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EliA Ro52 is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to Ro52 in human serum as an aid in the diagnosis of Sjögren's syndrome (SS), systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and idiopathic inflammatory myopathies (IIM) in conjunction with other laboratory and clinical findings. EliA Ro52 uses the EliA IgG method.

EliA Ro60 is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to Ro60 in human serum as an aid in the diagnosis of Sjögren's syndrome (SS) and systemic lupus erythematosus (SLE) in conjunction with other laboratory and clinical findings. EliA Ro60 uses the EliA IgG method.

The EliA Ro52 and EliA Ro60 Immunoassays are semi-quantitative solid-phase fluoroenzyme immunoassays, for the determination of autoantibodies against SS-A/Ro 52 kDa and 60 kDa proteins. The EliA Ro52 and EliA Ro60 test System is a fully integrated and automated system composed of assay-specific reagents, EliA method-specific reagents, and general reagents.

The provided document describes the EliA Ro52 and EliA Ro60 Immunoassays, which are intended for the semi-quantitative measurement of IgG antibodies directed to Ro52 and Ro60 in human serum, respectively. These devices aid in the diagnosis of specific autoimmune diseases. The document includes detailed analytical and clinical performance data to support the substantial equivalence claim.

Here's an analysis of the acceptance criteria and the study that proves the device meets them:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state formal "acceptance criteria" in a tabulated format. Instead, it presents various analytical and clinical performance metrics, implying that these metrics, when compared to the predicate device and established clinical utility, are deemed acceptable for the device's intended use. Based on the provided performance data, the implicit acceptance criteria would likely be related to aspects like precision, linearity, detection limits, specificity (interference), and clinical sensitivity/specificity.

Below is a table summarizing key performance indicators reported in the document:

Table 1: Key Performance Metrics for EliA Ro52 and EliA Ro60

The acceptance of these performance metrics is implicitly based on comparison with the predicate devices (QUANTA Flash Ro52 and QUANTA Flash Ro60) and the established clinical utility in diagnosing the mentioned autoimmune diseases. The FDA's substantial equivalence determination (K210902) confirms that the submitted data supports the claim that the new devices perform comparably to the predicate devices.

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

The document describes several test sets for different performance characteristics:

• Precision/Reproducibility:
  • Phadia 250: 5 samples, each with 252 replicate determinations (across 3 instruments, 7 days, 21 runs).
  • Within-lab Imprecision: Samples in 80 replicates on 1 instrument over 20 days (40 runs).
  • Phadia 2500 and Phadia 5000 series (E-module): 5 samples, each with 84 replicates (across 3 instruments, 7 days, 21 runs).
• Linearity/Assay Reportable Range: 3 patient serum samples serially diluted in at least 9 dilution steps, tested in quadruplicates.
• Detection Limit: 4 blank and 4 low-level samples, tested in 5-fold determination, across 2 different reagent sets (totaling 120 combined observations for blank and low-level per instrument type).
• Analytical Specificity (Interference): 3 serum samples (negative, equivocal, high positive), spiked with interfering substances, tested in triplicates.
• Method Comparison with Predicate Device:
  • EliA Ro52: 208 patient serum samples (only 181 used in agreement calculations due to samples outside measuring range).
  • EliA Ro60: 208 patient serum samples (only 104 used in agreement calculations due to samples outside measuring range).
• Clinical Sensitivity and Specificity:
  • EliA Ro52: 755 clinically and ethnically defined serum samples. These include:
    • Diagnostic group: SLE (n=120), Sjögren's syndrome (n=60), IIM (n=94), SSc (n=91) - total 365.
    • Disease control group: 390 samples (various autoimmune and infectious diseases).
  • EliA Ro60: 713 clinically and ethnically defined serum samples. These include:
    • Diagnostic group: SLE (n=120), Sjögren's syndrome (n=60) - total 180.
    • Disease control group: 533 samples (various autoimmune and infectious diseases, excluding SSc).

Data Provenance:
The document states that the clinical samples used for sensitivity and specificity determination were from "clinically and ethnically defined serum samples, including those of US origin." This indicates a mix of retrospective (clinically defined, likely banked samples) and potentially prospective (if US origin implies some form of fresh collection for the study) data. It is not explicitly stated whether it was purely retrospective or involved prospective collections, but the description "clinically and ethnically defined serum samples" strongly suggests retrospective use of samples with established diagnoses.

