The LIAISON® Anti-HAV assay is an in vitro chemiluminescent immunoassay intended for the qualitative detection of total antibodies to hepatitis A (anti-HAV) in human serum and sodium heparin plasma samples using the LIAISON® Analyzer family. The assay is indicated as an aid in the laboratory diagnosis of current or previous HAV infections in conjunction with other serological and clinical information and to determine the presponse to HAV in vaccine recipients.

The assay is not intended for screening blood or solid or soft tissue donors.

Device Description

The method for qualitative determination of anti-HAV is a competitive sandwich chemiluminescence immunoassay (CLIA) based on neutralization. The assay uses magnetic particles (solid phase) coated with IqG antibodies to HAV (mouse monoclonal), and a mouse monoclonal anti-HAV antibody conjugate linked to an isoluminol derivative (isoluminol-antibody conjuqate). The first incubation step consists of adding the HAV antigen to calibrators, samples or controls, during which anti-HAV present in calibrators, samples or controls binds to a fixed and limited amount of HAV. thus forming an HAV-anti-HAV immune complex. After this step the second incubation follows and it involves addition of magnetic microparticles and conjugate into the cuvette, during which the antibody conjugate and the solid-phase antibody compete with anti-HAV present in the specimen for HAV. This allows the conjugate to bind to the solid phase and to form a sandwich. If all HAV added is sequestered in an HAV-anti-HAV immune complex during the first incubation, no sandwich is formed during the second incubation. After the second 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 inversely indicative of anti-HAV present in calibrators, samples or controls.

AI/ML Overview

Here's an analysis of the provided text regarding the DiaSorin Inc. LIAISON® Anti-HAV device, outlining acceptance criteria and study details:

Acceptance Criteria and Device Performance

The provided document describes two main performance studies: a Method Comparison study and a Reproducibility study. The "acceptance criteria" are implied by the reported agreement percentages and coefficient of variation (%CV) values, which are generally expected to be high for agreement and low for variation in diagnostic assays.

Table of Acceptance Criteria and Reported Device Performance

Performance Metric	Acceptance Criteria (Implied)	Reported Device Performance
Method Comparison
Negative Agreement	High agreement (e.g., >85-90%) with predicate.	97.4% (38/39) 95% Cl: 86.8% to 99.5%
Positive Agreement	High agreement (e.g., >85-90%) with predicate.	96.7% (58/60) 95% Cl: 88.6% to 99.1%
Overall Agreement	High agreement (e.g., >90%) with predicate.	97.0% (96/99) 95% Cl: 91.5% to 99.0%
Reproducibility
Repeatability (within Day)	Low %CV (e.g., <10-15%) for various sample concentrations.	Ranged from 1.3% to 2.4% for samples; 1.7% for Negative Control, 2.4% for Positive Control.
Between Day %CV	Low %CV (e.g., <10-15%) for various sample concentrations.	Ranged from 3.5% to 6.2% for samples; 3.5% for Negative Control, 4.7% for Positive Control.
Between Laboratory %CV	Low %CV (e.g., <10-15%) across different testing sites.	Ranged from 0.0% to 5.0% for samples; 2.1% for Negative Control, 4.6% for Positive Control.
Reproducibility (Total) %CV	Low %CV (e.g., <15-20%) representing overall precision.	Ranged from 4.4% to 7.1% for samples; 4.5% for Negative Control, 7.0% for Positive Control.

Study Details for LIAISON® Anti-HAV

Here's a breakdown of the specific information requested, based on the provided text:

2. Sample Size Used for the Test Set and Data Provenance

Method Comparison Test Set: 100 frozen serum samples.
Data Provenance: Samples were "either selected or prepared by DiaSorin Inc." The text does not explicitly state the country of origin or if the samples were retrospective or prospective, but the selection/preparation by the manufacturer suggests a controlled, potentially retrospective or spiked sample set rather than a purely prospective real-world patient cohort. The testing was performed at "2 external sites and at DiaSorin Inc."
Reproducibility Study Test Set: A coded precision panel consisting of seven (7) serum specimens manufactured by DiaSorin S.p.A. and two (2) kit controls (a positive and negative from a single control lot). Each sample was run with 4 replicates per day for 12 days at each of the 3 sites, totaling 144 replicates per sample (4 replicates/day * 12 days * 3 sites) for both samples and controls.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications

The studies described are for an in vitro diagnostic (IVD) immunoassay, not an imaging device or AI-driven diagnostic that typically involves human expert interpretation for ground truth. Therefore, no human experts were used to establish ground truth in the traditional sense for these performance studies.

