(308 days)
The FIDIS™ VASCULITIS* kit is a semi-quantitative homogeneous fluorescent-based microparticle immunoassay using flow cytometry. The test system is used to simultaneously detect the presence of anti-neutrophil cytoplasmic antibodies (ANCA) directed against Myeloperoxidase (MPO), Serine Proteinase 3 (PR3) and antibodies directed against glomerular basement membrane (GBM) in human serum samples.
The results of the FIDIS™ VASCULITIS* test are to be used in conjunction with the clinical findings and the other laboratory tests to aid in the diagnosis of various primary systemic small blood vessel vasculitides and glomerular basement membrane disease.
Clinical utility:
The detection of ANCA is associated with primary systemic small blood vessel vasculitides: Wegener's granulomatosis, Churg Strauss syndromes, microscopic periarteritis and idiopathic crescentic glomerulonephritis; and the detection of anti-GBM antibodies is associated with Goodpasture's syndrome.
FIDIS™ VASCULITIS* kit uses serum only, and is to be run on the FIDIS™ Instrument and MLX-BOOSTER Software.
FIDIS™ VASCULITIS* kit may be used with the CARIS™ system (diluting and dispensing device).
This test is for In vitro diagnostic use.
- Detection of the serologic markers for primary systemic small blood vessel vasculitides (ANCA) and for Goodpasture syndrome (GBM).
The FIDIS™ VASCULITIS* kit is a semi-quantitative homogeneous fluorescent-based microparticle immunoassay using flow cytometry. The test system is used to simultaneously detect the presence of anti-neutrophil cytoplasmic antibodies (ANCA) directed against Myeloperoxidase (MPO), Serine Proteinase 3 (PR3) and antibodies directed against glomerular basement membrane (GBM) in human serum samples. The kit includes a 96 wells microplate, vials of color-coded microsphere beads coupled with MPO, PR3, and GBM, plus internal standard beads, sample dilution buffer, calibrator, positive control, negative control, anti-human IgG coupled to phycoerythrin, washing buffer, package insert, microplate assay configuration worksheet, and microplate sealing films. The test is run on the FIDIS™ Instrument and MLX-BOOSTER Software and may be used with the CARIS™ system (diluting and dispensing device).
Here's a summary of the acceptance criteria and study details for the FIDIS™ VASCULITIS assay, based on the provided document:
1. Table of Acceptance Criteria and Reported Device Performance
The document primarily focuses on demonstrating substantial equivalence to a predicate device (K053012 FIDIS™ VASCULITIS) and the equivalence of manual vs. automated assay preparation with the CARIS™ system. The "acceptance criteria" are therefore implicit in the comparison studies (e.g., high percentage agreement with the predicate device) and explicit in the precision studies.
Analytical Performance (Precision)
| Sample Range | Acceptance Criteria for Within-run and Between-run (%CV) | MPO, PR3, and GBM Parameters (Within-run) | MPO, PR3, and GBM Parameters (Between-run) |
|---|---|---|---|
| Less than 10 AU/mL | Not calculated | Not calculated | Not calculated |
| 10 to 19 AU/mL | ≤20% | Minimal: 5.3%, Maximal: 11.3% | Minimal: 11.2%, Maximal: 19.6% |
| 20 to 400 AU/mL | ≤15% | Minimal: 2.3%, Maximal: 12.4% | Minimal: 5.4%, Maximal: 14.2% |
Comparison Study with Predicate Device (K053012 FIDIS™ VASCULITIS)
The acceptance criteria for these sections are implied to be high agreement percentages indicating substantial equivalence.
| Antigenic Specificity | Positive Percent Agreement (Reported) | Negative Percent Agreement (Reported) | Overall Agreement (Reported) |
|---|---|---|---|
| MPO | 97.18% | 100% | 99.09% |
| PR3 | 95.92% | 99.41% | 98.63% |
| GBM | 100% | 100% | 100% |
Performance Data for Modified FIDIS™ VASCULITIS with CARIS™ (Precision)
| Sample Range | Acceptance Criteria for Within-run and Between-run (%CV) | MPO, PR3, and GBM Parameters (Within-run) | MPO, PR3, and GBM Parameters (Between-run) |
|---|---|---|---|
| Less than 10 AU/mL | Not calculated | Not calculated | Not calculated |
| 10 to 19 AU/mL | ≤20% | Minimal: 4.9%, Maximal: 6.9% | Minimal: 6.9%, Maximal: 13.6% |
| 20 to 400 AU/mL | ≤15% | Minimal: 2.6%, Maximal: 10.8% | Minimal: 5.9%, Maximal: 11.7% |
Comparison Studies (Manual vs. Automated Assay Preparation Steps with CARIS™)
The acceptance criteria for these sections are implied to be high agreement percentages indicating substantial equivalence.
