K Number
K041658
Device Name
BIOPLEX 200 ANA SCREEN ON THE BIOPLEX 2200 MULTI-ANALYTE DETECTION SYSTEM, MODEL BIOPLEX 2200
Date Cleared
2004-12-20

(185 days)

Product Code
Regulation Number
866.5100
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP Authorized
Intended Use
The Bio-Plex 2200 ANA Screen is intended for the qualitative screening of specific antinuclear antibodies (ANA), the quantitative detection of antibody to dsDNA, and the semi-quantitative detection of ten (10) separate antibody assays (Chromatin, Ribosomal Protein, SS-A, SS-B, Sm, SmRNP, RNP, Scl-70, Jo-1, and Centromere B.) in human serum and/or EDTA or heparinized plasma. The test system is used as an aid in the diagnosis of systemic rheumatic diseases. The ANA Screen is intended for use with the Bio-Rad BioPlex 2200 System. The test system is used to screen serum or plasma (EDTA, heparin) samples and detect the presence of antinuclear antibodies as an aid in the diagnosis of systemic rheumatic diseases (Systemic Lupus Erythematosus [SLE], Mixed Connective Tissue Disease [MCTD], Undifferentiated Connective Tissue Disease [UCTD], Sjögren's Syndrome [SS], Scleroderma [Systemic Sclerosis], Dermatomyositis, Polymyositis, Rheumatoid Arthritis [RA], CREST Syndrome, and Raynaud's Phenomenon) in conjunction with clinical findings and other laboratory tests.
Device Description
The ANA Screen detects the presence of clinically relevant circulating autoantibodies in serum or plasma. These autoantibodies may be useful as an aid in the diagnosis of systemic rheumatic diseases such as Systemic Lupus Erythematosus (SLE), Mixed Connective Tissue Disease (MCTD), Undifferentiated Connective Tissue Disease (UCTD), Sjogren's Syndrome (SS), Scleroderma (Systemic Sclerosis), Dermatomyositis, Polymyositis, Rheumatoid Arthritis (RA), CREST Syndrome, and Raynaud's Phenomenon. Bio-Rad's ANA Screen uses a comprehensive group of autoantigens. Beads are individually couted with individual antigens, so that the presence of each antinuclear and autoimmune antibody can be individually determined. Fluorescence detection facilitates the differentiation of normal and abnormal antibody concentrations. The ANA Screen uses multiplex flow immunoassay, a methodology that resembles traditional EIA, but permits simultaneous detection and identification of many antibodies in a single tube. Thirteen (13) different populations of dyed beads are coated with antigens associated with systemic autoimmune disease (dsDNA, Chromatin, Ribosomal Protein, SS-A 60, SS-A 52, SS-B, Sm, SmRNP, RNP A, RNP 68, Scl-70, Jo-1 and Centromere B)*. 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, murine monoclonal anti-human IgG antibody, conjugated to phycoerythrin (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 is suspended in sheath fluid and then passes through the detector and the identity of the dyed beads is determined by the fluorescence of the dyes. Individually dyed with combinations of two different fluorescent dyes (red and orange), a bead may have one of many possible levels of classifier dye fluorescent intensities. Based on it's fluorescent signature, each bead is classified to it's own unique region. Bio-Rad has used the various combinations of dyes to create 25 uniquely color-coded regions that are associated with 25 unique sets of beads (more can be added if needed). The detector measures at least 200 beads for each analyte, per specimen. The BioPlex 2200 ANA Screen utilizes one of these regions for each of the 13 analytes it detects. Three additional regions are assigned to beads used for quality control purposes.
More Information

K011244, K970227, 954723, 922830, 932419, 922831, 922833, 993589, 981237, 982603, 950031, 000489, 951798, 951850

None

No
The description focuses on the multiplex flow immunoassay technology and fluorescence detection for identifying antibodies. There is no mention of AI or ML algorithms being used for data analysis, classification, or interpretation. The performance studies describe standard statistical metrics like agreement and reproducibility, not metrics typically associated with AI/ML model evaluation.

No
This device is an in vitro diagnostic (IVD) device used for screening and detecting antinuclear antibodies as an aid in diagnosing systemic rheumatic diseases. It does not provide therapy.

