(65 days)
The Wielisa Anti-GBM, ANCA Screening Test Kit is an enzyme-linked immunosorbent assay (ELISA) for the qualitative detection of antibodies to glomerular basement membrane (GBM), Proteinase-3 (PR-3) and Myeloperoxidase (MPO) in human sera. The assay is used to detect antibodies in a single serum specimen. The results of the assay are to be used as an aid to the diagnosis of reno-pulmonary syndromes and rapidly progressive glomerulonephritis, especially Goodpasture syndrome (GP), Wegener's granulomatosis (WG) and microcopic polyangiitis (MP). The assay is intended for use in patients with signs and symptoms consistent with GP, WG, and MP. It is not intended for screening a healthy population. A positive result should always be confirmed by a semi-quantitative assay.
The Wielisa Anti-GBM, ANCA Screening Test Kit is an II. enzyme-linked immunosorbent assay (ELISA) for the qualitative detection of antibodies to glomerular basement membrane (GBM), Proteinase-3 (PR-3) and Myeloperoxidase (MPO) in human sera. The assay is used to detect antibodies in a single serum specimen. The results of the assay are to be used as an aid to the diagnosis of reno-pulmonary syndromes and rapidly progressive glomerulonephritis, especially Goodpasture syndrome (GP). Wegener's granulomatosis (WG) and microcopic polyangiitis (MP). The assay is intended for use in patients with signs and symptoms consistent with GP, WG, and MP. It is not intended for screening a healthy population. A positive result should always be confirmed by a semi-quantitative assay.
The wells of the microtiter strips are coated with purified proteinase 3 (Human Neutrophil source). MPO (Human Neutrophil source) and GBM (Bovine source) antigen. During the first incubation, specific antibodies in diluted serum, will bind to the antigen coating.
The wells are then washed to remove unbound antibodies and other components. A coniugate of alkaline phosphatase-labeled (Goat) antibodies to human IgG binds to the antibodies in the wells in this second incubation.
After a further washing step, detection of specific antibodies is obtained by incubation with substrate solution. The amount of bound antibodies correlates to the color intensity and is measured in terms of absorbance (optical density (OD)). The absorbance is then calculated and the results are given as a ratio to the negative control.
Here's a breakdown of the acceptance criteria and study information for the Wielisa Anti-GBM, ANCA Screening Test Kit, based on the provided text:
Device Description: The Wielisa Anti-GBM, ANCA Screening Test Kit is an enzyme-linked immunosorbent assay (ELISA) for the qualitative detection of antibodies to glomerular basement membrane (GBM), Proteinase-3 (PR-3), and Myeloperoxidase (MPO) in human sera. It's used as an aid to diagnose reno-pulmonary syndromes and rapidly progressive glomerulonephritis (Goodpasture syndrome, Wegener's granulomatosis, and microscopic polyangiitis).
1. Acceptance Criteria and Reported Device Performance
The acceptance criteria are implicitly defined by the clinical sensitivity and specificity results. The device aims to achieve high sensitivity (correctly identifying positive cases) and high specificity (correctly identifying negative cases) for each antibody against various disease states and controls.
