K Number

Device Name

LIAISON HAV IGM ASSAY, LIAISON CONTROL HAV IGM

Manufacturer

DIASORIN, INC.

Date Cleared

2008-11-03

(108 days)

Product Code

LOL PRE

Regulation Number

866.3310

Intended Use

The LIAISON® HAV IgM assay is an in vitro chemiluminescent immunoassay intended for the qualitative detection of IgM antibodies to hepatitis A virus (IgM anti-HAV) in human serum and sodium heparin plasma using the LIAISON® Analyzer. Assay results, in conjunction with other serological and clinical information, may be used for testing specimens from individuals who have signs and symptoms consistent with acute hepatitis as an aid in the laboratory diagnosis of acute or recent HAV infection. This assay is not intended for screening blood or solid or soft tissue donors. Assay performance characteristics have not been established for immunocompromised or immunosuppressed patients. The user is responsible for establishing their own assay performance characteristics in these populations. The LIAISON® Control HAV IgM (negative and reactive) is intended for use as assayed quality control samples to monitor the performance of the LIAISON® HAV IgM assay.

Device Description

The method for qualitative determination of HAV IgM is an antibody capture chemiluminescence immunoassay (CLIA). IgG to human IgM (mouse monoclonal) is used for coating magnetic particles (solid phase) and a mouse monoclonal antibody to HAV is linked to an isoluminol derivative (isoluminol-antibody conjugate). During the first incubation, IgM antibodies present in calibrators, samples or controls bind to the solid phase. During the second incubation, the antibody conjugate reacts with HAV antigen just added and the immune complex thus formed reacts with IgM already bound to the solid phase. After each incubation, the unbound material is removed with a wash cycle. Subsequently, the starter reagents are added and a flash chemiluminescence reaction is thus 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 anti-HAV IgM present in calibrators, samples or controls.

More Information

Contact

Type

Center

Panel

Date Received

Product Code

Subsequent Product Codes

Applicant Name (Manufacturer)

Device Name

Decision

Street 1

Street 2

City

State

Country Code

ZIP

Postal Code

Class Advise Committee

SSP Indicator

Third Party Reviewed

Expedited Review

Predicate Devices

P890014/S002

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The summary describes a standard chemiluminescent immunoassay (CLIA) for detecting antibodies. There is no mention of AI, ML, or any computational methods beyond basic signal processing and data analysis for calculating results and performance metrics.

Therapeutic

No.
The device is an in vitro diagnostic immunoassay intended for the qualitative detection of IgM antibodies to hepatitis A virus, aiding in the laboratory diagnosis of acute or recent HAV infection. It is used for diagnostic purposes and does not provide therapy.

Diagnostic

Yes

The Intended Use / Indications for Use section states that the device's results "may be used for testing specimens from individuals who have signs and symptoms consistent with acute hepatitis as an aid in the laboratory diagnosis of acute or recent HAV infection." This explicitly indicates its role as a diagnostic aid.

SaMD (Software as a Medical Device)

The device description clearly outlines a chemiluminescent immunoassay (CLIA) method involving magnetic particles, antibodies, and a chemiluminescence reaction measured by a photomultiplier. This involves physical reagents and hardware components, not just software.

IVD (In Vitro Diagnostic)

Yes, this device is an IVD (In Vitro Diagnostic).

Here's why:

Intended Use: The "Intended Use / Indications for Use" section explicitly states that the assay is "in vitro" and intended for the qualitative detection of IgM antibodies to hepatitis A virus in human serum and sodium heparin plasma. This directly aligns with the definition of an in vitro diagnostic device, which is used to examine specimens taken from the human body to provide information for diagnosis, monitoring, or screening.
Device Description: The description details a laboratory-based assay method (chemiluminescent immunoassay) performed on a specific analyzer (LIAISON® Analyzer) using biological samples (serum and plasma). This further confirms its nature as a laboratory diagnostic test.
Performance Studies: The document describes clinical trials and studies evaluating the performance of the assay using human samples, which is typical for IVD devices undergoing regulatory review.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

This assay is not intended for screening blood or solid or soft tissue donors. Assay performance characteristics have not been established for immunocompromised or immunosuppressed patients. The user is responsible for establishing their own assay performance characteristics in these populations.