Yes

The device is intended for the "qualitative screening of specific antinuclear antibodies (ANA), the quantitative detection of antibody to dsDNA, and the semi-quantitative detection of ten (10) separate antibody assays... in human serum and/or EDTA or heparinized plasma." It is also stated that "The test system is used as an aid in the diagnosis of systemic rheumatic diseases." This clearly indicates its use in diagnosing conditions.

No

The device description clearly details a physical test system involving beads, reagents, incubation, wash cycles, and fluorescence detection using the Bio-Rad BioPlex 2200 System, which is a hardware platform. This is not a software-only device.

Yes, this device is an IVD (In Vitro Diagnostic).

Here's why:

  • Intended Use: The "Intended Use / Indications for Use" section explicitly states that the device is "intended for the qualitative screening of specific antinuclear antibodies (ANA), the quantitative detection of antibody to dsDNA, and the semi-quantitative detection of ten (10) separate antibody assays... in human serum and/or EDTA or heparinized plasma." It also states that the "test system is used as an aid in the diagnosis of systemic rheumatic diseases." This clearly indicates that the device is used to examine specimens derived from the human body to provide information for diagnostic purposes.
  • Device Description: The "Device Description" further clarifies that the device "detects the presence of clinically relevant circulating autoantibodies in serum or plasma" and that these autoantibodies "may be useful as an aid in the diagnosis of systemic rheumatic diseases."
  • Specimen Type: The device uses human serum and/or plasma, which are biological specimens from the human body.
  • Purpose: The purpose is to detect specific antibodies that are markers for systemic rheumatic diseases, aiding in diagnosis.

These points align directly with the definition of an In Vitro Diagnostic device, which is a medical device intended to be used in vitro for the examination of specimens derived from the human body solely or principally for the purpose of providing information concerning a physiological or pathological state, or a congenital abnormality, or to determine the safety or suitability of a transfusion or transplantation, or to monitor therapeutic measures.

N/A

Intended Use / Indications for Use

The Bio-Plex 2200 ANA Screen is intended for the qualitative screening of specific antinuclear antibodies (ANA), the quantitative detection of antibody to dsDNA, and the semi-quantitative detection of ten (10) separate antibody assays (Chromatin, Ribosomal Protein, SS-A, SS-B, Sm, SmRNP, RNP, Scl-70, Jo-1, and Centromere B.) in human serum and/or EDTA or heparinized plasma. The test system is used as an aid in the diagnosis of systemic rheumatic diseases. The ANA Screen is intended for use with the Bio-Rad BioPlex 2200 System.

Uses:
The test system is used to screen serum or plasma (EDTA, heparin) samples and detect the presence of antinuclear antibodies as an aid in the diagnosis of systemic rheumatic diseases (Systemic Lupus Erythematosus [SLE], Mixed Connective Tissue Disease [MCTD], Undifferentiated Connective Tissue Disease [UCTD], Sjögren's Syndrome [SS], Scleroderma [Systemic Sclerosis], Dermatomyositis, Polymyositis, Rheumatoid Arthritis [RA], CREST Syndrome, and Raynaud's Phenomenon) in conjunction with clinical findings and other laboratory tests.

Product codes

LKJ, LRM, MQA, LKO, LJM, LLL

Device Description

The ANA Screen detects the presence of clinically relevant circulating autoantibodies in serum or plasma. These autoantibodies may be useful as an aid in the diagnosis of systemic rheumatic diseases such as Systemic Lupus Erythematosus (SLE), Mixed Connective Tissue Disease (MCTD), Undifferentiated Connective Tissue Disease (UCTD), Sjogren's Syndrome (SS), Scleroderma (Systemic Sclerosis), Dermatomyositis, Polymyositis, Rheumatoid Arthritis (RA), CREST Syndrome, and Raynaud's Phenomenon. Bio-Rad's ANA Screen uses a comprehensive group of autoantigens. Beads are individually couted with individual antigens, so that the presence of each antinuclear and autoimmune antibody can be individually determined. Fluorescence detection facilitates the differentiation of normal and abnormal antibody concentrations.

