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510(k) Data Aggregation

    K Number
    K173206
    Date Cleared
    2018-07-12

    (283 days)

    Product Code
    Regulation Number
    862.1373
    Reference & Predicate Devices
    Predicate For
    N/A
    AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP AuthorizedThirdpartyExpeditedreview
    Intended Use

    The SEKURE HbA1c assay is used to measure the percent concentration of hemoglobin A1c (NGSP) or the HbA1c fraction mmol/mol (IFCC) in human venous whole blood and hemolysate on the SK500 Clinical Chemistry System. Measurement of HbA 1c is used as an aid in the diagnosis of diabetes mellitus, as an aid in the identification of patients at risk for development of diabetes mellitus, and for the monitoring of long-term blood glucose with diabetes mellitus. For In Vitro Diagnostic Use Only.

    Device Description

    The SEKURE HbA1c assay is an enzymatic assay for the measurement of the percent hemoglobin A1c concentration. The assay consists of a pre-treatment hemolyzing buffer solution and two working reagents. Testing is performed on the SK500 K103531in conjunction with calibrators and controls which will be provided separately.

    AI/ML Overview

    The SEKURE HbA1c Assay is an in vitro diagnostic device used to measure the percentage concentration of hemoglobin A1c (HbA1c) in human venous whole blood and hemolysate. It's intended to aid in the diagnosis and monitoring of diabetes mellitus. The device's performance was evaluated through various non-clinical studies to demonstrate its substantial equivalence to a predicate device.

    1. Acceptance Criteria and Reported Device Performance

    Precision (NGSP Units, Whole Blood)

    TestAcceptance Criteria (NGSP Within-Laboratory %CV)Reported Performance (Total Precision %CV) (Range across samples)
    Precision (NGSP Units)≤ 2.5%0.8% - 1.6%
    Precision (IFCC Units)≤ 4.5%0.9% - 2.7%
    Linearity (NGSP)± 7% across 4.0 to 14.0 %HbA1cPass (linear across 4.0 to 14.0 %HbA1c)
    Linearity (IFCC)± 7% across 20.02 to 129.34 mmol/mol HbA1cPass (linear across 20.02 to 129.34 mmol/mol HbA1c)
    HbF InterferenceRelative % Difference < 5%-15.42% to -15.33% at ~6.0% and ~9.0% HbA1c
    Other Hb Variants InterferenceRelative % Difference < 5%Pass (No significant interference observed)
    Method Comparison (r)≥ 0.950.9977 (Whole Blood), 0.9981 (Hemolysate)
    Method Comparison (Slope, NGSP)1.1 ± 0.100.974/0.987 (Passing-Bablok/Deming) for Whole Blood, 0.969/0.984 (Passing-Bablok/Deming) for Hemolysate
    Bias (NGSP)≤ 3% at 5.0, 6.5, 8.0, and 12.0 %HbA1c-2.40% to -2.50% (Whole blood, Passing-Bablok)
    Anticoagulant %Bias5%0.72-0.80% (Tripotassium EDTA), -0.51 - -0.42% (Sodium Fluoride/Disodium EDTA)
    Anticoagulant Slope1.0 ± 0.11.015/0.998 (Tripotassium EDTA), 1.006/0.995 (Sodium Fluoride/Disodium EDTA)
    Anticoagulant Correlation≥ 0.950.9992 (Tripotassium EDTA), 0.9994 (Sodium Fluoride/Disodium EDTA)

