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.

Device Description

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.

AI/ML Overview

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

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.)
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.
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.
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.
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.
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.
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.
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.

Summary

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CONFIDENTIAL AND PROPRIETARY

SECTION 5: 510(k) SUMMARY

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

The assigned 510(k) number is: ڪرڪ 0 770

1 Submitter Name, Address and Contact

Ortho-Clinical Diagnostics, Inc. MC 881 100 Indigo Creek Drive Rochester. New York 14626-5101 (585) 453-3154

Contact Person: Sarah Parsons, RAC

2 Preparation Date

Date 510(k) prepared: March 20, 2006

3 Device Name

VITROS Immunodiagnostic Products Anti-HAV IgM Reagent Pack VITROS Immunodiagnostic Products Anti-HAV IgM Calibrators VITROS Immunodiagnostic Products Anti-HAV IgM Controls

Common Name: Anti-HAV IgM Assay Anti-HAV IgM Controls

Classification Name: Hepatitis A virus (HAV) serological assays (866.3310)

Single (specified) analyte controls (assayed and unassayed (862.1660

Assay Class: II special controls Controls Class: I

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4 Predicate Device

The VITROS Immunodiagnostic Products Anti-HAV IgM assay is substantially equivalent to the IMX HAVAB-M assay (PMA P790019).

The VITROS Immunodiagnostic Products Anti-HAV IgM Controls is substantially equivalent to Blackhawk BioSystems, Inc Virotrol III (K974613).

5 Device Description

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. The VITROS Immunodiagnostic System was cleared for market by a separate 510(k) pre-market notification (K962919).
Common reagents used by the VITROS System in each assay. The . VITROS Immunodiagnostic Products Signal Reagent and VITROS Immunodiagnostic Products Universal Wash Reagent were cleared as part of the VITROS Immunodiagnostic Products Total T3 Reagent Pack and VITROS Immunodiagnostic Products Total T3 Calibrators 510(k) premarket notification (K964310).

Note: High Sample Diluent B was cleared as part of the VITROS Immunodiagnostic Products Total β-hCG Reagent Pack and VITROS Immunodiagnostic Products Total ß-hCG Calibrators 510(k) premarket notification (K970894).

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The VITROS System and common reagents are dedicated specifically for use only with the VITROS Immunodiagnostic Products range of immunoassay products.

6 Device Intended Use

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.

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.

7 Comparison to Predicate Device

The VITROS Immunodiagnostic Products Anti-HAV IgM Reagent Pack and VITROS Immunodiagnostic Products Calibrators are substantially equivalent to Abbott IMX HAVAB-M assay which was cleared by FDA (P790019) for IVD use.

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The VITROS Immunodiagnostic Products Anti-HAV IgM Controls are substantially equivalent to Blackhawk BioSystems, Inc Virotrol III which was cleared by FDA (K974613) for IVD use.

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and the same of the same of the same of the same of the same of the same of

Comparison of the VITROS Immunodiagnostic Products Table 1 Anti-HAV IgM assay to the IMX HAVAB-M assay: Similarities

Similarities
DeviceCharacteristic	New Device	Predicate Device
Intended Use	For the qualitativedetermination of IgMantibody to hepatitis Avirus (anti-HAV IgM)...	For the qualitativedetermination of specificIgM antibody againsthepatitis A virus (IgM Anti-HAV)
Basic principle	Enzyme Linked ImmunoAssay	Enzyme Linked ImmunoAssay
Antigen	Hepatitis A virus	Hepatitis A virus
Antibody	Monoclonal antibody:Mouse anti-HAV	Monoclonal antibody:Mouse anti-HAV
Instrumentation	ECI/ECIQImmunodiagnosticSystem: Automatedanalyzer	IMX System: Automatedanalyzer
Sample type	Serum, plasma (heparin,citrate, EDTA)	Serum, plasma (heparin,citrate, EDTA)

Table 2 Comparison of the VITROS Immunodiagnostic Products Anti-HAV IgM assay to the IMX HAVAB-M assay: Differences

Differences
DeviceCharacteristic	New Device	Predicate Device
Antibody	Mouse anti-Human IgM	Goat anti-Human IgM
Tracer	Horseradish Peroxidase	Alkaline Phosphatase
Sample volume	10µL	150µL

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Table 3 Comparison of the VITROS Immunodiagnostic Products Anti-HAV IgM Controls to the Blackhawk BioSystems, Inc Virotrol III Controls: Similarities