The ANA Screen uses multiplex flow immunoassay, a methodology that resembles traditional EIA, but permits simultaneous detection and identification of many antibodies in a single tube. Thirteen (13) different populations of dyed beads are coated with antigens associated with systemic autoimmune disease (dsDNA, Chromatin, Ribosomal Protein, SS-A 60, SS-A 52, SS-B, Sm, SmRNP, RNP A, RNP 68, Scl-70, Jo-1 and Centromere B)*. 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, murine monoclonal anti-human IgG antibody, conjugated to phycoerythrin (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 is suspended in sheath fluid and then passes through the detector and the identity of the dyed beads is determined by the fluorescence of the dyes. Individually dyed with combinations of two different fluorescent dyes (red and orange), a bead may have one of many possible levels of classifier dye fluorescent intensities. Based on it's fluorescent signature, each bead is classified to it's own unique region. Bio-Rad has used the various combinations of dyes to create 25 uniquely color-coded regions that are associated with 25 unique sets of beads (more can be added if needed). The detector measures at least 200 beads for each analyte, per specimen. The BioPlex 2200 ANA Screen utilizes one of these regions for each of the 13 analytes it detects. Three additional regions are assigned to beads used for quality control purposes. The bead regions used by the BioPlex 2200 ANA Screen are defined in the table below.

Mentions image processing

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Mentions AI, DNN, or ML

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Input Imaging Modality

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Anatomical Site

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Indicated Patient Age Range

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Intended User / Care Setting

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Description of the training set, sample size, data source, and annotation protocol

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Description of the test set, sample size, data source, and annotation protocol

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Summary of Performance Studies

Reproducibility Studies:

  • Study Type: Reproducibility study.
  • Sample Size: 11 serum panel members (10 positive, 1 negative) and 3 lots of BioPlex 2200 ANA Screen Control Set (1 positive, 1 diluted positive, 1 negative).
  • Data Source: Internal at Bio-Rad Laboratories and three (3) US testing facilities.
  • Annotation Protocol: Each of the eleven panel members and the Autoimmune Control Set was tested in duplicate (x2) on two (2) runs per day (morning and afternoon) for ten (10) days using one (1) lot of Bio-Rad ANA Screen Reagent Pack and one (1) lot of Bio-Rad ANA Screen Calibrator Set at each of three (3) sites. (2 times x 2 runs x 10 days = 40 replicates per panel member per site. Total replicates at 3 sites = 120 replicates per panel member.)
  • Key Results: Intra-assay and inter-assay reproducibility were evaluated.
    • Intra-assay CV% ranged from 1.7% to 7.9% for all serum positive panel members for all analytes at Site 1.
    • Intra-assay CV% ranged from 2.1% to 8.6% for all serum positive panel members for all analytes at Site 2.
    • Intra-assay CV% ranged from 2.1% to 11.1% for all serum positive panel members for all analytes at Site 3.
    • Inter-assay CV% ranged from 2.8% to 12.8% for all serum positive panel members for all analytes at Site 1.
    • Inter-assay CV% ranged from 5.8% to 11.9% for all serum positive panel members for all analytes at Site 2.
    • Inter-assay CV% ranged from 3.6% to 12.0% for all serum positive panel members for all analytes at Site 3.

Clinical Testing - Prospective Testing:

  • Study Type: Comparison of ANA Screen and ANA Microplate EIA.
  • Sample Size: 908 prospective serum samples.
  • Data Source: Samples collected from patients seen at a rheumatology clinic and suspected of having systemic autoimmune disease at 3 U.S. clinical testing sites.
  • Annotation Protocol: ANA Screen results compared against a commercially available ANA Microplate EIA.
  • Key Results:
    • Positive Agreement: 351/500 = 70.2% (95% CI 66.1 - 74.3 %)
    • Negative Agreement: 369/708 = 90.4% (95% CI 87.5 - 93.4%)
    • Overall Agreement: 720/908 = 79.3% (95% CI 76.6 - 82%)

Clinical Testing - Prospective: Comparison of Selected Antibodies to EIA Methods:

  • Study Type: Comparison of specific autoantibodies detected by Bio-Rad and corresponding commercially available microplate EIA.
  • Sample Size: 908 prospective serum samples.
  • Data Source: Not explicitly stated beyond "samples positive by the ANA Screen for specific autoantibodies".
  • Annotation Protocol: Samples positive by ANA Screen for specific autoantibodies were also tested by a corresponding commercially available microplate EIA.
  • Key Results (% Overall Agreement):
    • dsDNA: 94% (95% CI 92-96%)
    • Chromatin: 86% (95% CI 83-88%)
    • Ribosomal-P: 98% (95% CI 97-99%)
    • SS-A: 97% (95% CI 95-98%)
    • SS-B: 97% (95% CI 95-98%)
    • Sm: 97% (95% CI 96-98%)
    • SmRNP: 96% (95% CI 95-97%)
    • RNP: 95% (95% CI 94-97%)
    • Scl-70: 98% (95% CI 97-99%)
    • Jo-1: 99% (95% CI 99-100%)
    • Centromere: 99% (95% CI 99-100%)

Clinical Testing - Retrospective: Comparison of Selected Antibodies to EIA Methods:

  • Study Type: Comparison of specific autoantibodies detected by Bio-Rad and corresponding commercially available microplate EIA.
  • Sample Size: 440 retrospective serum samples (known positive for ANA and one or more autoantibodies) + 100 serum samples (known negative for ANA).
  • Data Source: Not explicitly stated beyond "retrospective serum samples".
  • Annotation Protocol: Retrospective specimens tested by both ANA Screen and commercially available microplate EIA methods.
  • Key Results (% Overall Agreement):
    • dsDNA: 98% (95% CI 94-100%)
    • Chromatin: 86% (95% CI 80-92%)
    • Ribosomal-P: 96% (95% CI 92-99.5%)
    • SS-A: 99% (95% CI 96-100%)
    • SS-B: 99% (95% CI 98-100%)
    • Sm: 93% (95% CI 88-98%)
    • SmRNP: 99% (95% CI 96-100%)
    • RNP: 96% (95% CI 92-99.5%)
    • Scl-70: 94% (95% CI 90-99%)
    • Jo-1: 100% (95% CI 99.6-100%)
    • Centromere: 98% (95% CI 95-100%)

Clinical Testing - Combined Prospective and Retrospective: Comparison of Selected Antibodies to EIA Methods:

  • Study Type: Combined analysis of prospective and retrospective study results for comparison to EIA methods.
  • Sample Size:
    • dsDNA: 955
    • Chromatin: 1046
    • Ribosomal-P: 1046
    • SS-A: 1047
    • SS-B: 1048
    • Sm: 1047
    • SmRNP: 1047
    • RNP: 1017
    • Scl-70: 1047
    • Jo-1: 1038
    • Centromere: 1048
  • Data Source: Combined data from prospective and retrospective studies.
  • Annotation Protocol: Comparison of Bio-Rad and EIA methods.
  • Key Results (% Overall Agreement):
    • dsDNA: 94% (95% CI 93-96%)
    • Chromatin: 86% (95% CI 84-88%)
    • Ribosomal-P: 97% (95% CI 96-98 %)
    • SS-A: 97% (95% CI 96-98%)
    • SS-B: 97% (95% CI 96-98%)
    • Sm: 96% (95% CI 95-97%)
    • SmRNP: 96% (95% CI 95-98%)
    • RNP: 95% (95% CI 94-97%)
    • Scl-70: 97% (95% CI 96-98%)
    • Jo-1: 99.5% (95% CI 99-99.9%)
    • Centromere: 99% (95% CI 98.6-99.6%)

Cross-Reactivity Study:

  • Study Type: Evaluate interference from various disease states and potentially interfering factors.
  • Sample Size: 10 specimens for each of 11 autoantibodies. (Total N=10 for each cross reactant type)
  • Data Source: Previously characterized samples known to be negative for all autoantibodies detected by ANA Screen.
  • Annotation Protocol: Samples were tested with ANA Screen. Positive responses were also tested by corresponding commercially available EIA test method.
  • Key Results: Positive samples observed for various analytes when tested against cross-reactants such as Cardiolipin, Mitochondrial M2, ssDNA, histone, MPO, Gliadin, Smooth Muscle, Thyroid Peroxidase, and Thyroglobulin. Rheumatoid Factor did not show any positive results.

