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510(k) Data Aggregation

    K Number
    K073490
    Date Cleared
    2008-02-11

    (61 days)

    Product Code
    Regulation Number
    866.5510
    Reference & Predicate Devices
    Predicate For
    AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP AuthorizedThirdpartyExpeditedreview
    Intended Use

    System reagent for the quantitative determination of IgG immunoglobulins in human serum, plasma and cerebrospinal fluid on OLYMPUS analyzers.
    The measurement of IgG aids in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents.
    For in vitro diagnostic use.

    Device Description

    In this Olympus procedure:
    When a sample is mixed with R1 buffer and R2 antiserum solution, human IgG reacts specifically with anti-human IgG antibodies to yield insoluble aggregates.
    Immune complexes formed in solution scatter light in proportion to their size, shape and concentration.
    Turbidimeters measure the reduction of incidence light due to reflection, absorption or scatter.
    In the Olympus procedure, the decrease in intensity of light transmitted (increase in absorbance) through particles suspended in solution is as a result of complexes formed during the antigen-antibody reaction.

    AI/ML Overview

    The provided document is a 510(k) summary for a medical device called "Olympus IgG Reagent (OSR6X172)". This is an in vitro diagnostic device, specifically a reagent used for quantitative determination of IgG immunoglobulins. The acceptance criteria and supporting studies are presented by comparing the new device's performance characteristics with those of predicate devices already on the market.

    1. Table of Acceptance Criteria and Reported Device Performance

    Since this is an in vitro diagnostic reagent rather than an imaging or AI-driven diagnostic device, the "acceptance criteria" are not framed in terms of metrics like sensitivity, specificity, or AUC, but rather in terms of demonstrating substantial equivalence to predicate devices through various performance characteristics. The acceptance criterion is generally that the new device's performance characteristics (e.g., precision, assay range, method comparison) are comparable to or better than the predicate's, and suitable for its intended use.

    Here's a table summarizing the reported device performance and comparison to predicate devices, acting as de-facto acceptance criteria for substantial equivalence:

    Serum/Plasma Applications

    CharacteristicAcceptance Criteria (Predicate)Olympus IgG (OSR6X172) Performance (New Device)Status
    Intended UseQuantitative determination of IgG immunoglobulins in human serum on OLYMPUS analyzers.Quantitative determination of IgG immunoglobulins in human serum, plasma and cerebrospinal fluid on OLYMPUS analyzers.Meets/Exceeds
    MeasurementQuantitativeQuantitativeMeets
    Instrument RequiredOlympus AU400/400e, 600/640/640e and 2700/5400SameMeets
    Reagent HandlingReady for useReady for useMeets
    MethodologyImmunoturbidimetricSameMeets
    Reagent Storage FormLiquid, On-board storageSameMeets
    CalibrationOlympus Serum Protein Multi-Calibrator (ODR3021)SameMeets
    Calibration TraceabilityTraceable to CRM 470 (RPPHS lot 91/0619)SameMeets
    AntibodyGoat Anti-IgG antiserumSameMeets
    Expected Values635-1741 mg/dLSameMeets
    Reagent On-Board Stability90 days when stored refrigerated on analyzer.SameMeets
    Calibration Frequency90 daysSameMeets
    Assay Range75-3000 mg/dL75-3000 mg/dL (same)Meets
    Specimen TypeSerumSerum, Li-heparin or EDTA plasma, and cerebrospinal fluidExceeds (New CSF app. included)
    LoQNot specified75 mg/dLSpecified/Meets
    Prozone CapacityNot specifiedNo high dose effect at IgG concentrations up to 30,000 mg/dL (Much higher than typical physiological range, demonstrating robustness)Exceeds
    Precision (Total CV%)AU400/400e: Samples 1,2,3 (0.82, 1.06, 2.24); AU600: Samples 1,2,3 (2.50, 1.54, 1.92); AU640/640e: Samples 1,2 (1.00, 1.00); AU2700/5400: Samples 1,2,3 (1.54, 2.39, 2.84)AU400/400e: Samples 1,2,3 (2.18, 2.29, 3.43); AU600/640/640e: Samples 1,2,3 (3.29, 3.49, 4.66); AU2700/5400: Samples 1,2,3 (1.51, 1.87, 2.03) (Comparably low CVs, indicating good precision, generally within acceptable lab limits for immunoassays)Meets
    Method Comparison (Linear Regression)Intercept: -117, Slope: 1.086, R2: 0.993, n: 98, Range: 223-2633 mg/dLIntercept: 37.2, Slope: 0.945, R2: 0.998, n: 120, Range: 195-2986 mg/dL (R^2 > 0.99 indicates excellent correlation)Meets
    Interfering SubstancesBilirubin (AU400/400e: <1% up to 40 mg/dL); Hemolysis (AU400/400e: <2% up to 500 mg/dL); Lipemia (AU400/400e: <10% up to 1000 mg/dL); RF (Not Specified); Ascorbic Acid (AU400/400e: <1% up to 20 mg/dL)Bilirubin (AU400/400e: <2% up to 40 mg/dL); Hemolysate (AU400/400e: <3% up to 500 mg/dL); Lipemia (AU400/400e: <3% up to 1000 mg/dL); RF (<7% up to 1200 IU/mL) (Comparable or improved interference tolerance)Meets/Exceeds

