(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.
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BIOPLEX 2200 VASCULITIS KIT, CALIBRATORS AND CONTROLS 510(K) SUMMARY
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.
| ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------510/k) Number | CANILIRenort DateIImmary ! |
|---|---|
| A counts & com1/070000 | 0000Atanarand and and and the driver and the children the distribution of the country |
MANUFACTURER INFORMATION
| Manufacturer | |
|---|---|
| Manufacturer Address | Bio-Rad Laboratories, Inc.Clinical Systems Division4000 Alfred Nobel DriveHercules, CA 94547 |
| Telephone | (510) 724-7000 |
| Establishment Registration No. | 2915274 |
| Owner / Operator | Bio-Rad Laboratories, Inc.4000 Alfred Nobel DriveHercules, CA 94547 |
| Owner / Operator No. | 9929003 |
| Official Correspondent for the BioPlex 2200 Vasculitis | |
| Official Correspondent Address | Bio-Rad Laboratories6565 185th Ave NERedmond, WA 98052 |
| Telephone | 425-881-8300 |
| Establishment Registration No. | 3022521 |
| Owner / Operator | Bio-Rad Laboratories6565 185th Ave NERedmond, WA 98052 |
| Official Correspondent | Mr. Christopher Bentsen |
| Telephone | (425) 498-1709 |
| Fax | (425) 498-1651 |
CLASSIFICATION INFORMATION
| Classification Name | Test System, Antineutrophil Cytoplasmic Antibodies (ANCA),Devices, Measure, Antibodies to Glomerular BasementMembrane (GBM) |
|---|---|
| Common Name: | Multi-Analyte Detection System Vasculitis |
| Product Trade Name | BioPlex 2200 Vasculitis kit on the BioPlex 2200 Multi-AnalyteDetection SystemBioPlex 2200 Vasculitis Calibrator SetBioPlex 2200 Vasculitis Control Set |
| Device Class | Class II |
| Classification Panel | Immunology |
| Requlation Number | 866.5660-Multiple Autoantibodies Immunological Test System |
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LEGALLY MARKETED EQUIVALENT (SE) DEVICES
| Comparative FDA ClearedPREDICATE DEVICE | 510(k) Number | DecisionDate |
|---|---|---|
| Phadia Varelisa™ MPO EIA | K041040 | 06/16/04 |
| Phadia Varelisa™ PR3 EIA | K041043 | 07/02/04 |
| INOVA QUANTA Lite™ GBM ELISA | K984336 | 02/08/99 |
| INOVA NOVA Lite ANCA (Ethanol-fixed Slides) | K961340 | 07/10/96 |
DEVICE DESCRIPTION
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).
KIT COMPONENTS
BioPlex 2200 Vasculitis reagent pack (Catalog No. 665-1850). The reagent pack contains supplies sufficient for 100 tests.
| Vial | Description |
|---|---|
| Bead Set | One (1) 10 mL vial, containing dyed beads coated with Myeloperoxidase (MPO),Proteinase-3 (PR3) and Glomerular Basement Membrane (GBM); an InternalStandard bead (ISB), a Serum Verification bead (SVB), and a Reagent Blankbead (RBB) in a MOPS (3-[N-Morpholino] propanesulfonic acid) buffersupplemented with Glycerol and protein stabilizers (bovine). ProClin® 300(0.3%), sodium benzoate (0.1%) and sodium azide (<0.1%) are added aspreservatives. |
BioPlex 2200 Vasculitis Kit,Calibrator Set and Control Set 510(k) Summary (10-24-07) Page 2 of 21
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| ConjugateCONJ | One (1) 5 mL vial, containing phycoerythrin conjugated murine monoclonal anti-human IgG and phycoerythrin conjugated murine monoclonal anti-human FXIIIin phosphate buffer supplemented with murine and bovine protein stabilizers.ProClin® 300 (0.3%), sodium benzoate (0.1%) and sodium azide (<0.1%) areadded as preservatives. |
|---|---|
| SampleDiluent | One (1) 10 mL vial, containing bovine and murine protein stabilizers intriethanolamine buffer. ProClin® 300 (0.3%), sodium benzoate (0.1%) andsodium azide (<0.1%) are added as preservatives. |
ADDITIONAL REQUIRED ITEMS, AVAILABLE FROM BIO-RAD
| Description | |
|---|---|
| 663-1800 | BioPlex 2200 Vasculitis Calibrator Set: Four (4) 500 µL vials, each containinghuman antibodies to MPO, PR3 and GBM, in a human serum matrix made fromdefibrinated plasma. All calibrators contain ProClin® 300 (0.3%), sodiumbenzoate (0.1%) and sodium azide (<0.1%) as preservatives. |
| 663-1830 | BioPlex 2200 Vasculitis Control Set: Two (2) 1.5 mL Positive Control serum vials,each containing human antibodies to MPO, PR3 and GBM, in a human serummatrix made from defibrinated plasma; and two (2) 1.5 mL Negative Control serumvials, in a human serum matrix made from defibrinated plasma. All controlscontain ProClin® 300 (0.3%), sodium benzoate (0.1%) and sodium azide (<0.1%)as preservatives. |
| 660-0817 | BioPlex 2200 Sheath Fluid: Two (2) 4 L bottles containing Phosphate BufferedSaline (PBS). ProClin® 300 (0.03%) and sodium azide (<0.1%) are added aspreservatives. |
| 660-0818 | BioPlex 2200 Wash Solution: One (1) 10 L bottle containing Phosphate BufferedSaline (PBS) and Tween 20. ProClin® 300 (0.03%) and sodium azide (<0.1%)are added as preservatives. |
| 660-0000 | BioPlex 2200 Instrument and Software System |
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INTENDED USE
BioPlex™ 2200 Vasculitis Kit
The BioPlex™ 2200 Vasculitis kit is a multiplex flow immunoassay intended for the semiquantitative 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.
