Who is the manufacturer of BIOPLEX VASCULITIS KIT?

Bio-Rad Laboratories filed the 510(k) submission for BIOPLEX VASCULITIS KIT (K072358).

What is the FDA product code for BIOPLEX VASCULITIS KIT?

MVJ. It is classified under 21 CFR 866.5660 as a Class 2 device in the Immunology panel.

What is the regulatory pathway for BIOPLEX VASCULITIS KIT?

510(k) clearance (submission type: Traditional).

What are the predicate devices for BIOPLEX VASCULITIS KIT?

Phadia Varelisa™ MPO EIA (K041040); Phadia Varelisa™ PR3 EIA (K041043); INOVA QUANTA Lite™ GBM ELISA (K984336); INOVA NOVA Lite ANCA (Ethanol-fixed Slides) (K961340).

Who can help prepare an FDA 510(k) submission like BIOPLEX VASCULITIS KIT?

Innolitics — a medical-device software consultancy — provides regulatory and engineering support for FDA 510(k) submissions. See https://innolitics.com/services/510ks/ or contact https://innolitics.com/contact.

BIOPLEX VASCULITIS KIT

K072358 · Bio-Rad Laboratories · MVJ · Oct 31, 2007 · Immunology

Device Facts

Record ID	K072358
Device Name	BIOPLEX VASCULITIS KIT
Applicant	Bio-Rad Laboratories
Product Code	MVJ · Immunology
Decision Date	Oct 31, 2007
Decision	SESE
Submission Type	Traditional
Regulation	21 CFR 866.5660
Device Class	Class 2

Intended Use

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. 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.

Device Story

Multiplex flow immunoassay system; utilizes magnetic microbeads coated with MPO, PR3, and GBM antigens. Instrument combines patient serum, diluent, and bead reagent; incubates at 37°C. Phycoerythrin-conjugated anti-human IgG added; secondary incubation; wash cycles remove excess. Flow cytometer detector identifies bead populations via embedded fluorescent dye ratios and quantifies bound IgG via phycoerythrin fluorescence intensity. Internal Standard, Serum Verification, and Reagent Blank beads monitor detector response, serum presence, and non-specific binding. Used in clinical laboratories; operated by trained personnel. Output expressed as Antibody Index (AI). Results aid clinicians in diagnosing ANCA-associated vasculitides and Goodpasture's syndrome when combined with clinical findings.

Clinical Evidence

Bench testing only. Evaluated 293 normal blood donors and 300 unselected patient samples, plus 227 retrospective positive samples. Compared against commercial microplate EIA and ANCA IFA methods. Results showed high agreement across populations. Reproducibility tested at three sites over three days; intra-assay and inter-assay precision reported with %CVs generally <12%. Cross-reactivity studies with various disease states (ANA, ASCA, etc.) showed no significant interference.

Technological Characteristics

Multiplex flow immunoassay; magnetic microbeads coated with MPO, PR3, GBM antigens. Phycoerythrin-conjugated anti-human IgG detection. Fluorescence-based flow cytometry. Automated floor-standing analyzer. Connectivity to LIS. Software-controlled. Calibrators and controls in human serum matrix. Preservatives: ProClin 300, sodium benzoate, sodium azide.

Indications for Use

Indicated for the semi-quantitative detection of IgG autoantibodies to MPO, PR3, and GBM in human serum to aid in the diagnosis of ANCA-associated vasculitides (MPA, Necrotising Glomerulonephritis, Churg-Strauss Syndrome, Wegener's Granulomatosis) and autoimmune renal disorders (Goodpasture's syndrome) in conjunction with clinical findings.

Regulatory Classification

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).

Predicate Devices

Phadia Varelisa™ MPO EIA (K041040)
Phadia Varelisa™ PR3 EIA (K041043)
INOVA QUANTA Lite™ GBM ELISA (K984336)
INOVA NOVA Lite ANCA (Ethanol-fixed Slides) (K961340)

Related Devices

K100917 — FIDIS VASCULITIS ASSAY KIT AND ANALYZER AND CARIS SYSTEM · Biomedical Diagnostics (Bmd) SA · Nov 3, 2010

Submission Summary (Full Text)

