(167 days)
The LIAISON® Lyme IgG assay uses chemiluminescent immunoassay (CLIA) technology for the qualitative detection of IgG antibodies to Borrelia burgdorferi in human serum and plasma specimens (K2-EDTA, Li-heparin). This assay is intended for use on samples from patients with signs and symptoms consistent with or patients suspected of having Lyme disease to assess the presence of IgG antibodies and exposure to Borrelia burgdorferi. In addition, the LIAISON® Lyme Ig G assay may be used as a confirmatory test in the modified two-tier test (MTTT) in combination with the DiaSorin LIAISON® Lyme Total Antibody Plus assay.
If used as a first stage test, positive or equivocal results with the LIAISON® Lyme IgG assay should be confirmed through additional testing with a Standard two-tier test (STT) methodology using an IgG Borrelia burgdorferi Western blot test following current guidelines.
Positive supplemental results are supportive evidence of the presence of antibodies and exposure to Borrelia burgdorferi and may be used along with patient history, symptoms and other laboratory data to support a clinical diagnosis of Lyme disease.
Negative results by the LIAISON® Lyme IgG assay should not be used to exclude Lyme disease.
The test must be performed on the LIAISON® XL Analyzer.
The DiaSorin LIAISON® Lyme IgG Control Set is intended for use as assayed quality control samples to monitor the performance of the LIAISON® Lyme IgG assay. The performance characteristics of LIAISON® Lyme IgG controls have not been established for any other assays or instrument platforms different from the LIAISON® XL.
The LIAISON® Lyme IgG assay is an indirect chemilyminescence immunoassay (CLIA) for the qualitative detection of IgG antibodies to Borrelia burgdorferi in human serum and plasma samples. All assay steps (with the exception of magnetic particle resuspension) and incubations are performed by the Analyzer. The principal components of the test are magnetic particles (solid phase) coated with recombinant Borrelia antigens and a conjugate reagent containing an anti-human IgG mouse monoclonal antibody linked to an isoluminol derivative (isoluminol-antibody coniugate). During the first incubation, anti-Borrelia burgdorferi antibodies present in calibrators, samples or controls bind to the solid phase. Unbound material is then removed with a wash cycle. During the second incubation, the antibody conjugate reacts with anti-Borrelia burgdorferi IgG antibodies that have bound to the solid phase. Excess antibody conjugate is then removed with a wash cycle. Subsequently, the starter reagents are added and a flash chemiluminescence reaction is induced. The light signal, and hence the amount of isoluminol-antibody conjugate, is measured by a photomultiplier as relative light units (RLU) and is indicative of the presence of Borrelia burgdorferi IgG antibodies present in calibrators, samples or controls.
Here's a breakdown of the acceptance criteria and study details for the LIAISON® Lyme IgG assay, based on the provided FDA 510(k) summary:
1. Table of Acceptance Criteria and Reported Device Performance:
The document implicitly defines acceptance criteria through its performance study results, specifically for percentage agreement (sensitivity and specificity) when compared to a predicate device and STTT/MTTT protocols.
Acceptance Criteria (Implicitly defined by performance targets in studies)
| Performance Metric | Acceptance Criteria (from study context) | Reported Device Performance (LIAISON® Lyme IgG) | Study Context |
|---|---|---|---|
| First Tier Agreement with Predicate Device (ZEUS ELISA B. burgdorferi IgG Test System) | |||
| Positive % Agreement | Implied high agreement (no specific % mentioned but demonstrated acceptability) | 55.1% (166/301) | Comparison to Predicate ELISA IgG |
| Negative % Agreement | Implied high agreement (no specific % mentioned but demonstrated acceptability) | 96.5% (2210/2320) | Comparison to Predicate ELISA IgG |
| Standard Two-Tier Testing Methodology (STTT - WB IgG) | |||
| 2nd Tier PPA (Positive Percent Agreement) | Implied high PPA | 89.0% (97/109) | Comparison to STTT WB IgG |
| 2nd Tier NPA (Negative Percent Agreement) | Implied high NPA | 99.5% (2500/2512) | Comparison to STTT WB IgG |
| Modified Two-Tier Testing Methodology (MTTT - Prospective Population - STTT WB IgG as GT) | |||
| PPA (Positive Percent Agreement) | Implied high PPA | 96.9% (93/96) | Comparison to STTT WB IgG |
| NPA (Negative Percent Agreement) | Implied high NPA | 30.2% (39/129) | Comparison to STTT WB IgG |
| Modified Two-Tier Testing Methodology (MTTT - Retrospective CDC Panel - STTT WB IgG as GT) | |||
| Sensitivity (Stage I) | Implied high Sensitivity | 80% | Comparison to STTT WB IgG |
| Sensitivity (Stage II) | Implied high Sensitivity | 90% | Comparison to STTT WB IgG |
| Sensitivity (Stage III) | Implied high Sensitivity | 100% | Comparison to STTT WB IgG |
| Specificity (Healthy Controls) | Implied high Specificity | 100% | Comparison to STTT WB IgG |
| Specificity (Disease Controls) | Implied high Specificity | 97.8% | Comparison to STTT WB IgG |
Note on Acceptance Criteria: The document does not explicitly state numerical acceptance criteria for each metric (e.g., "PPA must be >X%"). Instead, it presents the device's performance results and concludes substantial equivalence, implying that these results met the FDA's expectations for equivalence to legally marketed predicate devices.
2. Sample Size Used for the Test Set and Data Provenance:
- Method Comparison (First Tier and STTT):
- Sample Size: 2621 human serum specimens.