BioPlex 2200 Vasculitis Calibrator Set
The BioPlex 2200 Vasculitis Calibrator Set is intended for the calibration of the BioPlex 2200 Vasculitis Reagent Pack.
BioPlex 2200 Vasculitis Control Set
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.
INDICATIONS FOR USE
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.
TECHNOLOGICAL CHARACTERISTICS
The following tables summarize similarities and differences between the BioPlex 2200 Vasculitis Kit and the predicate devices used in comparative studies with the BioPlex 2200 Vasculitis Kit.
A. BioPlex 2200 Vasculitis vs. Predicate Phadia Varelisa MPO ANCA ElA
| Similarities betweenComponents / Materials | BioPlex 2200 Vasculitis | Predicate Phadia Varelisa MPOANCA EIA |
|---|---|---|
| Reagents | Wash Buffer, Sample Diluent | Wash Buffer, Serum Diluent |
Table 1: Similarities between reagents and materials
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| Calibrators | Calibrators | Calibrators |
|---|---|---|
| Controls | Negative Control and Multi-AnalytePositive Control (MPO, PR3 and GBM) | Negative Control, Positive Control |
Table 2: Similarities between reagents with regard to function and use
| Similarities betweenFunction and Use | BioPlex 2200 Vasculitis | Predicate Phadia Varelisa MPOANCA EIA |
|---|---|---|
| Intended Use | Semi-quantitative detection of IgGautoantibodies to MPO, PR3 and GBMin human serum. | Semi-quantitative and qualitativedetermination of MPO Anti neutrophilcytoplasmic antibodies in human serumor plasma. |
| Matrices | Serum | Serum |
Table 3: Differences between reagents and materials
| Differences betweenComponents / Materials | BioPlex 2200 Vasculitis | Predicate Phadia Varelisa MPOANCA EIA |
|---|---|---|
| Solid Phase | Bead reagent - dyed antigen coatedbeads | 96 well microplate - antigen coatedmicrowells |
| Reagents | Conjugate: Anti-human IgG /Phycoerythrin | Conjugate: Anti-human IgG HRPconjugate/Substrate (TMB) |
| Sheath Fluid | Sheath Fluid is used to suspend the beadreagent and introduce it into the detector. | Not similar; not utilized in EIA 's |
Table 4: Differences between reagents with regard to function and use
| Differences betweenFunction and Use | BioPlex 2200 Vasculitis | Predicate Phadia Varelisa MPOANCA EIA |
|---|---|---|
| Analyte Detection | Multi-Analyte Detection (human IgG autoantibodies to MPO, PR3 and GBM) | Single Analyte Detection (Human IgG antibodies to MPO) |
| Matrices | Serum | Plasma |
B. BioPlex 2200 Vasculitis vs. Predicate Phadia Varelisa PR3 ANCA EIA
| Similarities betweenComponents / Materials | BioPlex 2200 Vasculitis | Predicate Phadia Varelisa PR3ANCA EIA |
|---|---|---|
| Reagents | Wash Buffer, Sample Diluent | Wash Buffer, Sample Diluent |
| Calibrators | Calibrators | Calibrators |
| Controls | Negative Control and Multi-AnalytePositive Control (MPO, PR3 and GBM) | Negative Control, Positive Control |
Table 5: Similarities between reagents and materials
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Table 6: Similarities between reagents with regard to function and use
| Similarities betweenComponents / Materials | BioPlex 2200 Vasculitis | Predicate Phadia Varelisa PR3ANCA EIA |
|---|---|---|
| Intended Use | Semi-quantitative detection of IgGautoantibodies to MPO, PR3 and GBMin human serum. | Semi-quantitative and qualitativedetermination of PR3 Anti neutrophilcytoplasmic antibodies in human serumor plasma. |
| Matrices | Serum | Serum |
| Differences betweenComponents / Materials | BioPlex 2200 Vasculitis | Predicate Phadia Varelisa PR3ANCA EIA |
|---|---|---|
| Solid Phase | Bead reagent - dyed antigen coatedbeads | 96 well microplate - antigen coatedmicrowells |
| Reagents | Conjugate: Anti-human IgG /Phycoerythrin | Conjugate: Anti-Human IgG HRPConjugate /Substrate (TMB) |
| Sheath Fluid | Sheath Fluid is used to suspend the beadreagent and introduce it into the detector. | Not similar; not utilized in EIA's. |
Table 7: Differences between reagents and materials
| Table 8: Differences between reagents with regard to function and use | ||||
|---|---|---|---|---|
| Differences betweenFunction and Use | BioPlex 2200 Vasculitis | Predicate Phadia Varelisa PR3ANCA EIA |
|---|---|---|
| Analyte Detection | Multi-Analyte Detection (human IgGautoantibodies to MPO, PR3 and GBM) | Single Analyte Detection (Human IgG antibodies to PR3) |
| Matrices | Serum | Plasma |
C. BioPlex 2200 Vasculitis vs. Predicate INOVA QUANTA-Lite GBM ELISA
| Similarities betweenComponents / Materials | BioPlex 2200 Vasculitis | Predicate INOVA QUANTA-LiteGBM ELISA |
|---|---|---|
