(215 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 kit is for In vitro diagnostic use.
- Detection of the serologic markers for primary systemic small blood vessel vasculitides (ANCA) and for Goodpasture syndrome (GBM).
FIDIS™ VASCULITIS* kit is a multiplex flow immunoassay, which allows simultaneous identification and detection of several antibodies.
FIDIS™ VASCULITIS* is based on the use of distinct uniform size color-coded microsphere sets and a benchtop flow cytometer interfaced to digital signal processing hardware and software. A red diode laser beam in the flow cytometer recognizes each set of microspheres on the basis of its unique fluorescence intensity (red and infrared) thus identifying which parameter is being tested. At the same time, a green laser beam illuminates the external second molecule fluorescence to quantify the reaction related to the specific antigen.
Three different fluorescently "colored" sets of microspheres are coated with antigens associated with various primary systemic small blood vessel vasculitides and glomerular basement membrane disease (MPO, PR3 and GBM). An additional microsphere (Internal Bead standard) set is coated with anti-IgG to ensure that false negative results due to operational error are detected.
The four different sets of microspheres are mixed together. The mixture is lyophilized and constitutes the final microspheres reagent.
The test is performed using a 96 wells microplate with a filtering membrane at the bottom of the wells.
In the first step, the sample is distributed in each well containing the reconstituted microspheres mixture, allowing any anti-MPO, anti-PR3 or anti-GBM antibodies present to bind to the immobilized antigens on the microspheres, as well as free IgG to bind to the anti-IgG microsphere.
After incubation, a wash step using a filtration process removes the unbound antibodies.
A phycoerythrin anti-human IgG conjugate is then added that binds to the previously bound antibodies.
A final wash step stops the reaction and eliminates the unbound conjugate.
The reaction is then measured directly by the flow cytometer, which distinguishes each set of microspheres by its fluorescence color while simultaneously measuring the average fluorescence emitted by the conjugate.
A calibration system allows the determination of the titer (AU/mL) of each sample by interpolation for each antigenic specificity.
Here's a breakdown of the acceptance criteria and the study details for the FIDIS™ VASCULITIS Assay kit, based on the provided document:
Acceptance Criteria and Device Performance:
The acceptance criteria for the FIDIS™ VASCULITIS Assay kit are derived from demonstrating substantial equivalence to a predicate device (K070458 FIDIS™ VASCULITIS system) and demonstrating comparable performance between manual and automated assay preparation. The performance metrics are Positive Percent Agreement (PPA), Negative Percent Agreement (NPA), and Overall Agreement (OA) for three specificities: MPO, PR3, and GBM. Precision (within-run and between-run %CV) was also assessed.
Table of Acceptance Criteria and Reported Device Performance:
| Performance Metric | Specificity | Acceptance Criteria (from predicate comparison) | Reported Device Performance (Modified vs. Predicate - equivocal negative) | Reported Device Performance (Modified vs. Predicate - equivocal positive) | Reported Device Performance (CARIS™ vs. Manual - equivocal negative) | Reported Device Performance (CARIS™ vs. Manual - equivocal positive) |
|---|---|---|---|---|---|---|
| Positive Percent Agreement (PPA) | MPO | Not explicitly stated as a numerical threshold, but implied to be high agreement | 100% (95/95) | 95.4% (103/108) | 95.2% (40/42) | 100% (42/42) |
| PR3 | Not explicitly stated | 98.9% (89/90) | 100% (90/90) | 97.6% (40/41) | 100% (44/44) | |
| GBM | Not explicitly stated | 100% (18/18) | 100% (18/18) | 100% (24/24) | 100% (24/24) | |
| Negative Percent Agreement (NPA) | MPO | Not explicitly stated | 99.4% (184/185) | 98.8% (170/172) | 100% (64/64) | 100% (64/64) |
| PR3 | Not explicitly stated | 100% (190/190) | 98.9% (188/190) | 96.9% (63/65) | 100% (62/62) | |
| GBM | Not explicitly stated | 100% (262/262) | 100% (262/262) | 100% (82/82) | 100% (82/82) | |
| Overall Agreement (OA) | MPO | Not explicitly stated | 99.6% (279/280) | 97.5% (273/280) | 98.1% (104/106) | 100% (106/106) |
| PR3 | Not explicitly stated | 99.6% (279/280) | 99.3% (278/280) | 97.2% (103/106) | 100% (106/106) | |