{0}------------------------------------------------ K072358 Image /page/0/Picture/1 description: The image shows the logo for Bio-Rad. The logo is white text on a black rounded rectangle. The text is in all capital letters and is bolded. # 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 | CANILI Renort Date IImmary ! | |-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------| | A counts & com 1/070000 | 0000 Atanar and and and and the driver and the children the distribution of the country | #### MANUFACTURER INFORMATION | | Manufacturer | |--------------------------------------------------------|----------------------------------------------------------------------------------------------------------| | Manufacturer Address | Bio-Rad Laboratories, Inc. Clinical Systems Division 4000 Alfred Nobel Drive Hercules, CA 94547 | | Telephone | (510) 724-7000 | | Establishment Registration No. | 2915274 | | Owner / Operator | Bio-Rad Laboratories, Inc. 4000 Alfred Nobel Drive Hercules, CA 94547 | | Owner / Operator No. | 9929003 | | Official Correspondent for the BioPlex 2200 Vasculitis | | | Official Correspondent Address | Bio-Rad Laboratories 6565 185th Ave NE Redmond, WA 98052 | | Telephone | 425-881-8300 | | Establishment Registration No. | 3022521 | | Owner / Operator | Bio-Rad Laboratories 6565 185th Ave NE Redmond, 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 Basement Membrane (GBM) | |----------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------| | Common Name: | Multi-Analyte Detection System Vasculitis | | Product Trade Name | BioPlex 2200 Vasculitis kit on the BioPlex 2200 Multi-Analyte Detection System BioPlex 2200 Vasculitis Calibrator Set BioPlex 2200 Vasculitis Control Set | | Device Class | Class II | | Classification Panel | Immunology | | Requlation Number | 866.5660-Multiple Autoantibodies Immunological Test System | {1}------------------------------------------------ Image /page/1/Picture/0 description: The image shows the logo for Bio-Rad Laboratories, a company that manufactures and distributes products for the life science research and clinical diagnostics markets. The logo is black and white and features the company name in a bold, sans-serif font. The letters are slightly rounded and have a three-dimensional appearance. The logo is simple and recognizable. #### LEGALLY MARKETED EQUIVALENT (SE) DEVICES | Comparative FDA Cleared PREDICATE DEVICE | 510(k) Number | Decision Date | |---------------------------------------------|---------------|------------------| | 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 Internal Standard bead (ISB), a Serum Verification bead (SVB), and a Reagent Blank bead (RBB) in a MOPS (3-[N-Morpholino] propanesulfonic acid) buffer supplemented with Glycerol and protein stabilizers (bovine). ProClin® 300 (0.3%), sodium benzoate (0.1%) and sodium azide (<0.1%) are added as preservatives. | BioPlex 2200 Vasculitis Kit,Calibrator Set and Control Set 510(k) Summary (10-24-07) Page 2 of 21 {2}------------------------------------------------ Image /page/2/Picture/0 description: The image shows the logo for Bio-Rad Laboratories, a company that manufactures and distributes products for the life science research and clinical diagnostics markets. The logo is displayed in white text on a black background. The text is bold and sans-serif. The logo is simple and recognizable. | Conjugate CONJ | One (1) 5 mL vial, containing phycoerythrin conjugated murine monoclonal anti- human IgG and phycoerythrin conjugated murine monoclonal anti-human FXIII in phosphate buffer supplemented with murine and bovine protein stabilizers. ProClin® 300 (0.3%), sodium benzoate (0.1%) and sodium azide (<0.1%) are added as preservatives. | |-------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | Sample Diluent | One (1) 10 mL vial, containing bovine and murine protein stabilizers in triethanolamine buffer. ProClin® 300 (0.3%), sodium benzoate (0.1%) and sodium 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 containing human antibodies to MPO, PR3 and GBM, in a human serum matrix made from defibrinated plasma. All calibrators contain ProClin® 300 (0.3%), sodium benzoate (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 serum matrix made from defibrinated plasma; and two (2) 1.5 mL Negative Control serum vials, in a human serum matrix made from defibrinated plasma. All controls contain 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 Buffered Saline (PBS). ProClin® 300 (0.03%) and sodium azide (<0.1%) are added as preservatives. | | 660-0818 | BioPlex 2200 Wash Solution: One (1) 10 L bottle