(185 days)
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.
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 BioPlex 2200 ANA Screen is an in-vitro diagnostic device for the qualitative screening of specific antinuclear antibodies (ANA), quantitative detection of anti-dsDNA antibodies, and semi-quantitative detection of ten other specific autoantibodies (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. It aids in diagnosing systemic rheumatic diseases.
Here's an analysis of its acceptance criteria and supporting studies as described in the provided document:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria (e.g., minimum percentage agreement for clinical performance or maximum CV for reproducibility). However, it reports observed performance metrics from various studies. For the purpose of this analysis, we will infer the desired performance from the presented results, particularly focusing on reproducibility (CV%) and agreement with predicate devices.
| Metric / Antibody Group | Acceptance Criteria (Inferred) | Reported Device Performance (Worst Case for Positive Samples) |
|---|---|---|
| Reproducibility (Intra-assay %CV) | (Not explicitly stated, but generally <15-20% is acceptable for immunoassays) | Site 1: 7.9% (SS-A 52 Low Positive Panel) Site 2: 8.6% (Sm Low Positive Panel) Site 3: 11.1% (Positive Control for SS-A 52) |
| Reproducibility (Inter-assay %CV) | (Not explicitly stated, but generally <15-20% is acceptable for immunoassays) | Site 1: 12.8% (Positive Control for SS-A 52) Site 2: 11.9% (Sm Low Positive Panel) Site 3: 12.0% (Positive Control for SS-A 52) |
| Prospective Study (Overall Agreement vs. predicate EIA) | >90% (Commonly desired for equivalence) | ANA Screen: 79.3% Individual Antibodies: dsDNA: 94% Chromatin: 86% Ribosomal-P: 98% SS-A: 97% SS-B: 97% Sm: 97% SmRNP: 96% RNP: 95% Scl-70: 98% Jo-1: 99% Centromere: 99% |
| Combined Prospective & Retrospective (Overall Agreement vs. predicate EIA) | >90% (Commonly desired for equivalence) | Individual Antibodies: 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% |
2. Sample Size Used for the Test Set and Data Provenance
- Reproducibility Studies: For each of the 11 panel members (10 positive, 1 negative) and the Autoimmune Control Set, 40 replicates were tested per site (2 duplicates x 2 runs x 10 days). Across 3 sites, this totals 120 replicates per panel member. The provenance is internal to Bio-Rad Laboratories (panel preparation) and 3 US testing facilities.
- Prospective Clinical Testing: 908 prospective serum samples. The samples were collected from patients seen at a rheumatology clinic and suspected of having systemic autoimmune disease at 3 U.S. clinical testing sites.
- Retrospective Clinical Testing: 440 retrospective serum samples (known positive for ANA and autoantibodies) and an additional 100 negative serum samples.
- CDC Panel: A masked reference serum panel provided by the Centers for Disease Control (CDC).
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document does not specify the number or qualifications of experts used to establish the ground truth for the test sets. Instead, the ground truth for the clinical studies (prospective and retrospective) was established by comparison to commercially available predicate microplate EIA methods. For the CDC panel, the "Expected Results" are based on the CDC's characterization of the reference sera.
4. Adjudication Method for the Test Set
Not applicable. The ground truth was established by predicate EIA methods or CDC characterization, not by expert adjudication of device results.
5. Multi Reader Multi Case (MRMC) Comparative Effectiveness Study
Not applicable. This device is an automated immunoassay system, and its performance is assessed against predicate assay methods, not human reader performance.
6. Standalone Performance
Yes, the device's standalone performance was evaluated extensively:
- Reproducibility studies directly measure the precision of the BioPlex 2200 ANA Screen without human interpretation affecting the result.
- Clinical testing (Prospective and Retrospective) compares the BioPlex 2200 ANA Screen's results directly against commercially available predicate EIA methods, which represents its standalone diagnostic capability.
- CDC Panel testing also evaluates the standalone performance of the device against a characterized reference panel.
7. Type of Ground Truth Used
- Reproducibility Studies: Internal characterization of panel members (known antibody status, often spiked concentrations to be near cutoff or high positive).
- Prospective Clinical Testing: Results from commercially available predicate microplate EIA methods.
- Retrospective Clinical Testing: Results from commercially available predicate microplate EIA methods. The samples themselves were selected based on being "known to be positive for ANA and one or more of the autoantibodies" or "known to be negative for ANA," implying prior characterization also likely by established methods.
- CDC Panel: "Expected Results" provided by the Centers for Disease Control (CDC) reference serum panel, which means these samples were characterized by the CDC through their own established methods.
8. Sample Size for the Training Set
The document does not explicitly mention a "training set" in the context of an algorithm or AI. This is a traditional IVD device (immunoassay) where the "training" happens during the development and calibration of the assay reagents and analytical measuring system. The data presented are for performance evaluation, not for training a machine learning model.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there is no explicitly defined "training set" or AI algorithm learning process detailed for this traditional IVD device. The calibration and optimization of the assay would rely on characterized samples and reference materials, but these are part of the assay development process rather than a machine learning training paradigm.