Similarities
DeviceCharacteristic	New Device	Predicate Device
Intended Use	For in vitro use inmonitoring theperformance of theVITROSImmunodiagnosticSystem when used forthe detection of anti-HAV IgM.	... determination ofimmunoglobulin Mantibodies to Hepatitis AVirus (HAV-IgM)...
Matrix of controls	Human plasma andantimicrobial agents	Human serum with addedhuman proteins andantimicrobial agents
Control level	Positive and negative	Positive

Table 4 Comparison of the VITROS Immunodiagnostic Products Anti-HAV IgM Controls to the Blackhawk BioSystems, Inc Virotrol III Controls: Differences

Differences
DeviceCharacteristic	New Device	Predicate Device
Intended use	Only Anti-HAV IgM isdetected in the positivecontrol.	Both anti-HAV and anti-HBV IgM antibodies areincluded in the control
Expected values	Each control has aquoted mean valuederived from a minimumof 10 assays and astandard deviationanticipated for singledeterminations of eachcontrol in a number ofdifferent laboratoriesusing different reagentlots. Values are lotspecific.	There is no assigned value.The VIROTROL IIIreagents have been designedto produce a positivereaction when used in theproper manner with manycommercial test kits. Levelsof reactivity and specificperformance characteristicswill vary with differentmanufacturers' kits andassay procedures.

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Summary of Performance

Precision was tested across three sites demonstrating total precision of a sample near the assay cutoff to be 13.2%. Precision of serum and plasma were also assessed supporting that there is no substantial difference based on samples matrix. A variety of common interferents and potential cross reactive subgroup were tested supporting that the samples do not interfere with the assay.

Expected results of the VITROS Anti-HAV IgM assay to detect IgM in presumably healthy individuals were determined from a US population residing in areas of high (Western, US) and low (Eastern US) HAV disease prevalence. The population represented the typical demographics of age, gender and race representative of the United States.

A multi-center study was conducted to establish the performance characteristics of the VITROS Anti-HAV IgM assay using samples obtained in the U.S. and India from individuals at high risk for hepatitis and/or with signs or symptoms of hepatitis.

The overall positive percent agreement among the combined prospectively collected samples was 100.0% (32/32). The overall negative percent agreement was 99.74% (1156/1159).

The VITROS Anti-HAV IgM assay was also positive in 100.0% (77/77) of samples from subjects known to be anti-HAV IgM reactive, and negative in 100.0% (110/110) of samples from pediatric subjects at low risk for hepatitis.

8 Conclusions

The data presented in the premarket notification provide a reasonable assurance that the VITROS Anti-HAV IgM assay and VITROS Anti-HAV IgM controls are safe and effective for the stated intended uses and is substantially equivalent to the cleared predicate devices.

The VITROS Immunodiagnostic Products Anti-HAV IgM assay was compared to the Abbott IMX HAVAB-M assay testing commercially available reagents and human samples.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/7/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle or bird-like figure with three curved lines forming its body and wings. The logo is surrounded by the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" in a circular arrangement.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

EP 1 5 2006

Ms. Sarah CV Parsons Manager, Regulatory Affairs Ortho-Clinical Diagnostics, Inc. 100 Indigo Creek Drive MC0881 Rochester, NY 14626-5101

K060770 Re:

Trade/Device Name: VITROS Immunodiagnostic Products Anti-HAV IgM Reagent Pack VITROS Immunodiagnostic Products Anti-HAV IgM Calibrators VITROS Immunodiagnostic Products Anti-HAV IgM Controls Regulation Number: 21 CFR 866.3310 Regulation Name: Hepatitis A virus (HAV) serological assays Regulatory Class: Class II Product Code: LOL Dated: August 3, 2006 Received: August 4, 2006

Dear Ms. Parsons:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240)276-0450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.

Sincerely yours,

Sally, attorn

Sally A. Hojvat, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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SECTION 4: INDICATIONS FOR USE STATEMENT

Page 1 of 1

260770 510(k) Number (if known):

Device Name:

VITROS Immunodiagnostic Products Anti-HAV IgM Reagent Pack VITROS Immunodiagnostic Products Anti-HAV IgM Calibrators

VITROS Immunodiagnostic Products Anti-HAV IgM Controls

Indications for Use:

VITROS Anti-HAV IgM Reagent Pack:

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

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.

Prescription Use _____________________________________________________________________________________________________________________________________________________________ (Per 21 CFR 801 Subpart D)

AND/OR Over-The-Counter Use _ (21 CFR 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

Ortho-Clinical Diagnostics, Inc.	Section 4, Page 1 of 1	March 20
510(k)	K060770

0, 2006

Regulation Number and Section

§ 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.