| Antigenic Specificity | Positive Percent Agreement (Reported) | Negative Percent Agreement (Reported) | Overall Agreement (Reported) |
|---|---|---|---|
| MPO | 100% | 97.59% | 98.29% |
| PR3 | 100% | 97.83% | 98.29% |
| GBM | 100% | 100% | 100% |
2. Sample Size Used for the Test Set and Data Provenance
- Comparison Study with Predicate Device:
- Sample Size: 219 samples.
- Data Provenance: Not explicitly stated, but samples were "characterized with the predicate test." The origin (e.g., country, retrospective/prospective) is not provided.
- Interfering Substances Study:
- Sample Size: 27 samples.
- Data Provenance: "obtained from a routine laboratory," suggesting retrospective clinical samples. Origin not specified.
- Threshold values study:
- Sample Size: 37 samples from blood donors and 28 samples selected for potential biological interferences (total = 65 samples).
- Data Provenance: Not explicitly stated, likely clinical samples. Origin not specified.
- CARIS™ Comparison Studies (Manual vs. Automated):
- Sample Size: 117 samples.
- Data Provenance: Not explicitly stated. The samples were "characterized with the modified FIDISTM VASCULITIS with manual assay preparation step." Origin not specified.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document does not describe the use of human experts to establish ground truth for the test sets. For the comparison studies, the "ground truth" for the modified device was the results obtained from the predicate device (K053012 FIDIS™ VASCULITIS) or the manual preparation method for the CARIS™ comparison. The predicate device itself would have undergone its own validation studies to establish its accuracy. Similarly, for precision, the "ground truth" is the assay's own measurement, with reproducibility being the focus.
4. Adjudication Method for the Test Set
No adjudication method involving experts is described. In the comparison studies, equivocal results were consistently treated as negative for the purpose of calculating agreement percentages.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and the Effect Size of How Much Human Readers Improve with AI vs. Without AI Assistance
This section is not applicable as the device is an in vitro diagnostic (IVD) assay for detecting autoantibodies, not an AI-assisted diagnostic imaging or interpretation tool designed to improve human reader performance. The device provides quantitative results, and the studies assess the analytical performance and agreement with a predicate device or different preparation methods.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
The device itself (FIDIS™ VASCULITIS kit and FIDIS™ Analyzer/MLX-BOOSTER software) is a standalone system in the sense that it performs the measurement and provides results without human interpretive input beyond following the assay protocol. The studies presented are essentially standalone performance studies demonstrating the analytical performance (precision, linearity, interference, stability) of the assay system itself, and its agreement with a previously cleared device. The CARIS™ system is an optional automated sample preparation component, and its impact on the assay's performance is also assessed in a standalone manner (automated vs. manual).
7. The Type of Ground Truth Used (Expert Consensus, Pathology, Outcomes Data, etc.)
The "ground truth" used in these studies is primarily:
- Predicate Device Results: For the comparison study of the modified FIDIS™ VASCULITIS against its predicate (K053012), the results obtained from the predicate device served as the reference or "ground truth" for determining agreement.
- Manual Assay Preparation Results: For the comparison study involving the CARIS™ system, the results obtained using manual assay preparation steps served as the reference for determining the agreement of the automated method.
- Internal Assay Measurements: For analytical performance studies like precision, linearity, interfering substances, and stability, the "ground truth" is typically established by the inherent physical/chemical properties of the samples and the expected performance characteristics of the assay itself, often with reference to spiked samples or known concentrations.
There is no mention of expert consensus, pathology, or outcomes data being used directly to establish ground truth for these performance evaluations.
8. The Sample Size for the Training Set
The document does not explicitly describe a "training set" in the context of machine learning or AI models. This device is an IVD assay, not an AI algorithm that undergoes a training phase. The samples used for establishing analytical performance parameters (precision, linearity, interference, stability) and for comparison against the predicate are test samples used for validation, not for training a model.
9. How the Ground Truth for the Training Set Was Established
As noted above, the concept of a "training set" and its associated ground truth establishment is not applicable to this in vitro diagnostic assay. The studies focus on validating the performance of a wet-lab assay and associated instrumentation.
§ 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).