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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) Number | 510(k) Summary Report Date |
|---|---|
| K041658 | December 13, 2004 |
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 ANA Screen | |
| Official Correspondent Address | Bio-Rad Laboratories6565 185th Ave NERedmond, WA 98052 |
| Telephone | 425-881-8300 |
| Establishment Registration No. | 3022521 |
| Owner / Operator | Bio-Rad Laboratories, Inc.4000 Alfred Nobel DriveHercules, CA 94547 |
| Official Correspondent | Mr. Christopher Bentsen |
| Telephone | (425) 498-1709 |
| Fax | (425) 498-1651 |
CLASSIFICATION INFORMATION
| Classification Name | Antinuclear Antibody (Enzyme-Labeled), Antigen, Controls |
|---|---|
| Common Name: | Multi-Analyte Detection System ANA Screen |
| Product Trade Name | BioPlex 2200 ANA Screen on the BioPlex 2200 Multi-AnalyteDetection System |
| Device Class | Class II |
| Classification Panel | Immunology and Microbiology |
| Regulation Number | 866.5100 |
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LEGALLY MARKETED EQUIVALENT (SE) DEVICES
Instrument
| BioPlex2200 System | Comparative FDA ClearedPREDICATE DEVICE | 510(k)Number | ProductCode | DecisionDate |
|---|---|---|---|---|
| BioPlex 2200 ANA Screenon the BioPlex 2200System | Zeus Athena Multi-Lyte ANA Test System | K011244 | LKJ | 12/10/2001 |
| Diagnostic Products Corporation (DPC) Immulite2000 Automated Immunoassay Analyzer | K970227 | JJE | 4/8/1997 |
Assay
| BioPlex2200 ANA Screen | Comparative FDA Cleared Device | 510(k)Number | ProductCode | DecisionDate |
|---|---|---|---|---|
| ANA Screen (based onresults of all analytes listedbelow) | Bio-Rad (Helix) Autoimmune EIAANA Screening Test | 954723 | LKJ | 12/15/1995 |
| BioPlex2200 ANAScreen Analyte | Comparative FDA ClearedPREDICATE DEVICE | 510(k)Number | ProductCode | DecisionDate | |
|---|---|---|---|---|---|
| 1. | SSA (SSA 60 andSSA 52) | Inova Diagnostics, Inc. QUANTA Lite™ SSA | 922830 | LLL | 9/18/1992 |
| 2. | SSB | Bio-Rad (Helix) Autoimmune EIASS-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 andRNP A) | Pharmacia Varelisa® RNP Antibodies | 993589 | LKO | 11/26/1999 |
| 6. | Ribosomal Protein | Inova Diagnostics, Inc. QUANTALite™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 EIAKit | 950031 | LRM | 3/10/1995 |
| 9. | Centromere | Bio-Rad (Helix) Autoimmune EIAAnti-Centromere Test | 000489 | LLL | 4/15/2000 |
| 10. | Scl-70 | Bio-Rad (Helix) Autoimmune EIAAnti-Scl-70 Test | 951798 | LJM | 7/17/1995 |
| 11. | Jo-1 | Bio-Rad (Helix) Autoimmune EIAAnti-Jo-1 Test | 951850 | LJM | 7/18/1995 |
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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 Region | Assay Name | Description |
|---|---|---|
| 17 | dsDNA | Antigen coated bead - dsDNA |
| 21 | Chromatin(DNP) | Antigen coated bead - Chromatin |
| 34 | ISB | Internal Standard Bead - verifies detector response and corrects forfluctuations in laser intensity due to voltage fluctuation and/ortemperature. |
| 36 | RNP-A | Antigen coated bead - RNP-A |
| 38 | SSB | Antigen coated bead - SSB |
| 52 | SSA-52 | Antigen coated bead - SSA-52 |
| 54 | Reagent BlankBead | Blank bead - verifies absence of significant non-specific binding inserum or plasma |
| 56 | Scl-70 | Antigen coated bead - Scl-70 |
| 71 | Sm | Antigen coated bead – Sm |
| 75 | Centromere B | Antigen coated bead - Centromere B |
| 79 | Sm/RNP | Antigen coated bead – Sm/RNP |
| 81 | Ribosomal P | Antigen coated bead - Ribosomal P |
| 92 | RNP-68 | Antigen coated bead - RNP-68 |
| 94 | SSA-60 | Antigen coated bead - SSA-60 |
| 96 | Jo-1 | Antigen coated bead - Jo-1 |
| 100 | SVB (FXIII) | Serum Verification Bead (coated with a monoclonal antibody to FactorXIII) - verifies the addition of serum or plasma to the reaction vessel |
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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 <1.0 are reported as negative.
- In cases where either SS-A 60 and/or SS-A 52 are positive, results are reported as positive for SS-A, and when either RNP A and/or RNP 68 are positive, results are reported as positive for RNP.
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.
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, 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.
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TECHNOLOGICAL CHARACTERISTICS
The following table summarize similarities and differences between the BioPlex 2200 System, the Zeus Athena Multi-Lyte™ System, and the Immulite® 2000 Automated Immunoassay Analyzer.
| Similarities andDifferences betweenInstruments | BioPlex 2200 System | Zeus Athena Multi-Lyte™ System | Immulite® 2000AutomatedImmunoassay Analyzer |
|---|---|---|---|
| Detection | Based on LuminexCorporation'smultiplex, bead-basedtechnology. | Based on LuminexCorporation's multiplex,bead-based technology. | Not similar: luminometer(photomultiplier tube) todetectchemiluminescence. |
| Sample Handling /ProcessingCapabilities | Automated samplehandling andprocessing. | Not similar: noautomated samplehandling or processingcapabilities. | Automated samplehandling and processing. |
| Reagent Storage | On-board, refrigeratedreagent storage. | Not similar: off-linereagent storage. | On-board, refrigeratedreagent storage. |
Table 1: Similarities and differences between instruments
The following tables summarize similarities and differences between the BioPlex 2200 ANA Screen and the predicate Autoimmune EIA devices used in comparative studies with the BioPlex 2200 ANA Screen.
Table 2(a:) Similarities between reagents and materials
| Similarities betweenComponents / Materials | BioPlex 2200 ANA Screen | Predicate Autoimmune EIA's |
|---|---|---|
| Reagents | Wash Buffer, Sample Diluent | Wash Buffer, Sample Diluent |
| Calibrators | Calibrators (quantitative andsemi-quantitative analytes) | Calibrators (quantitative and semi-quantitative analytes) |
| Controls | Single Negative Control | Single Negative Control |
| Table 2(b): Differences between reagents and materials | |||||
|---|---|---|---|---|---|
| -- | -- | -- | -- | -- | -------------------------------------------------------- |
| Differences betweenComponents / Materials | BioPlex 2200 ANA Screen | Predicate Autoimmune EIA's |
|---|---|---|
| Solid Phase | Bead reagent - dyed antigencoated beads | 96 well microplate - antigen coatedmicrowells |
| Reagents | Conjugate: Anti-human IgG /Phycoerythrin | Conjugate: Anti-Human IgG / Horse-radish Peroxidase, Substrate (TMB) |
| Calibrators | Calibrators (qualitative and semi-quantitative analytes) | Cut-off / Low Positive Controls(qualitative analytes) |
| Controls | One multi-analyte positive controlcovering all 11 analytes. | One positive control per analyte. |
| Sheath FluidSheath Fluid is used to suspendthe bead reagent and introduce itinto the detector. | Not similar; not utilized in EIA's. |
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| Similarities betweenFunction and Use | BioPlex 2200 ANA Screen | Predicate Autoimmune EIA's |
|---|---|---|
| Intended Use | Quantitative (dsDNA only) andsemi-quantitative/qualitativeautoimmune antibody detection | Quantitative (dsDNA only) and semi-quantitative/qualitative autoimmuneantibody detection |
| Matrices | Serum and Plasma (EDTA andHeparin) for all analytes | Serum and Plasma (Jo-1, dsDNA, RNP,SSB) |
3(a); Similarities hetween reagents with regard to function and use
Table 3(b): Differences between reagents with regard to function and use
| Differences betweenFunction and Use | BioPlex 2200 ANA Screen | Predicate Autoimmune EIA's |
|---|---|---|
| Matrices | Serum and Plasma (EDTA andHeparin) for all analytes | Serum (ANA Screen, SSA, Sm,Sm/RNP, Ribosome P, Chromatin,Centromere, Scl-70) |
PERFORMANCE SUMMARY
A. Expected Values
The following testing was tested internally at Bio-Rad Laboratories:
Expected values for the ANA Screen test are presented in the following table for a U.S. population of normal blood donors (N=222). For dsDNA, results of ≤4 IU/mL are negative, 5 -- 9 IU/mL are indeterminate, and ≥10 IU/mL or higher are reported as positive. For the other assays, results of <1.0 are negative and results of ≥1.0 AI are reported as positive.
