common for diagnostic imaging or clinical decision support AI devices.
8. The Sample Size for the Training Set
The Elecsys CMV IgG assay is an immunoassay, not a machine learning or AI algorithm in the contemporary sense that requires a "training set" for model development. The assay relies on established biochemical reactions (electrochemiluminescence immunoassay "ECLIA"), calibration curves, and reagent lot-specific master curves. Therefore, there is no "training set" in the context of typical AI/ML algorithm development.
9. How the Ground Truth for the Training Set Was Established
As there is no "training set" for an AI/ML algorithm, this question is not applicable to the Elecsys CMV IgG device as described. The assay's performance is driven by its chemical formulation, reagents, and instrument calibration, not by a learned model from a training dataset.
§ 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).