Key Metrics

  • Intra-assay precision (%CV): Ranged from 1.7% to 11.1%.
  • Inter-assay precision (%CV): Ranged from 2.8% to 12.8%.
  • Clinical Performance (Prospective):
    • Positive Agreement: 70.2%
    • Negative Agreement: 90.4%
    • Overall Agreement: 79.3%
  • Overall Agreement for specific autoantibodies (Combined Prospective and Retrospective):
    • dsDNA: 94%
    • Chromatin: 86%
    • Ribosomal-P: 97%
    • SS-A: 97%
    • SS-B: 97%
    • Sm: 96%
    • SmRNP: 96%
    • RNP: 95%
    • Scl-70: 97%
    • Jo-1: 99.5%
    • Centromere: 99%

Predicate Device(s)

K011244, K970227, 954723, 922830, 932419, 922831, 922833, 993589, 981237, 982603, 950031, 000489, 951798, 951850

Reference Device(s)

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information

Not Found

§ 866.5100 Antinuclear antibody immunological test system.

(a)
Identification. An antinuclear antibody immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the autoimmune antibodies in serum, other body fluids, and tissues that react with cellular nuclear constituents (molecules present in the nucleus of a cell, such as ribonucleic acid, deoxyribonucleic acid, or nuclear proteins). The measurements aid in the diagnosis of systemic lupus erythematosus (a multisystem autoimmune disease in which antibodies attack the victim's own tissues), hepatitis (a liver disease), rheumatoid arthritis, Sjögren's syndrome (arthritis with inflammation of the eye, eyelid, and salivary glands), and systemic sclerosis (chronic hardening and shrinking of many body tissues).(b)
Classification. Class II (performance standards).

0

Image /page/0/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 a black rounded rectangle with the words "BIO-RAD" in white letters. The letters are bold and sans-serif.

BIOPLEX 2200 ANA SCREEN 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) Number510(k) Summary Report Date
K041658December 13, 2004

MANUFACTURER INFORMATION

Manufacturer
Manufacturer AddressBio-Rad Laboratories, Inc.
Clinical Systems Division
4000 Alfred Nobel Drive
Hercules, CA 94547
Telephone(510) 724-7000
Establishment Registration No.2915274
Owner / OperatorBio-Rad Laboratories, Inc.
4000 Alfred Nobel Drive
Hercules, CA 94547
Owner / Operator No.9929003
Official Correspondent for the BioPlex 2200 ANA Screen
Official Correspondent AddressBio-Rad Laboratories
6565 185th Ave NE
Redmond, WA 98052
Telephone425-881-8300
Establishment Registration No.3022521
Owner / OperatorBio-Rad Laboratories, Inc.
4000 Alfred Nobel Drive
Hercules, CA 94547
Official CorrespondentMr. Christopher Bentsen
Telephone(425) 498-1709
Fax(425) 498-1651

CLASSIFICATION INFORMATION

Classification NameAntinuclear Antibody (Enzyme-Labeled), Antigen, Controls
Common Name:Multi-Analyte Detection System ANA Screen
Product Trade NameBioPlex 2200 ANA Screen on the BioPlex 2200 Multi-Analyte
Detection System
Device ClassClass II
Classification PanelImmunology and Microbiology
Regulation Number866.5100

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LEGALLY MARKETED EQUIVALENT (SE) DEVICES

Instrument

| BioPlex2200 System | Comparative FDA Cleared
PREDICATE DEVICE | 510(k)
Number | Product
Code | Decision
Date |
|----------------------------------------------------------|---------------------------------------------------------------------------------------|------------------|-----------------|------------------|
| BioPlex 2200 ANA Screen
on the BioPlex 2200
System | Zeus Athena Multi-Lyte ANA Test System | K011244 | LKJ | 12/10/2001 |
| | Diagnostic Products Corporation (DPC) Immulite
2000 Automated Immunoassay Analyzer | K970227 | JJE | 4/8/1997 |