| Result | N = 222 | Positive | Negative | Indeterminate | |||
|---|---|---|---|---|---|---|---|
| # | (%) | # | (%) | # | (%) | ||
| ANA Screen* | 15 | 6.8 | 207 | 93.2 | N/A | N/A | |
| dsDNA | 3 | 1.4 | 211 | 95.0 | 8 | 3.6 | |
| Chromatin | 2 | 0.9 | 220 | 99.1 | |||
| Ribosomal Protein | 0 | 0 | 222 | 100.0 | |||
| SS-A | 2 | 0.9 | 220 | 99.1 | |||
| SS-B | 0 | 0 | 222 | 100 | |||
| Sm | 1 | 0.5 | 221 | 99.5 | N/A | N/A | |
| SmRNP | 2 | 0.9 | 220 | 99.1 | |||
| RNP | 6 | 2.7 | 216 | 97.3 | |||
| Scl-70 | 1 | 0.5 | 221 | 99.5 | |||
| Jo-1 | 0 | 0.0 | 222 | 100.0 | |||
| Centromere B | 3 | 1.4 | 219 | 98.6 |
*results calculated based on testing of all analytes.
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Expected values for the ANA Screen test are presented in the following table for patients from the BioPlex 2200 ANA Screen prospective study conducted at three clinical sites (N=908). For dsDNA, results of ≤4 IU/mL are negative, 5 – 9 IU/mL are indeterminate, and ≥10 IU/mL or higher are reported as positive. For the other assays, results of <1.0 are negative and results of ≥1.0 AI are reported as positive.
| Result | Positive (%) | Negative (%) | Indeterminate (%) |
|---|---|---|---|
| ANA Screen1 | 390(43.0%) | 518 (57.0%) | N/A |
| dsDNA | 119 (13.1)% | 741 (81.6%) | 48(5.3%) |
| Chromatin | 168 (18.5%) | 740 (81.5%) | N/A |
| Ribosomal Protein | 37 (4.1%) | 871 (95.9%) | N/A |
| SS-A | 173 (19.0%) | 735 (81.0%) | N/A |
| SS-B | 76 (8.4%) | 832 (91.6%) | N/A |
| Sm | 60 (6.6%) | 848 (93.4%) | N/A |
| SmRNP | 103 (11.3%) | 805 (88.7%) | N/A |
| RNP | 112 (12.3%) | 796 (87.7%) | N/A |
| Scl-70 | 23 (2.5%) | 885 (97.5%) | N/A |
| Jo-1 | 6 (0.7%) | 902 (99.3%) | N/A |
| Centromere B | 38 (4.2%) | 870 (95.8%) | N/A |
B. Reproducibility Studies
A reproducibility panel, consisting of 11 serum panel members, was prepared at Bio-Rad Laboratories. Fach of ten (10) positive panel members was prepared by combining one (1) or more antibody positive patient samples for one (1) or more of the 13 analytes contained in the Bio-Rad BioPlex 2200 ANA Screen (dsDNA, Chromatin, SS-A 52, SS-A 60, SS-B, Sm, RNP 68, RNP A, SmRNP, Centromere, Ribosomal Protein. Scl-70. Jo-1). Five (5) of the ten (10) members had higher levels of the antibodies and five (5) of the ten (10) members had antibody levels near the cutoff. One (1) panel member was negative for all 13 analytes. In addition, three (3) lots of the BioPlex 2200 ANA Screen Control Set [1 positive control (antibody positive for all 13 analytes), I diluted positive control (antibody negative control (antibody negative for all 13 analytes)] were also tested.
Reproducibility testing was performed at three (3) US testing facilities on a total of three (3) lots of the Bio-Rad ANA Screen. Each testing facility evaluated reproducibility using one (1) kit lot of the Bio-Rad ANA Screen. The eleven (11) panel members were provided to each of the testing sites. Each of the eleven (11) 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.] The data were then analyzed for intra-assay and inter-assay reproducibility according to the National Committee for Clinical Laboratory Standards (NCCLS EP5-A, Vol. 19, No. 2. p7, Eg. (1) and p8 Eq. (4)). The mean Antibody Index (AD), standard deviation (SD), and percent coefficient of variation (%CV) for each panel member is presented. For dsDNA, the mean International Units per ml (IU/mL), standard deviation (SD), and percent coefficient of variation (%CV) for each panel member is presented.
Intra-assay and inter-assay reproducibility on the BioPlex 2200 ANA Screen for the serum panel members from three sites and three lots are presented in the tables below.
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| Clinical Site #1Lot 1 | dsDNA(IU/ml) | Chromatin(AI) | RibosomalProtein (AI) | SS-A 52 (AI) | SS-A 60 (AI) | SS-B (AI) | Sm (AI) | SmRNP (AI) | RNP-A (AI) | RNP-68 (AI) | Scl-70 (AI) | Jo-1 (AI) | Centromere (AI) | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| HighPositivePanel | Mean | 45.6 | 2.7 | 2.4 | 4.1 | 3.4 | 3.6 | 3.3 | 4.0 | 4.1 | 3.8 | 3.3 | 3.9 | 3.7 |
| SD* | 0.89 | 0.08 | 0.07 | 0.19 | 0.07 | 0.07 | 0.09 | 0.08 | 0.10 | 0.13 | 0.08 | 0.10 | 0.08 | |
| %CV | 2.0% | 2.9% | 2.7% | 4.6% | 1.9% | 2.0% | 2.9% | 2.0% | 2.4% | 3.5% | 2.4% | 2.5% | 2.2% | |
| N= | 40 | 40 | 40 | 36 | 36 | 36 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | |
| Low PositivePanel | Mean | 17.0 | 1.3 | 1.2 | 2.2 | 1.8 | 1.7 | 1.5 | 2.2 | 1.9 | 1.8 | 1.9 | 1.9 | 2.0 |
| SD* | 0.05 | 0.06 | 0.04 | 0.17 | 0.07 | 0.05 | 0.05 | 0.06 | 0.05 | 0.09 | 0.06 | 0.09 | 0.05 | |
| %CV | 2.9% | 4.4% | 3.9% | 7.9% | 3.9% | 3.1% | 3.2% | 2.6% | 2.6% | 4.9% | 2.9% | 5.0% | 2.7% | |
| N= | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 36 | 40 | 40 | |
| NegativePanel | Mean | 0.0 | 0.1 | 0.1 | 0.0 | 0.0 | 0.0 | 0.1 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 |
| SD* | 0.00 | 0.03 | 0.00 | 0.00 | 0.02 | 0.00 | 0.00 | 0.04 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | |
| %CV | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | |
| N= | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | |
| PositiveControl | Mean | 23.2 | 2.5 | 1.7 | 3.1 | 2.5 | 2.7 | 2.8 | 3.0 | 2.7 | 2.5 | 2.7 | 2.7 | 2.8 |
| SD* | 0.62 | 0.10 | 0.04 | 0.16 | 0.04 | 0.07 | 0.07 | 0.07 | 0.08 | 0.16 | 0.06 | 0.08 | 0.05 | |
| %CV | 2.7% | 4.0% | 2.6% | 5.1% | 1.7% | 2.6% | 2.4% | 2.2% | 3.0% | 6.6% | 2.0% | 2.9% | 1.9% | |
| N= | 36 | 36 | 40 | 36 | 36 | 36 | 36 | 40 | 36 | 36 | 36 | 36 | 36 | |
| NegativeControl | Mean | 0.0 | 0.2 | 0.1 | 0.0 | 0.1 | 0.1 | 0.1 | 0.5 | 0.2 | 0.0 | 0.1 | 0.0 | 0.0 |
