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 presence of an antibody response to HAV in vaccine recipients.

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

Device Description

The DiaSorin LIAISON® XS Analyzer is a fully automated, closed, continuous loading of samples and reagents in vitro diagnostic immunoassay system utilizing chemiluminescent technology to provide rapid sample results. The analyzer uses DiaSorin proprietary reagents in which chemiluminescence of an analyte is measured in a sample by the reaction of a magnetic particle solid phase coated with antigen or antibody and a chemiluminescent tracer. The LIAISON® XS Analyzer is intended for use in professional clinical laboratories only.

AI/ML Overview

The provided text describes a 510(k) premarket notification for a modified medical device, the LIAISON® XS Analyzer, used with the LIAISON® Anti-HAV assay. However, the document does not contain specific details about acceptance criteria, reported device performance (in terms of sensitivity, specificity, etc.), sample sizes for test sets, data provenance, number of experts, adjudication methods, MRMC studies, standalone performance, or ground truth details for either test or training sets.

The submission is for a device modification (moving fluid canisters onboard) to an already cleared device (K210272). The focus of the provided text is on demonstrating that these modifications do not negatively impact the device's performance or safety/effectiveness, rather than a full de novo performance study of the Anti-HAV assay itself.

Therefore, most of the requested information cannot be extracted from this document. The "Summary of Performance Data" section states that "Non-clinical verification and validation activities conducted with the LIAISON® XS Analyzer demonstrate that the modified device met predetermined acceptance criteria," but it does not specify what those criteria were or quantitatively report the performance. It merely lists the types of studies conducted.

Here is what can be inferred or stated based on the provided text:

1. A table of acceptance criteria and the reported device performance

The document does not explicitly list the acceptance criteria or quantitative performance results (e.g., sensitivity, specificity, accuracy) for the LIAISON Anti-HAV assay after the modifications. It broadly states: "Non-clinical verification and validation activities conducted with the LIAISON® XS Analyzer demonstrate that the modified device met predetermined acceptance criteria, supporting equivalency of the modified device to the cleared device." And "Testing verified all acceptance criteria were met."

The primary goal of this 510(k) is to demonstrate that the modifications to the analyzer (moving fluid canisters onboard) do not alter the safety and effectiveness of the existing cleared device. The previous clearance (K210272) would have contained the detailed performance data for the LIAISON® Anti-HAV assay itself.

2. Sample sized used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

Not provided in this document. The document refers to "non-clinical verification and validation activities" which are typically internal testing, not necessarily clinical studies with patient test sets.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

Not applicable and not provided. This information would be relevant for a de novo clinical study with expert ground truth, which is not the focus of this modification submission.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

Not applicable and not provided.

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

Not applicable. The LIAISON® XS Analyzer is an in vitro diagnostic immunoassay system, not an AI-assisted diagnostic tool that requires human reader interpretation.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

The LIAISON® Anti-HAV assay on the LIAISON® XS Analyzer is a standalone diagnostic test. Its performance is evaluated based on its accuracy in detecting antibodies, as indicated by the chemiluminescence signal, and does not involve human interpretation of complex images or signals in the same way an AI algorithm might. The document does not provide the specific performance metrics (e.g., sensitivity, specificity, NPV, PPV) for this standalone device in the context of this specific 510(k) submission, as it refers to these having been established in the previous clearance (K210272).

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)

Not explicitly stated in this specific document. For an immunoassay like this, the ground truth for clinical studies would typically be established through a combination of:

Established reference methods: Usually another FDA-cleared or gold standard HAV antibody test.
Clinical diagnosis: Based on patient symptoms, epidemiological information, and other laboratory markers.
Seroconversion panels: Well-characterized samples from individuals demonstrating progression of infection or immune response.

Since this 510(k) is for a modification to an existing device, it relies on the ground truth established during the original clearance of the LIAISON® Anti-HAV assay.

8. The sample size for the training set

Not applicable and not provided. Immunoassays are not "trained" in the same way machine learning models are. Performance characteristics are established through various analytical and clinical studies.

9. How the ground truth for the training set was established

Not applicable and not provided (see point 8).

Summary

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December 9, 2022

Image /page/0/Picture/1 description: The image shows 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 FDA logo is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

DiaSorin Inc. Kerrie Oetter Director, Regulatory Affairs 1951 Northwestern Ave. P.O. Box 285 Stillwater, Minnesota 55082

Re: K223403

Trade/Device Name: LIAISON Anti-HAV; LIAISON XS Regulation Number: 21 CFR 866.3310 Regulation Name: Hepatitis A Virus (HAV) Serological Assays Regulatory Class: Class II Product Code: LOL Dated: November 8, 2022 Received: November 9, 2022

Dear Kerrie Oetter:

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

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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 803) 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 (OS) 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 I. Garcia -S

Maria Garcia, Ph.D. Assistant Director Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics 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) K223403

Device Name LIAISON Anti-HAV LIAISON XS

Indications for Use (Describe)