Assay

| BioPlex2200 ANA Screen | Comparative FDA Cleared Device | 510(k)
Number | Product
Code | Decision
Date |
|------------------------------------------------------------------|------------------------------------------------------|------------------|-----------------|------------------|
| ANA Screen (based on
results of all analytes listed
below) | Bio-Rad (Helix) Autoimmune EIA
ANA Screening Test | 954723 | LKJ | 12/15/1995 |

| | BioPlex2200 ANA
Screen Analyte | Comparative FDA Cleared
PREDICATE DEVICE | 510(k)
Number | Product
Code | Decision
Date |
|-----|-----------------------------------|---------------------------------------------------------|------------------|-----------------|------------------|
| 1. | SSA (SSA 60 and
SSA 52) | Inova Diagnostics, Inc. QUANTA Lite™ SSA | 922830 | LLL | 9/18/1992 |
| 2. | SSB | Bio-Rad (Helix) Autoimmune EIA
SS-B / La Test | 932419 | LLL | 8/5/1993 |
| 3. | Sm | Inova Diagnostics, Inc. QUANTA Lite™ Sm | 922831 | LLL | 9/18/1992 |
| 4. | SmRNP | Inova Diagnostics, Inc. QUANTA Lite™ RNP
(Sm/RNP) | 922833 | LLL | 9/18/1992 |
| 5. | RNP (RNP 68 and
RNP A) | Pharmacia Varelisa® RNP Antibodies | 993589 | LKO | 11/26/1999 |
| 6. | Ribosomal Protein | Inova Diagnostics, Inc. QUANTA
Lite™Ribosome P | 981237 | MQA | 6/5/1998 |
| 7. | Chromatin | Inova Diagnostics, Inc. QUANTA Lite™
Chromatin ELISA | 982603 | LLL | 10/7/1998 |
| 8. | dsDNA
(quant. / semi-quant.) | Pharmacia Varelisa® ds-DNA ANTIBODY EIA
Kit | 950031 | LRM | 3/10/1995 |
| 9. | Centromere | Bio-Rad (Helix) Autoimmune EIA
Anti-Centromere Test | 000489 | LLL | 4/15/2000 |
| 10. | Scl-70 | Bio-Rad (Helix) Autoimmune EIA
Anti-Scl-70 Test | 951798 | LJM | 7/17/1995 |
| 11. | Jo-1 | Bio-Rad (Helix) Autoimmune EIA
Anti-Jo-1 Test | 951850 | LJM | 7/18/1995 |

2

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DEVICE DESCRIPTION

The ANA Screen detects the presence of clinically relevant circulating autoantibodies in serum or plasma. These autoantibodies may be useful as an aid in the diagnosis of systemic rheumatic diseases such as Systemic Lupus Erythematosus (SLE), Mixed Connective Tissue Disease (MCTD), Undifferentiated Connective Tissue Disease (UCTD), Sjogren's Syndrome (SS), Scleroderma (Systemic Sclerosis), Dermatomyositis, Polymyositis, Rheumatoid Arthritis (RA), CREST Syndrome, and Raynaud's Phenomenon. Bio-Rad's ANA Screen uses a comprehensive group of autoantigens. Beads are individually couted with individual antigens, so that the presence of each antinuclear and autoimmune antibody can be individually determined. Fluorescence detection facilitates the differentiation of normal and abnormal antibody concentrations.

The ANA Screen uses multiplex flow immunoassay, a methodology that resembles traditional EIA, but permits simultaneous detection and identification of many antibodies in a single tube. Thirteen (13) different populations of dyed beads are coated with antigens associated with systemic autoimmune disease (dsDNA, Chromatin, Ribosomal Protein, SS-A 60, SS-A 52, SS-B, Sm, SmRNP, RNP A, RNP 68, Scl-70, Jo-1 and Centromere B)*. 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, murine monoclonal anti-human IgG antibody, conjugated to phycoerythrin (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 is suspended in sheath fluid and then passes through the detector and the identity of the dyed beads is determined by the fluorescence of the dyes. Individually dyed with combinations of two different fluorescent dyes (red and orange), a bead may have one of many possible levels of classifier dye fluorescent intensities. Based on it's fluorescent signature, each bead is classified to it's own unique region. Bio-Rad has used the various combinations of dyes to create 25 uniquely color-coded regions that are associated with 25 unique sets of beads (more can be added if needed). The detector measures at least 200 beads for each analyte, per specimen. The BioPlex 2200 ANA Screen utilizes one of these regions for each of the 13 analytes it detects. Three additional regions are assigned to beads used for quality control purposes. The bead regions used by the BioPlex 2200 ANA Screen are defined in the table below.