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

The document does not provide information on the number of experts used to establish the ground truth for the test sets (e.g., for diagnoses of SLE, SS, IIM, SSc). It only states that samples were "clinically and ethnically defined." This typically implies that patient diagnoses were established through standard clinical practice by medical professionals, but the specifics of these experts' qualifications or the consensus process are not detailed in this submission summary.

4. Adjudication Method for the Test Set

The document does not specify an adjudication method for establishing the ground truth for the test set. It refers to diagnoses as "clinically defined," which generally suggests diagnosis was made by treating physicians following clinical guidelines, but no adjudication process like 2+1 or 3+1 by independent experts is mentioned for the study.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This document describes an in vitro diagnostic (IVD) device, specifically an immunoassay for measuring antibody levels. MRMC studies are typically performed for imaging devices or other diagnostic tools where human interpretation is involved and needs to be compared with and/or augmented by AI. This device is an automated laboratory test, and its performance is evaluated directly through analytical measurements and comparison to a predicate device, as well as clinical sensitivity and specificity against established clinical diagnoses.

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

Yes, this is a standalone device. The EliA Ro52 and EliA Ro60 Immunoassays are "automated semi-quantitative solid phase fluoroenzymeimmunoassays" run on "Phadia 250 instrument and the Phadia 5000 instrument series (E-modules)." The results are automatically converted to EliA U/mL. The performance characteristics described (precision, linearity, detection limit, analytical specificity, clinical sensitivity, specificity) are all based on the output of the automated instrument and reagents, independent of human interpretation during the actual test process itself. The interpretation of results (negative, equivocal, positive) is based on defined cut-off values.

7. The Type of Ground Truth Used (Expert Consensus, Pathology, Outcomes Data, etc.)

For the clinical sensitivity and specificity studies, the ground truth was clinical diagnosis. The samples were "clinically and ethnically defined serum samples" with established diagnoses of various autoimmune diseases (SLE, SS, IIM, SSc) and control conditions. This implies that the diagnosis was based on the standard clinical criteria and medical records established by healthcare professionals, rather than a separate expert consensus panel or specific pathology results for the study.

8. The Sample Size for the Training Set

The document does not describe a "training set" in the context of machine learning or AI models, as this is an immunoassay and not an AI/ML-based device.

However, if "training set" is generally interpreted as samples used for assay development, optimization, or establishing parameters like cut-offs, the relevant information is:

• Cut-off definition: A cohort of 69 healthy blood donors, 19 SLE patients, and 9 Sjögren's syndrome (SS) patients for EliA Ro52, and 70 healthy blood donors, 22 SLE patients, and 6 Sjögren's syndrome patients for EliA Ro60, were used to define the cut-off values. This can be considered the 'development' or 'calibration' set for determining the interpretive thresholds.

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

As noted above, this device does not utilize a machine learning "training set" in the conventional sense. For the samples used to establish the cut-off values (which could be considered analogous to determining a 'decision boundary' in an ML context), the ground truth was established based on the clinical diagnoses of the patient samples (healthy blood donors, SLE patients, Sjögren's syndrome patients). The document states that the initial cut-off for EliA Ro52, set using SLE and SS patients, was later verified with additional IIM and SSc patient sera. This indicates clinical diagnosis as the gold standard.

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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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1. EliA™ CENP is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to CENP in human serum and plasma (heparin, EDTA, citrate) as an aid in the clinical diagnosis of scleroderma (CREST Syndrome) in conjunction with other laboratory and clinical findings. EliA™ CENP uses the EliA IgG method on the instruments ImmunoCAP® 100 and ImmunoCAP® 250.

2. EliA™ UIRNP is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to UIRNP in human serum and plasma (heparin, EDTA, citrate) as an aid in the clinical diagnosis of mixed connective tissue disease (MCTD) and systemic lupus erythematosus (SLE) in conjunction with other laboratory and clinical findings. EliA™ UIRNP uses the EliA IgG method on the instruments ImmunoCAP® 100 and ImmunoCAP® 250.

