(70 days)
The BioPlex™ 2200 Vasculitis kit is a multiplex flow immunoassay intended for the semi-quantitative detection of IgG autoantibodies to Myeloperoxidase (MPO), Proteinase 3 (PR3) and Glomerylar Basement Membrane (GBM) in human serum. In conjunction with clinical findings, the test system is used as an aid in the diagnosis of anti-neutrophil cytoplasmic antibodies (ANCA)associated vasculitides: Microscopic Polyangitis (MPA), Necrotising Glomerulonephritis, Churg-Strauss Syndrome, Wegener's Granulomatosis and the autoimmune renal disorder, Goodpasture's syndrome.
The BioPlex 2200 Vasculitis kit is intended for use with the Bio-Rad BioPlex 2200 System.
The BioPlex 2200 Vasculitis Calibrator Set is intended for the calibration of the BioPlex 2200 Vasculitis Reagent Pack.
The BioPlex 2200 Vasculitis Control Set is intended for use as an assayed quality control to monitor the overall performance of the BioPlex 2200 Instrument and BioPlex 2200 Vasculitis Reagent Pack in the clinical laboratory. The performance of the BioPlex 2200 Vasculitis Control Set has not been established with any other Vasculitis assays.
The BioPlex 2200 Vasculitis kit is a multiplex flow immunoassav intended for the semiquantitative detection of IgG autoantibodies to Myeloperoxidase (MPO), serine proteinase 3 (PR3) and Glomerular Basement Membrane (GBM) in human serum.
The BioPlex 2200 Vasculitis kit is intended for use with the Bio-Rad BioPlex 2200 System.
Uses:
The test system is used to detect the presence of antibodies in serum samples, as an aid in the diagnosis of certain autoimmune vasculitides such as Microscopic Polyangilitis (MPA), Necrotising Glomerulonephritis, Churg-Strauss Syndrome, Wegener's Granulomatosis and autoimmune renal disorders, such as Goodpasture's syndrome, in conjunction with clinical findings and other laboratory tests.
The Vasculitis kit uses multiplex flow immunoassay, a methodology that greatly resembles traditional EIA, but permits simultaneous detection and identification of many antibodies in a single tube. Three (3) different populations of beads are coated with antigens associated with vasculitis disease (MPO, PR3 and GBM). The BioPlex 2200 System combines an aliquot of patient sample, sample diluent, and bead reagent into a reaction vessel. The mixture is incubated at 37°C. After a wash cycle, antibody, conjugated to phycoerythin (PE), is added to the dyed beads and this mixture is incubated at 37°C. The excess conjugate is removed in another wash cycle, and the beads are re-suspended in wash buffer. The bead mixture then passes through the detector. The identity of the dyed beads is determined by the fluorescence of the dyes, and the amount of antibody captured by the antigen is determined by the fluorescence of the attached PE. Raw data is calculated in relative fluorescence intensity (RFI),
Three additional dyed beads, an Internal Standard Bead (ISB), a Serum Verification Bead (SVB) and a Reagent Blank Bead (RBB) are present in each reaction mixture to verify detector response, the addition of serum or plasma to the reaction vessel and the absence of significant non-specific binding in serum or plasma. Refer to the BioPlex 2200 System Operation Manual for more information.
The instrument is calibrated using a set of four (4) distinct calibrator vials, supplied separately by Bio-Rad Laboratories. A combination of four (4) vials representing four (4) different antibody concentrations are used for semi-quantitative calibration. The result for each of these antibodies is expressed as an antibody index (Al).
The provided text describes the BioPlex 2200 Vasculitis kit, calibrators, and controls. The document focuses on the performance summary, including expected values, reproducibility studies, and comparative testing against predicate devices and IFA methods.
However, the document does not explicitly state "acceptance criteria" for performance metrics in a clear, tabulated format. It presents performance results and compares them to predicate devices, implying that these results met internal criteria for substantial equivalence.
Therefore, the response below will synthesize the implied acceptance criteria from the reported performance, as direct acceptance criteria are not explicitly stated.
Acceptance Criteria and Study to Prove Device Meets Criteria: BioPlex 2200 Vasculitis Kit
1. Table of Acceptance Criteria and Reported Device Performance
As explicit acceptance criteria are not stated, the table below infers the criteria based on the reported comparative performance in the 510(k) summary, specifically focusing on agreement with predicate EIA and IFA methods. The reported performance demonstrates substantial equivalence to predicate devices, which is the underlying requirement for 510(k) clearance.