The LIAISON® Control HAV IgM (negative and Reactive) is intended for use as assayed quality control samples to monitor the performance of the LIAISON® HAV IgM assay.

Product codes (comma separated list FDA assigned to the subject device)

LOL

Device Description

Subsequently, the starter reagents are added and a flash chemiluminescence reaction is thus 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 anti-HAV IgM present in calibrators, samples or controls.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Not Found

Indicated Patient Age Range

Not Found

Intended User / Care Setting

Not Found

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

Not Found

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

COMPARATIVE CLINICAL TRIALS: Prospective and Retrospective studies were performed to evaluate the performance of the LIAISON® HAV IgM assay among individuals who were sent to the lab for Hepatitis A testing and those at high risk for viral hepatitis.

The prospective study consisted of 500 samples from Individuals who were sent to the lab for HAV testing, 239 individuals at risk for viral hepatitis, and 108 Pediatric patients. The retrospective study consisted of 123 samples from individuals with an Acute Hepatitis A infection including 42 pediatric patients with an acute infection.

Prospective:
Individuals sent to the Lab for HAV testing: 500 samples collected from the Northeastern US. 59.8% female (n=299) ranging in age from 20 - 101 yrs. and 40.2% male (n=201) ranging in age from 17 to 89.
Individuals At Risk for Viral Hepatitis: 239 individuals from homosexual males (n=38), healthcare workers (n=10), commercial sex workers (n=34), drug users (n=77), prison inmates (n=49), dialysis patients (n=25) and hemophiliacs (n=6). 29.7% females (n=71), ranging in age from 17 to 79, and 43.1% males (n=103) ranging in age from 16 to 79. Age and gender unknown for remaining 27.2% (n=65).
Table 1: Combined populations (739 total samples) compared to Comparator ELISA.
Negative Percent Agreement: 738/739 (99.9%) with Exact 95% Confidence Interval: 99.4 – 100%.

Pediatric Population: 108 prospectively collected pediatric samples from the United States. 57.4% female (n=62) and 42.6% male (n=46), ranging in age from 2 to 17.
Table 2: Pediatric Population (108 total samples) compared to Comparator ELISA.
Negative Percent Agreement: 108/108 (100%) with Exact 95% Confidence Interval: 97.3 — 100%.

Acute HAV Infection (Retrospective): 123 samples from individuals with an (Acute) HAV infection. 42 acute pediatrics from children in Egypt. 32.5% females (n=40) ranging in age from 4 to 51, 51.2% males (n=63) ranging in age from 4 to 51. 15.5% age and gender unknown. One sample (0.8%) age 18, gender unknown.
Table 3: Acute HAV Infection (123 total samples) compared to Comparator ELISA.
Reactive Percent Agreement: 119/123 (96.7%) with Exact 95% Confidence Interval: 92.7 - 98.9%.

Conclusion: The LIAISON® HAV IgM assay showed equivalent performance to the FDA approved comparison method. The LIAISON® HAV IgM demonstrated overall agreement with the Comparator ELISA as follows:
Prospective Population "At Risk" and "HAV Testing" - 99.9% (95% Cl = 99.1 - 100%)
Pediatric Population - 100.0% (95% Cl = 97.3 - 100%)
Retrospective Population Acute HAV Infection - 96.7% (95% Cl = 92.7 - 98.9%)

The results demonstrate that the LIAISON® HAV IgM assay can be used with the LIAISON® Analyzer for the qualitative detection of IgM antibodies to hepatitis A virus.

SEROCONVERSION PANEL: Analytical Sensitivity as Seroconversion Panel Performance. Five commercially available HAV seroconversion panels were tested using LIAISON® HAV IgM and the FDA approved comparator assay.
The sensitivity of the LIAISON® HAV IgM was equivalent to or more sensitive than the comparator assay in the five seroconversion panels tested.

