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510(k) Data Aggregation

    K Number
    DEN150035
    Device Name
    SEEKER System
    Manufacturer
    Date Cleared
    2017-02-03

    (548 days)

    Product Code
    Regulation Number
    862.1488
    Type
    Direct
    Reference & Predicate Devices
    N/A
    Why did this record match?
    Device Name :

    SEEKER System

    AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP AuthorizedThirdpartyExpeditedreview
    Intended Use

    The SEEKER System, including the SEEKER Instrument and the SEEKER LSD Reagent Kit-IDUA|GAA|GBA|GLA for use on the SEEKER Instrument, is intended for quantitative measurement of the activity of a-L-iduronidase, a-D-glucosidase, Bglucocerebrosidase and a-D-galactosidase A from newborn dried blood spot specimens as an aid in screening newborns for Mucopolysaccharidosis Type I, Pompe, Gaucher and Fabry diseases. Reduced activity of these enzymes may be indicative of these lysosomal storage diseases. The enzymes measured using the SEEKER LSD Reagent Kit-IDUA|GAA|GBA|GLA and their associated lysosomal storage diseases are listed below.

    Enzyme (abbreviation)Disease
    α-L-iduronidase (IDUA)Mucopolysaccharidosis Type I (MPS I)
    α-D-glucosidase (GAA)Pompe
    β-glucocerebrosidase (GBA)Gaucher
    α-D-galactosidase A (GLA)Fabry
    Device Description

    The SEEKER System employs digital microfluidic technology to measure multiple lysosomal enzymatic activities quantitatively from newborn dried blood spot specimens. The following components are provided:

      1. SEEKER Instrument (including USB and power cables), Desktop PC with monitor, keyboard, mouse, and the Spot Logic software.
      1. SEEKER LSD Reagent Kit IDUA|GAA|GBA|GLA containing enzyme specific substrate reagents, dried blood spot extraction buffer, reaction stop buffer, 4 levels of calibrators and quality control dried blood spots containing 4 levels of quality control (OC) material. Each Reagent Kit contains sufficient consumables for 1440 tests. The contents of the kit are listed below:
    ComponentContentsQuantity
    Quality control
    dried blood spotsQC-Base Pool (QCBP)1x15 spots
    QC-Low (QCL)1x15 spots
    QC-Medium (QCM)1x15 spots
    QC-High (QCH)1x15 spots
    Enzyme substratesIDUA9x100 µL
    GAA9x100 µL
    GBA9x100 µL
    GLA9x100 µL
    CalibratorsCalibrant A (CALA)9x50 µL
    Calibrant B (CALB)9x50 µL
    Calibrant C (CALC)9x50 µL
    Calibrant D (CALD)9x50 µL

    Other components needed to run tests include the following:

    ComponentContentsQuantity
    Other ReagentsExtraction Buffer (EXT)9 x 30 mL
    Filler Fluid9 x 10 mL
    CartridgeSEEKER cartridge1 x 36

    The composition of the enzyme reagents and buffers are summarized below:

    Reagent (Description)Composition
    IDUA
    (α-L-iduronidase substrate)2 mM 4-MU-α-L-iduronide sodium salt
    3mM D-saccharolactone
    0.04 M acetate buffer, pH 3.5
    20 mM methyl β-cyclodextrin
    0.01% Tween20
    GAA
    (α-D-glucosidase substrate)5 mM 4-MU-α-glucopyranoside
    12 µM acarbose
    0.04 M acetate buffer, pH 3.8
    20 mM methyl β-cyclodextrin
    0.01% Tween20
    GBA
    (β-glucocerebrosidase substrate)16 mM 4-MU-β-glucopyranoside
    0.05 M/0.1M citrate phosphate buffer, pH 5.2
    0.01% Tween20
    1.5% sodium taurocholate
    GLA
    (α-D-galactosidase A substrate)10 mM 4-MU-α-galactopyranoside
    145 μM N-acetyl galactosamine
    0.04 M acetate buffer, pH 4.6
    20 mM methyl β-cyclodextrin
    0.01% Tween20
    Stop Buffer STB
    (reaction stopping buffer)0.6 M NaHCO3, pH 11.0 in 0.04% Tween 20
    Extraction Buffer EXT
    (dried blood spot extraction buffer)0.1% Tween 20 in water
    Filler Fluid
    (medium for droplet movement)0.1% Triton X-15 in 5cSt silicone oil

    The Seeker Calibrators are supplied as part of the SEEKER LSD Reagent Kit -IDUA|GAA|GBA|GLA. The calibrators consist of 4 levels of aqueous preparation of 4methylumbelliferone sodium salt (4-MU) in 0.6M sodium bicarbonate buffer, pH 11.0 with 0.01% Tween 20. The concentration of 4-MU in each of the 4 calibrators is indicated in the table below:

    Calibrator LevelConcentration of 4-MU
    Calibrant A (CAL A)0.0375 µM
    Calibrant B (CAL B)0.0750 µM
    Calibrant C (CAL C)0.1500 µM
    Calibrant D (CAL D)0.3000 µM

    The quality control dried blood spots include 4 levels of control material: OC Low (QCL), QC Medium (QCM) and QC High (QCH). The composition of the 4 quality control dried blood spot (DBS) is summarized below. QCBP is used to fill empty wells on a cartridge.