| Reagents | Wash Buffer, Sample Diluent | Wash Buffer, Serum Diluent |
| Controls | Negative Control and Multi-AnalytePositive Control (MPO, PR3 and GBM) | Negative Control, Positive Control |
Table 9: Similarities between reagents and materials
Table 10: Similarities between reagents with regard to function and use
| Similarities betweenComponents / Materials | BioPlex 2200 Vasculitis | Predicate INOVA QUANTA-LiteGBM ELISA |
|---|---|---|
| Intended Use | Semi-quantitative detection of IgGautoantibodies to MPO, PR3 and GBMin human serum. | Semi-quantitative determination of antineutrophil cytoplasmic antibodies toGBM in human serum |
Table 11: Differences between reagents and materials
| Differences betweenComponents / Materials | BioPlex 2200 Vasculitis | Predicate INOVA QUANTA-LiteGBM ELISA |
|---|---|---|
| Solid Phase | Bead reagent - dyed antigen coated beads | 96 well microplate - antigen coated microwells |
BioPlex 2200 Vasculitis Kit,Calibrator Set and Control Set 510(k) Summary (10-24-07) Page 6 of 21
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| Reagents | Conjugate: Anti-human IgG /Phycoerythrin | Conjugate: Anti-Human IgG / Horse-radish Peroxidase, Substrate (TMB) |
|---|---|---|
| Sheath Fluid | Sheath Fluid is used to suspend the beadreagent and introduce it into the detector | Not similar; not utilized in EIA's. |
| Calibrators | Calibrators | None |
Table 12: Differences between reagents with regard to function and use
| Differences betweenFunction and Use | BioPlex 2200 Vasculitis | Predicate INOVA QUANTA-LiteGBM ELISA |
|---|---|---|
| Analyte Detection | Multi-Analyte Detection (human IgGautoantibodies to MPO, PR3 and GBM) | Single Analyte Detection (Human IgGantibodies to GBM) |
D. BioPlex 2200 Vasculitis vs. Predicate INOVA Lite, ANCA, Ethanol Fixed Slides
Table 13: Similarities between reagents and materials
| Similarities betweenComponents / Materials | BioPlex 2200 Vasculitis | Predicate INOVA NOVA Lite,ANCA, Ethanol Fixed Slides |
|---|---|---|
| Controls | Negative Control and Multi-AnalytePositive Control (MPO, PR3 and GBM) | IFA Negative Control, p-ANCAPositive Control, c-ANCA PositiveControl |
Table 14: Similarities between reagents with regard to function and use
| Similarities betweenComponents / Materials | BioPlex 2200 Vasculitis | Predicate INOVA NOVA Lite,ANCA, Ethanol Fixed Slides |
|---|---|---|
| Intended Use | Semi-quantitative detection of IgGautoantibodies to MPO, PR3 and GBMin human serum. | Semi-quantitative determination ofAnti neutrophil cytoplasmic antibodiesin human serum. |
| Matrices | Serum | Serum |
Table 15: Differences between reagents and materials
| Differences betweenComponents / Materials | BioPlex 2200 Vasculitis | Predicate INOVA NOVA Lite,ANCA, Ethanol Fixed Slides |
|---|---|---|
| Solid Phase | Bead reagent - dyed antigen coatedbeads | ANCA, Ethanol fixed neutrophilsSubstrate slides |
| Reagents | Conjugate: Anti-human IgG /Phycoerythrin | Conjugate: Anti-Human IgG / Horse-radish Peroxidase |
| Sheath Fluid | Sheath Fluid is used to suspend the beadreagent and introduce it into the detector. | Not similar; not utilized in EIA's. |
| Calibrators | Calibrators | None |
Table 16: Differences between reagents with regard to function and use
| Differences betweenFunction and Use | BioPlex 2200 Vasculitis | Predicate INOVA NOVA Lite,ANCA, Ethanol Fixed Slides |
|---|---|---|
| Analyte Detection | Multi-Analyte Detection (human IgGautoantibodies to MPO, PR3 and GBM) | Single Analyte Detection (Human IgG antibodies) |
BioPlex 2200 Vasculitis Kit,Calibrator Set and Control Set 510(k) Summary (10-24-07) Page 7 of 21
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| Solid Phase | Bead reagent - dyed antigen coated beads | ANCA, Ethanol fixed neutrophilsSubstrate slides |
|---|---|---|
| ------------- | ------------------------------------------ | ----------------------------------------------------- |
PERFORMANCE SUMMARY
A. Expected Values
Expected values for the BioPlex 2200 Vasculitis kit are presented in the following tables for serum samples from normal blood donors (N=293) and unselected patient samples previously tested with vasculitis tests (N=300). A total of 300 serum samples from the normal blood donor population were tested. Seven (7) samples from the normal blood donor population were excluded due to "Serum Verification Bead (SVB) signal too low" analysis error messages during BioPlex 2200 Vasculitis kit testing. For all analytes, results of <1.0 Al are negative and results of 1.0 Al or greater are reported as positive.
