(104 days)
The Wielisa PR-3 ANCA Test Kit is an enzyme-linked immunosorbent assay (ELISA) for the detection and semi-quantitation of antibodies to Proteinase-3 (PR-3) 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 Wegener's granulomatosis.
The Wielisa PR-3 ANCA Test Kit is an enzyme-linked immunosorbent assay (ELISA) for the detection and semi-quantitation of lgG antibodies to Proteinase-3 (PR-3) 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 Wegener's granulomatosis. FOR IN VITRO DIAGNOSTIC USE.
The wells of the microtiter strips are coated with purified proteinase 3. 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 conjugate of alkaline phosphatase-labeled 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 against a calibrator curve and the results are given in arbitrary units.
The provided text is a summary of safety and effectiveness information for the Wielisa PR-3 ANCA Test Kit, a medical device cleared by the FDA in 1998. It primarily focuses on demonstrating substantial equivalence to a predicate device and presenting performance data from various studies.
Here's an attempt to extract the requested information, acknowledging that specific "acceptance criteria" (i.e., predefined thresholds for performance that the device must meet) are not explicitly stated as typical in modern regulatory submissions. Instead, the document presents the reported performance and implicitly expects these results to be sufficient to demonstrate substantial equivalence to the predicate.
Acceptance Criteria and Device Performance for Wielisa PR-3 ANCA Test Kit
1. Table of Acceptance Criteria and Reported Device Performance
As explicit, pre-defined acceptance criteria (e.g., "Sensitivity must be >90%") are not stated in the document, the "Reported Device Performance" column reflects what was achieved in the studies, which implicitly served as the basis for FDA clearance. The predicate device's performance is not detailed in this document, so direct comparison against a numerical benchmark from the predicate is not possible from the given text.
| Performance Metric | Implicit Acceptance Criteria (based on predicate equivalence) | Reported Device Performance (Wielisa PR-3 ANCA Test Kit) | Study Reference |
|---|---|---|---|
| Clinical Sensitivity (WG) | Sufficient for aid in diagnosis | 92.9% (95% CI: 86.7-99.0%) | Table 1 |
| Clinical Sensitivity (MP) | Sufficient for aid in diagnosis | 50.0% (95% CI: 36.1-63.9%) | Table 1 |
| Clinical Specificity (SLE) | Sufficient for aid in diagnosis | 97.4% (95% CI: 92.4-100%) | Table 1 |
| Clinical Specificity (RA) | Sufficient for aid in diagnosis | 100% (95% CI: 82.7-100%) | Table 1 |
| Clinical Specificity (GBM) | Sufficient for aid in diagnosis | 93.6% (95% CI: 87.3-99.8%) | Table 1 |
| Clinical Specificity (Normals) | Sufficient for aid in diagnosis | 100% (95% CI: 97.5-100%) | Table 1 |
| Relative Sensitivity (vs C-ANCA IFA) | Comparable to predicate device | 96.3% (95% CI: 92.1-100.0%) | Table 2 |
| Relative Specificity (vs C-ANCA IFA) | Comparable to predicate device | 91.9% (95% CI: 87.6-96.2%) | Table 2 |
| Relative Accuracy (vs C-ANCA IFA) | Comparable to predicate device | 93.4% (95% CI: 90.2-96.6%) | Table 2 |
| Relative Sensitivity (vs Alternate ELISA) | Comparable to predicate device | 100% (95% CI: 92.0-100%) | Table 3 |
| Relative Specificity (vs Alternate ELISA) | Comparable to predicate device | 97.5% (95% CI: 94.1-100%) | Table 3 |
| Relative Accuracy (vs Alternate ELISA) | Comparable to predicate device | 98.3% (95% CI: 95.9-100%) | Table 3 |
| Batch-to-Batch Mean CV | Acceptable for IVD use | 8.9% - 14.3% (for various samples) | Table 4 |
| Inter-Assay Mean CV | Acceptable for IVD use | Not clearly reported due to OCR error; likely ≤ 15% | Table 5 |
| Intra-Assay Mean CV | Acceptable for IVD use | Not clearly reported due to OCR error; likely ≤ 10% | Table 6 |
| Linearity (r value) | Demonstrated linear relationship | 0.811 - 0.945 (for various positive sera) | Table 7 |
2. Sample Size Used for the Test Set and the Data Provenance
- Clinical Sensitivity and Specificity (Table 1):
- Sample Size: 364 frozen retrospective human sera.