3. EliATM Sm is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to Sm in human serum and plasma (heparin, EDTA, citrate) as an aid in the clinical diagnosis of systemic lupus erythematosus (SLE) in conjunction with other laboratory and clinical findings. EliA™ Sm uses the EliA IgG method on the instruments ImmunoCAP® 100 and ImmunoCAP® 250.

4. EliA™ Ro is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to Ro in human serum and plasma (heparin, EDTA, citrate) as an aid in the clinical diagnosis of Sjögren's syndrome and systemic lupus erythematosus (SLE) in conjunction with other laboratory and clinical findings. EliA™ Ro uses the EliA IgG method on the instruments ImmunoCAP® 100 and ImmunoCAP® 250.

5. EliATM La is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to La in human serum and plasma (heparin, EDTA, citrate) as an aid in the clinical diagnosis of Siögren's syndrome and systemic lupus erythematosus (SLE) in conjunction with other laboratory and clinical findings. EliA™ La uses the EliA IgG method on the instruments ImmunoCAP® 100 and ImmunoCAP® 250.

The new devices belong to a fully integrated and automated system for immunodiagnostic testing. It comprises a Fluorescence-Immunoassay test system using EliA single wells as the solid phase and is intended to be performed on the instruments ImmunoCAP 100 and ImmunoCAP 250. The conjugate for the EliA IgG method is mouse anti-human IgG beta-galactosidase, which uses 4-Methylumbelliferyl-BD-Galactoside as substrate. The total IgG calibration is based on a set of six WHOstandardized IgG Calibrators derived from human serum. They are used to establish an initial calibration curve, which may be used for up to 28 days on additional assays and can be stored by the instrument. Each additional assay includes calibrator (curve) controls that have to recover in defined ranges to ensure that the stored calibration curve is still valid. The Fluorescence-Immunoassay test system includes test-, method specific and general reagents that are packaged as separate units.

The provided text describes EliA™ CENP, EliA™ U1RNP, EliA™ Sm, EliA™ Ro, and EliA™ La immunoassays, which are intended for the semi-quantitative measurement of IgG antibodies to specific antigens in human serum and plasma to aid in the clinical diagnosis of various autoimmune diseases.

Here's an analysis of the acceptance criteria and study information provided:

1. Table of Acceptance Criteria

The document does not explicitly state numerical acceptance criteria for the devices (e.g., minimum sensitivity, specificity, accuracy thresholds). Instead, the method for demonstrating performance is through "comparability" and "substantial equivalence" to predicate devices. The "reported device performance" is summarized as supporting substantial equivalence.

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

The document states that the comparability of the new devices and predicate devices is supported by a "data set" that includes results obtained from:

• A comparison study between new and predicate devices.
• Clinically defined sera.
• Samples from apparently healthy subjects (normal population).

However, the specific sample sizes for these studies are not provided. The data provenance (e.g., country of origin, retrospective or prospective) is also not specified.

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

The document does not provide information on the number of experts used or their qualifications to establish ground truth for the test set. The ground truth appears to be based on "clinically defined sera" and "samples from apparently healthy subjects," implying clinical diagnosis rather than expert interpretation of raw data for the immunoassay itself.

4. Adjudication Method for the Test Set

The document does not specify any adjudication method (e.g., 2+1, 3+1, none) for the test set.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

An MRMC study is typically for evaluating the performance of readers with and without AI assistance in interpreting diagnostic images or data. Since these devices are in-vitro diagnostic immunoassays, rather than AI-assisted interpretation tools, a MRMC comparative effectiveness study was not performed or described. Therefore, there is no effect size of human readers improving with AI vs without AI assistance. The study described is a comparison of the new devices against predicate devices and clinical samples.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study

The EliA™ system is described as a "fully integrated and automated system for immunodiagnostic testing" performed on ImmunoCAP® 100/ImmunoCAP® 250 instruments, which "include software for evaluation of test results." This implies that the device itself is the "algorithm" or automated test. The performance described (comparability to predicate, clinical samples, healthy subjects) is inherently the standalone performance of the device system.