REPRODUCIBILITY: A 5 day reproducibility/precision study was conducted at three external laboratories. CLSI document EP15-A2 was consulted.
A coded panel comprised of 12 frozen "engineered" serum samples was prepared by DiaSorin S.p.A. and provided to the sites. The coded panel samples were prepared by spiking reactive samples into negative sample to achieve high negative, low reactive and high reactive results. The two negative panel samples were not spiked. The LIAISON® Control HAV IgM set were also included in the 5 day study.
Table 4 (combined sites): Mean Index value, standard deviation, and coefficient of variation (%CV) for each tested specimen.
Overall CV ranged from 10.7% to 54.2% for controls and 12.6% to 23.5% for samples.

CROSS-REACTIVITY: Evaluated potential interference from other viruses, organisms, and conditions.
195 samples representing various organisms/conditions (EBV, CMV, Rubella, Measles, Mumps, HBV, HCV, VZV, HSV, HIV, Toxoplasma gondii, rheumatoid factor, ANA, HAMA, etc.) were tested.
All 195 samples showed Negative results for LIAISON® HAV IgM.

POTENTIALLY INTERFERING SUBSTANCES: Controlled studies were performed.
Highest concentrations considered not to impact results:

Hemolysis: 1000 mg/dL hemoglobin
Lipemia: 3000 mg/dL triglycerides
Icterus: 20 mg/dL bilirubin
Serum albumin: 5 g/dL
Gamma-Globulin: 4 g/dL

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Negative Percent Agreement: 99.9% (95% Cl = 99.4 – 100%) for HAV testing and At risk populations.
Negative Percent Agreement: 100.0% (95% Cl = 97.3 – 100%) for Pediatric Population.
Reactive Percent Agreement: 96.7% (95% Cl = 92.7 - 98.9%) for Acute HAV Infection.
Reproducibility: Overall %CV ranged from 10.7% to 54.2%.
Cross-reactivity: 0 reactive results out of 195 tested samples.

Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.

DiaSorin Inc. ETI-HA-IGMK Plus Kit (PMA #P890014/S002)

Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).

Not Found

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.

Summary

K082050

5.0 510(k) SUMMARY

NOV - 3 2008

Carol A. DePouw Regulatory Affairs Specialist DiaSorin Inc. 1951 Northwestern Avenue P.O. Box 285 Stillwater, MN 55082-0285

Phone (651) 351-5850 Fax (651) 351-5669 Email: carol.depouw@diasorin.com

NAME OF DEVICE:

SUBMITTED BY:

Trade Name:

Common Names/Descriptions:	He
----------------------------	----

Classification Names:

Product Code:

PREDICATE DEVICES

LIAISON® HAV IgM

patitis A Virus (HAV Serological Reagents)

Hepatitis A Test (Antibody and IgM Antibody)

LOL

DiaSorin Inc. ETI-HA-IGMK Plus Kit (PMA #P890014/S002)

DEVICE DESCRIPTION:

INTENDED USE: The LIAISON® HAV IgM assay is an in vitro chemiluminescent immunoassay intended for the qualitative detection of IgM antibodies to hepatitis A virus (IgM anti-HAV) in human serum and sodium heparin plasma using the LIAISON® Analyzer. Assay results, in conjunction with other serological and clinical information, may be used for testing specimens from individuals who have signs and symptoms consistent with acute hepatitis as an aid in the laboratory diagnosis of acute or recent HAV infection.

The LIAISON® Control HAV IgM (negative and Reactive) is intended for use as assayed quality control samples to monitor the performance of the LIAISON® HAV IgM assay.

KIT DESCRIPTION: The method for qualitative determination of HAV IgM is an antibody capture chemiluminescence immunoassay (CLIA). lgG to human IgM (mouse monoclonal) is used for coating magnetic particles (solid phase) and a mouse monoclonal antibody to HAV is linked to an isoluminol derivative

(isoluminol-antibody conjugate). During the first incubation, IgM antibodies present in calibrators, samples or controls bind to the solid phase. During the second incubation, the antibody conjugate reacts with HAV antigen just added and the immune complex thus formed reacts with IgM already bound to the solid phase. After each incubation, the unbound material is removed with a wash cycle.

