(177 days)
VITROS Anti-HAV IgM Reagent Pack: For the in vitro qualitative determination of IgM antibody to hepatitis A virus (anti-HAV IgM) in human adult and pediatric serum or plasma (EDTA, heparin or citrate) using the VITROS ECi/ECiQ Immunodiagnostic System. The assay is indicated for testing specimens from individuals who have signs and symptoms consistent with acute hepatitis. Assay results in conjunction with other clinical information, may be used for the laboratory diagnosis of individuals with acute or recent hepatitis A.
VITROS Anti-HAV IgM Calibrator: For in vitro use in the calibration of the VITROS Immunodiagnostic System for the qualitative determination of IgM antibody to hepatitis A viral antigen (HAV) in human serum and plasma (EDTA, heparin or citrate.
VITROS Anti-HAV IgM Controls: For in vitro use in monitoring the performance of the VITROS Immunodiagnostic System when used for the detection of anti-HAV IgM.
The VITROS Immunodiagnostic System uses luminescence as the signal in the quantitative and semi-quantitative determination of selected analytes in human body fluids, commonly serum and plasma. Coated microwells are used as the solid phase separation system. The system is comprised of three main elements: The VITROS Immunodiagnostic Products range of immunoassay products (in this case the VITROS Immunodiagnostic Products Anti-HAV IgM Reagent Pack and the VITROS Immunodiagnostic Products Anti-HAV IgM Calibrators) and VITROS Immunodiagnostic Products High Sample Diluent B which are combined by the VITROS Immunodiagnostics System to perform the VITROS Anti-HAV IgM assay. The VITROS Immunodiagnostic System instrumentation, which provides automated use of the immunoassay kits. Common reagents used by the VITROS System in each assay. The VITROS Immunodiagnostic Products Signal Reagent and VITROS Immunodiagnostic Products Universal Wash Reagent.
The VITROS Anti-HAV IgM assay utilizes an antibody class capture assay design, for the measurement of IgM antibodies to hepatitis A antigen, in human serum or plasma. The assay involves dilution of the sample and the simultaneous reaction of IgM in the diluted sample with biotinylated mouse monoclonal anti-human IgM antibody. The immune complex is captured by streptavidin on the wells, unbound materials are removed by washing. Horseradish peroxidase (HRP)-labeled mouse monoclonal anti-HAV antibody that has been complexed with inactivated HAV antigen (conjugate) is then captured by anti-HAV specific IgM bound to the wells. Unbound material is removed by washing. Enzyme substrate is then added and bound HRP conjugate is measured by a luminescent reaction. He binding of HRP conjugate is indicative of the presence of anti-HAV IgM.
Here's a summary of the acceptance criteria and study details for the VITROS Immunodiagnostic Products Anti-HAV IgM assay, based on the provided document:
Acceptance Criteria and Device Performance
The document does not explicitly state pre-defined acceptance criteria in terms of specific sensitivity/specificity thresholds. Instead, it presents the "Summary of Performance" as the demonstration that the device is "safe and effective for the stated intended uses and is substantially equivalent to the cleared predicate devices."
The performance data presented serve as the evidence that the device meets an implied standard of effectiveness in line with its predicate.
| Metric | Reported Device Performance |
|---|---|
| Overall Positive Percent Agreement | 100.0% (32/32) among combined prospectively collected samples from individuals at high risk for hepatitis and/or with signs or symptoms of hepatitis. |
| Overall Negative Percent Agreement | 99.74% (1156/1159) among combined prospectively collected samples from individuals at high risk for hepatitis and/or with signs or symptoms of hepatitis. |
| Positive Agreement (Known Anti-HAV IgM Reactive) | 100.0% (77/77) of samples from subjects known to be anti-HAV IgM reactive. |
| Negative Agreement (Low-risk pediatric subjects) | 100.0% (110/110) of samples from pediatric subjects at low risk for hepatitis. |
| Precision | Total precision of a sample near the assay cutoff was 13.2%. |
| Interferent/Cross-Reactivity | A variety of common interferents and potential cross-reactive subgroups were tested, supporting that they do not interfere with the assay. |
| Expected Results (Healthy Individuals) | Determined from a US population residing in areas of high (Western, US) and low (Eastern US) HAV disease prevalence, representing typical demographics of age, gender, and race. (Specific values not provided, but implies the assay performs as expected in this population.) |
Study Details
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Sample Size Used for the Test Set and Data Provenance:
- Prospectively Collected Samples (High-Risk/Symptomatic):
- Positive: 32 samples
- Negative: 1159 samples
- Total: 1191 samples
- Provenance: Samples obtained in the U.S. and India. The study was multi-center.