7. Type of Ground Truth Used

The ground truth for the performance evaluation appears to be based on:

• Clinical diagnosis: "clinically defined sera" and diagnoses like scleroderma (CREST Syndrome), mixed connective tissue disease (MCTD), systemic lupus erythematosus (SLE), and Sjögren's syndrome.
• Healthy status: "samples from apparently healthy subjects (normal population)."

This is a form of clinical ground truth, derived from established medical diagnoses and healthy cohorts.

8. Sample Size for the Training Set

The document does not provide information on a separate "training set" sample size. For IVD devices, a dedicated "training set" in the machine learning sense is often not explicitly mentioned in this type of submission unless a new algorithm is being developed. The "calibration" of the device uses six WHO-standardized IgG Calibrators, but this is for assay calibration, not algorithm training data.

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

Since a dedicated "training set" for an algorithm in the machine learning context is not described, the method for establishing its ground truth is not applicable/not provided. The device calibration uses a set of six WHO-standardized IgG Calibrators.

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AESKULISA ANA-HEp2 is a solid phase enzyme immunoassay for the combined qualitative detection of IgG artibodies against HEp2 cells in human serum. Each well is coated with lysed HEp2 cells and spectic antigens. The test collectively detects, in one well, total ANAs against double stranded DNA (dsDNA), histones, SS-A (Ro), SS-B (La), Sm, snRNP/Sm, Scl-70, Jo-1 and centromeric antigens along with sera positive for HEp2 immunofluorescence test (IFT).

The assay is a tool in the diagnosis of certain systemic theumatic diseases and should be used in conjunction with other serological tests and clinical findings.

AESKULISA ANA-HEp2 is a solid phase enzyme immunoassay for the combined qualitative detection of IgG artibodies against HEp2 cells in human serum. Each well is coated with lysed HEp2 cells and spectic antigens.

I am sorry, but the provided text does not contain the detailed information necessary to complete all sections of your request regarding the acceptance criteria and the study proving the device meets those criteria. The document is an FDA 510(k) clearance letter for a device called "AESKULISA ANA-HEp2," and while it states the device has been found substantially equivalent to a predicate device, it does not include the specific study details you are asking for.

Here's a breakdown of what I can and cannot provide based on the given text:

Information I CAN extract:

• Device Name: AESKULISA ANA-Hep2
• Indication for Use: A solid phase enzyme immunoassay for the combined qualitative detection of IgG antibodies against HEp2 cells in human serum. It collectively detects total ANAs against dsDNA, histones, SS-A (Ro), SS-B (La), Sm, snRNP/Sm, Scl-70, Jo-1, and centromeric antigens, along with sera positive for HEp2 immunofluorescence test (IFT). It's a tool in the diagnosis of certain systemic rheumatic diseases and should be used with other serological tests and clinical findings.
• Regulatory Information: Class II device, Product Code LKJ.

Information NOT present in the provided text:

• A table of acceptance criteria and the reported device performance: This document does not detail specific acceptance criteria or the performance metrics (e.g., sensitivity, specificity, accuracy) from the study.
• Sample sizes used for the test set and data provenance: The document does not mention the sample size of any test set or the origin of the data.
• Number of experts used to establish the ground truth for the test set and their qualifications: There is no mention of experts or ground truth establishment.
• Adjudication method: Not mentioned.
• Multi-reader multi-case (MRMC) comparative effectiveness study: Not mentioned.
• Effect size of human readers improving with AI vs. without AI assistance: Not applicable as this is not an AI-assisted device based on the description.
• Standalone (algorithm only) performance: Not applicable as this is an immunoassay, not an algorithm.
• Type of ground truth used: Not specified.
• Sample size for the training set: There is no mention of a training set as this is an immunoassay, not a machine learning model.
• How the ground truth for the training set was established: Not applicable.

Therefore, I cannot fulfill your request for the specific study details as they are not contained within the provided FDA 510(k) clearance letter. This type of information would typically be found in the 510(k) submission summary or the actual study report, neither of which is present here.

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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.