- Provenance: Retrospective, country of origin not specified, but the submission is from a Swedish company (Wieslab AB), implying European or international samples are possible.
- Relative Sensitivity and Specificity vs. C-ANCA IFA (Table 2):
- Sample Size: 245 frozen retrospective human sera.
- Provenance: Retrospective, country of origin not specified.
- Relative Sensitivity and Specificity vs. Alternate ELISA (Table 3):
- Sample Size: 120 frozen retrospective human sera.
- Provenance: Retrospective, country of origin not specified.
- Batch-to-batch variation (Table 4): 4 samples tested in duplicate across four different batches.
- Inter-assay precision (Table 5): 2 samples tested in duplicate across six different runs.
- Intra-assay precision (Table 6): 1 sample tested in 80 wells.
- Linearity (Table 7): 7 positive sera, serially diluted.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and the Qualifications of Those Experts
The document states that the sera for clinical sensitivity and specificity (Table 1) had "clinical characterization." However, it does not specify the number or qualifications of experts used to establish the ground truth (diagnosis of Wegener's granulomatosis, microscopic polyangiitis, etc.). It can be inferred that these diagnoses were established through standard clinical practice by medical professionals, but no details are provided regarding the adjudication or consensus process for these diagnoses in the context of this study.
For the comparative studies in Tables 2 and 3 (C-ANCA IFA and Alternate ELISA), the ground truth was the result of the comparator device. These are not human expert adjudications but rather comparisons against other laboratory tests.
4. Adjudication Method for the Test Set
- For the clinical characterization (Table 1), the document only states "clinical characterization." There is no explicit description of an adjudication method (e.g., 2+1, 3+1, none) for the diagnoses of the disease groups.
- For the comparative studies (Tables 2 and 3), the "ground truth" was established by the predicate or comparator assay (C-ANCA IFA or an alternate commercial ELISA). This is a direct comparison to a reference test, rather than human expert adjudication of images or clinical cases.
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 device is an in-vitro diagnostic (IVD) ELISA kit designed for laboratory use, not for direct human interpretation of medical images or complex clinical cases where MRMC studies are typically performed to assess human reader performance with and without AI assistance. The studies here compare the device's performance against clinical diagnoses or other established laboratory tests.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, this entire submission represents a standalone performance evaluation. The Wielisa PR-3 ANCA Test Kit is a laboratory assay. The reported measurements of sensitivity, specificity, and precision are derived directly from the assay's output (absorbance readings converted to arbitrary units), without inherent human interpretation as part of the primary diagnostic output. Human intervention occurs at the level of performing the test and interpreting the final quantitative result within a clinical context, but the performance metrics presented are of the device itself.
7. The Type of Ground Truth Used
- Clinical Sensitivity & Specificity (Table 1): The ground truth was based on clinical characterization of the disease groups (Wegener's granulomatosis, microscopic polyangiitis, systemic lupus erythematosus, rheumatoid arthritis, anti-GBM nephritis, and healthy normals). This implies established clinical diagnoses, likely confirmed by a combination of clinical signs, symptoms, and other diagnostic tests, but not exclusively a single definitive "pathology" in all cases.
- Relative Sensitivity & Specificity (Tables 2 and 3): The ground truth was established by comparison to other laboratory tests: C-ANCA IFA (Table 2) and an alternate commercial ELISA (Table 3).
8. The Sample Size for the Training Set
The document does not provide information on a specific "training set" for the device. As an ELISA kit from 1998, it predates the widespread application of machine learning or AI models that require distinct training sets. The "development" of such a test would involve formulation, optimization of reagents, and establishment of cutoff values, rather than a machine learning training phase on a dedicated dataset. The data presented are performance evaluation data.
9. How the Ground Truth for the Training Set Was Established
Since no specific "training set" is mentioned (as the device is not an AI/ML diagnostic model), this question is not applicable in the context of the provided document. The "ground truth" for establishing the kit's parameters (e.g., calibrator values, cutoffs) would have been determined through internal development and validation processes using characterized samples, but these are not explicitly detailed as a "training set" in the provided text.
§ 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).