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510(k) Data Aggregation

    K Number
    K201089
    Date Cleared
    2021-08-05

    (469 days)

    Product Code
    Regulation Number
    862.3350
    Reference & Predicate Devices
    Predicate For
    N/A
    AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP AuthorizedThirdpartyExpeditedreview
    Intended Use

    The ARK Lacosamide Assay is a homogeneous enzyme immunoassay intended for the quantitative determination of lacosamide in human serum on automated clinical chemistry analyzers. The measurements obtained are used in monitoring levels of lacosamide to help ensure appropriate therapy.

    Device Description

    The ARK Lacosamide Assay is a homogeneous enzyme immunoassay based on competition between drug in the specimen and lacosamide labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH) for binding to the antibody reagent. As the latter binds antibody, enzyme activity decreases. In the presence of drug from the specimen, enzyme activity increases and is directly related to the drug concentration. Active enzyme converts the coenzyme nicotinamide adenine dinucleotide (NAD) to NADH that is measured spectrophotometrically as a rate of change in absorbance. Endogenous serum G6PDH does not interfere with the results because the coenzyme NAD functions only with the bacterial enzyme used in the assay.

    The ARK Lacosamide Assay consists of reagents R1 anti-lacosamide polyclonal antibody with substrate and R2 lacosamide labeled with bacterial G6PDH enzyme.

    AI/ML Overview

    The provided text describes the ARK Lacosamide Assay, a homogeneous enzyme immunoassay for quantitative determination of lacosamide in human serum. This device is intended for monitoring lacosamide levels to ensure appropriate therapy. The substantial equivalence is demonstrated through comparative testing against a predicate device (ARKTM Topiramate Assay, K083799) and various performance characteristic studies.

    Here's a breakdown of the acceptance criteria and study details:

    1. Table of Acceptance Criteria and Reported Device Performance:

    Performance CharacteristicAcceptance CriteriaReported Device Performance
    Limit of Quantitation (LoQ)Acceptable inter-assay precision (<20% CV) and recovery (±15%)0.40 ug/mL, with CVs ranging from 3.4% to 5.0% and recoveries from 83.2% to 94.1% for tested concentrations.
    Measurement RangeN/A (Range established)0.40 - 24.00 µg/mL
    RecoveryWithin ±10% of expected sample concentrationRecoveries for various concentrations from 0.40 to 20.00 µg/mL were between 90.4% and 105.8%.
    LinearityPercent difference ±10% (for >1.00 µg/mL) or ≤0.20 µg/mL (for ≤1.00 µg/mL) between 1st and 2nd order regressed values.Linear relationship demonstrated between 0.40 and 25.00 µg/mL (y = 0.9998x - 0.0170). Differences within acceptable limits.
    Precision (Total CV)≤10% total CVFor controls and human serum samples, total CVs ranged from 3.9% to 4.5%.
    Interfering SubstancesMeasurement of lacosamide resulted in ≤10% errorAll tested interfering substances resulted in ≤10% error (recoveries ranging from 95.8% to 103.5%).
    Specificity (O-Desmethyl Metabolite)Not clinically significant (< 3.0% crossreactivity)Crossreactivity of O-desmethyl lacosamide metabolite was not clinically significant.
    Crossreactivity (Other Drugs)Recoveries within 10% of the expected levelRecoveries for 77 compounds ranged from 90.9% to 109.5%.
    Sample StabilityN/A (Stability demonstrated)Stable for at least 48 hours at room temperature, 28 days refrigerated, and 34 months frozen. Stable after 3 freeze/thaw cycles.
    Shelf-life StabilityN/A (Stability demonstrated)Up to 18 months when stored unopened at 2-8°C.
    On-Board StabilityN/A (Stability demonstrated)Up to 60 days on-board the instrument.
    Calibration Curve StabilityN/A (Stability demonstrated)Effective up to at least 14 days.
    Method Comparison (vs. LC-MS/MS)N/A (Correlation established)Slope: 1.01 (0.99 to 1.04), y-intercept: 0.03 (-0.10 to 0.15), r2: 0.98 (0.98 to 0.99)