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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The Zeus Scientific, Inc. AtheNA Multi-Lyte® ANA Test System is intended for the semiquantitative detection of IgG class antibody to 8 separate analytes (SSA, SSB, Sm, RNP, Scl-70, Jo-1, Centromere B, and Chromatin) in human serum, the quantitative detection of IgG class antibody to dsDNA in human serum and the qualitative detection of IgG class antibody to ANA in human serum. The test system is intended to be used as an aid in the diagnosis of various autoimmune disorders. This test is for in vitro diagnostic use.

Not Found

I apologize, but the provided text is a cover letter from the FDA regarding a 510(k) premarket notification and identifies the device as the "AtheNA Multi-Lyte™ ANA-II Test System." It states the indications for use but does not contain any information about acceptance criteria or a study that proves the device meets such criteria.

Therefore, I cannot fulfill your request to describe the acceptance criteria and the study that proves the device meets the acceptance criteria, nor can I provide information on:

• A table of acceptance criteria and reported device performance
• Sample size used for the test set or data provenance
• Number of experts and their qualifications for ground truth
• Adjudication method
• MRMC comparative effectiveness study or effect size
• Standalone performance (algorithm only)
• Type of ground truth used
• Sample size for the training set
• How ground truth for the training set was established

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For the detection and quantitation of anti-dsDNA antibodies in individuals with systemic lupus erythematosus (SLE).

Not Found

The provided text is a 510(k) clearance letter from the FDA for a diagnostic test kit (REAADS® Anti-dsDNA Quantitative Test Kit). It does not contain information about acceptance criteria or a study proving the device meets those criteria. The letter primarily states that the device is substantially equivalent to a legally marketed predicate device for the detection and quantitation of anti-dsDNA antibodies in individuals with systemic lupus erythematosus (SLE).

Therefore, I cannot provide the requested information based on the input document.

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These are qualitative calibrators/controls to confirm the presence of antibodies to autoantigens (Jo-1, Scl-70, or PCNA) in human serum. Antibodies to Jo-1 are found in patients with polymyositis and dermatomyositis, antibodies to Scl-70 are found in patients with scleroderma, and antibodies to PCNA are found in patients with systemic lupus erythematosus. These optional controls are intended for use with the Immuno Concepts AUTO-ID® Autoantibody Test System.

AUTO-I.D.® Jo-1 Positive Control Serum (Catalog number 6004) AUTO-I.D.® Sc1-70 Positive Control Serum (Catalog number 6005) AUTO-I.D.® PCNA Positive Control Serum (Catalog number 6006)

This document is a 510(k) premarket notification approval letter for the Immuno Concepts Incorporated's Auto I.D.® Jo-1, Scl-70, and PCNA Positive Controls. It indicates the products are substantially equivalent to legally marketed predicate devices. This type of document does not contain details about specific acceptance criteria or an in-depth study proving device performance against those criteria.

The purpose of a 510(k) submission is to demonstrate substantial equivalence, not necessarily to provide detailed performance studies in the way you might find for a novel, high-risk device. The approval letter confirms the device can be legally marketed, but it doesn't typically elaborate on the specific performance study results that were part of the submission package.

Therefore, I cannot provide the requested information because the provided text does not contain it. The text focuses on the regulatory approval, indicating the device is a "qualitative calibrator/control to confirm the presence of antibodies to autoantigens." This implies performance validation related to its role as a control, likely confirming the presence of the respective antibodies, but the details of such validation are not in this approval letter.

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Liquichek Anti-SS-B Control, Positive, is intended for use as an unassayed quality control to monitor indirect immunofluorescent testing for the detection of SS-B autoantibodies.

This product is prepared from human serum with added preservatives. The control is provided in liquid form for convenience.

Here's a breakdown of the acceptance criteria and the study details for the Liquichek™ Anti-SS-B Control, Positive, based on the provided document:

This document describes a new quality control device, and the "performance" referenced refers to its stability rather than diagnostic accuracy for patient samples. Therefore, typical metrics like sensitivity, specificity, or AUC based on clinical outcomes are not applicable.

Acceptance Criteria and Device Performance Study for Liquichek™ Anti-SS-B Control, Positive

1. Table of Acceptance Criteria and Reported Device Performance

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

The document does not specify a separate "test set" in the context of clinical performance, as this is a quality control product. The performance studies relate to the stability of the control material itself.