containing Phosphate Buffered Saline (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 | {3}------------------------------------------------ Image /page/3/Picture/0 description: The image shows the logo for Bio-Rad. The logo is white text on a black, rounded rectangle. The text is in a bold, sans-serif font. #### 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 between Components / Materials | BioPlex 2200 Vasculitis | Predicate Phadia Varelisa MPO ANCA EIA | |------------------------------------------------|-----------------------------|-------------------------------------------| | Reagents | Wash Buffer, Sample Diluent | Wash Buffer, Serum Diluent | #### Table 1: Similarities between reagents and materials {4}------------------------------------------------ Image /page/4/Picture/0 description: The image shows the logo for BIO-RAD. The logo is in white text on a black background. The text is bold and sans-serif. The logo is enclosed in a rounded rectangle. | Calibrators | Calibrators | Calibrators | |-------------|---------------------------------------------------------------------------|------------------------------------| | Controls | Negative Control and Multi-Analyte Positive Control (MPO, PR3 and GBM) | Negative Control, Positive Control | Table 2: Similarities between reagents with regard to function and use | Similarities between Function and Use | BioPlex 2200 Vasculitis | Predicate Phadia Varelisa MPO ANCA EIA | |------------------------------------------|---------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------| | Intended Use | Semi-quantitative detection of IgG autoantibodies to MPO, PR3 and GBM in human serum. | Semi-quantitative and qualitative determination of MPO Anti neutrophil cytoplasmic antibodies in human serum or plasma. | | Matrices | Serum | Serum | Table 3: Differences between reagents and materials | Differences between Components / Materials | BioPlex 2200 Vasculitis | Predicate Phadia Varelisa MPO ANCA EIA | |-----------------------------------------------|-----------------------------------------------------------------------------------------|------------------------------------------------------------| | Solid Phase | Bead reagent - dyed antigen coated beads | 96 well microplate - antigen coated microwells | | Reagents | Conjugate: Anti-human IgG / Phycoerythrin | Conjugate: Anti-human IgG HRP conjugate/Substrate (TMB) | | Sheath Fluid | Sheath Fluid is used to suspend the bead reagent 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 between Function and Use | BioPlex 2200 Vasculitis | Predicate Phadia Varelisa MPO ANCA 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 between Components / Materials | BioPlex 2200 Vasculitis | Predicate Phadia Varelisa PR3 ANCA EIA | |------------------------------------------------|---------------------------------------------------------------------------|-------------------------------------------| | Reagents | Wash Buffer, Sample Diluent | Wash Buffer, Sample Diluent | | Calibrators | Calibrators | Calibrators | | Controls | Negative Control and Multi-Analyte Positive Control (MPO, PR3 and GBM) | Negative Control, Positive Control | Table 5: Similarities between reagents and materials {5}------------------------------------------------ Image /page/5/Picture/0 description: The image shows the logo for Bio-Rad Laboratories, a company that manufactures and distributes products for the life science research and clinical diagnostics markets. The logo is in white text on a black background. The text is in a bold, sans-serif font. The logo is surrounded by a black rounded rectangle. Table 6: Similarities between reagents with regard to function and use | Similarities between Components / Materials | BioPlex 2200 Vasculitis | Predicate Phadia Varelisa PR3 ANCA EIA | |------------------------------------------------|---------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------| | Intended Use | Semi-quantitative detection of IgG autoantibodies to MPO, PR3 and GBM in human serum. | Semi-quantitative and qualitative determination of PR3 Anti neutrophil cytoplasmic antibodies in human serum or plasma. | | Matrices | Serum | Serum | | Differences between Components / Materials | BioPlex 2200 Vasculitis | Predicate Phadia Varelisa PR3 ANCA EIA | |-----------------------------------------------|-----------------------------------------------------------------------------------------|-------------------------------------------------------------| | Solid Phase | Bead reagent - dyed antigen coated beads | 96 well microplate - antigen coated microwells | | Reagents | Conjugate: Anti-human IgG / Phycoerythrin | Conjugate: Anti-Human IgG HRP Conjugate /Substrate (TMB) | | Sheath Fluid | Sheath Fluid is used to suspend the bead reagent 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 between Function and Use | BioPlex 2200 Vasculitis | Predicate Phadia Varelisa PR3 ANCA EIA | |-----------------------------------------|---------------------------------------------------------------------------|--------------------------------------------------------| | Analyte Detection | Multi-Analyte Detection (human IgG autoantibodies 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 between Components / Materials | BioPlex 2200 Vasculitis | Predicate INOVA QUANTA-Lite GBM ELISA | |------------------------------------------------|---------------------------------------------------------------------------|------------------------------------------| | Reagents | Wash Buffer, Sample Diluent | Wash Buffer, Serum Diluent | | Controls | Negative Control and Multi-Analyte Positive 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 between Components / Materials | BioPlex 2200 Vasculitis | Predicate INOVA QUANTA-Lite GBM ELISA | |------------------------------------------------|---------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------| | Intended Use | Semi-quantitative detection of IgG autoantibodies to MPO, PR3 and GBM in human serum. | Semi-quantitative determination of anti neutrophil cytoplasmic antibodies to GBM in human serum | #### Table 11: Differences between reagents and materials | Differences between Components / Materials | BioPlex 2200 Vasculitis | Predicate INOVA QUANTA-Lite GBM 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 {6}------------------------------------------------ Image /page/6/Picture/0 description: The image shows the logo for Bio-Rad Laboratories, a company that manufactures and distributes products for the life science research and clinical diagnostics markets. The logo is displayed in white text on a black background. The text is bold and sans-serif, and the letters are spaced closely together. The logo is simple and recognizable. | Reagents | Conjugate: Anti-human IgG / Phycoerythrin | Conjugate: Anti-Human IgG / Horse- radish Peroxidase, Substrate (TMB) | |--------------|----------------------------------------------------------------------------------------|--------------------------------------------------------------------------| | Sheath Fluid | Sheath Fluid is used to suspend the bead reagent 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 between Function and Use | BioPlex 2200 Vasculitis | Predicate INOVA QUANTA-Lite GBM ELISA | |-----------------------------------------|---------------------------------------------------------------------------|-----------------------------------------------------------| | Analyte Detection | Multi-Analyte Detection (human IgG autoantibodies to MPO, PR3 and GBM) | Single Analyte Detection (Human IgG antibodies to GBM) | #### D. BioPlex 2200 Vasculitis vs. Predicate INOVA Lite, ANCA, Ethanol Fixed Slides Table 13: Similarities between reagents and materials | Similarities between Components / Materials | BioPlex 2200 Vasculitis | Predicate INOVA NOVA Lite, ANCA, Ethanol Fixed Slides | |------------------------------------------------|---------------------------------------------------------------------------|------------------------------------------------------------------------------| | Controls | Negative Control and Multi-Analyte Positive Control (MPO, PR3 and GBM) | IFA Negative Control, p-ANCA Positive Control, c-ANCA Positive Control | Table 14: Similarities between reagents with regard to function and use | Similarities between Components / Materials | BioPlex 2200 Vasculitis | Predicate INOVA NOVA Lite, ANCA, Ethanol Fixed Slides | |------------------------------------------------|---------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------| | Intended Use | Semi-quantitative detection of IgG autoantibodies to MPO, PR3 and GBM in human serum. | Semi-quantitative determination of Anti neutrophil cytoplasmic antibodies in human serum. | | Matrices | Serum | Serum | #### Table 15: Differences between reagents and materials | Differences between Components / Materials | BioPlex 2200 Vasculitis | Predicate INOVA NOVA Lite, ANCA, Ethanol Fixed Slides | |-----------------------------------------------|-----------------------------------------------------------------------------------------|----------------------------------------------------------| | Solid Phase | Bead reagent - dyed antigen coated beads | ANCA, Ethanol