This 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	K223403
Submitted by:	Kerrie OetterDirector, Regulatory AffairsDiaSorin Inc.1951 Northwestern AvenueP.O. Box 285Stillwater, MN 55082-0285Phone: (651) 369-9806Fax: (651) 351-5669Email: kerrie.oetter@diasorin.com
Date prepared:	December 8, 2022
Name of device:Trade Name:	LIAISON® Anti-HAV;LIAISON® XS
Common Name:	Hepatitis Anti-HAV, serological assay;Automated Chemiluminescent ImmunoassayAnalyzer
Classification Name:	Hepatitis A Test (antibody and IgM antibody):Class II, 21 CFR 866.3310; Microbiology;Analyzer, Chemistry, Micro, For Clinical Use:Class I, 21 CFR 862.2170; Microbiology, Clinical
Product Code:	LOLJJF
Predicate Device:	LIAISON® Anti-HAV, LIAISON® XS (K210272)

Device Description

LIAISON® XS Analyzer

The general operation of the Analyzer is described below.

The gripper transports the cuvette inside the incubator in which dedicated positions allowed . the pipetting of reagents and samples. The incubator is provided with 32 plus 25 positions for the placement of cuvettes.

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DiaSorin LIAISON® XS Analyzer Special 510(k): Device modification 510(k) Summary

At the end of the incubation time, the gripper transports the cuvette from its position in the ● incubator into the washer with three wash positions. The washer transport mechanism moves the cuvette, using the analyzer time cycle, from one washing station to the next.
. After passing through the washer, the gripper moves the cuvette:
. CASE 1: Return transport for 2-step process Back in the incubator for addition of second-step reagent(s). After incubation, the gripper moves back the cuvette in the washer.
. CASE 2: Transport into the measuring chamber for 1-step process In the measuring chamber.
. After the measurement, the reaction solution is removed by suction and the cuvette is then automatically disposed of into the waste container.

LIAISON® Anti-HAV Assay

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 IgG antibodies to HAV (mouse monoclonal), and a mouse monoclonal anti-HAV antibody conjugate linked to an isoluminol derivative (isoluminolantibody conjugate). 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.

Intended Use/Indications for Use

The Intended Use/Indications for Use of the device as described in its current labeling (K210272) has not changed as a result of the modifications.

The LIAISON® XS Analyzer is a Diagnostic System that measures chemiluminescence. It is intended strictly for professional in-vitro Diagnostic use. It is to be used only with Chemiluminescence Immunoassays, authorized by DiaSorin Italia S.p.A. for the LIAISON® XS instrument.

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

Comparison to Predicate Device

The device configuration of the LIAISON® XS Analyzer was modified to return it to the initial configuration (cleared under K193532) where onboard canisters for the supply of liquids are moved back onboard the Analyzer. These modifications include:

1. Hardware (HW) configuration, adapted to the new onboard canisters;
1. Firmware (FW) and Software (SW), adapted to support the re-arranged HW and provide proper information about the various supplies in the main User Interface;
1. New version of Wash Buffer consumable, adapted to the new onboard canister.

A comparison of the similarities and differences between the devices is provided in the following table.