| SD* | 0.00 | 0.02 | 0.00 | 0.00 | 0.02 | 0.02 | 0.00 | 0.03 | 0.03 | 0.00 | 0.02 | 0.02 | 0.00 | |
| %CV | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | |
| N= | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 36 | 40 | 40 |
Reproducibility Results; Intra-assay – Site 1 - Serum
- NCCLS EP5 -- A Vol. 19, No. 2, page 7 equation 1
1 Cumulative results of positive control and diluted positive control.
As can be seen in the above table, the CV% for intra-assay precision ranged from 1.7% to 7.9% for all serum positive panel members for all analytes when tested at Site 1 on the BioPlex 2200 ANA Screen Lot l.
{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 black and white, with the words "BIO-RAD" in bold, sans-serif font. The logo is simple and recognizable. The logo is encased in a rounded rectangle.
| Clinical Site #2Lot 2 | dsDNA(IU/ml) | Chromatin(AI) | RibosomalProtein (AI) | SS-A 52 (AI) | SS-A 60 (AI) | SS-B (AI) | Sm (AI) | SmRNP (AI) | RNP-A (AI) | RNP-68 (AI) | Scl-70 (AI) | Jo-1 (AI) | Centromere (AI) | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| HighPositivePanel | Mean | 44.9 | 2.9 | 2.7 | 3.8 | 3.6 | 3.5 | 3.9 | 3.4 | 3.8 | 3.9 | 3.2 | 3.1 | 2.9 |
| SD* | 1.06 | 0.09 | 0.07 | 0.09 | 0.09 | 0.07 | 0.11 | 0.12 | 0.10 | 0.16 | 0.10 | 0.12 | 0.10 | |
| %CV | 2.4% | 3.2% | 2.8% | 2.4% | 2.6% | 2.1% | 2.9% | 3.4% | 2.7% | 4.2% | 3.3% | 4.0% | 3.3% | |
| N= | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | |
| LowPositivePanel | Mean | 18.2 | 1.5 | 1.6 | 2.2 | 1.9 | 1.6 | 1.7 | 1.9 | 1.8 | 1.8 | 1.8 | 1.4 | 1.6 |
| SD* | 0.52 | 0.09 | 0.07 | 0.09 | 0.07 | 0.05 | 0.15 | 0.07 | 0.08 | 0.09 | 0.13 | 0.07 | 0.08 | |
| %CV | 2.9% | 5.5% | 4.4% | 4.3% | 3.9% | 3.1% | 8.6% | 3.5% | 4.3% | 5.2% | 7.1% | 5.1% | 5.2% | |
| N= | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | |
| NegativePanel | Mean | 0.0 | 0.1 | 0.1 | 0.0 | 0.0 | 0.0 | 0.1 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 |
| SD* | 0.00 | 0.00 | 0.04 | 0.00 | 0.00 | 0.00 | 0.00 | 0.02 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | |
| %CV | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | |
| N= | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | |
| PositiveControl | Mean | 24.7 | 2.3 | 2.7 | 2.8 | 2.8 | 3.8 | 3.0 | 2.7 | 2.9 | 3.4 | 2.4 | 3.6 | 2.4 |
| SD* | 0.72 | 0.09 | 0.07 | 0.13 | 0.10 | 0.12 | 0.09 | 0.07 | 0.11 | 0.14 | 0.08 | 0.14 | 0.09 | |
| %CV | 2.9% | 4.1% | 2.5% | 4.7% | 3.5% | 3.1% | 3.0% | 2.5% | 3.8% | 4.2% | 3.2% | 3.8% | 3.7% | |
| N= | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | |
| NegativeControl | Mean | 1.1 | 0.2 | 0.1 | 0.0 | 0.0 | 0.0 | 0.2 | 0.1 | 0.1 | 0.0 | 0.1 | 0.0 | 0.0 |
| SD* | 0.22 | 0.02 | 0.00 | 0.00 | 0.02 | 0.00 | 0.03 | 0.02 | 0.00 | 0.00 | 0.02 | 0.00 | 0.00 | |
| %CV | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | |
| N= | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 |
Reproducibility Results; Intra-assay – Site 2 - Serum
- NCCLS EP5 – A Vol. 19, No. 2, page 7 equation 1
・
1 Cumulative results of positive control and diluted positive control.
As can be seen in the above table, the CV% for intra-assay precision ranged from 2.1% to 8.6% for all serum positive panel members for all analytes when tested at Site 2 on the BioPlex 2200 ANA Screen Lot 2.
{9}------------------------------------------------
Image /page/9/Picture/0 description: The image shows the logo for Bio-Rad Laboratories. The logo is white text on a black, rounded rectangle. The text is in a bold, sans-serif font.
