(46 days)
The Varelisa ReCombi ANA Profile EIA kit is designed for the qualitative determination of eight antinuclear antibodies in human serum or plasma to aid in the diagnosis of SLE (systemic lupus erythematosus), scleroderma (progressive systemic sclerosis and CREST syndrome), MCTD (mixed connective tissue disease), SS (Sjögren's syndrome) and polymyositis/dermatomyositis. The Varelisa ReCombi ANA Profile individually detects antibodies against dsDNA, U1 RNP (RNP 70 kDa,A,C), SmD, SS-A/Ro(52 kDa, 60 kDa), SS-B/La, Scl-70, CENP-B and Jo-1.
The new device is an enzyme-linked immunosorbent assay (ELISA) using microtiter plates as the solid phase. Plate wells each coated with 1 of 8 different ANA antigens are included to allow corresponding antibodies in the patient samples react with the immobilized antigens. The conjugate is rabbit anti-human IgG horseradish peroxidase (HRP), which uses 3, 3'5, 5' tetramethylbenzidine dihydrochloride (TMB) as substrate. The kit contains a calibrator and a negative control. The kit also contains sample diluent, wash buffer concentrate and stop solution.
Here's an analysis of the acceptance criteria and study information based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The provided text does not explicitly state numerical acceptance criteria for the Varelisa ReCombi ANA Profile. Instead, it focuses on demonstrating "substantial equivalence" to predicate devices through comparability studies. Therefore, reported device performance is framed in terms of agreement with predicate devices and established reference standards.
| Criterion Type | Acceptance Criteria (Explicitly Stated in Document) | Reported Device Performance |
|---|---|---|
| Comparability (General) | Substantial equivalence to predicate device. | "all available data support that the new device is substantially equivalent to the predicate device and that the new device performs according to state-of-the-art expectations." |
| Agreement with Predicate (New vs. K993109) | Qualitative determination of IgG antibodies against seven antinuclear proteins and dsDNA, recommending same sample dilutions and using identical reagents. | Both assays are indirect noncompetitive enzyme immunoassays for the qualitative determination of IgG antibodies against seven antinuclear proteins and dsDNA. Both recommend the same sample dilutions and use identical reagents (including the conjugate). The difference is the use of a synthetic SmD peptide instead of native Sm antigen. |
| Agreement with Predicate (New SmD vs. K042629) | Qualitative determination of IgG antibodies against SmD antigens, recommending same sample dilutions and using identical reagents and solid phase. | Both assays are indirect noncompetitive enzyme immunoassays for the qualitative determination of IgG antibodies against SmD antigens. Both recommend the same sample dilutions and use identical reagents (including the conjugate). The solid phase used in the new device is identical to the solid phase used in the predicate device. |
| Laboratory Equivalence | Demonstrating comparability via analysis of positive, equivocal, and negative sera, international reference sera, and samples from apparently healthy subjects. | Comparability is supported by: |
- results obtained within a comparison study analyzing positive, equivocal, and negative sera.
- results obtained for international reference sera.
- results obtained for samples from apparently healthy subjects (normal population). |
2. Sample Size Used for the Test Set and Data Provenance
The document mentions "a comparison study analyzing positive, equivocal and negative sera" and "samples from apparently healthy subjects (normal population)" but does not specify the exact sample size for the test set or the country of origin of the data. It can be inferred that the data is retrospective as it refers to a "comparison study" and "available data," suggesting pre-collected samples.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
The document does not specify the number of experts used or their qualifications for establishing ground truth. The nature of the device (an immunoassay for antibody detection) suggests that ground truth would likely be established through clinical diagnosis of autoimmune diseases or by established reference methods for antibody detection, rather than expert interpretation of images or complex data.
4. Adjudication Method for the Test Set
The document does not provide information on any adjudication method used for the test set.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
A Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study is more relevant for diagnostic devices that rely on human interpretation of images or complex data, where the AI might assist a reader. The Varelisa ReCombi ANA Profile is an automated immunoassay where the output is a qualitative determination (positive/negative) based on optical density readings, not a human interpretation task.
6. Standalone (Algorithm Only) Performance Study
Yes, a standalone performance study was done implicitly. The entire evaluation described for the Varelisa ReCombi ANA Profile relates to its performance as a standalone assay, comparing its results directly to predicate devices and reference materials. The device is the algorithm, producing results without human-in-the-loop assistance for interpretation of the test itself.
7. Type of Ground Truth Used
The ground truth used appears to be a composite of:
- Clinical Diagnosis: The intended use states the kit "aids in the diagnosis of SLE... scleroderma... MCTD... SS and polymyositis/dermatomyositis," implying that patient samples from individuals with confirmed diagnoses of these conditions would serve as ground truth for "positive" samples.
- Established Reference Materials: The study mentions "results obtained for international reference sera," indicating that recognized standard antibody preparations were used as ground truth.
- Predicate Device Results (as a gold standard proxy): A significant part of the study involves comparing the new device's results to those obtained with the predicate devices for positive, equivocal, and negative sera. This suggests the predicate device's performance served as a de-facto "ground truth" for demonstrating equivalence.
- Healthy Controls: "Samples from apparently healthy subjects (normal population)" were used to establish negative ground truth.
8. Sample Size for the Training Set
The document does not mention a training set or its sample size. This is typical for a traditional immunoassay device. "Training" in the context of an AI/ML device would refer to the data used to develop the algorithm. For this device, the "algorithm" is the biochemical assay itself and its reading protocol, not a machine learning model that learns from large datasets. The development process would involve optimization and validation runs rather than distinct "training" and "test" sets in the AI sense.
9. How the Ground Truth for the Training Set Was Established
As no training set is mentioned in the AI/ML context, this question is not applicable. The "ground truth" for the development of the assay would have been established through a combination of chemical and biological principles, known antibody-antigen reactions, and clinical validation against diagnosed patient samples and controls, rather than a specific "ground truth for a training set."
§ 866.5100 Antinuclear antibody immunological test system.
(a)
Identification. An antinuclear antibody immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the autoimmune antibodies in serum, other body fluids, and tissues that react with cellular nuclear constituents (molecules present in the nucleus of a cell, such as ribonucleic acid, deoxyribonucleic acid, or nuclear proteins). The measurements aid in the diagnosis of systemic lupus erythematosus (a multisystem autoimmune disease in which antibodies attack the victim's own tissues), hepatitis (a liver disease), rheumatoid arthritis, Sjögren's syndrome (arthritis with inflammation of the eye, eyelid, and salivary glands), and systemic sclerosis (chronic hardening and shrinking of many body tissues).(b)
Classification. Class II (performance standards).