Feature	LIAISON® XS Analyzer (current version cleared asK210272)	LIAISON® XS Analyzermodified version
Intended Use	Automated chemiluminescent analyzer for clinical use	Same
Principles of operation	Chemiluminescence using magnetic particle solid phase andchemiluminescent tracer	Same
Optical System	High-sensitive, low-noise photomultiplier tube (PMT) operatingas an ultra-fast photon counter. Pulses are amplified by a rapidelectronic amplifier.	Same
	Circuit that suppresses PMT signal noise.	Same
	Linear measuring range = 300 - 650 nm	Same
	Light peak of chemiluminescence emitted at 450 nm	Same
Temperature Control: ReactionTemperature	36°C±1°C	Same
Temperature Control: ReagentStorage Temperature	11-15°C	Same
Dispense System	Automated pipetting of samples and reagents. Left pipetting unitused for samples; right pipetting unit used for reagents.Sample pipetting: disposable tip	Same
	Precision syringesLeft pipetting unit operates an air displacement syringe.Right pipetting unit operates a liquid filled syringe.	Same
	Sample Probe (disposable tip):Liquid Level Detection and Clot Detection feature(pressure)	Same
	Disposable tips: 2 trays of 96 tips each can be loaded onboard.Monitored through software counter and presence sensor upontip pick-up.Reloading allowed before run, or pausing the ongoing tasksduring a routine.	Same
	Reagent Probe:Liquid Level Detection (capacitive), with softwaretracking of reagent levelOptical Liquid Verification (real-time monitoring ofliquid flow inside the probe)	Same
Sample Handling	Capacity: Holds 4 sample racks, 12 places per rack	Same
	Tube types:- primary tube- aliquot tube- pediatric	Same
Feature	LIAISON® XS Analyzer (current version cleared asK210272)	LIAISON® XS Analyzermodified version
	Sample presence, sample type (calibrator, control, patient), tubesize, and processing completion tracked by operating softwareand sample barcode	Same
Reagent Handling	Capacity: 10 Reagent Integrals (RI), plus 4 positions forAncillary Reagents	Same
	RI contains all reagents required for any given assay (up to 7vials per RI, first vial always contains magnetic particles).	Same
	Assay-specific processing and analysis parameters, calibration,lot number, expiration date, and usage (number of tests run) arecontrolled by operating software as communicated by RF-Tag(RF-ID).	Same
Additional Reagents	Control Set (2 levels)•LIAISON Light Check (diagnostic tool only, reserved forservice intervention)•LIAISON® EASY Cleaning Tool	Same
Starter reagents	The system can host one set of Starter Reagents.Recognition of Starter Reagents: via RF-Tag	Same
	One bottle of each Starter reagent can be loaded on board	Same
	Injection of Starter Reagents through high precision/accuracypump (fixed dispensing volume)	Same
	dispense monitoring through optical sensor	Same
	injection of Starter Reagents occurs at controlled temperature(33-37°C)	Same
Reaction Modules	Capacity: Single-cavity Cuvettes	Same
	Storage capacity: up to 172 cuvettes	Same
	Same	Same
	Reloading allowed before run, or pausing the ongoing tasksduring a routine	Same
	Unloading automatic into waste container	Same
Test Processing	Random Access and Batch	Same
	Continuous operation	Same
	Sample scheduling optimized for throughput	Same
Assay Protocols	1-Step assays: 1 incubation sequence / 1 wash sequence; averageincubation time = 10 minutes	Same
	2-Step assays: 2 incubation sequence / 1 or 2 wash sequence(s);average incubation time = 10 minutes	Same
	Two-point and one-point calibration of assays	Same
Human Interface	Same	Same
	Touch-screen On Screen Keyboard (keyboard and mouse notsupplied)	Same
	Same (integrated with the computer)	Same
	Printer (optional)	Same
	Stationary barcode scanner for identification of samples.Stationary RF-Tag reader for identification of reagents. (ReagentIntegrals and Starter Reagents).Handheld barcode scanner for identification of controls.Computer LIS Interface	Same
Data Analysis	Automated data reduction	Same
	Assay-specific Master Curve with two-point or one-pointrecalibration	Same
	Assay-specific data reduction	Same
Specimens	Serum or plasma or other body fluids or their extract	Same
	Sampling from primary, aliquot, or pediatric tubes	Same
Disposables	Reagent Integrals	Same
	Light Check (tool for service intervention only)LIAISON® EASY Wash Buffer	SameOnly difference is that LIAISON®EASY Wash Buffer is supplied inbottles with 300 mL filling volumeinstead of 500 mL filling volume.Product code and chemical formulationare the same.
	LIAISON® EASY System Liquid	Same
	LIAISON EASY Starter Kit	Same
	Cuvettes	Same
Feature	LIAISON® XS Analyzer (current version cleared asK210272)	LIAISON® XS Analyzermodified version
	Disposable Tips	Same
	Waste box, single use (dedicated)	Same
	Cleaning Kit(dedicated)	Same
Software	Based on:● Windows	Same
Hardware	● Bench-top, integrated design (PC, monitor, keyboard areintegrated in the design)● average throughput optimized for medium/smalllaboratories● Data exchange for Reagent Integrals, Ancillary Reagents,Starter Reagents via RF-ID technology: higher dataexchange, higher reagent traceability allowed● Disposable tip for sample pipetting	Same with the following designoptimization:● Internal 5 L canister to housediluted LIAISON® EASY SystemLiquid● Internal 3L canister to houseLIAISON® EASY Wash Buffer● Changes in the liquid supply linesconnected to the new internalcanisters
Software	Software version 1.4.9	Software version 1.5.2.It integrates the changes needed tosupport the use of the two internal tanksand minor bug fixing from the previousversion.

Table 1: Comparison of the LIAISON® XS Analyzer with the predicate device

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Summary of Performance Data

Non-clinical verification and validation activities conducted with the LIAISON® XS Analyzer demonstrate that the modified device met predetermined acceptance criteria, supporting equivalency of the modified device to the cleared device. All verification and validation activities were performed in accordance with relevant standards, established plans, protocols, and Design Control procedures. Testing verified all acceptance criteria were met. Verification of the changes did not raise any new items of safety and effectiveness. Evidence is demonstrated through the following studies:

Non-regression testing of immunometrical performance
Hardware reliability evaluation .
Usability testing ●
Software verification and validation .

Based on the results from the verification and validation activities, the modifications to the LIAISON® XS Analyzer do not introduce any new risks to the performance of the device and do no alter safety and effectiveness.

Conclusion

The material submitted in this premarket notification is complete and supports a determination of substantial equivalence to the previous System configuration. The labeling is sufficient and satisfies the requirements of 21 CFR 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.