| BioPlex2200 ANA Screen Intra-assay | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Clinical Site #3Lot 3 | dsDNA(IU/ml) | Chromatin(AI) | RibosomalProtein (AI) | SS-A 52 (AI) | SS-A 60 (AI) | SS-B (AI) | Sm (AI) | SmRNP (AI) | RNP-A (AI) | RNP-68 (AI) | Scl-70 (AI) | Jo-1 (AI) | Centromere (AI) | |
| HighPositivePanel | Mean | 52.8 | 2.8 | 2.6 | 4.7 | 4.2 | 4.0 | 3.7 | 3.7 | 4.7 | 4.3 | 3.8 | 3.9 | 4.2 |
| SD* | 1.16 | 0.11 | 0.07 | 0.41 | 0.11 | 0.10 | 0.09 | 0.11 | 0.13 | 0.16 | 0.09 | 0.13 | 0.09 | |
| %CV | 2.2% | 3.9% | 2.9% | 8.7% | 2.6% | 2.4% | 2.3% | 3.0% | 2.7% | 3.8% | 2.5% | 3.4% | 2.1% | |
| N= | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | |
| Low PositivePanel | Mean | 19.9 | 1.4 | 1.3 | 2.8 | 2.2 | 2.1 | 1.8 | 1.9 | 2.2 | 2.3 | 2.3 | 2.0 | 2.5 |
| SD* | 0.72 | 0.07 | 0.05 | 0.25 | 0.10 | 0.08 | 0.05 | 0.05 | 0.07 | 0.10 | 0.06 | 0.10 | 0.08 | |
| %CV | 3.6% | 4.7% | 3.5% | 9.1% | 4.4% | 3.7% | 3.0% | 2.8% | 3.1% | 4.5% | 2.7% | 4.8% | 3.0% | |
| N= | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | |
| NegativePanel | Mean | 0.0 | 0.1 | 0.1 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 |
| SD* | 0.00 | 0.04 | 0.00 | 0.00 | 0.00 | 0.00 | 0.03 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | |
| %CV | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | |
| N= | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | |
| PositiveControl | Mean | 26.1 | 2.7 | 2.5 | 3.4 | 3.1 | 3.1 | 2.7 | 3.4 | 3.5 | 2.8 | 2.9 | 3.1 | 2.9 |
| SD* | 0.60 | 0.07 | 0.08 | 0.38 | 0.08 | 0.08 | 0.07 | 0.07 | 0.10 | 0.09 | 0.07 | 0.11 | 0.09 | |
| %CV | 2.3% | 2.7% | 3.1% | 11.1% | 2.8% | 2.5% | 2.5% | 2.2% | 3.0% | 3.4% | 2.5% | 3.6% | 3.1% | |
| N= | 36 | 36 | 36 | 36 | 36 | 36 | 36 | 36 | 36 | 36 | 36 | 36 | 36 | |
| NegativeControl | Mean | 1.0 | 0.3 | 0.1 | 0.0 | 0.0 | 0.1 | 0.1 | 0.1 | 0.2 | 0.0 | 0.1 | 0.0 | 0.0 |
| SD* | 0.00 | 0.03 | 0.00 | 0.05 | 0.00 | 0.02 | 0.00 | 0.00 | 0.02 | 0.00 | 0.02 | 0.00 | 0.00 | |
| %CV | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | |
| N= | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 |
Reproducibility Results; Intra-assay – Site 3 - Serum
- NCCLS EP5 -- A Vol. 19, No. 2, page 7 equation 1
1 Cumulative results of positive control and diluted positive control.
As can be seen in the above table, the CV% for intra-assay precision ranged from 2.1% to 11.1% for all serum positive panel members for all analytes when tested at Site 3 on the BioPlex 2200 ANA Screen Lot 3.
{10}------------------------------------------------
Image /page/10/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 consists of the words "BIO-RAD" in a bold, sans-serif font. The letters are white against a black background. The logo is enclosed in a rounded rectangle.
| Clinical Site #1Lot 1 | dsDNA(IU/ml) | Chromatin(AI) | RibosomalProtein (AI) | SS-A 52 (AI) | SS-A 60 (AI) | SS-B (AI) | Sm (AI) | SmRNP (AI) | RNP-A (AI) | RNP-68 (AI) | Scl-70 (AI) | Jo-1 (AI) | Centromere (AI) | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| HighPositivePanel | Mean | 45.6 | 2.7 | 2.4 | 4.1 | 3.4 | 3.6 | 3.3 | 4.0 | 4.1 | 3.8 | 3.3 | 3.9 | 3.7 |
| SD* | 1.82 | 0.13 | 0.16 | 0.28 | 0.20 | 0.21 | 0.10 | 0.14 | 0.14 | 0.20 | 0.12 | 0.20 | 0.10 | |
| %CV | 4.0% | 4.8% | 6.7% | 6.8% | 5.8% | 5.8% | 3.2% | 3.5% | 3.5% | 5.4% | 3.7% | 5.0% | 2.8% | |
| N= | 40 | 40 | 40 | 36 | 36 | 36 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | |
| LowPositivePanel | Mean | 17.0 | 1.3 | 1.2 | 2.2 | 1.8 | 1.7 | 1.5 | 2.2 | 1.9 | 1.8 | 1.9 | 1.9 | 2.0 |
| SD* | 0.60 | 0.08 | 0.06 | 0.21 | 0.08 | 0.08 | 0.07 | 0.09 | 0.08 | 0.12 | 0.12 | 0.12 | 0.11 | |
| %CV | 3.5% | 6.1% | 5.6% | 9.7% | 4.6% | 5.0% | 5.0% | 4.0% | 4.0% | 6.3% | 6.3% | 6.2% | 5.3% | |
| N= | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 36 | 40 | 40 | |
| NegativePanel | Mean | 0.0 | 0.1 | 0.1 | 0.0 | 0.0 | 0.0 | 0.1 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 |
| SD* | 0.00 | 0.03 | 0.00 | 0.00 | 0.02 | 0.00 | 0.00 | 0.05 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | |
| %CV | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | |
| N= | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | |
| PositiveControl | Mean | 23.2 | 2.5 | 1.7 | 3.1 | 2.5 | 2.7 | 2.8 | 3.0 | 2.7 | 2.5 | 2.7 | 2.7 | 2.8 |
| SD* | 2.09 | 0.29 | 0.10 | 0.39 | 0.25 | 0.29 | 0.26 | 0.10 | 0.26 | 0.29 | 0.28 | 0.27 | 0.27 | |
| %CV | 9.0% | 11.7% | 5.8% | 12.8% | 10.0% | 10.7% | 9.5% | 3.2% | 9.7% | 11.6% | 10.5% | 10.1% | 9.8% | |
| N= | 36 | 36 | 40 | 36 | 36 | 36 | 36 | 40 | 36 | 36 | 36 | 36 | 36 | |
| NegativeControl | Mean | 0.0 | 0.2 | 0.1 | 0.0 | 0.1 | 0.1 | 0.1 | 0.5 | 0.2 | 0.0 | 0.1 | 0.0 | 0.0 |
| SD* | 0.00 | 0.02 | 0.00 | 0.00 | 0.04 | 0.05 | 0.00 | 0.08 | 0.05 | 0.02 | 0.04 | 0.02 | 0.00 | |
| %CV | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | |
| N= | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 36 | 40 | 40 |
Reproducibility Results; Inter-assay – Site I - Serum
- NCCLS EP5 – A Vol. 19, No. 2, page 8 equation 4
1 Cumulative results of positive control and diluted positive control.
As can be seen in the above table, the CV% for inter-assay precision ranged from 2.8% to 12.8% for all serum positive panel members for all analytes when tested at Site 1 on the BioPlex 2200 ANA Screen Lot 1.
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Image /page/11/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 enclosed in a rounded rectangle.
