LogoFDA 510(k) Search
K Number
K050590
Device Name
ENZY-WELL SYPHILIS IGG, MODEL 91106
Manufacturer
DIESSE DIAGNOSTICA SENESE S.P.A
Date Cleared
2006-08-10

(520 days)

Product Code
LIP
Regulation Number
866.3830
Type
Traditional
Panel
MI
Reference & Predicate Devices
N/A
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP AuthorizedThirdpartyExpeditedreview
Intended Use

ENZY-WELL SYPHILIS IgG is an immunoenzymatic method for the qualitative detection of IgG antibodies to Treponema pallidum in human serum by a manual technique. The test may be used in conjunction with non-treponemal testing to provide serological evidence of infection with T. pallidum. For in vitro diagnostic use only.

Device Description

ENZY-WELL SYPHILIS IgG is an immunoenzymatic method for the qualitative detection of IgG antibodies to Treponema pallidum in human serum/ plasma. The test may be used in conjunction with non-treponemal testing to provide serological evidence of infection with T. pallidum. The ENZY-WELL SYPHILIS IgG test is based on the ELISA technique (Enzyme-linked immunosorbent assay). Diluted patient sample is incubated in microplate wells coated with T. pallidum. During this incubation specific immunoglobulins, if present, bind to the antigen on the well. After washing, to eliminate unbound proteins, a second incubation is performed with the conjugate, composed of human IgG monoclonal antibodies labeled with peroxidase. After washing to remove unbound conjugate from the wells, the substrate is added, which will react to produce color in the presence of the peroxidase. An acidic solution is added to stop the reaction and the absorbance of the developed color is read at 450 nm

AI/ML Overview

Here's a summary of the acceptance criteria and the study details for the ENZY-WELL SYPHILIS IgG device, based on the provided document:

Acceptance Criteria and Device Performance

Acceptance Criteria CategorySpecific MetricAcceptance CriteriaReported Device Performance (ENZY-WELL SYPHILIS IgG)
Clinical PerformanceSensitivityNot explicitly stated as a numerical threshold, but implied to be high based on predicate comparison.100% agreement positive with CAPTIA Syphilis - G (for syphilitic sera), Clinical Sensitivity with FTA: 96.7% (Lab A).
SpecificityNot explicitly stated as a numerical threshold, but implied to be high based on predicate comparison.99.6% agreement negative with CAPTIA Syphilis - G (for negative sera), Analytical Specificity: 100% (Cross-reactivity study). Clinical Specificity with FTA: 88.4% (Lab A).
PrecisionWithin-run CV%CV lower than 15%Generally well within 15%, with a few exceptions (e.g., Neg serum2 on Day 2 Run 2, and some values for C and D in Lab A & B intra-run).
Between-run CV%Not explicitly stated as a numerical threshold, but implied to be low for consistency.Ranges from 2.5% to 21% (for positives) and up to NA for negatives (due to very low O.D.).
Interlaboratory CV%Not explicitly stated as a numerical threshold, but implied to be low for consistency.Ranges from 19% to 27% (for positives), and up to NA for negatives.
Cross-ReactivityInterferenceNo interferencesNo interferences shown, 100% analytical specificity. One HCV positive sample was reactive but confirmed positive by TPHA.

Study Details

  1. Sample sizes used for the test set and data provenance:

    • Clinical Sample Correlation (Primary Study):
      • First group (syphilitic sera): 125 samples (pediatric and adult, male and female patients). Data provenance not explicitly stated (e.g., country), but implied to be clinical. Retrospective/prospective not specified.
      • Second group (negative sera): 300 samples (150 from clinical sources/blood donors, 150 from normal donors). Data provenance not explicitly stated, but implied to be clinical. Retrospective/prospective not specified.
      • Third group (different pathologies): 100 samples (no known history/serological evidence of syphilis, suspected for other infective/clinical pathology). Data provenance not explicitly stated. Retrospective/prospective not specified.
    • Clinical Studies (Independent Labs): 387 specimens across two independent clinical laboratories (Lab B and Lab C).
    • Cross-Reactivity & Interference Studies: 332 sera with known diseases collected from a "seroteque" (implying retrospective sourcing).
    • Precision Studies: Various control and serum samples (number not detailed for each type beyond "3 replicates" for specific samples in each run/day experiment).

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

    • The document primarily relies on "comparative testing methods" and "confirmatory tests" (FTA-ABS, TPHA, VDRL) rather than direct expert consensus on raw data.
    • For the 'First group' of 125 syphilitic sera, it states "no disagreement between two comparative testing methods." This suggests at least two methods or interpretations were used, but not necessarily by human experts on individual cases.
    • For discordant results in the negative and pathological groups, confirmatory tests like FTA-ABS, TPHA, and VDRL were used. The interpretation of these confirmatory tests would likely be performed by qualified laboratory personnel, but the number and specific qualifications of such "experts" are not detailed.

  3. Adjudication method for the test set:

    • For the primary clinical sample correlation, disputes between the ENZY-WELL SYPHILIS IgG and the predicate device (CAPTIA Syphilis - G) were resolved using confirmatory tests like FTA-ABS, TPHA, and VDRL.
    • For the 10 discordant samples in the independent clinical study, a "third commercially available test" (referee test) was used, and it agreed with the Diesse test for 8 out of 10 samples.

  4. 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:

    • No, this device is an immunoassay (laboratory test kit), not an AI-assisted diagnostic device. Therefore, an MRMC study related to human readers improving with AI assistance is not applicable and was not performed.

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

    • Yes, the performance data presented is for the standalone performance of the ENZY-WELL SYPHILIS IgG immunoassay kit. It measures the qualitative detection of IgG antibodies directly from human serum/plasma. There is no "human-in-the-loop" component in the interpretive function of the device itself, although human laboratory technicians perform the assay.

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

    • Clinical Status: Ground truth was established based on clinical diagnosis of syphilis ("patients with syphilis") or confirmed negative status ("negative to Syphilis").
    • Confirmatory Tests: For validation and adjudication of discordant results, established laboratory confirmatory tests were used:
      • FTA-ABS (Fluorescent Treponemal Antibody Absorption)
      • TPHA (Treponema Pallidum Hemagglutination Assay)
      • VDRL (Venereal Disease Research Laboratory)

  7. The sample size for the training set:

    • This is an immunoassay kit, not a machine learning or AI model. Therefore, there isn't a traditional "training set" in the computational sense. The "development" of the assay involves optimizing reagents and conditions using internal samples, but these are not typically referred to as a "training set" in the context of device validation. The provided data focuses on the validation of the finalized kit.

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

    • As noted above, there is no explicit "training set" for an AI or machine learning model. The ground truth for the performance evaluation (test set) samples was established based on clinical diagnosis, serological history, and confirmatory laboratory tests (FTA-ABS, TPHA, VDRL).

§ 866.3830

Treponema pallidum treponemal test reagents.(a)
Identification. Treponema pallidum treponemal test reagents are devices that consist of the antigens, antisera and all control reagents (standardized reagents with which test results are compared) which are derived from treponemal sources and that are used in the fluorescent treponemal antibody absorption test (FTA-ABS), theTreponema pallidum immobilization test (T.P.I.), and other treponemal tests used to identify antibodies toTreponema pallidum directly from infecting treponemal organisms in serum. The identification aids in the diagnosis of syphilis caused by bacteria belonging to the genusTreponema and provides epidemiological information on syphilis.(b)
Classification. Class II (performance standards).