    2. Sample Size and Data Provenance

    • Precision:
      • 2 levels of controls and 4 levels of human whole blood pools.
      • Each assayed in 2 replicates at 2 separate times per day for 20 different days.
    • Analytical Sensitivity (LoB and LoD):
      • 5 blank samples and 5 low concentration samples.
      • Analyzed in quadruplicate for 3 days (total of 60 measurements per level).
      • Low concentration samples were dilutions of dipotassium EDTA venous whole blood.
    • Linearity/Reportable Range:
      • 11 levels configured as a dilution series by mixing high and low HbA1c dipotassium EDTA venous whole blood samples.
      • Samples run in quadruplicate.
    • Analytical Specificity (Interference):
      • All interferents and potential drug interferents tested at ~6.5% and 8.0% HbA1c concentrations in replicates of ten.
    • Hemoglobin Variants:
      • HbA2: 36 samples (4.1% - 6.2% abnormal variant, 4.06% - 10.0% HbA1c)
      • HbC: 14 samples (27.4% - 38.4% abnormal variant, 4.81% - 10.46% HbA1c)
      • HbD: 25 samples (19.6% - 40.0% abnormal variant, 4.79% - 12.62% HbA1c)
      • HbE: 22 samples (24.0% - 28.0% abnormal variant, 5.2% - 10.0% HbA1c)
      • HbF: 25 samples (4.4% - 29.3% abnormal variant, 5.1% - 12.8% HbA1c)
      • HbS: 15 samples (28.2% - 37.5% abnormal variant, 4.45% - 12.31% HbA1c)
    • Method Comparison with Predicate Device:
      • 130 dipotassium EDTA whole blood specimens.
      • Assayed over 5 operating days in duplicate.
    • Matrix Comparison:
      • 41 matched patient specimens.
      • Analyzed in duplicate.
    • Reference Range Verification:
      • 20 fresh blood samples from clinically healthy patients.
      • Tested in singlicate.

    Data Provenance: The document does not explicitly state the country of origin for the patient data used in these studies. The studies are non-clinical performance evaluations, conducted to support the device's substantial equivalence. The nature of the studies indicates a prospective collection for the purpose of device validation.

    3. Number of Experts and Qualifications for Ground Truth

    • Precision, Analytical Sensitivity, Linearity, Interferents, Matrix Comparison, Reference Range Verification: The ground truth for these studies is established by the methods, instrumentation, and protocols themselves (e.g., control values, dilution series, analytical measurements). No human experts are explicitly mentioned for establishing ground truth in these specific sections.
    • Hemoglobin Variants (Comparative Method): The HbA1c values for samples containing hemoglobin variants were compared to a "comparative method" which serves as the ground truth. The specific nature and qualifications of experts associated with this comparative method are not detailed.
    • Method Comparison (NGSP Secondary Reference Laboratory Method): The device's performance was compared to an "NGSP secondary reference laboratory method." The NGSP (National Glycohemoglobin Standardization Program) provides standardization and certification for HbA1c methods, implying that the reference lab adheres to established standards. However, the number of experts or their specific qualifications at this reference laboratory are not provided.

    4. Adjudication Method

    The document does not describe an adjudication method for a test set in the context of expert review. The studies are primarily analytical performance evaluations where results are compared against established analytical standards, reference methods, or statistical criteria.

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

    No MRMC comparative effectiveness study is mentioned. This device is an in vitro diagnostic assay, meaning its performance is evaluated based on its analytical accuracy and precision in measuring a biomarker, not on human reader interpretation of images or other subjective data. Therefore, the concept of "human readers improve with AI vs without AI assistance" is not applicable.

    6. Standalone (Algorithm Only) Performance

    Yes, the studies described are essentially a standalone evaluation of the SEKURE HbA1c Assay. The performance metrics (precision, linearity, bias, interference, method comparison) quantify the analytical capability of the assay system (reagents plus SK500 analyzer) independent of human interpretation of the results beyond the technical execution of the test.

    7. Type of Ground Truth Used

    • Precision: Internal control values and human whole blood pools with calculated means.
    • Analytical Sensitivity (LoB and LoD): Based on statistical analysis of blank and low-concentration measurements to determine the lowest detectable limit.
    • Linearity/Reportable Range: Based on theoretical expected values of a dilution series.
    • Traceability: Traceable to the International Federation of Clinical Chemistry (IFCC) reference calibrators and NGSP certification.
    • Analytical Specificity (Interference): Established by comparing results in the presence of interferents to control samples (without interferents).
    • Hemoglobin Variants: A "comparative method" for HbA1c measurement.
    • Method Comparison: An "NGSP secondary reference laboratory method" for HbA1c.
    • Matrix Comparison: Dipotassium EDTA whole blood (control tube) serves as the reference for comparison against other anticoagulants.
    • Reference Range Verification: A published "Reference Range for Adults" (Source: ROCHE - Reference Ranges for Adults, Pre-Analytical Considerations - 2008).

    8. Sample Size for the Training Set

    The document describes performance studies for the SEKURE HbA1c Assay, not the development or training of an AI algorithm. Therefore, there is no "training set" in the context of machine learning. The data presented are for validation of the assay's analytical performance.

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

    As there is no AI algorithm being trained, the concept of establishing ground truth for a training set is not applicable to this document. The ground truth for the validation studies is established as described in section 7.

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