Table A. BioPlex 2200 Vasculitis Kit -Normal Blood Donors (N=293)
| BioPlex Result | Positive# (%) | Negative# (%) |
|---|---|---|
| Anti-MPO | 0/293 (0.0%) | 293/293 (100.0%) |
| Anti-PR3 | 0/293 (0.0%) | 293/293 (100.0%) |
| Anti-GBM | 2/293 (0.7%) | 291/293 (99.3%) |
Table B. BioPlex 2200 Vasculitis Kit -Unselected Patient Samples Previously Tested With Vasculitis Tests (N=300)
| BioPlex Result | Positive# (%) | Negative# (%) |
|---|---|---|
| Anti-MPO | 14/300 (4.7%) | 286/300 (95.3%) |
| Anti-PR3 | 8/300 (2.7%) | 292/300 (97.3%) |
| Anti-GBM | 1/300 (0.3%) | 299/300 (99.7%) |
B. Reproducibility Studies
A reproducibility panel, consisting of ten (10) serum panel members, was prepared by Bio-Rad Laboratories. The positive panel members were prepared by combining patient samples positive for
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antibodies to MPO, PR3 and GBM. Two (2) of the ten (10) had high levels of the antibodies to MPO, PR3 and GBM; two (2) members had low levels of the antibodies to MPO, PR3 and GBM; and two (2) members had antibody levels near the cutoff. There was also one (1) high negative and one (1) low negative panel member. In addition, a BioPlex 2200 Vasculitis positive control (antibody positive for MPO, PR3 and GBM) and a negative control (antibody negative for all 3 analytes) were included and tested as panel members.
Reproducibility testing was performed at two (2) US testing facilities and an internal site (Bio-Rad Laboratories) on a total of two (2) lots of the BioPlex 2200 Vasculitis kit. The ten (10) panel members were provided to the each of the testing sites. Two (2) of the three (3) testing facilities evaluated reproducibility using one (1) kit lot of the BioPlex 2200 Vasculitis kit and the third site evaluated the second lot of the BioPlex 2200 Vasculitis kit. Each of the ten (10) panel members was tested in duplicate (x2) on two runs per day for three days at each testing site (2 times x 2 runs x 3 days x 3 sites = 36 replicates per panel member and controls). The data were then analyzed for intra assay and inter-assay reproducibility according to the Clinical and Laboratory Standards Institute quidance (formerly NCCLS) EP5-A2, revised November 2004 and ISO/TR 22971:2005. The mean Antibody Index (AI), standard deviation (SD), and percent coefficient of variation (%CV) for each panel member were calculated. Results can be found in the below table:
| VasculitisKit PanelMembers | BioPlex 2200 Vasculitis Kit | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SampleN | MeanAI | Within-Run | Between-Run | Between-Day | Between-Site* | Total | |||||||
| Vasculitis Anti-MPO | HighPositive1 | 36 | 4.0 | 0.277 | 7.0% | 0.156 | 3.9% | 0.022 | 0.6% | 0.326 | 8.2% | 0.456 | 11.5% |
| HighPositive2 | 36 | 5.5 | 0.295 | 5.4% | 0.249 | 4.5% | 0.000 | 0.0% | 0.254 | 4.6% | 0.462 | 8.4% | |
| LowPositive1 | 36 | 1.5 | 0.065 | 4.4% | 0.041 | 2.8% | 0.043 | 3.0% | 0.017 | 1.2% | 0.089 | 6.2% | |
| LowPositive2 | 36 | 1.9 | 0.169 | 8.6% | 0.000 | 0.0% | 0.000 | 0.0% | 0.025 | 1.3% | 0.170 | 8.7% | |
| Near | 36 | 1.0 | 0.058 | 5.6% | 0.000 | 0.0% | 0.032 | 3.1% | 0.048 | 4.6% | 0.082 | 7.9% |
| Table. Reproducibility; BioPlex 2200 Vasculitis | ||
|---|---|---|
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| Cutoff 1 | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| NearCutoff 2 | 36 | 1.3 | 0.053 | 3.9% | 0.033 | 2.5% | 0.041 | 3.1% | 0.000 | 0.0% | 0.075 | 5.6% | |
| PositiveControl | 36 | 2.9 | 0.198 | 6.8% | 0.000 | 0.0% | 0.000 | 0.0% | 0.102 | 3.5% | 0.223 | 7.7% | |
| NegativeControl | 36 | 0.2 | 0.000 | 0.0% | 0.000 | 0.0% | 0.000 | 0.0% | 0.000 | 0.0% | 0.000 | 0.0% | |
| HighPositive1 | 36 | 4.2 | 0.301 | 7.2% | 0.000 | 0.0% | 0.101 | 2.4% | 0.076 | 1.8% | 0.326 | 7.8% | |
| HighPositive2 | 36 | 4.5 | 0.171 | 3.8% | 0.202 | 4.5% | 0.000 | 0.0% | 0.267 | 6.0% | 0.376 | 8.4% | |
| LowPositive1 | 36 | 1.4 | 0.067 | 4.9% | 0.024 | 1.7% | 0.075 | 5.5% | 0.033 | 2.4% | 0.108 | 7.9% | |
| Vasculitis Anti-PR3 | LowPositive2 | 36 | 1.5 | 0.128 | 8.3% | 0.032 | 2.1% | 0.000 | 0.0% | 0.085 | 5.5% | 0.157 | 10.2% |
| NearCutoff 1 | 36 | 1.2 | 0.062 | 5.1% | 0.000 | 0.0% | 0.057 | 4.7% | 0.027 | 2.2% | 0.088 | 7.3% | |
| NearCutoff 2 | 36 | 1.1 | 0.053 | 4.7% | 0.024 | 2.1% | 0.045 | 3.9% | 0.000 | 0.0% | 0.073 | 6.4% | |