- Known Anti-HAV IgM Reactive Samples: 77 samples. (Provenance not explicitly stated, but likely from clinical settings.)
- Low-Risk Pediatric Subjects: 110 samples. (Provenance not explicitly stated, but implies healthy pediatric population.)
- Prospectively Collected Samples (High-Risk/Symptomatic):
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Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications: Not explicitly stated in the provided document. The ground truth for hepatitis A IgM status would typically be established through a combination of clinical diagnosis, other reference laboratory tests (e.g., PCR, serology), and patient history. The document refers to "samples from subjects known to be anti-HAV IgM reactive," implying an established ground truth.
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Adjudication Method for the Test Set: Not explicitly stated. Given that it's an in vitro diagnostic assay, adjudication typically refers to the process of resolving discrepancies between the new device's results and the established ground truth. This is generally handled by the study design and statistical analysis method rather than a reader adjudication process.
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Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study: No, this type of study was not conducted. MRMC studies are typically for imaging or interpretive devices where human readers evaluate cases. This document describes an in vitro diagnostic assay, which does not involve human readers interpreting results in the same way. The comparative effectiveness assessment is against a predicate device and established ground truth.
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Standalone Performance: Yes, the described study assesses the standalone performance of the VITROS Anti-HAV IgM assay. The performance metrics (positive percent agreement, negative percent agreement) are purely based on the algorithm's output compared to the ground truth, without human intervention in the result determination process.
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Type of Ground Truth Used: The ground truth appears to be based on:
- Clinical Diagnosis/Known Status: For the prospectively collected samples, they were from "individuals at high risk for hepatitis and/or with signs or symptoms of hepatitis." For validation, "samples from subjects known to be anti-HAV IgM reactive" and "pediatric subjects at low risk for hepatitis" were used. This implies reliance on established clinical diagnoses, reference laboratory tests, and patient histories to classify samples as positive or negative for anti-HAV IgM.
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Sample Size for the Training Set: Not explicitly stated. The document focuses on the performance study (test set). For in vitro diagnostic devices, the "training set" might refer to samples used during the assay development and optimization phases, which are rarely detailed in 510(k) summaries unless they contribute directly to a specific algorithm's performance claim within the submission.
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How the Ground Truth for the Training Set Was Established: Not explicitly stated. As with point 7, details about development/training phases are not typically provided in this level of summary for IVD assays. It's presumed that standard methods for establishing HAV IgM status (e.g., reference assays, clinical correlation) would have been used during development.
§ 866.3310 Hepatitis A virus (HAV) serological assays.
(a)
Identification. HAV serological assays are devices that consist of antigens and antisera for the detection of hepatitis A virus-specific IgM, IgG, or total antibodies (IgM and IgG), in human serum or plasma. These devices are used for testing specimens from individuals who have signs and symptoms consistent with acute hepatitis to determine if an individual has been previously infected with HAV, or as an aid to identify HAV-susceptible individuals. The detection of these antibodies aids in the clinical laboratory diagnosis of an acute or past infection by HAV in conjunction with other clinical laboratory findings. These devices are not intended for screening blood or solid or soft tissue donors.(b)
Classification. Class II (special controls). The special control is “Guidance for Industry and FDA Staff: Class II Special Controls Guidance Document: Hepatitis A Virus Serological Assays.” See § 866.1(e) for the availability of this guidance document.