:
| Clinical Site #2Lot 2 | dsDNA(IU/ml) | Chromatin(AI) | RibosomalProtein (AI) | SS-A 52 (AI) | SS-A 60 (AI) | SS-B (AI) | Sm (AI) | SmRNP (AI) | RNP-A (AI) | RNP-68 (AI) | Scl-70 (AI) | Jo-1 (AI) | Centromere (AI) | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| HighPositivePanel | Mean | 44.9 | 2.9 | 2.7 | 3.8 | 3.6 | 3.5 | 3.9 | 3.4 | 3.8 | 3.9 | 3.2 | ||
| SD* | 3.40 | 0.25 | 0.19 | 0.28 | 0.24 | 0.30 | 0.22 | 0.25 | 0.24 | 0.28 | 0.21 | 0.28 | 0.18 | |
| %CV | 7.6% | 8.8% | 7.2% | 7.4% | 6.8% | 8.4% | 5.8% | 7.2% | 6.3% | 7.2% | 6.5% | 9.0% | 6.2% | |
| N= | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | |
| LowPositivePanel | Mean | 18.2 | 1.5 | 1.6 | 2.2 | 1.9 | 1.6 | 1.7 | 1.9 | 1.8 | 1.8 | 1.8 | 1.4 | 1.6 |
| SD* | 1.15 | 0.16 | 0.10 | 0.19 | 0.15 | 0.14 | 0.20 | 0.13 | 0.15 | 0.18 | 0.17 | 0.12 | 0.17 | |
| %CV | 6.3% | 10.2% | 6.6% | 8.4% | 8.1% | 8.8% | 11.9% | 6.8% | 8.7% | 10.2% | 9.5% | 9.0% | 10.6% | |
| N= | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | |
| NegativePanel | Mean | 0.0 | 0.1 | 0.1 | 0.0 | 0.0 | 0.0 | 0.1 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 |
| SD* | 0.00 | 0.00 | 0.05 | 0.00 | 0.00 | 0.00 | 0.00 | 0.02 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | |
| %CV | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | |
| N= | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | |
| PositiveControl | Mean | 24.7 | 2.3 | 2.7 | 2.8 | 2.8 | 3.8 | 3.0 | 2.7 | 2.9 | 3.4 | 2.4 | 3.6 | 2.4 |
| SD* | 1.71 | 0.19 | 0.19 | 0.24 | 0.21 | 0.32 | 0.23 | 0.18 | 0.24 | 0.29 | 0.18 | 0.30 | 0.20 | |
| %CV | 7.0% | 8.3% | 7.1% | 8.6% | 7.3% | 8.4% | 7.8% | 6.8% | 8.4% | 8.6% | 7.3% | 8.2% | 8.6% | |
| N= | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | |
| NegativeControl | Mean | 1.1 | 0.2 | 0.1 | 0.0 | 0.0 | 0.0 | 0.2 | 0.1 | 0.1 | 0.0 | 0.1 | 0.0 | 0.0 |
| SD* | 0.27 | 0.02 | 0.00 | 0.00 | 0.02 | 0.03 | 0.03 | 0.02 | 0.00 | 0.00 | 0.03 | 0.00 | 0.00 | |
| %CV | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | |
| N= | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 |
Reproducibility Results; Inter-assay – Site 2 - Serum
- NCCLS EP5 – A Vol. 19, No. 2, page 8 equation 4
1 Cumulative results of positive control and diluted positive control.
As can be seen in the above table, the CV% for inter-assay precision ranged from 5.8% to 11.9% for all . serum positive panel members for all analytes when tested at Site 2 on the BioPlex 2200 ANA Screen Lot 2.
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Image /page/12/Picture/0 description: The image shows the Bio-Rad company logo. The logo is white text on a black rounded rectangle. The text is bold and sans-serif.
| BioPlex2200 ANA Screen Inter-assay | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Clinical Site #3Lot 3 | dsDNA(IU/ml) | Chromatin(AI) | RibosomalProtein (AI) | SS-A 52 (AI) | SS-A 60 (AI) | SS-B (AI) | Sm (AI) | SmRNP (AI) | RNP-A (AI) | RNP-68 (AI) | Scl-70 (AI) | Jo-1 (AI) | Centromere (AI) | |
| HighPositivePanel | Mean | 52.8 | 2.8 | 2.6 | 4.7 | 4.2 | 4.0 | 3.7 | 3.7 | 4.7 | 4.3 | 3.8 | 3.9 | 4.2 |
| SD* | 2.05 | 0.16 | 0.15 | 0.47 | 0.21 | 0.20 | 0.17 | 0.18 | 0.20 | 0.23 | 0.16 | 0.24 | 0.15 | |
| %CV | 3.9% | 5.6% | 5.9% | 9.8% | 5.1% | 5.0% | 4.5% | 5.1% | 4.2% | 5.5% | 4.3% | 6.0% | 3.6% | |
| N= | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | |
| Low PositivePanel | Mean | 19.9 | 1.4 | 1.3 | 2.8 | 2.2 | 2.1 | 1.8 | 1.9 | 2.2 | 2.3 | 2.3 | 2.0 | 2.5 |
| SD* | 1.29 | 0.11 | 0.09 | 0.28 | 0.15 | 0.15 | 0.10 | 0.11 | 0.13 | 0.13 | 0.13 | 0.15 | 0.14 | |
| %CV | 6.5% | 7.9% | 7.0% | 10.0% | 6.8% | 7.2% | 5.5% | 5.8% | 5.6% | 5.9% | 5.7% | 7.2% | 5.5% | |
| N= | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | |
| NegativePanel | Mean | 0.0 | 0.1 | 0.1 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 |
| SD* | 0.00 | 0.04 | 0.00 | 0.00 | 0.00 | 0.00 | 0.04 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | |
| %CV | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | |
| N= | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | |
| Positive'Control | Mean | 26.1 | 2.7 | 2.5 | 3.4 | 3.1 | 3.1 | 2.7 | 3.4 | 3.5 | 2.8 | 2.9 | 3.1 | 2.9 |
| SD* | 1.06 | 0.15 | 0.23 | 0.41 | 0.15 | 0.14 | 0.12 | 0.25 | 0.16 | 0.18 | 0.13 | 0.19 | 0.14 | |
| %CV | 4.1% | 5.6% | 9.5% | 12.0% | 5.0% | 4.5% | 4.5% | 7.5% | 4.6% | 6.4% | 4.4% | 6.0% | 4.8% | |
| N= | 36 | 36 | 40 | 36 | 36 | 36 | 36 | 40 | 36 | 36 | 36 | 36 | 36 | |
| NegativeControl | Mean | 1.0 | 0.3 | 0.1 | 0.0 | 0.0 | 0.1 | 0.1 | 0.1 | 0.2 | 0.0 | 0.1 | 0.0 | 0.0 |
| SD* | 0.00 | 0.04 | 0.00 | 0.05 | 0.04 | 0.04 | 0.00 | 0.00 | 0.04 | 0.00 | 0.03 | 0.00 | 0.00 | |
| %CV | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | |
| N= | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 | 40 |
Reproducibility Results; Inter-assay - Site 3 - Serum
- NCCLS EP5 – A Vol. 19, No. 2, page 8 equation 4
1 Cumulative results of positive control and diluted positive control.
As can be seen in the above table, the CV% for inter-assay precision ranged from 3.6% to 12.0% for all serum positive panel members for all analytes when tested at Site 3 on the BioPlex 2200 ANA Screen Lot 3.