In the method comparison study, the ground truth for samples was based on the results from a predicate device (LIAISON® Anti-HAV, Reference K082049).
In the reproducibility study, the "ground truth" for the precision panel samples would be their known or assigned concentration/status based on their manufacturing and characterization, against which the assay's consistency is measured. The text doesn't specify how these concentrations were established, but it would typically be through reference methods or rigorous characterization during manufacturing.

4. Adjudication Method for the Test Set

Given that these are performance studies for an in vitro diagnostic where comparison is primarily against a predicate device or known sample characteristics, no human adjudication method (e.g., 2+1, 3+1) was mentioned or would typically be applicable. The "adjudication" is effectively the direct comparison of results between the new device and the predicate device or the statistical analysis of quantitative measurements against expected values (for reproducibility).

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. MRMC studies are typically performed for medical imaging or AI diagnostics where multiple human readers interpret cases and their performance is compared with and without AI assistance. This document describes an in vitro diagnostic assay that determines the presence of antibodies in serum/plasma, not a technology that human readers interpret.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

The LIAISON® Anti-HAV assay itself is a standalone in vitro diagnostic device, meaning its performance is evaluated based on its own output (chemiluminescence signal leading to qualitative detection of antibodies) without direct human interpretation of complex patterns or images. The "algorithm" in this context refers to the assay's chemical and instrumental process, which produces results independently. The provided studies directly assess this standalone performance (e.g., agreement with a predicate, and reproducibility).

7. The Type of Ground Truth Used

Method Comparison Study: The ground truth for the test set was established by the predicate device (LIAISON® Anti-HAV, Reference K082049) results. This is a common practice for demonstrating substantial equivalence for IVDs.
Reproducibility Study: The ground truth, in terms of expected values for precision, was based on the known characteristics of the manufactured serum specimens and kit controls. This is not "expert consensus" or "pathology" but rather scientifically characterized samples.

8. The Sample Size for the Training Set

The document does not specify a training set sample size. This is expected because the LIAISON® Anti-HAV assay is a chemiluminescent immunoassay, which is a traditional laboratory diagnostic method based on biochemical reactions, not a machine learning or AI algorithm that requires a "training set" in the context of model development. The development of such an assay involves extensive R&D, reagent optimization, and analytical validation but not a "training set" in the computational sense.

9. How the Ground Truth for the Training Set Was Established

Since there is no "training set" in the AI/ML sense, this question is not applicable based on the provided information. The development of the assay would have relied on established scientific principles, method validation, and characterization of reagents and controls.

Summary

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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

DiaSorin Inc. Mari Meyer Vice President, Regulatory and Clinical Affairs, North America 1951 Northwestern Ave Stillwater, Minnesota 55082

Re: K193532

Trade/Device Name: Liaison Anti-HAV Regulation Number: 21 CFR 866.3310 Regulation Name: Hepatitis A Virus (HAV) Serological Assays Regulatory Class: Class II Product Code: LOL, JJE Dated: December 17, 2019 Received: December 20, 2019

Dear Mari Meyer:

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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. 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 Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR

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for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely.

Maria Garcia, Ph.D. Branch Chief Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known)

K193532

Device Name LIAISON® Anti-HAV

Indications for Use (Describe)

The assay is not intended for screening blood or solid or soft tissue donors.

Type of Use (Select one or both, as applicable)
☑ Prescription Use (Part 21 CFR 801 Subpart D)	☐ Over-The-Counter Use (21 CFR 801 Subpart C)

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510(k) SUMMARY

SUBMITTED BY:

Mari Meyer Vice President, Regulatory and Clinical Affairs, North America DiaSorin Inc. 1951 Northwestern Avenue P.O. Box 285 Stillwater, MN 55082-0285 Phone (651) 439-9710 Fax (651) 351-5669 Email: mari.meyer@diasorin.com

NAME OF DEVICE:

Trade Name:	LIAISON® Anti-HAV
Common Names/Descriptions:	Hepatitis A Virus (HAV Serological Reagents)
Classification Names:	Hepatitis A Test (Antibody and IgM Antibody)
Product Code:	LOL
ICATE DEVICES	LIAISON® Anti-HAV

PREDICATE DEVICES

AISON® Anti-HAV Reference K082049

DEVICE DESCRIPTION:

INTENDED USE:

This assay is not intended for screening blood or solid or soft tissue donors.

DESCRIPTION:

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anti-HAV present in the specimen for HAV. This allows the conjugate to bind to the solid phase and to form a sandwich. If all HAV added is sequestered in an HAV-anti-HAV immune complex during the first incubation, no sandwich is formed during the second incubation. After the second 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 inversely indicative of anti-HAV present in calibrators, samples or controls.