| PositiveControl | 36 | 2.3 | 0.134 | 5.8% | 0.000 | 0.0% | 0.095 | 4.1% | 0.032 | 1.4% | 0.167 | 7.3% | |
| NegativeControl | 36 | 0.2 | 0.019 | 8.9% | 0.000 | 0.0% | 0.027 | 12.6% | 0.024 | 10.9% | 0.041 | 18.8% |
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| Vasculitis Anti-GBM | HighPositive1 | 36 | 4.3 | 0.249 | 5.8% | 0.000 | 0.0% | 0.000 | 0.0% | 0.204 | 4.7% | 0.322 | 7.5% |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| HighPositive2 | 36 | 4.8 | 0.162 | 3.4% | 0.194 | 4.1% | 0.000 | 0.0% | 0.280 | 5.9% | 0.377 | 7.9% | |
| LowPositive1 | 36 | 1.4 | 0.081 | 5.6% | 0.000 | 0.0% | 0.064 | 4.5% | 0.087 | 6.0% | 0.135 | 9.4% | |
| LowPositive2 | 36 | 1.7 | 0.093 | 5.5% | 0.052 | 3.1% | 0.000 | 0.0% | 0.047 | 2.8% | 0.116 | 6.9% | |
| NearCutoff 1 | 36 | 1.1 | 0.037 | 3.4% | 0.045 | 4.1% | 0.000 | 0.0% | 0.079 | 7.2% | 0.099 | 9.0% | |
| NearCutoff 2 | 36 | 1.2 | 0.060 | 5.0% | 0.041 | 3.4% | 0.017 | 1.4% | 0.081 | 6.7% | 0.110 | 9.2% | |
| PositiveControl | 36 | 2.8 | 0.139 | 4.9% | 0.000 | 0.0% | 0.000 | 0.0% | 0.063 | 2.3% | 0.153 | 5.4% | |
| NegativeControl | 36 | 0.2 | 0.000 | 0.0% | 0.000 | 0.0% | 0.000 | 0.0% | 0.000 | 0.0% | 0.000 | 0.0% |
- Between-site variance includes between lot variance
C. Comparative Testing
Three hundred (300) normal blood donors and three hundred (300) unselected patient samples previously tested with vasculitis tests were tested with the BioPlex 2200 Vasculitis kit. Seven (7) of the three hundred (300) normal blood donor samples were excluded due to "Serum Verification Bead (SVB) signal too low" analysis error during BioPlex 2200 Vasculitis kit testing. All samples were also tested by the corresponding commercially available microplate EIA methods. The results can be observed in Tables A - F.
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| EIA Result | Positive | Negative | Total | Positive (+) % Agreement | 95% Confidence Interval | Negative (-) % Agreement | 95% Confidence Interval | Overall % Agreement | 95% Confidence Interval | |
|---|---|---|---|---|---|---|---|---|---|---|
| Positive | 0 | 0 | 0 | N/A | N/A | 100.0%(293/293) | 98.7%,100% | 100.0%(293/293) | 98.7%,100% | |
| Equivocal | 0 | 0 | 0 | |||||||
| Negative | 0 | 293 | 293 | |||||||
| Total | 0 | 293 | 293 |
Table A. BioPlex 2200 vs. Anti-MPO EIA - Normal Blood Donors (N=293)
N/A = Not Applicable
Table B. BioPlex 2200 vs. Anti-PR3 EIA - Normal Blood Donors (N=293)
| BioPlex 2200 Vasculitis Anti-PR3 Result | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Positive | Negative | Total | Positive (+)% Agreement | 95% ConfidenceInterval | Negative (-)% Agreement | 95% ConfidenceInterval | Overall% Agreement | 95% ConfidenceInterval | |||
| EIA Result | Positive | 0 | 0 | 0 | N/A | N/A | |||||
| Equivocal | 0 | 0 | 0 | 100.0%(293/293) | 98.7%,100% | 100.0%(293/293) | 98.7%,100% | ||||
| Negative | 0 | 293 | 293 | ||||||||
| Total | 0 | 293 | 293 |
N/A = Not Applicable
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| Positive | Negative | Total | Positive (+) % Agreement | 95% Confidence Interval | Negative (-) % Agreement | 95% Confidence Interval | Overall % Agreement | 95% Confidence Interval | ||
|---|---|---|---|---|---|---|---|---|---|---|
| EIA Result | Positive | 0 | 2* | 2 | N/A | N/A | 99.3% (289/291) | 97.5%,99.8% | 98.6% (289/293) | 96.5%,99.5% |
| Negative | 2 | 289 | 291 | |||||||
| Total | 2 | 291 | 293 |
Table C. BioPlex 2200 vs. Anti-GBM EIA - Normal Blood Donors (N=293)
- Two (2) positive anti-GBM EIA results were weak positive. N/A = Not Applicable
Table D. BioPlex 2200 vs. Anti-MPO EIA - Unselected Patient Samples Previously Tested With Vasculitis Tests (N=300)
| BioPlex 2200 Vasculitis Anti-MPO Result | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| EIA Result | Positive | Negative | Total | Positive (+) % Agreement | 95% Confidence Interval | Negative (-) % Agreement | 95% Confidence Interval | Overall % Agreement | 95% Confidence Interval | |
| Positive | 5 | 2 | 7 | 71.4%(5/7) | 35.9%,91.8% | 97.6%(284/291) | 95.1%,98.8% | 96.3%(289/300) | 93.6%,97.9% | |
| Equivocal* | 2 | 0 | 2 | |||||||
| Negative | 7 | 284 | 291 | |||||||
| Total | 14 | 286 | 300 |
- Two (2) anti-MPO EIA equivocal results are included in the Overall Agreement.