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

    • LoQ: 40 replicates (8 replicates x 5 runs) for each of 3 concentrations. Data provenance is implied to be laboratory-generated (pooled human serum supplemented with lacosamide).
    • Measurement Range: Not a directly tested "test set" in terms of patient samples; rather, it refers to the range characterized by other studies like recovery and linearity.
    • Recovery: Not explicitly stated as a separate "test set" size for recovery studies, but involved adding concentrated lacosamide to pooled human serum. "Two analytical runs of three replicates of each sample were assayed."
    • Linearity: Dilutions of a 30.00 µg/mL lacosamide serum sample. "Two analytical runs of three replicates of each sample were assayed."
    • Method Comparison: 150 unaltered, human serum specimens. The data provenance is described as "human serum specimens" which implies retrospective clinical samples, but the country of origin is not specified. They are "not individually identifiable."
    • Precision: 160 replicates for each of 6 samples/controls (quadruplicate twice a day for 20 days). Implied laboratory-generated (tri-level controls and pooled human serum with lacosamide).
    • Interfering Substances: For each interfering substance, lacosamide was present at 2 concentrations (2.0 and 15.0 µg/mL). "Two analytical runs of three replicates of each sample (6 replicates total) were assayed." Implied laboratory-generated.
    • Specificity (O-Desmethyl Metabolite): Assayed lacosamide at 2 concentrations (2.00 and 15.00 µg/mL) in the absence and presence of the metabolite at 2 concentrations (5.0 and 30.0 µg/mL). Implied laboratory-generated.
    • Crossreactivity (Other Drugs): For each of 77 compounds, lacosamide was present at 2 concentrations (2.00 and 15.00 µg/mL). Implied laboratory-generated.
    • Sample Stability: Not a statistical "test set" but based on supporting data; implies samples stored under different conditions.

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

    • This device is an in vitro diagnostic assay that measures a chemical compound (lacosamide concentration). The "ground truth" for method comparison studies is established by a reference method, not by expert interpretation.
    • In the method comparison study, the ARK Lacosamide Assay results were compared against LC-MS/MS (Liquid Chromatography-Mass Spectrometry/Mass Spectrometry). LC-MS/MS is a highly accurate and sensitive analytical chemistry technique, often considered a "gold standard" for quantifying small molecules like drugs in biological matrices.
    • Therefore, no human experts were used to establish the ground truth; instead, an established analytical method served as the reference.

    4. Adjudication method for the test set:

    • Not applicable as the ground truth is established by a quantitative analytical method (LC-MS/MS), not by human interpretation or consensus.

    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 device is an in vitro diagnostic assay, not an AI-powered diagnostic imaging or interpretation tool that assists human readers.

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

    • Yes, the performance characteristics described (LoQ, Measurement Range, Recovery, Linearity, Precision, Interfering Substances, Specificity, Crossreactivity, Stability) are all standalone algorithm (assay) performance studies. The method comparison study also evaluated the standalone performance of the ARK Lacosamide Assay against LC-MS/MS.
    • The device explicitly states it is "intended for the quantitative determination of lacosamide in human serum on automated clinical chemistry analyzers," indicating standalone operation with human oversight rather than human-in-the-loop interpretation of complex data.

    7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):

    • For the method comparison study, the ground truth was "results from LC-MS/MS," which is a reference analytical method.
    • For other performance studies (LoQ, recovery, linearity, precision, interference, specificity, cross-reactivity), the ground truth was based on the known concentrations of lacosamide and interfering substances added to human serum samples.

    8. The sample size for the training set:

    • This is an in vitro diagnostic assay, not a machine learning or AI model that requires a "training set" in the conventional sense. The development of the assay's reagents and methodologies involves analytical chemistry and biochemical principles rather than statistical training on data.

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

    • Not applicable for the reasons stated in point 8. The "ground truth" for the development of this assay would be the accurate chemical characterization of lacosamide and its antibodies, and the optimization of the enzymatic reaction to accurately reflect lacosamide concentration.
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