| Performance Metric (Implied Acceptance Criteria) | Reported Device Performance (BioPlex 2200 Vasculitis Kit) |
|---|---|
| Normal Blood Donors (N=293) vs. EIA | |
| Anti-MPO Positive Agreement | N/A (0 positive per EIA); Negative Agreement: 100.0% (293/293) |
| Anti-PR3 Positive Agreement | N/A (0 positive per EIA); Negative Agreement: 100.0% (293/293) |
| Anti-GBM Positive Agreement | N/A (0 positive per EIA, 2 weak positive); Negative Agreement: 99.3% (289/291); Overall Agreement: 98.6% (289/293) |
| Unselected Patient Samples (N=300) vs. EIA | |
| Anti-MPO Positive Agreement | 71.4% (5/7); Negative Agreement: 97.6% (284/291); Overall Agreement: 96.3% (289/300) |
| Anti-PR3 Positive Agreement | 100.0% (5/5); Negative Agreement: 99.0% (292/295); Overall Agreement: 99.0% (297/300) |
| Anti-GBM Positive Agreement | Not Accurate (0/1); Negative Agreement: 99.7% (298/299); Overall Agreement: 99.3% (298/300) |
| Retrospective Positive Samples vs. EIA & IFA | |
| Anti-MPO Positive Agreement (EIA) | 93.9% (92/98); Overall Agreement: 93.0% (93/100) |
| Anti-MPO Positive Agreement (IFA) | 93.3% (83/89); Overall Agreement: 84.0% (84/100) |
| Anti-PR3 Positive Agreement (EIA) | 100.0% (79/79); Overall Agreement: 83.0% (83/100) |
| Anti-PR3 Positive Agreement (IFA) | 94.9% (93/98); Overall Agreement: 93.0% (93/100) |
| Anti-GBM Positive Agreement (EIA) | 88.9% (16/18); Overall Agreement: 92.6% (25/27) |
| Reproducibility (Total %CV) | Ranges from 5.6% to 11.5% for positive and near-cutoff samples (MPO, PR3, GBM), with higher %CVs for negative controls (e.g., Anti-PR3 Negative Control: 18.8%). (Implied acceptance: %CV values within acceptable limits for diagnostic assays, demonstrating precision across different sites, lots, and days). |
2. Sample Size and Data Provenance for Test Set
- Normal Blood Donors: N=293, tested with BioPlex 2200 and corresponding commercial EIA methods.
- Unselected Patient Samples: N=300, previously tested with vasculitis tests, and tested with BioPlex 2200 and corresponding commercial EIA methods.
- Retrospective Anti-MPO Positive Samples: N=100, tested with BioPlex 2200, corresponding commercial EIA, and ANCA IFA.
- Retrospective Anti-PR3 Positive Samples: N=100, tested with BioPlex 2200, corresponding commercial EIA, and ANCA IFA.
- Retrospective Anti-GBM Positive Samples: N=27, tested with BioPlex 2200 and corresponding commercial EIA.
- Cross-reactivity study: 10 samples per cross-reactant (except 7 for anti-tTG), tested with BioPlex 2200 and corresponding commercial EIA.
Data Provenance: Not explicitly stated (e.g., country of origin, specific institutions). The samples are referred to as "normal blood donors," "unselected patient samples previously tested with vasculitis tests," and "retrospective samples positive for anti-MPO/PR3/GBM." The study was conducted at "two (2) US testing facilities and an internal site (Bio-Rad Laboratories)" for reproducibility, suggesting at least some US data. The studies are retrospective as they utilize "previously tested" and "retrospective" samples.
3. Number of Experts and Qualifications for Ground Truth
The document does not mention the use of experts to establish ground truth for the test set. Instead, it relies on comparative testing against "corresponding commercially available microplate EIA methods" and "ANCA IFA methods" which are presumably well-established and accepted diagnostic tests.
4. Adjudication Method for the Test Set
No adjudication method involving experts is mentioned. The ground truth for comparative effectiveness is established by the results of existing commercial assays (EIA and IFA). Discrepancies are reported (e.g., weak positive results, equivocal results) without specific details of an adjudication process beyond categorization.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No MRMC comparative effectiveness study was performed or described. This device is an in-vitro diagnostic kit for laboratory use, not typically subject to MRMC studies designed for imaging or complex diagnostic interpretations by multiple human readers. The study focuses on direct comparison of analyte detection performance between the new kit and predicate laboratory assays.
6. Standalone Performance
Yes, the standalone performance (algorithm only, without human-in-the-loop performance) is intrinsically what is presented. The device is a 'multiplex flow immunoassay' system designed to semi-quantitatively detect autoantibodies. Its performance metrics (e.g., agreement with predicate devices, reproducibility, cross-reactivity) are all measures of the device's standalone analytical capabilities.
7. Type of Ground Truth Used
The primary ground truth used is comparator assay results.
- Results from "corresponding commercially available microplate EIA methods" for MPO, PR3, and GBM.
- Results from "ANCA IFA method using ethanol-fixed slides" for anti-MPO (pANCA IFA) and anti-PR3 (cANCA IFA).
8. Sample Size for the Training Set
The document does not explicitly mention a separate "training set" or its sample size. The studies described are performance validation studies. In the context of IVD devices, a "training set" is not a standard concept as it might be for AI algorithms. The calibrator sets are used for instrument calibration, not for training a machine learning model.
9. How Ground Truth for the Training Set was Established
As no "training set" for an AI algorithm is mentioned, this question is not applicable. The device is an immunoassay kit, where calibration and control materials are used to ensure accurate measurement in routine use.
- Calibrators: "supplied separately by Bio-Rad Laboratories. A combination of four (4) vials representing four (4) different antibody concentrations are used for semi-quantitative calibration." The ground truth for these calibrators would be established through careful characterization and quantification of the antibody concentrations by the manufacturer.
- Controls: Used "to monitor the overall performance." The positive and negative controls would have their status (positive/negative for each antibody) established by the manufacturer through rigorous testing.
§ 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).