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| BioPlex 2200 Vasculitis Anti-PR3 Result | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Positive | Negative | Total | Positive (+)% Agreement | 95%ConfidenceInterval | Negative (-)% Agreement | 95%ConfidenceInterval | Overall% Agreement | 95%ConfidenceInterval | ||
| EIA Result | Positive | 5 | 0 | 5 | 100.0%(5/5) | 56.5%,100% | 99.0%(292/295) | 97%,99.7% | 99.0%(297/300) | 97.1%,99.7% |
| Equivocal | 0 | 0 | 0 | |||||||
| Negative | 3 | 292 | 295 | |||||||
| Total | 8 | 292 | 300 |
Table E. BioPlex 2200 vs. Anti-PR3 EIA – Unselected Patient Samples Previously Tested With Vasculitis Tests (N=300)
Table F. BioPlex 2200 vs. Anti-GBM EIA - Unselected Patient Samples Previously Tested With Vasculitis Tests (N=300)
| BioPlex 2200 Vasculitis Anti-GBM Result | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Positive | Negative | Total | Positive (+) % Agreement | 95% Confidence Interval | Negative (-) % Agreement | 95% Confidence Interval | Overall % Agreement | 95% Confidence Interval | ||
| EIA Result | Positive | 0 | 1* | 1 | Not Accurate (0/1) | Not Accurate | 99.7% (298/299) | 98.1%, 99.9% | 99.3% (298/300) | 97.6%, 99.8% |
| Negative | 1 | 298 | 299 | |||||||
| Total | 1 | 299 | 300 |
- One (1) anti-GBM EIA results was a weak positive.
The BioPlex 2200 Vasculitis kit was further evaluated by testing 227 retrospective samples positive for anti-MPO (N=100), anti-PR3 (N=100), and anti-GBM (N=27). All samples were also tested by the corresponding commercially available microplate EIA methods. In addition, the anti-MPO and anti-PR3 positive samples were tested by an ANCA IFA method using ethanol-fixed slides. The
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results can be observed in Tables G - K.
Table G. BioPlex 2200 vs. Anti-MPO EIA – Retrospective Anti-MPO Positive Samples (N=100)
| Positive | Negative | Total | Positive (+)% Agreement | 95% ConfidenceInterval | Negative (-)% Agreement | 95% ConfidenceInterval | Overall% Agreement | 95% ConfidenceInterval | ||
|---|---|---|---|---|---|---|---|---|---|---|
| EIA Result | Positive | 92 | 6 | 98 | 93.9%(92/98) | 87.3%,97.2% | N/A | N/A | 93.0%(93/100) | 86.2%,96.6% |
| Equivocal* | 1 | 0 | 1 | |||||||
| Negative | 0 | 1 | 1 | |||||||
| Total | 93 | 7 | 100 |
- One (1) anti-MPO EIA equivocal result is included in the Overall Agreement.
N/A = Not Applicable
| Table H. BioPlex 2200 vs. Anti-PR3 EIA - Retrospective Anti-PR3 Positive Samples | ||||
|---|---|---|---|---|
| (N=100) |
| BioPlex 2200 Vasculitis Anti-PR3 Result | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Positive | Negative | Total | Positive (+)% Agreement | 95% ConfidenceInterval | Negative (-)% Agreement | 95% ConfidenceInterval | Overall% Agreement | 95% ConfidenceInterval | ||
| EIA Result | Positive | 79 | 0 | 79 | 100.0%(79/79) | 95.4%,100% | N/A | N/A | 83.0%(83/100) | 74.4%,89.1% |
| Equivocal* | 9 | 1 | 10 | |||||||
| Negative | 7 | 4 | 11 | |||||||
| Total | 95 | 5 | 100 |
-
Ten (10) anti-PR3 ElA equivocal results are included in the Overall Agreement.
-
N/A = Not Applicable
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| BioPlex 2200 Vasculitis Anti-GBM Result | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Positive | Negative | Total | Positive (+)% Agreement | 95% ConfidenceInterval | Negative (-)% Agreement | 95% ConfidenceInterval | Overall% Agreement | 95% ConfidenceInterval | ||
| EIA Result | Positive | 16* | 2** | 18 | 88.9%(16/18) | 67.2%,96.9% | N/A | N/A | 92.6%(25/27) | 76.6%,97.9% |
| Negative | 0 | 9 | 9 | |||||||
| Total | 16 | 11 | 27 |
Table I. BioPlex 2200 vs. Anti-GBM ElA - Retrospective Anti-GBM Positive Samples (N=27)
*Two (2) of the sixteen (16) anti-GBM ElA positive results were weak positive.
** One (1) of the two (2) anti-GBM EIA positive results were weak positive.
The remaining fifteen (15) of the eighteen (18) anti-GBM EIA results were moderate to strong positive.
N/A = Not Applicable
| Table J. BioPlex 2200 vs. pANCA IFA - Retrospective Anti-MPO Positive Samples | |
|---|---|
| (N=100) |
| BioPlex 2200 Vasculitis Anti-MPO Result | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Positive | Negative | Total | Positive (+) % Agreement | 95% Confidence Interval | Negative (-) % Agreement | 95% Confidence Interval | Overall % Agreement | 95% Confidence Interval | ||
| pANCA IFA Result | Positive | 83 | 6 | 89 | 93.3%(83/89) | 86.1%,96.9% | N/A | N/A | 84.0%(84/100) | 75.6%,89.9% |
| Negative | 10 | 1 | 11 | |||||||
| Total | 93 | 7 | 100 |
N/A = Not Applicable
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| BioPlex 2200 Vasculitis Anti-PR3 Result | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Positive | Negative | Total | Positive (+)% Agreement | 95%ConfidenceInterval | Negative (-)% Agreement | 95%ConfidenceInterval | Overall% Agreement | 95%ConfidenceInterval | ||
| cANCA IFA Result | Positive | 93 | 5 | 98 | 94.9%(93/98) | 88.6%,97.8% | N/A | N/A | 93.0%(93/100) | 86.2%,96.6% |
| Negative | 2 | 0 | 2 | |||||||
| Total | 95 | 5 | 100 |
Table K. BioPlex 2200 vs. cANCA IFA – Retrospective Anti-PR3 Positive Samples (N=100)
N/A = Not Applicable
Tables L and M compare EIA results from the retrospective positive samples for anti-MPO EIA (N=100) and anti-PR3 EIA (N=100) with ANCA IFA results.
