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The BioPlex® 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 autoimmune diseases.

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

The BioPlex 2200 Medical Decision Support Software (MDSS), used in conjunction with the ANA Screen, is an optional laboratory tool that associates patient antibody results with predefined MDSS profiles that have been correlated with the following systemic autoimmune diseases: Systemic Lupus Erythematosus (SLE), Mixed Connective Tissue Disease (MCTD), Sjögren's Syndrome (SS), Scleroderma (Systemic Sclerosis) and Polymyositis.

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

The BioPlex 2200 Medical Decision Support Software (MDSS), used in conjunction with the ANA Screen, is an optional laboratory tool that associates patient antibody results from the ANA Screen with predefined MDSS profiles that have been correlated with the following systemic autoimmune diseases: Systemic Lupus Erythematosus (SLE), Mixed Connective Tissue Disease (MCTD), Sjögren's Syndrome (SS), Scleroderma (Systemic Sclerosis) and Polymyositis.

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 coated with individual antigens, so that the presence of each antinuclear and autoimmune antibody can be individually determined. Fluorescence detection facilitates the differentiation of normal 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.

While the identity of the dyed beads is determined by the fluorescence of the dyes, 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 Reagent Blank Bead (RBB) are present in each reaction mixture to verify detector response, the addition of serum or plasma to the reaction vessel and the absence of significant non-specific binding in serum or plasma. Refer to the BioPlex 2200 System Operation Manual for more information. The instrument is calibrated using a calibrator set, supplied separately by Bio-Rad Laboratories. For dsDNA, 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 semi-quantitative 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

Here's a breakdown of the acceptance criteria and study information for the BioPlex® 2200 ANA Screen with MDSS, based on the provided document:

1. Table of Acceptance Criteria and Reported Device Performance

The provided text focuses on changes to QC testing frequency and reagent composition, not directly on the acceptance criteria for the diagnostic performance of the ANA Screen or MDSS. The document states that the "Design Control Activities include Risk Analysis method to identify the verification and validation activities required. test used and acceptance criteria." However, the specific acceptance criteria (e.g., sensitivity, specificity thresholds) and the reported device performance against those criteria for the ANA Screen's diagnostic accuracy or the MDSS's disease association capabilities are not explicitly detailed in this 510(k) summary.

The closest information related to performance is for the predicate device, which this device is stated to be substantially equivalent to, and the general description of how results are reported:

Note: The 510(k) focuses on demonstrating substantial equivalence to a predicate device (K043341) despite minor modifications (QC frequency, reagent composition). The performance claims for the diagnostic aspects of the ANA Screen and MDSS are likely based on studies conducted for the predicate device, which are not included in this document.

2. Sample Size Used for the Test Set and Data Provenance

The document mentions that the MDSS compares "unknown" samples to a "pre-established database that contains the results for over 1,400 characterized sera/plasma." This database serves as a reference or a form of internal test set for the MDSS algorithm.

• Sample size for the MDSS test set (reference database): Over 1,400 characterized sera/plasma.
• Data Provenance: Not specified (e.g., country of origin, retrospective/prospective). The term "characterized" implies these samples had known clinical diagnoses.

For the ANA Screen itself, the document does not specify a separate "test set" sample size for validation in this 510(k), as the modifications primarily concern QC and reagent stability, not fundamental analytical performance that would require new clinical validation studies for the antibody detection.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts

• Number of experts: Not specified.
• Qualifications of experts: Not specified.
• Method of establishing ground truth (for the "1,400 characterized sera/plasma"): The term "characterized sera/plasma" implies established clinical diagnoses for autoimmune diseases, likely determined by treating physicians and specialists, but the specific process or number/qualifications of experts involved is not detailed in this document.

4. Adjudication Method for the Test Set

Not specified. The document does not describe any adjudication process for the "1,400 characterized sera/plasma."

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and the Effect Size of How Much Human Readers Improve with AI vs without AI Assistance

• No, an MRMC comparative effectiveness study was not done as described in this document.
• The MDSS is an "optional laboratory tool" that "can enhance the performance of the ANA Screen by identifying associated diagnostic patterns." It is described as a "pattern recognition algorithm" and an "aid in the diagnosis," suggesting it provides supplementary information rather than directly assisting human readers in interpreting images or subjective data. The document does not provide any quantitative effect size regarding how human readers improve with MDSS assistance.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Study Was Done

• Yes, a standalone performance is implied for the MDSS. The MDSS operates as an algorithm that takes the 11 individual antibody results and generates an "Association with Disease" or "No Association" output directly. This is an algorithm-only function. However, the document does not present quantitative standalone performance metrics (e.g., sensitivity, specificity, accuracy) for the MDSS's ability to "associate with disease" compared to a clinical ground truth. It implies this was part of the original predicate device's pre-market notification.

7. The Type of Ground Truth Used

• Clinical Diagnoses / Outcomes Data: For the MDSS, the "1,400 characterized sera/plasma" imply that the ground truth for these samples was based on established clinical diagnoses of systemic autoimmune diseases.

8. The Sample Size for the Training Set

The document does not explicitly mention a separate "training set" with a specified sample size. It states that the MDSS is based on the "k-nearest neighbor" statistical technique and uses a "pre-established database that contains the results for over 1,400 characterized sera/plasma." In the context of k-NN, this database itself serves as the reference or "training" data against which new, "unknown" samples are compared.

• Training Set Sample Size: Over 1,400 characterized sera/plasma (this database likely serves both as the reference for k-NN and implicitly as the "training" data).

9. How the Ground Truth for the Training Set Was Established

The ground truth for the "over 1,400 characterized sera/plasma" was established because these samples were "characterized." This strongly implies that these samples had established clinical diagnoses of systemic autoimmune diseases by healthcare professionals. The specific methodology for this characterization (e.g., clinical diagnosis, pathology, long-term outcomes) or the number/qualifications of experts involved are not detailed in this 510(k) summary.

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