| Metric (Antibody) | Target/Acceptance Criteria (Implicit) | Reported Device Performance |
|---|---|---|
| Clinical Sensitivity | ||
| PR3-ANCA (WG) | High | 92.9% (95% CI: 84.9 – 100%) |
| PR3-ANCA (MP) | High | 51.2% (95% CI: 35.6-66.8%) |
| MPO-ANCA (WG) | High | 9.8% (95% CI: 4.9 – 19.0%) |
| MPO-ANCA (MP) | High | 46.5% (95% CI: 31.3-61.7%) |
| Anti-GBM (GP) | High | 100% (95% CI: 92.2 – 100%) |
| Clinical Specificity | ||
| PR3-ANCA (SLE) | High | 100% (95% CI: 90.4 – 100%) |
| PR3-ANCA (RA) | High | 100% (95% CI: 92.7 - 100%) |
| PR3-ANCA (NS) | High | 100% (95% CI: 97.7 - 100%) |
| MPO-ANCA (SLE) | High | 82.8% (95% CI: 68.7 - 96.8%) |
| MPO-ANCA (RA) | High | 100% (95% CI: 92.6 - 100%) |
| MPO-ANCA (NS) | High | 100% (95% CI: 97.6 - 100%) |
| Anti-GBM (SLE) | High | 100% (95% CI: 90.4 -100%) |
| Anti-GBM (RA) | High | 100% (95% CI: 92.7 - 100%) |
| Anti-GBM (NS) | High | 100% (95% CI: 97.6 – 100%) |
| Relative Sensitivity (vs. Semi-quantitative ELISA) | ||
| PR3-ANCA | High | 98.3% (95% CI: 95.0 - 100%) |
| MPO-ANCA | High | 95.8% (95% CI: 87.7 - 100%) |
| Anti-GBM | High | 100% (95% CI: 92.0 - 100%) |
| Relative Specificity (vs. Semi-quantitative ELISA) | ||
| PR3-ANCA | High | 100% (95% CI: 98.0 - 100%) |
| MPO-ANCA | High | 100% (95% CI: 98.4 - 100%) |
| Anti-GBM | High | 100% (95% CI: 97.7 - 100%) |
| Precision | Low CV% (for intra-assay, inter-assay, batch-to-batch) | All reported CV% values are below 21%, indicating good precision. |
2. Sample Size Used for the Test Set and Data Provenance
- Clinical Sensitivity and Specificity Study:
- Sample Size: A total of 326 frozen serum samples.
- Data Provenance: Retrospective sera. The country of origin is not explicitly stated.
- Blood donors (NS): 131 samples
- Wegener's granulomatosis (WG): 42 samples
- Microscopic polyangiitis (MP): 43 samples
- Systemic lupus erythematosus (SLE): 31 samples
- Rheumatoid arthritis (RA): 41 samples
- Goodpasture syndrome (GP): 38 samples
- Relative Sensitivity and Specificity Study (vs. Predicate Device):
- Sample Size:
- 216 frozen retrospective sera for PR-3 and MPO comparison.
- 169 frozen retrospective sera for anti-GBM comparison.
- Data Provenance: Retrospective sera. The country of origin is not explicitly stated.
- Sample Size:
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
The text states that the sera had "clinical characterisation" for the clinical sensitivity and specificity study, and were compared against an "alternative semi-quantitative ELISA" for the relative sensitivity and specificity study. However, the number of experts, their qualifications, or the specific methodology (beyond "clinical characterization") used to establish the ground truth for these samples is not provided in the given text.
4. Adjudication Method for the Test Set
The adjudication method for establishing the ground truth is not provided in the given text.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, an MRMC comparative effectiveness study was not done as this is an in-vitro diagnostic (IVD) device (ELISA kit) that produces quantitative or qualitative results, not interpretations by human readers that would be assisted by AI. Thus, there is no AI assistance or human reader involvement in the primary assay performance.
6. If a Standalone Study Was Done
Yes, the studies presented are standalone (algorithm only) performance studies for the ELISA kit. The "device performance" refers to the output of the ELISA kit itself, without human interpretation or intervention in the diagnostic process beyond performing the assay according to instructions. The device generates an optical density (OD) which is then calculated as a ratio, and categorized as negative, equivocal, or positive.
7. The Type of Ground Truth Used
- Clinical Sensitivity and Specificity Study: "Clinical characterisation" was used as the ground truth for the disease groups (WG, MP, SLE, RA, GP) and blood donors. This implies diagnosis based on clinical evidence, potentially confirmed by other laboratory tests or pathology (though not specified).
- Relative Sensitivity and Specificity Study: The ground truth was established by comparison to results from an "alternative semi-quantitative ELISA" for PR-3, MPO, and anti-GBM. This suggests that the predicate device or a similar established method served as the reference standard.
8. The Sample Size for the Training Set
The text does not provide any information about a training set. This is typical for ELISA kits, where the assay design, antigen selection, and analytical parameters are developed through R&D, rather than an explicit "machine learning training set." The studies described focus on validation of the final product.
9. How the Ground Truth for the Training Set Was Established
As no training set is mentioned or described, the method for establishing its ground truth is not applicable/provided.
§ 866.5660 Multiple autoantibodies immunological test system.
(a)
Identification. A multiple autoantibodies immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the autoantibodies (antibodies produced against the body's own tissues) in serum and other body fluids. Measurement of multiple autoantibodies aids in the diagnosis of autoimmune disorders (disease produced when the body's own tissues are injured by autoantibodies).(b)
Classification. Class II (performance standards).