• Sample Size: Not explicitly stated as a number of distinct "samples" in the traditional sense. The studies would have involved multiple aliquots or units of the control material tested over time.
• Data Provenance: The studies were performed internally by Bio-Rad Laboratories. The data is retrospective in the sense that the studies were performed and data collected prior to this submission, but the "real-time studies will be ongoing" suggests a prospective element for shelf-life confirmation. Country of origin for data is implied to be within Bio-Rad's facilities, likely in the USA given the submission location (Irvine, California).

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

Not applicable. For a quality control material, the "ground truth" is defined by the stability of the analyte within the control. This is determined through chemical and immunological assays over time, not by expert interpretation.

4. Adjudication Method

Not applicable. Adjudication methods are relevant for subjective interpretations (e.g., image reading) or conflicting results in diagnostic studies. This is a stability study for a quality control product.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

Not applicable. MRMC studies are used to evaluate the diagnostic performance of a device with and without AI assistance on human readers. This is a quality control product, not a diagnostic device for clinical use by human readers.

6. Standalone (Algorithm Only) Performance Study

Not applicable. This device is a biochemical control, not an algorithm. Its performance is chemical/biological stability.

7. Type of Ground Truth Used

The ground truth for the stability studies would be analytical measurements of the Anti-SS-B autoantibodies' concentration or activity within the control over time, under specified storage conditions. These measurements would be compared against predefined acceptable ranges for stability.

8. Sample Size for the Training Set

Not applicable. This document describes a quality control product, not an AI/algorithm-based device that requires a training set. The "training" for this product involves its manufacturing process and subsequent stability testing.

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

Not applicable. As above, there is no "training set" in the context of this chemical/biological quality control product. The product's intended performance (stability) is established through rigorous analytical testing and adherence to manufacturing specifications.

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Liquichek Anti-SS-A Control, Positive, is intended for use as an unassayed quality control to monitor indirect immunofluorescent testing for the detection of SS-A autoantibodies.

This product is prepared from human serum with added preservatives. The control is provided in liquid form for convenience.

Here's a breakdown of the acceptance criteria and the study information for the Liquichek™ Anti-SS-A Control, Positive, based on the provided document:

This document describes a quality control product, not a diagnostic device that directly assesses patient conditions. Therefore, the typical "performance" metrics for a diagnostic device (e.g., sensitivity, specificity, AUC) are not applicable. Instead, the acceptance criteria relate to the stability and consistency of the control material.

Acceptance Criteria and Reported Device Performance

Study Details:

Based on the provided document, the study conducted is a stability study.

1. Sample size used for the test set and the data provenance:

• Test Set Sample Size: Not explicitly stated. The document refers to "supporting data" and "real time studies" but doesn't provide specific sample numbers of control vials tested.
• Data Provenance: Not explicitly stated regarding country of origin. The study is described as "Real-time studies will be ongoing," which suggests a prospective study design for shelf life, and the open vial stability would also be prospective. All data is retained by Bio-Rad Laboratories.

2. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

• Not applicable directly. This is a quality control product, not a diagnostic device requiring expert interpretation for ground truth. The "ground truth" here is the inherent stability of the control material over time, measured through established laboratory assays.

3. Adjudication method for the test set:

• Not applicable as there's no diagnostic interpretation requiring adjudication.

4. If a multi-reader, multi-case (MRMC) comparative effectiveness study was done:

• No, an MRMC study was not done. This type of study is for evaluating observer performance with and without an assist device for diagnostic tasks.

5. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:

• Not applicable. This is not an algorithm-based device.

6. The type of ground truth used:

• The ground truth for this device's performance is the measured stability of the Anti-SS-A analyte within the control material over defined time periods (60 days open, 2 years unopened) when subjected to specific storage conditions. This would be determined by repeatedly testing the control material using accepted laboratory methods for Anti-SS-A detection and ensuring the results remain within a predefined acceptable range.

7. The sample size for the training set:

• Not applicable. This is a quality control product undergoing stability testing, not a machine learning algorithm that requires a training set.

8. How the ground truth for the training set was established:

• Not applicable. (See #7).

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