fixed neutrophils Substrate slides | | Reagents | Conjugate: Anti-human IgG / Phycoerythrin | Conjugate: Anti-Human IgG / Horse- radish Peroxidase | | Sheath Fluid | Sheath Fluid is used to suspend the bead reagent 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 between Function and Use | BioPlex 2200 Vasculitis | Predicate INOVA NOVA Lite, ANCA, Ethanol Fixed Slides | |-----------------------------------------|---------------------------------------------------------------------------|----------------------------------------------------------| | Analyte Detection | Multi-Analyte Detection (human IgG autoantibodies 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 {7}------------------------------------------------ Image /page/7/Picture/0 description: The image shows the logo for Bio-Rad. The logo is white text on a black background. The text is in a bold, sans-serif font and is slightly distorted. | Solid Phase | Bead reagent - dyed antigen coated beads | ANCA, Ethanol fixed neutrophils Substrate 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 BioPlex 2200 Vasculitis Kit,Calibrator Set and Control Set 510(k) Summary (10-24-07) Page 8 of 21 {8}------------------------------------------------ Image /page/8/Picture/0 description: The image shows the logo for Bio-Rad Laboratories, a company that manufactures and distributes products for the life science research and clinical diagnostics markets. The logo is in white text on a black background. The text is bold and sans-serif. 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: | Vasculitis Kit Panel Members | | BioPlex 2200 Vasculitis Kit | | | | | | | | | | | | |------------------------------------|-----------------------|-----------------------------|------------|------------|------|-----------------|------|-----------------|------|-------------------|------|-------|-------| | | | Sample N | Mean AI | Within-Run | | Between- Run | | Between- Day | | Between- Site* | | Total | | | Vasculitis Anti-MPO | High Positive 1 | 36 | 4.0 | 0.277 | 7.0% | 0.156 | 3.9% | 0.022 | 0.6% | 0.326 | 8.2% | 0.456 | 11.5% | | | High Positive 2 | 36 | 5.5 | 0.295 | 5.4% | 0.249 | 4.5% | 0.000 | 0.0% | 0.254 | 4.6% | 0.462 | 8.4% | | | Low Positive 1 | 36 | 1.5 | 0.065 | 4.4% | 0.041 | 2.8% | 0.043 | 3.0% | 0.017 | 1.2% | 0.089 | 6.2% | | | Low Positive 2 | 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 | | | |-------------------------------------------------|--|--| | | | | BioPlex 2200 Vasculitis Kit,Calibrator Set and Control Set 510(k) Summary (10-24-07) Page 9 of 21 {9}------------------------------------------------ Image /page/9/Picture/0 description: The image shows the logo for BIO-RAD. The text is in white and the background is black. The logo is in a rounded rectangle. | | Cutoff 1 | | | | | | | | | | | | | |---------------------|-----------------------|----|-----|-------|------|-------|------|-------|-------|-------|-------|-------|-------| | | Near Cutoff 2 | 36 | 1.3 | 0.053 | 3.9% | 0.033 | 2.5% | 0.041 | 3.1% | 0.000 | 0.0% | 0.075 | 5.6% | | | Positive Control | 36 | 2.9 | 0.198 | 6.8% | 0.000 | 0.0% | 0.000 | 0.0% | 0.102 | 3.5% | 0.223 | 7.7% | | | Negative Control | 36 | 0.2 | 0.000 | 0.0% | 0.000 | 0.0% | 0.000 | 0.0% | 0.000 | 0.0% | 0.000 | 0.0% | | | High Positive 1 | 36 | 4.2 | 0.301 | 7.2% | 0.000 | 0.0% | 0.101 | 2.4% | 0.076 | 1.8% | 0.326 | 7.8% | | | High Positive 2 | 36 | 4.5 | 0.171 | 3.8% | 0.202 | 4.5% | 0.000 | 0.0% | 0.267 | 6.0% | 0.376 | 8.4% | | | Low Positive 1 | 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 | Low Positive 2 | 36 | 1.5 | 0.128 | 8.3% | 0.032 | 2.1% | 0.000 | 0.0% | 0.085 | 5.5% | 0.157 | 10.2% | | | Near Cutoff 1 | 36 | 1.2 | 0.062 | 5.1% | 0.000 | 0.0% | 0.057 | 4.7% | 0.027 | 2.2% | 0.088 | 7.3% | | | Near Cutoff 2 | 36 | 1.1 | 0.053 | 4.7% | 0.024 | 2.1% | 0.045 | 3.9% | 0.000 | 0.0% | 0.073 | 6.4% | | | Positive Control | 36 | 2.3 | 0.134 | 5.8% | 0.000 | 0.0% | 0.095 | 4.1% | 0.032 | 1.4% | 0.167 | 7.3% | | | Negative Control | 36 | 0.2 | 0.019 | 8.9% | 0.000 | 0.0% | 0.027 | 12.6% | 0.024 | 10.9% | 0.041 | 18.8% | {10}------------------------------------------------ Image /page/10/Picture/0 description: The image shows the logo for Bio-Rad. The logo is white text on a black rounded rectangle. The text is in all caps and is a sans-serif font. | Vasculitis Anti-GBM | High Positive 1 | 36 | 4.3 | 0.249 | 5.8% | 0.000 | 0.0% | 0.000 | 0.0% | 0.204 | 4.7% | 0.322 | 7.5% | |---------------------|-----------------------|----|-----|-------|------|-------|------|-------|------|-------|------|-------|------| | | High Positive 2 | 36 | 4.8 | 