    CSF Application

    CharacteristicAcceptance Criteria (Predicate)Olympus IgG (OSR6X172) Performance (New Device)Status
    Intended UseQuantitative determination of IgG in human serum, plasma and cerebrospinal on Roche/Hitachi Cobas c systems.Quantitative determination of IgG immunoglobulins in human serum, plasma and cerebrospinal fluid on OLYMPUS analyzers.Meets
    MeasurementQuantitativeSameMeets
    Specimen TypeSerum, plasma, and cerebrospinal fluidSameMeets
    AntibodyGoat Anti-IgG antiserumSameMeets
    Instrument RequiredRoche/Hitachi Cobas c systems.Olympus AU400/400°, 600/640/640° and 2700/5400Different but specific
    Expected Values1-3 mg/dL15 – 20 y 3.5 mg/dL ± 2.0 mg/dL. 21 – 40 y 4.2 mg/dL ± 1.4 mg/dL. 41 – 60 y 4.7 mg/dL ± 1.0 mg/dL (Different value range, but provided with context of age, indicating physiological relevance)Meets
    Reagent On-Board Stability84 days when stored refrigerated.90 days when stored refrigerated in compartment of the analyzer.Exceeds
    Assay Range0.4-20 mg/dL2-50 mg/dL (Wider range for the new device)Exceeds
    LoQNot specified2 mg/dLSpecified/Meets
    Prozone CapacityNo high dose effect at IgG concentrations up to 100 mg/dLNo high dose effect at IgG concentrations up to 6,000 mg/dL (Significantly higher, indicating better robustness)Exceeds
    Precision (Total CV%)Samples 1,2: (2.1, 1.1)AU400/400e: Samples 1,2,3 (9.82, 4.08, 3.61); AU600/640/640e: Samples 1,2,3 (9.53, 3.67, 2.81); AU2700/5400: Samples 1,2,3 (10.24, 6.29, 3.83) (Comparably low CVs, indicating good precision, generally within acceptable lab limits for immunoassays)Meets
    Method Comparison (Linear Regression)Intercept: -0.17, Slope: 0.997, R2: 1.000, Range: 1.07-18.6 mg/dLIntercept: -0.069, Slope: 1.067, R2: 0.998, Range: 2.0-42.9 mg/dL (R^2 > 0.99 indicates excellent correlation)Meets
    Interfering SubstancesBilirubin (<10% up to 15 mg/dL); Hemolysis (<10% up to 200 mg/dL)Bilirubin (<10% up to 36 mg/dL); Hemolysis (<10% up to 500 mg/dL) (Improved interference tolerance)Exceeds

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

    • Serum/Plasma Method Comparison:
      • Sample Size (n): 120 samples for the new device study. The predicate had n=98.
      • Data Provenance: Not explicitly stated (e.g., country of origin). However, given the context of a 510(k) submission for the US market, it's typically assumed to be relevant clinical samples, likely from a US-based or similar regulated environment unless specified otherwise. No indication of retrospective or prospective.
    • CSF Method Comparison:
      • Sample Size (n): Not explicitly stated numbers for the new device in the table for CSF, but linear regression data is provided. The predicate's study data (R2=1.000) shows a range of 1.07-18.6 mg/dL indicative of using patient samples, but the 'n' is not mentioned.
      • Data Provenance: Not explicitly stated (e.g., country of origin, retrospective or prospective).
    • Precision: 3 samples (levels) were tested for each instrument platform (AU400/400e, AU600/640/640e, AU2700/5400) for both serum/plasma and CSF applications. These would typically be control materials or pooled patient samples.
    • Interfering Substances: Testing was conducted at specific concentrations of bilirubin, hemolysate, lipemia, and RF (for serum/plasma) or bilirubin and hemolysis (for CSF). The number of individual samples tested at these concentrations is not specified.

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

    This document describes the performance of an in vitro diagnostic reagent measuring a biochemical analyte (IgG). "Ground truth" in this context refers to the true concentration of IgG in the samples, which would usually be established by a reference method or a highly accurate, often predicate, measurement system. Expert consensus or interpretation (e.g., radiologists) is not applicable here. The "ground truth" for the method comparison studies is the result obtained from the predicate device or a recognized reference method.

    4. Adjudication Method for the Test Set

    Not applicable. As described above, this is for an in vitro diagnostic reagent, not a diagnostic imaging or AI-driven device requiring human adjudication of results. The performance is assessed by comparing quantitative results to a predicate device's results.

    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 in vitro diagnostic reagent, not an AI-assisted diagnostic device, and therefore does not involve human readers or MRMC studies.

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

    This device is a standalone diagnostic test in the sense that it performs a quantitative measurement on a biochemical analyzer without direct human interpretation of a complex output. The tables provided illustrate the performance of the reagent on various Olympus AU analyzers. This data directly represents the "algorithm only" performance (i.e., the reagent's performance on the specified instruments).

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

    The "ground truth" for the test set (method comparison) was obtained by running the same patient samples on the predicate device(s).

    • For Serum/Plasma, the predicate was "Olympus (OSR6145) IgG Reagent".
    • For CSF, the predicate was "Roche Tina-Quant IgG GEN.2".
      The precision and interference studies use contrived samples (e.g., spiked samples, control materials) where the "true" value or concentration is known or independently verified.

    8. The Sample Size for the Training Set

    Not applicable in the conventional sense of machine learning. This is a biochemical reagent, not a machine learning model. The "development" or "optimization" of the reagent would involve chemical formulation and analytical testing, not a "training set" in the AI context.

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

    Not applicable for a biochemical reagent. The formulation and performance characteristics of the reagent are established through standard chemical and biological assay development and validation practices.

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