(184 days)
VITROS Anti-HAV Total Reagent Pack: For the in vitro qualitative detection of total antibody (IgG and IgM) to hepatitis A virus (anti-HAV) in human adult and pediatric serum and plasma (EDTA, heparin or citrate) using the VITROS ECi/ECiQ Immunodiagnostic System. The assay is indicated, in conjunction with other serological and clinical information, as an aid in the clinical laboratory diagnosis of individuals with acute or past hepatitis A virus infection, or as an aid in the identification of HAV-susceptible individuals prior to HAV vaccination. The detection of HAV-specific antibodies in human serum or plasma is laboratory evidence of acute or recent HAV infection.
VITROS Anti-HAV Total Calibrator: For in vitro use in the calibration of the VITROS Immunodiagnostic System for the qualitative detection of antibodies to hepatitis A virus (anti-HAV) in human serum and plasma (EDTA, heparin or citrate).
VITROS Anti-HAV Total Controls: For in vitro use in monitoring the performance of the VITROS Immunodiagnostic System when used for the detection of antibodies to Hepatitis A virus (anti-HAV).
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 Total Reagent Pack and the VITROS Immunodiagnostic Products Anti-HAV Total Calibrators) and VITROS Immunodiagnostic Products High Sample Diluent B which are combined by the VITROS Immunodiagnostics System to perform the VITROS Anti-HAV Total 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 System and common reagents are dedicated specifically for use only with the VITROS Immunodiagnostic Products range of immunoassay products. The VITROS Anti-HAV Total assay utilizes a competitive assay design for the measurement of antibody to HAV Total (IgG and IgM). The competitive assay technique is used which involves pre-incubation of anti-HAV in the sample with HAV antigen in the Assay Reagent followed by incubation with a Conjugate Reagent that contains biotinylated mouse monoclonal anti-HAV antibody and horseradish peroxidase (HRP)-labeled mouse monoclonal anti-HAV antibody. The immune complex is captured by streptavidin on the wells, unbound materials are removed by washing. The bound HRP conjugate is measured by a luminescent reaction. A reagent containing luminogenic substrates (a luminol derivative and a peracid salt) and an electron transfer agent, is added to the wells. The HRP in the bound conjugate catalyzes the oxidation of the luminol derivative, producing light. The electron transfer agent (a substituted acetanilide) increases the level of light produced and prolongs its emission. The light signals are read by the VITROS System. The binding of HRP is indicative of the absence anti-HAV antibody. The VITROS Immunodiagnostic Products Anti-HAV Total Controls is comprised of two levels of human plasma that have been targeted to produce negative or positive results when used with the VITROS Immunodiagnostic Products Anti-HAV Total assay.
Here's a breakdown of the acceptance criteria and study information for the VITROS Immunodiagnostic Products Anti-HAV Total assay, based on the provided 510(k) summary:
1. Table of Acceptance Criteria and Reported Device Performance
The 510(k) summary does not explicitly state pre-defined acceptance criteria in terms of numerical thresholds for positive percent agreement (PPA) and negative percent agreement (NPA). However, it reports performance metrics from a multi-center study. The implication is that these reported numbers met the internal standards for substantial equivalence.
| Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|
| High Positive Percent Agreement | 99.74% (Overall combined prospective samples) |
| High Negative Percent Agreement | 96.49% (Overall combined prospective samples) |
| Agreement with reference anti-HAV assay for IgM reactive samples | 96.1% (74/77 samples) |
| Acceptable Positive Percent Agreement for pediatric samples at low risk | 93.75% |
| Acceptable Negative Percent Agreement for pediatric samples at low risk | 97.85% |
| Precision | Less than 6.7% total precision |
| No substantial difference in precision between serum and plasma matrices | Assessed and supported |
| No interference from common interferents and potential cross-reactive subgroups | Assessed and supported |
2. Sample Sizes Used for the Test Set and Data Provenance
- Overall Multi-center Study: The specific total sample size for this study is not explicitly stated, but it involved "samples obtained in the U.S. and India from individuals at high risk for hepatitis and/or with signs or symptoms of hepatitis."
- Anti-HAV IgM Reactive Samples: 77 samples were tested against a reference assay.
- Pediatric Samples: The sample size for the pediatric study is not explicitly stated beyond the percentages reported.
- Provenance: Data was collected from the U.S. and India. The section states the study was "multi-center" and involved "combined prospective samples," indicating a prospective data collection. Additionally, plasma from healthy individuals from "US population residing in areas of high (Western, US) and low (Eastern US) HAV disease prevalence" was used to determine expected results.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The 510(k) summary does not provide information on the number of experts used or their qualifications for establishing ground truth for the test set. It mentions comparison to a "reference anti-HAV assay" and "subjects known to be anti-HAV IgM reactive" for some parts of the study, implying established diagnostic methods and clinical status were used as ground truth.
4. Adjudication Method for the Test Set
The 510(k) summary does not describe an adjudication method (like 2+1 or 3+1 consensus) for the test set. Ground truth appears to be based on "reference anti-HAV assay" results or known clinical status ("subjects known to be anti-HAV IgM reactive").
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
This information is not applicable as this device is an in vitro diagnostic (IVD) assay designed to detect antibodies, not an imaging or AI-assisted diagnostic tool for human readers. Therefore, an MRMC study and effect size for human reader improvement with AI are not relevant to this submission.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was Done
Yes, this was a standalone performance study of the VITROS Immunodiagnostic Products Anti-HAV Total assay. The device itself is an automated system for detecting antibodies, and its performance reported is its output, not an output requiring human interpretation of assisted results. The results (positive/negative) are directly generated by the device.
7. The Type of Ground Truth Used
The ground truth used in the studies appears to be a combination of:
- Reference Anti-HAV Assay: Explicitly mentioned for comparison where "the percent agreement was 96.1% (74/77) as three subjects were negative for HAV in the reference assay."
- Known Clinical Status: "samples from subjects known to be anti-HAV IgM reactive" and "pediatric subjects at low risk for hepatitis."
- Serological/Clinical Information: The intended use statement also refers to the assay as an "aid in the clinical laboratory diagnosis of individuals with acute or past hepatitis A virus infection," implying the results would be interpreted in conjunction with other patient data.
8. The Sample Size for the Training Set
The 510(k) summary does not mention a training set for this device. This is typical for an IVD assay where the "training" (development and optimization) would occur during the assay's design and formulation, rather than through a machine learning training set as seen with AI/ML devices. The studies described are performance validation studies.
9. How the Ground Truth for the Training Set Was Established
Since no training set is mentioned in the context of machine learning, there is no information provided on how ground truth for a training set was established.
§ 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.