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510(k) Data Aggregation

    K Number
    K081338
    Manufacturer
    Date Cleared
    2008-09-11

    (121 days)

    Product Code
    Regulation Number
    866.5775
    Reference & Predicate Devices
    Predicate For
    N/A
    AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP AuthorizedThirdpartyExpeditedreview
    Intended Use

    (1) Elecsys Anti-CCP immunoassay: Immunoassay for the in vitro semi-quantitative determination of human IgG autoantibodies to cyclic citrullinated peptides in human serum and plasma. The results of the assay are intended to be used as an aid in the diagnosis of rheumatoid arthritis in combination with other clinical and laboratory findings.
    The electrochemiluminescence immunoassay "ECLIA" is intended for use on Elecsys and cobas e immunoassay analyzers.
    (2) Elecsys PreciControl Anti-CCP is used for quality control of the Elecsys Anti-CCP immunoassay on the Elecsys and cobas e immunoassay analyzers.

    Device Description

    (1) The Elecsys Anti-CCP immunoassay is a two step IgG-capture test principle immunoassay with streptavidin-coated microparticles and electrochemiluminescence detection. Results are determined using a calibration curve that is generated specifically on each instrument by a 2 point calibration and a master curve provided with the reagent bar code. The Elecsys Anti-CCP reagent kit consists of a Reagent Pack (R1, R2 and M[streptavidin-coated microparticles]) and lyophilized calibrators 1 and 2.
    (2) The Elecsys PreciControl Anti-CCP is a lyophilized product consisting of human serum with added Anti-CCP antibody (human) in two concentration ranges. During manufacture, the antibody is spiked into the matrix at the desired concentration levels.
    Note: The reagent is packaged with calibrators; controls are packaged separately.

    AI/ML Overview

    Here's a summary of the acceptance criteria and study findings for the Elecsys Anti-CCP Immunoassay, based on the provided text:

    1. Table of Acceptance Criteria and Reported Device Performance

    The acceptance criteria for the Elecsys Anti-CCP Immunoassay are implicitly defined by its performance in comparison to the predicate device, the Eurodiagnostica IMMUNOSCAN RA Anti-CCP Test Kit (K052133). The goal is to demonstrate "substantial equivalence."

    Feature/Acceptance Criteria CategoryElecsys Anti-CCP Assay PerformancePredicate Device Performance (Eurodiagnostica IMMUNOSCAN RA Anti-CCP Test Kit)
    PrecisionElecsys 2010 and cobas e 411:Total CV:3.1% CV @ 16.9 U/mL4.5% CV @ 356 U/mL3.0% CV @ 24.6 U/mL2.5% CV @ 137 U/mLWithin-run CV:0.6% CV @ 16.9 U/mL2.3% CV @ 356 U/mL1.0% CV @ 24.6 U/mL1.4% CV @ 137 U/mLIntra-assay Precision:12.8%CV @ 1007.4 U/mL6.5% CV @ 240.1 U/mL7.0%CV @ 95.7 U/mL8.4% CV @ 51.7 U/mL8.1% CV @ 33.6 U/mL4.3% CV @ 88.1 U/mLInter-assay Precision:11.7% CV @ 1105.9 U/mL7.9% CV @ 257.4 U/mL6.0% CV @ 93.1 U/mL7.8% CV @ 52.5 U/mL14.5% CV @ 33.3 U/mL17.7% CV @ 94.9 U/mL
    LoQ (Functional Sensitivity)8 U/mLN/A (Not given for predicate)
    LoB (Limit of Blank)≤ 7 U/mLN/A (Not given for predicate)
    LoD (Limit of Detection / Analytical Sensitivity)≤ 8 U/mLN/A (Not given for predicate, but LDL is 1.6 U/mL)
    LDL (Lower Detection Limit)N/A (Not given for Elecsys)1.6 U/mL
    Measuring Range8 – 1000 U/mL (defined by the limit of detection and the maximum of the master curve)1.6 – 1600 U/mL
    Method Comparison (Agreement vs. Predicate)Positive Percent Agreement = 94.3% (95% CI = 91.7 – 96.2)Negative Percent Agreement = 98.4% (95% CI = 97.5 – 99.1)Total Percent Agreement = 97.3% (95% CI = 96.3 – 98.0)Predicate compared to alternative ELISA:Positive Percent Agreement = 99.3% (95% CI = 93.2 – 100%)Negative Percent Agreement = 96.7% (95% CI = 81.6 – 99.9%)Overall Percent Agreement = 97.8% (95% CI = 93.2 – 100%)
    Interference (Bilirubin)Unaffected by: < 25 mg/dLUnaffected by: ≤ 0.2 mg/mL
    Interference (Hemoglobin)Unaffected by: < 0.5 g/dLUnaffected by: ≤ 400 mg/dL
    Interference (Intralipid/Lipid)Unaffected by: < 1500 mg/dLUnaffected by: ≤ 15 mg/mL
    Interference (Biotin)Unaffected by: < 30 ng/mLN/A (Not given for predicate)
    Interference (Rheumatoid factor)Interference observed above 150 IU/mLUnaffected by: ≤ 200 IU/mL
    Hook EffectNo high-dose hook effect at anti-CCP concentrations up to 7000 U/mLNot given.

    Study that proves the device meets the acceptance criteria:

    A "Method Comparison" study was conducted to demonstrate substantial equivalence between the Elecsys Anti-CCP Immunoassay and the predicate device.

    2. Sample size used for the test set and the data provenance

    • Test Set Sample Size: 1606 samples.
    • Data Provenance: Not explicitly stated (e.g., country of origin, retrospective/prospective). The predicate device's comparison mentions "320 frozen retrospective sera" with 175 from RA patients and 145 normals from a blood bank, suggesting the Elecsys study likely used a retrospective collection as well, but this is not explicitly stated for the Elecsys study itself.

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

    The document does not mention the use of experts to establish a "ground truth" for the test set. Instead, the performance of the Elecsys Anti-CCP Immunoassay was compared directly to the results obtained from the predicate device (IMMUNOSCAN RA Anti-CCP test kit). Therefore, the predicate device's results served as the reference for comparison, not a ground truth established by independent experts for the purpose of validating the new device.

    4. Adjudication method for the test set

    Not applicable. The study compares the new device directly against a predicate device, rather than against an adjudicated ground truth from experts.

    5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

    Not applicable. This is an immunoassay device, not an imaging device requiring human reader interpretation in the context of an MRMC study.

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

    Yes, the study describes the standalone performance of the Elecsys Anti-CCP Immunoassay. It's an automated immunoassay where the result is generated directly by the instrument, without a human "in-the-loop" making interpretive decisions of the assay output. The method comparison data (positive, negative, and total percent agreement) directly reflects this standalone performance against the predicate device.

    7. The type of ground truth used

    For the method comparison study, the "ground truth" was established by the results of the predicate device, the Eurodiagnostica IMMUNOSCAN RA Anti-CCP Test Kit. This is an indirect form of ground truth, relying on the established performance of an already marketed device.

    8. The sample size for the training set

    The document does not provide information on a specific "training set" for the Elecsys Anti-CCP Immunoassay. As an immunoassay, the calibration curve and master curve are provided with the reagent and generated on each instrument, respectively, rather than a "training set" in the machine learning sense. The assay is "standardized against a commercially available anti-CCP assay."

    9. How the ground truth for the training set was established

    Not applicable, as a "training set" in the context of algorithm development with an established ground truth is not explicitly mentioned for this immunoassay in the provided text. The assay itself relies on its inherent chemical and detection principles, calibrated against reference materials.

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