PERFORMANCE DATA:

Prospective

Individuals sent to the Lab for HAV testing

A total of 500 samples collected from the Northeastern US were included in this study. Of the samples from individuals sent to the lab for HAV testing, 59.8% were female (n=299) ranging in age from 20 - 101 yrs. and 40.2% were male (n=201) ranging in age from 17 to 89.

Individuals At Risk for Viral Hepatitis

A total of 239 individuals at risk for viral hepatitis due to lifestyle, behavior or occupation were included in this study. The 239 individuals were from the following at risk groups: homosexual males (n=38), healthcare workers (n=10), Commercial sex workers (n=34), drug users (n=77), prison inmates (n=49), dialysis patients (n=25) and hemophiliacs (n=6). Of the at risk individuals, 29.7% were females (n=71), ranging in age from 17 to 79, and 43.1% were males (n=103) ranging in age from 16 to 79. The age and gender were unknown for the remaining 27.2% (n=65).

The data for the combined populations are shown in Table 1.

| LIAISON®

HAV IgM	Comparator ELISA			Total
	Reactive	Equivocal	Negative
Reactive	0	0	1	1
Equivocal	0	0	0	0
Negative	0	0	738	738
Total	0	0	739	739

Table 1: HAV testing population and At risk
population comparison of LIAISON® HAV IgM and the Comparator ELISA

	Negative Percent Agreement	Exact 95% Confidence Interval
Negative	738/739 99.9%	99.4 – 100%

Pediatric Population

One hundred eight (108) prospectively collected pediatric samples were tested. The 108 pediatric samples were collected from children in the United States. Of these 108 samples 57.4% were female (n=62) and 42.6% were male (n=46), ranging in age from 2 to 17.

The results are presented in the Table 2.

Table 2: Pediatric Population Comparison of LIAISON® HAV IgM and Comparator ELISA

| LIAISON®

HAV IgM	Comparator ELISA			Total
	Reactive	Equivocal	Negative
Reactive	0	0	0	0
Equivocal	0	0	0	0
Negative	0	0	108	108
Total	0	0	108	108

		Negative Percent Agreement
Negative	108/108	adversions of analy of the first from Public Print Prints of Prints of Prints of Property of Children Comments of Children Comments of Children Comments of Children
100%	Acres and any of the first of the first and the comments
97.3 — 100%

Acute HAV Infection;

A retrospective population was tested which consisted of 123 samples from individuals who had an (Acute) HAV infection. Of these 123 samples, 42 were acute pediatrics collected from children in Eqypt. There were 32.5% females (n=40) ranging in age from 4 to 51, 51.2% males (n=63) ranging in age from 4 to 51. For 15.5% of the samples gender and age were unknown. One sample (0.8%) age 18, but gender was unknown. The results are presented in the Table 3.

| LIAISON®

HAV IgM	Comparator ELISA			Total
	Reactive	Borderline	Negative
Reactive	119	4	0	123
Equivocal	0	0	0	0
Negative	0	0	0	0
Total	119	4	0	123

Table 3: Comparison of LIAISON® HAV IgM and the Comparator ELISA

	and and the will be will be will be the world and the world and the world be and the comments of the count	Reactive Percent Agreement	Exact 95% Confidence Interval
Reactive	119/123	96.7%	92.7 - 98.9%

Conclusion: The LIAISON® HAV IgM assay showed equivalent performance to the FDA approved comparison method. The LIAISON® HAV IgM demonstrated overall agreement with the Comparator ELISA as follows:

Prospective Population "At Risk" and "HAV Testing" - 99.9% (95% Cl = 99.1 - 100%) Pediatric Population - 100.0% (95% Cl = 97.3 - 100%) Retrospective Population Acute HAV Infection - 96.7% (95% Cl = 92.7 - 98.9%)

The results demonstrate that the LIAISON® HAV IgM assay can be used with the LIAISON® Analyzer for the qualitative detection of IgM antibodies to hepatitis A virus.