0.162 | 3.4% | 0.194 | 4.1% | 0.000 | 0.0% | 0.280 | 5.9% | 0.377 | 7.9% | | | Low Positive 1 | 36 | 1.4 | 0.081 | 5.6% | 0.000 | 0.0% | 0.064 | 4.5% | 0.087 | 6.0% | 0.135 | 9.4% | | | Low Positive 2 | 36 | 1.7 | 0.093 | 5.5% | 0.052 | 3.1% | 0.000 | 0.0% | 0.047 | 2.8% | 0.116 | 6.9% | | | Near Cutoff 1 | 36 | 1.1 | 0.037 | 3.4% | 0.045 | 4.1% | 0.000 | 0.0% | 0.079 | 7.2% | 0.099 | 9.0% | | | Near Cutoff 2 | 36 | 1.2 | 0.060 | 5.0% | 0.041 | 3.4% | 0.017 | 1.4% | 0.081 | 6.7% | 0.110 | 9.2% | | | Positive Control | 36 | 2.8 | 0.139 | 4.9% | 0.000 | 0.0% | 0.000 | 0.0% | 0.063 | 2.3% | 0.153 | 5.4% | | | Negative Control | 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. {11}------------------------------------------------ Image /page/11/Picture/0 description: The image shows the logo for BIO-RAD. The logo is white text on a black rounded rectangle. The text is in all caps and bolded. | 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% Confidence Interval | Negative (-) % Agreement | 95% Confidence Interval | Overall % Agreement | 95% Confidence Interval | | | 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 {12}------------------------------------------------ Image /page/12/Picture/0 description: The image shows the logo for BIO-RAD. The logo is in white text on a black background. The text is bold and sans-serif. | | | 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. {13}------------------------------------------------ Image /page/13/Picture/0 description: The image shows the logo for Bio-Rad. The logo is in white text on a black rounded rectangle. The text is bold and sans-serif. | | | BioPlex 2200 Vasculitis Anti-PR3 Result | | | | | | | | | |------------|-----------|-----------------------------------------|----------|-------|-----------------------------|-------------------------------|-----------------------------|-------------------------------|------------------------|-------------------------------| | | | Positive | Negative | Total | Positive (+) % Agreement | 95% Confidence Interval | Negative (-) % Agreement | 95% Confidence Interval | Overall % Agreement | 95% Confidence Interval | | 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 BioPlex 2200 Vasculitis Kit,Calibrator Set and Control Set 510(k) Summary (10-24-07) Page 14 of 21 {14}------------------------------------------------ Image /page/14/Picture/0 description: The image shows the logo for Bio-Rad. The logo is in white text on a black background. The text is bold and sans-serif. The logo is enclosed in a rounded rectangle. 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% Confidence Interval | Negative (-) % Agreement | 95% Confidence Interval | Overall % Agreement | 95% Confidence Interval | |------------|------------|----------|----------|-------|-----------------------------|----------------------------|-----------------------------|----------------------------|------------------------|----------------------------| | 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% Confidence Interval | Negative (-) % Agreement | 95% Confidence Interval | Overall % Agreement | 95% Confidence Interval | | 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 BioPlex 2200 Vasculitis Kit,Calibrator Set and Control Set 510(k) Summary (10-24-07) Page 15 of 21 {15}------------------------------------------------ Image /page/15/Picture/0 description: The image shows the logo for Bio-Rad. The logo is in white text on a black background. The text is in a bold, sans-serif font. The logo is surrounded by a rounded rectangle. | | | 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 | 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 {16}------------------------------------------------ Image /page/16/Picture/0 description: The image shows the logo for Bio-Rad Laboratories, a company that manufactures and distributes products for the life science research and clinical diagnostics markets. The logo is in white text on a black background. The text is in a bold, sans-serif font. The logo is surrounded by a rounded rectangle. | | | BioPlex 2200 Vasculitis Anti-PR3 Result | | | | | | | | | |------------------|----------|-----------------------------------------|----------|-------|-----------------------------|-------------------------------|-----------------------------|-------------------------------|------------------------|-------------------------------| | | | Positive | Negative | Total | Positive (+) % Agreement | 95% Confidence Interval | Negative (-) % Agreement | 95% Confidence Interval | Overall % Agreement | 95% Confidence Interval | | 