Bead RegionAssay NameDescription
17dsDNAAntigen coated bead - dsDNA
21Chromatin
(DNP)Antigen coated bead - Chromatin
34ISBInternal Standard Bead - verifies detector response and corrects for
fluctuations in laser intensity due to voltage fluctuation and/or
temperature.
36RNP-AAntigen coated bead - RNP-A
38SSBAntigen coated bead - SSB
52SSA-52Antigen coated bead - SSA-52
54Reagent Blank
BeadBlank bead - verifies absence of significant non-specific binding in
serum or plasma
56Scl-70Antigen coated bead - Scl-70
71SmAntigen coated bead – Sm
75Centromere BAntigen coated bead - Centromere B
79Sm/RNPAntigen coated bead – Sm/RNP
81Ribosomal PAntigen coated bead - Ribosomal P
92RNP-68Antigen coated bead - RNP-68
94SSA-60Antigen coated bead - SSA-60
96Jo-1Antigen coated bead - Jo-1
100SVB (FXIII)Serum Verification Bead (coated with a monoclonal antibody to Factor
XIII) - verifies the addition of serum or plasma to the reaction vessel

3

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While the identity of the dyed beads is determined by the fluorescence of 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) and fluorescence ratio (FR).

Three additional dyed beads, Internal Standard Bead (ISB), Serum Verification Bead (SVB) and a Blank Bead (BB) 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 six (6) distinct calibrator vials, supplied separately by Bio-Rad Laboratories. For dsDNA, six (6) vials, representing six (6) different levels of antibody concentrations, are used for quantitative calibration, and results for patient samples are expressed in IU/mL. Results of ≤4 IU/mL are negative, 5 - 9 IU/mL are indeterminate, and results of 10 IU/mL or higher are considered positive for dsDNA antibody. For the other twelve (12) beads, four (4) vials representing four (4) different antibody concentrations are used for semiquantitative calibration. The result for each of these antibodies is expressed as an antibody index (AI). An AI of 1.0 indicates an antibody cut-off concentration that corresponds to approximately the 99th percentile of values obtained from a non-diseased population; results of 1.0 or higher are reported as positive. Results of Device Name: | BioPlex 2200 ANA Screen on the
BioPlex 2200 Multi-Analyte Detection System |

----------------------------------------------------------------------------------------------------

Indications for Use:

The Bio-Plex 2200 ANA Screen is intended for the qualitative screening of specific antinuclear antibodies (ANA), the quantitative detection of antibody to dsDNA, and the semi-quantitative detection of ten (10) (1 11 ); de qualitiative debosomal Protein, SS-A, SS-B, Sm, Sm/RNP, RNP, Scl-70, Jo-1, and Centromere B.) in human serum and/or EDTA or heparinized plasma.

The ANA Screen is intended for use with the Bio-Rad BioPlex 2200 System.

Uses:

The test system is used to screen serum or plasma (EDTA, heparin) samples and detect the presence of antinuclear antibodies as an aid in the diagnosis of systemic rheumatic diseases (Systemic Lupus Erythematosus [SLE], Mixed Connective Tissue Disease [MCTD], Undifferentiated Connective Tissue Disease [UCTD], Sjögren's Syndrome [SS], Scleroderma [Systemic Sclerosis], Dermatomyositis, Polymyositis, Rheumatoid Arthritis [RA], CREST Syndrome, and Raynaud's Phenomenon) in conjunction with clinical findings and other laboratory tests.

Prescription Use: ____________________________________________________________________________________________________________________________________________________________ X ____________________________________________________________________________________________________________________________________________________________________________ (Per 21 CFR 801.109)

AND/OR

Over-The-Counter Use: ________________________________________________________________________________________________________________________________________________________ (Optional Format 1-2-96)

(PLEASE DO NOT WRITE BELOW THIS LINE – CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

ia va chan

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

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510(k) K041658