EXPECTED VALUES :

Prevalence

The expected prevalence results of the LIAISON® HAV IgM assay were determined in 802 apparently healthy adults from the Western (historically high prevalence) and the Eastern (historically lower prevalence) regions of the U.S. Three hundred one (301) samples were from the Western U.S. and 501 were samples from the Eastern U.S.

Of the Western U.S. individuals 53.8% were females (n=162) ranging in age from 9 to 87 and 46.2% were males (n=139) ranging in age from 16 to 76. The majority of the individuals were Caucasian (60.8%), with other ethnic groups represented as follows: Hispanic (17.6%), African Americans (15.3%), Asian (6.0%) and Middle Eastern (0.3%). In the study group from the Western region, none of the individuals were found to be reactive for HAV IgM antibodies.

Of the Eastern U.S. individuals 46.5% were females (n=233) ranging in age from 17 to 83, and 53.5% were males (n=268) ranging in age from 17 to 82. The majority of the individuals were Caucasian (69.9%), with other ethnic groups represented as follows: Hispanic (14.0%), African American (12.1%) and Asian (4.0%).

In the study group from the Eastern region none of the individuals were found to be reactive for HAV IqM antibodies.

The expected results for the Western and Eastern regions of the U.S. are presented in the tables below.

| | N | Negative | Equivocal | Reactive | Reactive
Prevalence |
|-------------------|-----|----------|-----------|----------|------------------------|
| Total | 301 | 301 | 0 | 0 | NA |
| Gender | | | | | |
| Female | 162 | 162 | 0 | 0 | NA |
| Male | 139 | 139 | 0 | 0 | NA |
| Age range (years) | N | (-) | (E) | (+) | |
| ≤18 | 12 | 12 | 0 | 0 | NA |
| Trade/Device Name: LIAISON® HAV IgM Regulation Number: 21 CFR 866.3310 Regulation Name: Hepatitis A virus (HAV) serological assays Regulatory Class: Class II Product Code: LOL Dated: October 24, 2008 Received: October 27, 2008

Dear Ms. DePouw:

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).

Page 2 -

and and the first of the start of the county of the comment of the many of the may be and the may be any and

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 1egally marketed predicate device results in a classification for your device and thus, permitts your device to proceed to the market.

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Carles Canada Career Statistic Cases (1) Canada Career (1) Canada (1) Canada (1) Canada (1) Canada (1) Career (1) Carder (1) Can (1) Can (1) Carder (1) Can (1) Carder (1) Car

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), 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). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at 240-276-3474. For questions regarding the reporting of device adverse events (Medical Device Reporting (MDR)), please contact the Division of Surveillance Systems at 240-276-3464. You may obtain (1122 general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (240) 276-3150 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours.

Sally attaym

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

510(k) Number (if known): K082050

Device Name:

LIAISON® HAV IgM and LIAISON® Control HAV IqM

Indication For Use: The LIAISON® HAV IgM assay is an in vitro chemiluminescent immunoassay intended for the qualitative detection of IqM antibodies to hepatitis A virus (IgM anti-HAV) in human serum and sodium heparin plasma using the LIAISON® Analyzer. Assay results, in conjunction with other serological and clinical information, may be used for testing specimens from individuals who have signs and symptoms consistent with acute hepatitis as an aid in the laboratory diagnosis of acute or recent HAV infection.

This assay is not intended for screening blood or solid or soft tissue donors. Assay performance characteristics have not been established for immunocompromised or immunosuppressed patients. The user is responsible for establishing their own assay performance characteristics in these populations.

The LIAISON® Control HAV IgM (negative and reactive) is intended for use as assayed quality control samples to monitor the performance of the LIAISON® HAV IgM assay.

Prescription Use X (21 CFR Part 801 Subpart D) Over the Counter Use (21 CFR Part 801 Subpart C)

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

And/Or

Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD)

Souy attyr

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K062050