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% Confidence Interval | Negative (-) % Agreement | 95% Confidence Interval | Overall % Agreement | 95% Confidence Interval | | 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 {17}------------------------------------------------ Image /page/17/Picture/0 description: The image shows the logo for Bio-Rad. The logo is in white text on a black, rounded rectangle. The text is bold and slightly slanted. | | | Anti-PR3 EIA Result | | | | | | | | | | |------------------|----------|---------------------|------------|----------|-------|-----------------------------|-------------------------------|-----------------------------|-------------------------------|------------------------|-------------------------------| | | | Positive | Equivocal* | Negative | Total | Positive (+) % Agreement | 95% Confidence Interval | Negative (-) % Agreement | 95% Confidence Interval | Overall % Agreement | 95% Confidence Interval | | 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. {18}------------------------------------------------ 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 EIA Result | | | pANCA IFA Result | | | Anti-PR3 EIA Result | | | cANCA IFA Result | | | Anti-GBM EIA Result | | | |--------------------------------|------------------------------------------------|------------------------|--------------------|------------------------|---------------------|--------------------|------------------------|------------------------|--------------------|------------------------|---------------------|--------------------|------------------------|--------------------------|--------------------|------------------------| | | | % Pos Agreement | % Neg Agreement | % Overall Agreement | % Pos Agreement | % Neg Agreement | % Overall Agreement | % Pos Agreement | % Neg Agreement | % Overall Agreement | % Pos Agreement | % Neg Agreement | % Overall Agreement | % Pos Agreement | % Neg Agreement | % Overall Agreement | | BioPlex 2200 Vasculitis Result | Normal Blood Donors* | N/A | 293/293 100.0% | 293/293 100.0% | NT | NT | NT | N/A | 293/293 100.0% | 293/293 100.0% | NT | NT | NT | N/A | 289/291 99.3% | 289/291 98.6% | | | Unselected Patient Samples Previously | 5/7 71.4% | 284/291 97.6% | 289/300 96.3% | NT | NT | NT | 5/5 100.0% | 292/295 99.0% | 297/300 99.0% | NT | NT | NT | Not Accurate (0/1) | 298/299 99.7% | 298/300 99.3% | | | Retrospective Positive Samples | 92/98 93.9% | N/A | 93/100 93.0% | 83/89 93.3% | N/A | 84/100 84.0% | 79/79 100.0% | N/A | 83/100 83.0% | 93/98 94.9% | N/A | 93/100 93.0% | 16/18 88.9% | N/A | 25/27 92.6% | 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 | |--|-------------------------| |--|-------------------------| | Cross Reactives | 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- Saccharomyces Cerevisiae (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 | | Rheumatoid Factor (RF) | 10 | BioPlex 2200 | 0 | 0 | 0 | | | | EIA | 0 | 0 | 0 | | | | Discrepants | 0 | 0 | 0 | | Anti-Thyroid Peroxidase (TPO) | 10 | BioPlex 2200 | 0 | 0 | 0 | | | | EIA | 0 | 0 | 0 | | | | Discrepants | 0 | 0 | 0 | | Anti-tissue Transglutaminase (tTG) | 7* | BioPlex 2200 | 0 | 0 | 0 | | | | EIA | 0 | 0 | 0 | | | | Discrepants | 0 | 0 | 0 | | Anti-Smooth Muscle (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 | BioPlex 2200 Vasculitis Kit,Calibrator Set and Control Set 510(k) Summary (10-24-07) Page 19 of 21 {19}------------------------------------------------ Image /page/19/Picture/0 description: The image shows the logo for Bio-Rad. The logo is white text on a black background. The text is in a bold, sans-serif font. The logo is surrounded by a black oval shape. BioPlex 2200 Vasculitis Kit,Calibrator Set and Control Set 510(k) Summary (10-24-07) Page 20 of 21 {20}------------------------------------------------ Image /page/20/Picture/0 description: The image shows the logo for Bio-Rad. The logo is in white text on a black background. The text is in a bold, sans-serif font. The logo is enclosed in a rounded rectangle. * Due to limited availability of samples, only seven tTG specimens were evaluated. {21}------------------------------------------------ DEPARTMENT OF HEALTH & HUMAN SERVICES Image /page/21/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized caduceus symbol, which is a staff with two snakes entwined around it, and the text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" arranged in a circular pattern around the symbol. The text is in all caps and is evenly spaced around the circle. 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…

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