    Quality Control LevelComposition
    QCBPHeat inactivated human serum, adjusted to ~50% hematocrit
    using human red blood cells
    QCL5% cord blood and 95% heat inactivated serum, adjusted to
    ~50% hematocrit using human red blood cells
    QCM50% cord blood and 50% heat inactivated serum adjusted to
    ~50% hematocrit using human red blood cells
    QCHHuman umbilical cord blood, adjusted to ~50% hematocrit
    using human red blood cells

    The enzymatic activity values for the quality control DBS measured by the manufacturer are given on the lot specific quality control certificate included in each assay kit for all levels except QCBP. Each laboratory should establish its own mean and acceptable ranges for the quality control materials.

    3. SEEKER Cartridges

      1. Finnipipette Novus 8-channel automatic pipette 1-10 uL
      1. Finnipipette Novus 1-channel automatic pipette 10-100 uL
    AI/ML Overview

    The SEEKER System is a device designed for quantitative measurement of the activity of α-L-iduronidase (IDUA), α-D-glucosidase (GAA), β-glucocerebrosidase (GBA), and α-D-galactosidase A (GLA) from newborn dried blood spot specimens. This serves as an aid in screening newborns for Mucopolysaccharidosis Type I (MPS I), Pompe, Gaucher, and Fabry diseases.

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

    1. Acceptance Criteria and Reported Device Performance

    The acceptance criteria for the SEEKER System are implicitly defined by the analytical and clinical performance standards required for its De Novo classification as a Class II device with special controls. These controls mandate thorough demonstration of performance characteristics, including clinical validity, reference intervals, carry-over, detection limits, and imprecision. The clinical validity is primarily demonstrated by the false positive and false negative rates observed in the pivotal clinical study.

    Table: Acceptance Criteria (Implied by Regulatory Requirements) and Reported Device Performance

    Performance CharacteristicAcceptance Criteria (Implied)Reported Device Performance (Pivotal Phase Study)Notes
    Clinical Validity (False Positive Rate)Acceptable false positive rates to minimize unnecessary confirmatory testing and emotional burden.IDUA: 0.035%
    GAA: 0.092%
    GBA: 0.047%
    GLA: 0.097%These rates are considered acceptable, particularly given the benefits of early detection and the fact that newborns with "presumed normal" results after risk assessment were not followed up, potentially leading to an overestimation of the false positive rate.
    Clinical Validity (False Negative Rate)Acceptable false negative rates to ensure affected newborns are detected and receive timely therapy.IDUA: 0%
    GAA: 0%
    GBA: 0%
    GLA: 0% (Note: 2 newborns that would have been FN at 7.0µmol/L/hr cutoff were TP at 8.0µmol/L/hr cutoff. Labeling specifies known limitations for female Fabry and late-onset Pompe).The reported 0% false negative rate for IDUA, GAA, and GBA is based on active surveillance and the assumption that early-onset cases would be reported. However, some limitations are disclosed in the labeling, acknowledging potential false negatives due to clinical variability (e.g., late-onset Pompe, female Fabry patients). The adjustment of cutoffs over time also indicates complexities in achieving a perfect 0% FN rate. The note about GLA false negatives suggests that the 0% reported might be dependent on the specific cutoff used at the time.
    Imprecision (Reproducibility)Reproducibility across different instruments, reagent lots, and days, within acceptable limits.
    (No explicit %CV target stated, but general medical device standards suggest low CVs for reliable quantitative assays).IDUA: 14.2% - 28.5% CV (depending on concentration)
    GAA: 12.0% - 17.0% CV
    GBA: 15.7% - 38.0% CV
    GLA: 9.4% - 16.3% CVThese CVs are generally considered acceptable for screening assays, especially at lower concentrations where biological variability or technical limitations might be higher. The CLSI EP5-A3 guideline was followed.
    Linearity/Reportable RangeLinear response over the intended measurement range, covering normal and disease-associated values.IDUA: 2.77 to 50.75 µmol/L/h
    GAA: 2.18 to 94.66 µmol/L/h
    GBA: 2.14 to 73.24 µmol/L/h
    GLA: 4.88 to 153.74 µmol/L/h. Max deviation from linearity 88 mg/mL and hematocrit at 66% caused significant negative bias; heparin increased imprecision.Generally good, but specific interferences identified for IDUA (high protein, high hematocrit, heparin) are crucial for laboratories to consider. These are included in the package insert.
    Carry-overDemonstrate minimal or no significant impact from carry-over.Most assays showed minimal bias (
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