PERFORMANCE DATA: METHOD COMPARISON WITH PREDICATE DEVICE:

The agreement study consisted of testing 100 frozen serum samples on the LIAISON® XS and the LIAISON® XL Analyzers with the LIAISON® Anti-HAV Assay. The samples were either selected or prepared by DiaSorin Inc. to reach different levels of anti-HAV antibody. They were randomly divided among three (3) sites for testing. LIAISON® XS testing was performed at 2 external sites and at DiaSorin Inc., with the LIAISON® XL Analyzer testing performed internally at DiaSorin Inc. The categorical agreement results are presented in the following table.

	Agreement Study Results
	LIAISON® XL Analyzer
LIAISON®XS®Analyzer	Eqv	High Neg	HighPos	Low Pos	Mod Pos	Neg	GrandTotal
High Neg	-	23	-	-	-	1	24
High Pos	-	-	23	-	2	-	25
Low Pos	1	-	-	13	2	-	16
Mod Pos	-	-	-	4	14	-	18
Eqv	1	-	-	2	-	-	3
Neg	-	1	-	-	-	13	14
Grand Total	2	24	23	19	18	14	100

Agreement Study Results

Negative Agreement: 97.4% (38/39) 95% Cl: 86.8% to 99.5% Positive Agreement: 96.7% (58/60) 95% Cl: 88.6% to 99.1% Overall Agreement: 97.0% (96/99) 95% Cl: 91.5% to 99.0%

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REPRODUCIBILITY:

A 12 day precision/reproducibility study was conducted internally at DiaSorin Inc. and at two (2) external sites to verify the precision of the LIAISON® XS Analyzer with the LIAISON® Anti-HAV Assay, with one (1) lot of LIAISON® Anti-HAV (#310200) and one (1) lot of LIAISON® Control Anti-HAV (#310201). One (1) LIAISON® XS Analyzer was used for testing at each site and at least two (2) operators performed the testing at each site.

A coded precision panel was used in this study, consisting of seven (7) serum specimens manufactured by DiaSorin S.p.A. and two (2) kit controls (a positive and negative from a single control lot). All precision panel samples (n=7) were stored at -20°C or lower prior to testing and Positive and Negative kit controls were handled according to the Instructions for Use.

Each day for 12 days a single run of four replicates was generated by a single operator for each member of the precision panel which included seven (7) samples and two (2) kit controls for a total of 48 replicates at each site per sample.

The mean, standard deviation, and coefficient of variation (%CV) of the results were computed for each of the tested specimens for each of the sites and across sites. The within-Day results were used to calculate the assay's repeatability and the between-Day results were used to calculate the assay's reproducibility.

Results

The 12-day Index results are summarized in the following (combined sites). The %CVs are computed for repeatability (within day), between day and within laboratory, between laboratory and reproducibility (total) precision.

SampleDescription	Mean	N	Repeatability (withinDay)		Between Day		BetweenLaboratory		Reproducibility(Total)
			SD	%CV	SD	%CV	SD	%CV	SD	%CV
NegativeControl	175186*	144	3012	1.7%	6194	3.5%	3757	2.1%	7846	4.5%
PositiveControl	0.43	144	0.011	2.4%	0.020	4.7%	0.020	4.6%	0.030	7.0%
Sample 1	0.23	144	0.005	2.1%	0.010	4.6%	0.011	5.0%	0.016	7.1%
Sample 2	0.48	144	0.008	1.8%	0.029	6.0%	0.000	0.0%	0.030	6.3%
Sample 3	0.51	144	0.008	1.6%	0.021	4.2%	0.012	2.3%	0.026	5.1%
Sample 4	0.91	144	0.015	1.7%	0.049	5.3%	0.032	3.5%	0.060	6.6%
Sample 5	2.09	144	0.026	1.3%	0.085	4.1%	0.025	1.2%	0.092	4.4%
Sample 6	1.71	144	0.026	1.5%	0.105	6.2%	0.004	0.2%	0.108	6.3%
Sample 7	0.94	144	0.018	1.9%	0.035	3.7%	0.041	4.3%	0.057	6.0%

12-Day Precision Study Results (3 sites)

*Dose was above the reading range of the assay. Precision calculations are based on signal (RLU) for this sample.

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CONCLUSION:

The material submitted in this premarket notification is complete and supports a substantial equivalence decision. The labelling is sufficient and it satisfies the requirements of 21CFR 809.10

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.