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C. Clinical Testing
Prospective Testing
Prospective: Comparison of ANA Screen and ANA Microplate EIA
Performance of the ANA Screen was evaluated against a commercially available ANA Microplate EIA. A total of 908 prospective serum samples were tested at 3 U.S. clinical testing sites. The samples were collected from patients seen at a rheumatology clinic and suspected of having systemic autoimmune disease. Results are summarized in the table below.
| PositiveANA Screen1 | NegativeANA Screen1 | Total | |
|---|---|---|---|
| Positive EIA* | 351 | 149 | 500 |
| Negative EIA | 39 | 369 | 408 |
| Total | 390 | 518 | 908 |
The results of comparative prospective testing demonstrated the following:
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%)
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Prospective: Comparison of Selected Antibodies to EIA Methods
Of the 908 prospective serum samples tested, samples positive by the ANA Screen for specific autoantibodies were also tested by a corresponding commercially available microplate EIA. Results can be seen in the table below.
| Antibody/AntibodyGroup | dsDNA | Chromatin | Ribosomal-P | SS-A | SS-B | Sm | SmRNP | RNP | Scl-70 | Jo-1 | Centromere |
|---|---|---|---|---|---|---|---|---|---|---|---|
| N | 832* | 908 | 908 | 908 | 908 | 908 | 908 | 879** | 908 | 908 | 908 |
| Bio-Rad andEIA Positive | 83 | 98 | 18 | 156 | 57 | 35 | 90 | 79 | 9 | 6 | 31 |
| Bio-RadPositive andEIA Negative | 25 | 70 | 19 | 17 | 19 | 25 | 13 | 25 | 14 | 0 | 7 |
| Bio-Rad andEIA Negative | 699 | 680 | 868 | 721 | 820 | 843 | 782 | 759 | 877 | 897 | 869 |
| Bio-RadNegative andEIA Positive | 25 | 60 | 3 | 14 | 12 | 5 | 23 | 16 | 8 | 5 | 1 |
| % OverallAgreement | 94% | 86% | 98% | 97% | 97% | 97% | 96% | 95% | 98% | 99% | 99% |
| 95%ConfidenceInterval | 92-96% | 83-88% | 97-99% | 95-98% | 95-98% | 96-98% | 95-97% | 94-97% | 97-99% | 99-100% | 99-100% |
- 76 BioPlex dsDNA indeterminate or predicate dsDNA equivocal results excluded.
** 29 predicate RNP equivocal results excluded.
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Retrospective Testing
Retrospective: Comparison of Selected Antibodies to EIA Methods
Performance of the ANA Screen was further evaluated by testing 440 retrospective serum samples, all known to be positive for ANA and one or more of the autoantibodies listed below. An additional 100 serum sample known to be negative for ANA were also tested. The retrospective specimens were tested by both the ANA Screen and commercially available microplate EIA methods that were specific for the corresponding autoantibodies. Results can be found in the tables below.
| Antibody / Antibody Group | dsDNA | Chromatin | Ribosomal-P | SS-A | SS-B | Sm | SmRNP | RNP | Scl-70 | Jo-1 | Centromere |
|---|---|---|---|---|---|---|---|---|---|---|---|
| N | 123*‡ | 138† | 138† | 139† | 140 | 139† | 139† | 138** | 139† | 130† | 140 |
| Bio-Rad andEIA Positive | 19 | 11 | 14 | 37 | 39 | 25 | 38 | 37 | 13 | 30 | 36 |
| Bio-RadPositive andEIA Negative | 0 | 2 | 3 | 0 | 1 | 0 | 0 | 2 | 4 | 0 | 3 |
| Bio-Rad andEIA Negative | 101 | 108 | 118 | 100 | 100 | 104 | 99 | 95 | 118 | 100 | 101 |
| Bio-RadNegative andEIA Positive | 3 | 17 | 3 | 2 | 0 | 10 | 2 | 4 | 4 | 0 | 0 |
| % OverallAgreement | 98% | 86% | 96% | 99% | 99% | 93% | 99% | 96% | 94% | 100% | 98% |
| 95%ConfidenceInterval | 94-100% | 80-92% | 92-99.5% | 96-100% | 98-100% | 88-98% | 96-100% | 92-99.5% | 90-99% | 99.6-100% | 95-100% |
- 16 BioPlex dsDNA indeterminate or predicate dsDNA equivocal results excluded.
**2 predicate RNP equivocal results are excluded.
+A total of 19 (1 dsDNA, 2 Chromatin, 2 Ribosomal-P, 1SS-A, 1Sm, 1SmRNP, 1Scl-70, and 10 Jo-1 retrospective study samples with repeatedly low Serum Verification Bead (SVB) results were excluded.
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Combined Prospective and Retrospective Testing
Combined Prospective and Retrospective: Comparison of Selected Antibodies to EIA Methods The combined results from the prospective and retrospective studies were analyzed for performance in comparison to the EIA methods. Results from the combined analysis can be found in the table below.
| Antibody/AntibodyGroup | dsDNA | Chromatin | Ribosomal-P | SS-A | SS-B | Sm | SmRNP | RNP | Scl-70 | Jo-1 | Centromere |
|---|---|---|---|---|---|---|---|---|---|---|---|
| N | 955*† | 1046† | 1046† | 1047† | 1048 | 1047† | 1047† | 1017** | 1047† | 1038† | 1048 |
| Bio-Rad andEIA Positive | 102 | 109 | 32 | 193 | 96 | 60 | 128 | 116 | 22 | 36 | 67 |
| Bio-RadPositive andEIA Negative | 25 | 72 | 22 | 17 | 20 | 25 | 13 | 27 | 18 | 0 | 10 |
| Bio-Rad andEIA Negative | 800 | 788 | 986 | 821 | 920 | 947 | 881 | 854 | 995 | 997 | 970 |
| Bio-RadNegative andEIA Positive | 28 | 77 | 6 | 16 | 12 | 15 | 25 | 20 | 12 | 5 | 1 |
| % OverallAgreement | 94% | 86% | 97% | 97% | 97% | 96% | 96% | 95% | 97% | 99.5% | 99% |
| 95%ConfidenceInterval | 93-96% | 84-88% | 96-98 % | 96-98% | 96-98% | 95-97% | 95-98% | 94-97% | 96-98% | 99-99.9% | 98.6-99.6% |
- 92 BioPlex dsDNA indeterminate or predicate dsDNA equivocal results excluded
** 31 predicate RNP equivocal results are excluded
†A total of 19 (1 dsDNA, 2 Chromatin, 2 Ribosomal-P, 1SS-A, 1Sm, 1SmRNP, 1Scl-70, and 10 Jo-1 retrospective study samples with repeatedly low Serum Verification Bead (SVB) results were excluded.