| GBM | Not explicitly stated | 100% (280/280) | 100% (280/280) | 100% (106/106) | 100% (106/106) | |
| Precision (%CV) | ≤25 AU/mL | No explicit numerical acceptance criteria, but generally low %CV is desired | Within-run: 3-6% | N/A | Within-run: 5-8% | N/A |
| Between-run: 4-11% | N/A | Between-run: 4-16% | N/A | |||
| 26-400 AU/mL | No explicit numerical acceptance criteria | Within-run: 2-9% | N/A | Within-run: 5-12% | N/A | |
| Between-run: 2-12% | N/A | Between-run: 2-12% | N/A |
Study Proving Acceptance Criteria:
The document describes two primary studies to demonstrate that the device meets acceptance criteria:
- Comparison study with predicate - Using Manual Pipetting: This study aimed to show substantial equivalence of the modified FIDIS™ VASCULITIS kit to the legally marketed predicate device (K070458).
- Comparison studies (manual versus automated assay preparation steps) with CARIS™: This study aimed to demonstrate that the use of the CARIS™ system for automated sample preparation provided comparable results to manual preparation with the modified FIDIS™ VASCULITIS kit.
Detailed Study Information:
1. Sample sized used for the test set and the data provenance:
- Comparison with predicate Study:
- Test set sample size: 280 samples.
- Data provenance: Not explicitly stated, but given that both the original and modified device are from "Biomedical Diagnostics S.A." in France, it is highly likely the data is from French or European sources. The study is retrospective as it compares the modified device against previously characterized samples with the predicate test.
- CARIS™ Comparison Study:
- Test set sample size: 106 samples.
- Data provenance: Not explicitly stated, but also likely from French or European sources. The study seems to be prospective or concurrent comparison of two methods on the same set of samples.
2. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
The document does not mention the use of experts or their qualifications for establishing ground truth. The "ground truth" for these studies is not clinical diagnosis by experts, but rather the results obtained from the predicate device (K070458 FIDIS™ VASCULITIS system) for the first study, and the modified FIDIS™ VASCULITIS with manual assay preparation for the second study. These methods are considered the reference for comparison.
3. Adjudication method (e.g. 2+1, 3+1, none) for the test set:
Not applicable. There was no explicit adjudication described as the "ground truth" was established by the reference assays (predicate device or modified device with manual preparation). The document mentions how equivocal results were handled for calculation purposes (included with negative or positive results), but this is not an adjudication method for ground truth.
4. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:
Not applicable. This device is an in vitro diagnostic (IVD) assay kit, not an AI-assisted diagnostic tool that involves human readers. The performance is based on agreement between two assay methods.
5. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
The device itself (FIDIS™ VASCULITIS Assay kit) is essentially a standalone algorithm/test in the context of generating a quantitative result (AU/mL). The "standalone" performance is assessed by its agreement with the predicate device and the manual method. There is no human-in-the-loop directly interpreting raw data beyond what is typical for laboratory technicians running an assay and interpreting its results. The comparison studies effectively represent "standalone" performance against a defined reference.
6. The type of ground truth used (expert consensus, pathology, outcomes data, etc):
The "ground truth" in these studies is the results of a reference in-vitro diagnostic method.
- For the predicate comparison study, the ground truth was the results obtained from the predicate device (K070458 FIDIS™ VASCULITIS).
- For the CARIS™ comparison study, the ground truth was the results obtained from the modified FIDIS™ VASCULITIS with manual assay preparation.
7. The sample size for the training set:
Not applicable. This is an IVD assay kit, not an AI/machine learning model that typically requires a distinct training set. The performance is established through analytical validation studies (precision, method comparison).
8. How the ground truth for the training set was established:
Not applicable, as there is no training set in the AI/ML sense.
§ 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).