| Table L. pANCA IFA vs. Anti-MPO EIA - Retrospective Anti-MPO Positive Samples | ||
|---|---|---|
| (N=100) |
| Anti-MPO EIA Result | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Positive | Equivocal* | Negative | Total | Positive (+)% Agreement | 95%ConfidenceInterval | Negative (-)% Agreement | 95%ConfidenceInterval | Overall% Agreement | 95%ConfidenceInterval | ||
| pANCA IFA Result | Positive | 87 | 1 | 1 | 89 | 97.8%(87/89) | 92.2%-99.4% | N/A | N/A | 87.0%(87/100) | 79%,92.2% |
| Negative | 11 | 0 | 0 | 11 | |||||||
| Total | 98 | 1 | 1 | 100 |
- One (1) anti-MPO EIA equivocal result is included in the Overall Agreement. N/A = Not Applicable
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| Anti-PR3 EIA Result | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Positive | Equivocal* | Negative | Total | Positive (+)% Agreement | 95%ConfidenceInterval | Negative (-)% Agreement | 95%ConfidenceInterval | Overall% Agreement | 95%ConfidenceInterval | ||
| cANCA IFA Result | Positive | 78 | 10 | 10 | 98 | 79.6%(78/98) | 70.6%,86.4% | N/A | N/A | 79.0%(79/100) | 70.0%-85.8% |
| Negative | 1 | 0 | 1 | 2 | |||||||
| Total | 79 | 10 | 11 | 100 |
Table M. cANCA IFA vs. Anti-PR3 EIA - Retrospective Anti-PR3 Positive Samples (N=100)
- Ten (10) anti-PR3 EIA equivocal results are included in the Overall Agreement. N/A = Not Applicable
A combined positive agreement of 94.1% (176/187) was observed between BioPlex 2200 Vasculitis anti-MPO/anti-PR3 and ANCA IFA results (from Tables L and M), compared to a combined positive agreement of 88.2% (165/187) between anti-MPO/anti-PR3 EIA and ANCA IFA results (from Tables N and O). Also, a combined overall agreement of 88.5% (177/200) was observed between BioPlex 2200 Vasculitis anti-MPO/anti-PR3 and ANCA IFA results compared to a combined overall agreement of 83.0% (166/200) observed between anti-MPO/anti-PR3 and ANCA IFA results.
Table N summarizes the test results (positive percent agreement, negative percent agreement and overall percent agreement) for each of the three antibodies (anti-MPO, anti-PR3 and anti-GBM) from normal blood donors (N=293), unselected patient samples previously tested with vasculitis tests (N=300), and retrospective positive samples (N=100 for anti-MPO, N=100 for anti-PR3 and N=27 for anti-GBM). These sample populations were tested by the BioPlex 2200 Vasculitis kit and anti-MPO, anti-PR3 and anti-GBM ElAs. In addition, anti-MPO and anti-PR3 known positive samples were tested by an ANCA IFA method.
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Table N. Summary of Positive, Negative and Overall Percent Agreement for Normal Blood Donors (N=293), Unselected Patient Samples Previously Tested With Vasculitis Tests (N=300), and Retrospective Positive Samples (N=100 for anti-MPO, N=100 for anti-PR3 and N=27 for anti-GBM)
| Anti-MPO EIAResult | pANCA IFAResult | Anti-PR3 EIAResult | cANCA IFAResult | Anti-GBM EIAResult | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| % PosAgreement | % NegAgreement | % OverallAgreement | % PosAgreement | % NegAgreement | % OverallAgreement | % PosAgreement | % NegAgreement | % OverallAgreement | % PosAgreement | % NegAgreement | % OverallAgreement | % PosAgreement | % NegAgreement | % OverallAgreement | ||
| BioPlex 2200 Vasculitis Result | Normal BloodDonors* | N/A | 293/293100.0% | 293/293100.0% | NT | NT | NT | N/A | 293/293100.0% | 293/293100.0% | NT | NT | NT | N/A | 289/29199.3% | 289/29198.6% |
| UnselectedPatientSamplesPreviously | 5/771.4% | 284/29197.6% | 289/30096.3% | NT | NT | NT | 5/5100.0% | 292/29599.0% | 297/30099.0% | NT | NT | NT | NotAccurate(0/1) | 298/29999.7% | 298/30099.3% | |
| RetrospectivePositiveSamples | 92/9893.9% | N/A | 93/10093.0% | 83/8993.3% | N/A | 84/10084.0% | 79/79100.0% | N/A | 83/10083.0% | 93/9894.9% | N/A | 93/10093.0% | 16/1888.9% | N/A | 25/2792.6% |
Normal blood donors and unselected patient samples previously tested with vascultis tests were not tested by ANCA IFA. N/A = Not Applicable NT = Not Tested
E. Cross-Reactivity
A cross-reactivity study was performed to determine if samples from various disease states and other potentially interfering factors interfere with test results when tested with the BioPlex 2200 Vasculitis kit. A panel of ten (10) specimens positive for each cross reactant were evaluated for possible cross reactivity with the BioPlex 2200 Vascultis kit for each of the three (3) autoantibodies. Samples were also tested on a corresponding commercially available microplate ElAs. Most of the samples evaluated were high positive for each disease state. The results demonstrated that the various disease state samples evaluated do not cross react with the three (3) autoantibodies in the BioPlex 2200 Vasculitis kit. Results can be found in the below table:
| Table. Cross-Reactivity | |
|---|---|
| -- | ------------------------- |
| CrossReactives | N | Method | Anti-MPO | Anti-PR3 | Anti-GBM |
|---|---|---|---|---|---|
| ANA | 10 | BioPlex 2200 | 0 | 0 | 0 |
| ANA | 10 | EIA | 0 | 0 | 0 |
| ANA | 10 | Discrepants | 0 | 0 | 0 |
| Anti-SaccharomycesCerevisiae(ASCA) | 10 | BioPlex 2200 | 0 | 1 | 0 |
| EIA | 0 | 1 | 0 | ||
| Discrepants | 0 | 0 | 0 | ||
| Anti-Cardiolipin | 10 | BioPlex 2200 | 0 | 0 | 0 |
| EIA | 1 | 0 | 0 | ||
| Discrepants | 1 | 0 | 0 | ||
| Anti-dsDNA | 10 | BioPlex 2200 | 0 | 0 | 0 |
| EIA | 0 | 0 | 0 | ||
| Discrepants | 0 | 0 | 0 | ||
| Anti-Histone | 10 | BioPlex 2200 | 2 | 2 | 0 |
| EIA | 1 | 0 | 0 | ||
| Discrepants | 1 | 2 | 0 | ||
| RheumatoidFactor (RF) | 10 | BioPlex 2200 | 0 | 0 | 0 |
| EIA | 0 | 0 | 0 | ||
| Discrepants | 0 | 0 | 0 | ||
| Anti-ThyroidPeroxidase(TPO) | 10 | BioPlex 2200 | 0 | 0 | 0 |
| EIA | 0 | 0 | 0 | ||
| Discrepants | 0 | 0 | 0 | ||
| Anti-tissueTransglutaminase (tTG) | 7* | BioPlex 2200 | 0 | 0 | 0 |
| EIA | 0 | 0 | 0 | ||
| Discrepants | 0 | 0 | 0 | ||
| Anti-SmoothMuscle (ASMA) | 10 | BioPlex 2200 | 0 | 0 | 0 |
| EIA | 0 | 0 | 0 | ||
| Discrepants | 0 | 0 | 0 | ||
| HCV | 10 | BioPlex 2200 | 0 | 0 | 0 |
| EIA | 0 | 0 | 0 | ||
| Discrepants | 0 | 0 | 0 | ||
| HIV | 10 | BioPlex 2200 | 0 | 0 | 0 |
| EIA | 0 | 0 | 0 | ||
| Discrepants | 0 | 0 | 0 |
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BioPlex 2200 Vasculitis Kit,Calibrator Set and Control Set 510(k) Summary (10-24-07)
Page 20 of 21
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- Due to limited availability of samples, only seven tTG specimens were evaluated.
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DEPARTMENT OF HEALTH & HUMAN SERVICES
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Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Bio-Rad Laboratories c/o Ms. Priya Bondre Regulatory Affairs Representative 6565 185th Avenue NE Redmond, WA 98052
Re: K072358
Trade/Device Name: BioPlex™ 2200 Vasculitis kit BioPlex™ 2200 Vasculitis Calibrator Set BioPlex™ 2200 Vasculitis Control Set Regulation Number: 21 CFR 866.5660 Regulation Name: Multiple Autoantibodies Immunological Test System Regulatory Class: Class II Product Code: MOB, MVJ, JIX, JJY Dated: August 20, 2007 Received: August 22, 2007
Dear Ms Bondre:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.
OCT 3 1 2007
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter will allow you to begin marketing your device as described in your Section 510(k) premarket
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notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at 240-276-0450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at 240-276-3474. For questions regarding the reporting of device adverse events (Medical Device Reporting (MDR)), please contact the Division of Surveillance Systems at 240-276-3464. You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (240) 276-3150 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely vours.
Fobert Becker
Robert L. Becker, Jr., M.D., Ph. D. Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number: K072358
Device Name: BioPlex™ 2200 Vasculitis kit on the BioPlex™ 2200 Multi-Analyte Detection System BioPlex™ 2200 Vasculitis Calibrator Set BioPlex™ 2200 Vasculitis Control Set
Indications For Use:
BioPlex™ 2200 Vasculitis kit
The BioPlex™ 2200 Vasculitis kit is a multiplex flow immunoassay intended for the semi-quantitative detection of IgG autoantibodies to Mveloperoxidase (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 Polyangiitis (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.
BioPlex™ 2200 Vasculitis Calibrator Set
The BioPlex 2200 Vasculitis Calibrator Set is intended for the BioPlex 2200 Vasculitis Reagent Pack.
BioPlex™ 2200 Vasculitis Control Set
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.
Prescription Use _ V (Part 21 CFR 801 Subpart D)
AND/OR
Over-The-Counter Use (21 CFR 807 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE -CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH. Office of In Vitro Diagnostic Devices (OIVD)
Maria M Chen
Division Sign Off
Division Sign-Off
Office of In Vitro Diagnostic
Device Evaluation and Safety
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510(k) KO12358
§ 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).