:
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D. CDC Panel
The Centers for Disease Control (CDC) provides a reference serum panel, which was tested to evaluate characteristics of the ANA Screen. The results are presented as a means to convey further information on the performance of the ANA Screen with a masked, characterized serum panel. This does not imply an endorsement of the ANA Screen by the CDC. A summary of results can be found in the table below.
| CENTER FOR DISEASECONTROL (CDC)* Reference Sera | BioPlex 2200 ANA Screen Results | ||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Expected Results | ANA Screen | dsDNA | Chromatin (DNP) | RNP A | RNP 68 | RNP (Compound) | SSB 48 | SSA 52 | SSA 60 | SSA (Compound) | Scl-70 | Sm | Sm RNP | Ribosomal P | Centromere B | Jo-1 | |
| CDC-1 | Homogeneous / rim | + | + | + | + | + | |||||||||||
| CDC-2 | Speckled/La | + | + | + | + | + | |||||||||||
| CDC-3 | Speckled | + | + | + | + | + | + | + | + | + | |||||||
| CDC-4 | U1-RNP | + | + | + | + | + | + | ||||||||||
| CDC-5 | Sm | + | + | + | + | + | |||||||||||
| CDC-6 | Nucleolar | + | + | ||||||||||||||
| CDC-7 | SSA/Ro | + | + | + | |||||||||||||
| CDC-8 | Centromere | + | + | ||||||||||||||
| CDC-9 | Scl-70 | + | + | ||||||||||||||
| CDC-10 | Jo-1 | + | + | + | + | ||||||||||||
| CDC-11 | PM/Scl | + | + |
-
Committee on ANA Serology of the Arthritis Foundation
-
results calculated based on testing of all analytes.
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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 ANA Screen. A panel of ten (10) specimens with potentially interfering disease states was tested with the ANA Screen for each of the eleven (11) autoantibodies. All panel specimens were previously characterized and known to be negative for all autoantibodies detected by the ANA Screen. Samples that elicited a positive response by the BioPlex 2200 ANA Screen were also tested by a corresponding commercially available EIA test method
| Cross Reactants | N | Method | CentromereB | Chromatin | dsDNA | Jo1 | Ribosomal P | RNP | SCL-70 | Smith | Sm-RNP | SSA | SSB |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| # of Positive Samples | |||||||||||||
| Cardiolipin | 10 | BioPlex | 0 | 3 | 1 | 1 | 0 | 0 | 0 | 1 | 2 | 4 | 0 |
| EIA | NT | 3 | 1 | 1 | NT | NT | NT | 0 | 2 | 4 | NT | ||
| Mitochondrial M2 | 10 | BioPlex | 6 | 3 | 1 | 0 | 0 | 2 | 0 | 0 | 1 | 4 | 1 |
| EIA | 4 | 2 | 0 | NT | NT | 1 | NT | NT | 1 | 4 | 1 | ||
| Single-strandedDNA (ssDNA) | 10 | BioPlex | 1 | 4 | 4 | 0 | 2 | 1 | 2 | 1 | 1 | 4 | 2 |
| EIA | 1 | 4 | 4* | NT | 1 | EQ | 1 | 1 | 1 | 4 | 2 | ||
| Histone | 10 | BioPlex | 0 | 7 | 6 | 0 | 4 | 5 | 1 | 5 | 6 | 3 | 1 |
| EIA | NT | 7 | 6 | NT | 2 | 5 | 1 | 5 | 6 | 3 | 1 | ||
| Myeloperoxidase(MPO) | 10 | BioPlex | 1 | 1 | 2 | 0 | 2 | 0 | 0 | 0 | 0 | 1 | 0 |
| EIA | 0 | 0 | 0 | NT | 0 | NT | NT | NT | NT | 0 | NT | ||
| Proteinase 3(PR3) | 10 | BioPlex | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| EIA | 1 | 0 | NT | NT | NT | NT | NT | NT | NT | NT | NT | ||
| Gliadin | 10 | BioPlex | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| EIA | NT | NT | NT | NT | NT | NT | NT | NT | NT | 1 | NT | ||
| Smooth Muscle | 10 | BioPlex | 0 | 2 | 2 | 0 | 2 | 1 | 0 | 1 | 2 | 1 | 0 |
| EIA | NT | 2 | 2 | NT | 2 | 1 | NT | 1 | 2 | 1 | NT | ||
| ThyroidPeroxidase (TPO) | 10 | BioPlex | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| EIA | 2 | NT | NT | NT | NT | NT | NT | NT | NT | NT | NT | ||
| Thyroglobulin(Tg) | 10 | BioPlex | 2 | 2 | 1 | 0 | 0 | 2 | 0 | 1 | 1 | 1 | 0 |
| EIA | 2 | 0 | 0 | NT | NT | 1 | NT | 0 | 1 | 0 | NT | ||
| RheumatoidFactor (RF) | 10 | BioPlex | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| EIA | NT | NT | NT | NT | NT | NT | NT | NT | NT | NT | NT |
NT= Not Tested
*BioPlex dsDNA indeterminate sample excluded.
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/19/Picture/1 description: The image shows the logo for the Department of Health & Human Services. The logo consists of a stylized eagle-like symbol with three curved lines representing wings or feathers. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged in a circular fashion around the symbol.
Public Health Service
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
DEC 2 0 2004
Bio-Rad Laboratories, Inc c/o Mr. Christopher Bensten 6565 185th Ave, NE Redmond, WA 98052
Re: K041658
K041036
Trade/Device Name: BioPlex 2200 ANA Screen on the BioPlex 2200 Multi-Analyte Detection System Regulation Number: 21 CFR 866.5100 Regulation Name: Antinuclear Antibody Immunological Test System Regulatory Class: Class II Product Code: LKJ, LRM, MQA, LKO, LJM, LLL Dated: June 15, 2004 Received: June 18, 2004
Dear Mr Bensten:
We have reviewed your Section 510(k) premarket notification of intent to market the device we nave feviewed your bootion of the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce use stated in the eneround date of the Medical Device Amendments, or to devices that prov to May 20, 1770, inc charactions air the provisions of the Federal Food, Drug, and Cosmetic liave occh recuired in are approval of a premarket approval application (PMA). You may, Act (Act) that ao not require appled to the general controls provisions of the Act. The general therefore, mance the act include requirements for annual registration, listing of devices, good Controls provisions or allabeling, and prohibitions against misbranding and adulteration.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it If your device to such additional controls. Existing major regulations affecting your device can be may be subject to suen adations, Title 21, Parts 800 to 898. 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 r hat FDA has made a determination that your device complies with other requirements of the Act or that I Dri has mude a deceministered 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); an the Ave 3 requirements) ; good manufacturing practice requirements as set forth in the quality iabening (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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Page 2 - Mr. Christopher Bensten
This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to 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 Compliance at (240) 276-3084. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). 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 (301) 443-6597 or at its Internet address
http://www.fda.gov/cdrh/dsma/dsmamain.html
Sincerely yours,
Pbo. W. Rockey
Robert L. Becker, Jr., M.D. PhD 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 STATEMENT
510(k) Number (if known):
| Device Name: | BioPlex 2200 ANA Screen on theBioPlex 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
Page 1 of 1
510(k) K041658
§ 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).