- Data Provenance: Collected in 14 states across five (5) distinct U.S. geographical regions. This was a prospective study ("All 2621 prospective (all comer) specimens").
- Modified Two Tier Testing Methodology (Prospective Population):
- Sample Size: 225 specimens (from the initial 2621 that were positive or equivocal by the first-tier assay).
- Data Provenance: U.S. geographical regions, prospective.
- Characterized Lyme Panel (CDC Panel):
- Sample Size: 280 samples.
- Data Provenance: Acquired from the CDC (Centers for Disease Control), making it a retrospective panel.
- Modified Two Tier Testing Methodology (Retrospective Population from CDC Panel):
- Sample Size: 279 samples (1 sample from the 280 CDC panel lacked sufficient volume). 82 of these were further tested with STTT WB IgG or MTTT.
- Data Provenance: CDC, retrospective.
- Cross-reactivity Study:
- Sample Size: 222 specimens (from 22 different disease states).
- Data Provenance: Not specified, but likely obtained from various sources or commercial vendors for specific disease states. Retrospective by nature of obtaining specific disease samples.
- Matrix Equivalence Study:
- Sample Size: 32 matched patient sets.
- Data Provenance: Not specified.
3. Number of Experts Used to Establish Ground Truth and Qualifications:
The document does not explicitly state the "number of experts" or their specific "qualifications" for establishing ground truth. However, the ground truth for some studies is based on established laboratory methods:
- For the Method Comparison and STTT/MTTT studies: The ground truth for confirming Borrelia burgdorferi infection or exposure is primarily established by Western blot testing (IgG Borrelia burgdorferi Western blot test) following current guidelines. This is a recognized laboratory "gold standard" or highly accepted confirmatory method for Lyme disease. While experts interpret WBs, the document doesn't detail the number or qualifications of individuals performing or interpreting these specific Western blots.
- For the Characterized Lyme Panel (CDC Panel): The samples were "characterized" by the CDC. This implies that the CDC itself, a leading public health agency with extensive expertise in infectious diseases, established the reference classification for these samples. The ground truth here is the CDC's reference classification, which would involve robust testing and expert consensus within the CDC, though specific expert numbers or qualifications are not provided in this submission summary.
4. Adjudication Method for the Test Set:
Not explicitly described in the document. The studies primarily compare the LIAISON® Lyme IgG assay results against either a predicate ELISA assay or Western Blot results (STTT/MTTT). There isn't mention of a separate adjudication process beyond the defined "ground truth" method (e.g., WB results).
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done:
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study, as typically understood for AI-assisted image analysis where human readers improve with AI vs without AI assistance, was not explicitly mentioned or performed. This device is an in-vitro diagnostic (IVD) assay designed to detect antibodies, not an AI-powered diagnostic imaging system requiring human interpretation with AI assistance. Its performance is measured directly against other laboratory tests or characterized panels.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done:
Yes, the performance studies described are essentially standalone evaluations of the LIAISON® Lyme IgG assay. The assay is an automated chemiluminescent immunoassay (CLIA) performed on the LIAISON® XL Analyzer. The results (Index values) lead to a qualitative positive, negative, or equivocal determination by the instrument's algorithm based on a predefined cutoff. There is no human-in-the-loop performance described in the context of interpreting the assay's primary output. Human involvement is in running the test and interpreting the final qualitative result provided by the system within a clinical context.
7. The Type of Ground Truth Used:
- Expert Consensus / Established Gold Standard:
- For the prospective and retrospective studies that compare the LIAISON® assay to STTT (Standard Two-Tier Test) or MTTT (Modified Two-Tier Test), the ground truth is primarily based on IgG Borrelia burgdorferi Western Blot testing following current guidelines. Western blot is generally considered the confirmatory "gold standard" for Lyme disease serology.
- For the "Characterized Lyme Panel" (from CDC), the ground truth is the CDC Reference Classification, which would be based on comprehensive testing and expert knowledge.
- Predicate Device Comparison: In the initial method comparison, the ground truth for calculating agreement percentages is the ZEUS ELISA B. burgdorferi IgG Test System (predicate device).
8. The Sample Size for the Training Set:
The document describes performance studies (method comparison, STTT, MTTT, cross-reactivity, precision, reproducibility, etc.) of the LIAISON® Lyme IgG assay. It does not explicitly mention a "training set" or "validation set" in the context of an algorithm or AI model development. The reported studies represent the testing and validation of the already developed assay.
- However, for the assay development process itself (not detailed in this summary), a training phase would typically occur during the R&D of the assay to establish optimal reagent concentrations, cut-offs, and assay parameters. This information is generally proprietary to the manufacturer and not typically included in a 510(k) summary unless the device is a novel AI/ML product.
- The calibration described ("Two-point verification (in triplicate) of stored 10 point master curve") indicates a specific calibration approach for the instrument, which would have been established during initial assay development using a set of characterized samples. The number of samples for developing this master curve is not provided.
9. How the Ground Truth for the Training Set Was Established:
As noted above, a distinct "training set" for an AI/ML algorithm is not described here, as this is an immunoassay. For the development of the assay itself (e.g., establishing optimal cut-offs), the ground truth would have been established using well-characterized samples from known Lyme disease patients and healthy controls, likely confirmed by established methods like Western blot and/or clinical diagnosis, similar to the methods used to establish the ground truth for the test sets presented. The specifics of this internal R&D process are not detailed in the FDA summary.
§ 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).