LIAISON Anti-HAV Assay

K193532 · DiaSorin, Inc. · LOL · Mar 2, 2020 · Microbiology

Device Facts

• Record ID: K193532
• Device Name: LIAISON Anti-HAV Assay
• Applicant: DiaSorin, Inc.
• Product Code: LOL · Microbiology
• Decision Date: Mar 2, 2020
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.3310
• Device Class: Class 2

Intended Use

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 Story

LIAISON Anti-HAV is a competitive sandwich chemiluminescence immunoassay (CLIA) for detecting total anti-HAV antibodies. Input: human serum or sodium heparin plasma samples. Operation: samples incubated with HAV antigen; anti-HAV binds to HAV. Second incubation adds magnetic microparticles coated with mouse monoclonal anti-HAV and isoluminol-labeled anti-HAV conjugate; conjugate and solid-phase antibody compete for remaining HAV. Unbound material washed away; starter reagents induce flash chemiluminescence. Output: relative light units (RLU) measured by photomultiplier, inversely proportional to anti-HAV concentration. Used in clinical laboratories on LIAISON Analyzer family. Healthcare providers use results to diagnose HAV infection or evaluate vaccine response.

Clinical Evidence

Bench testing only. Method comparison study (n=100) across three sites comparing LIAISON XS and LIAISON XL analyzers showed 97.0% overall agreement (95% CI: 91.5%–99.0%), 97.4% negative agreement, and 96.7% positive agreement. 12-day reproducibility study (n=144 replicates per sample) demonstrated total precision (%CV) ranging from 4.4% to 7.1% across various sample concentrations.

Technological Characteristics

Competitive sandwich chemiluminescence immunoassay (CLIA). Solid phase: magnetic microparticles coated with mouse monoclonal anti-HAV. Conjugate: isoluminol-labeled mouse monoclonal anti-HAV. Energy source: chemiluminescent reaction. Platform: LIAISON Analyzer family (automated).

Indications for Use

Indicated for qualitative detection of total anti-HAV antibodies in human serum and sodium heparin plasma. Used as an aid in diagnosing current or previous HAV infection and assessing vaccine response. Not for blood, solid, or soft tissue donor screening.

Regulatory Classification

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.

Special Controls

*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.

Predicate Devices

• LIAISON® Anti-HAV (K082049)

Submission Summary (Full Text)

{0}------------------------------------------------

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

{1}------------------------------------------------

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 (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 ([e-mail]) or phone [phone] 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

{2}------------------------------------------------

# Indications for Use

510(k) Number (if known)

K193532

Device Name LIAISON® Anti-HAV

#### Indications for Use (Describe)

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.

| Type of Use (Select one or both, as applicable) | |
|------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------|
| <span style="font-size:16px">☑</span> Prescription Use (Part 21 CFR 801 Subpart D) | <span style="font-size:16px">☐</span> Over-The-Counter Use (21 CFR 801 Subpart C) |

#### CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

#### *DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.*

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

> Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff [e-mail]

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

{3}------------------------------------------------

# 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 [phone] Fax [phone] Email: [e-mail]

# 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:

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.

### 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

{4}------------------------------------------------

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®<br>XS®<br>Analyzer | Eqv | High Neg | High<br>Pos | Low Pos | Mod Pos | Neg | Grand<br>Total |
| 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%

{5}------------------------------------------------

# 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.

| Sample<br>Description | Mean | N | Repeatability (within<br>Day) | | Between Day | | Between<br>Laboratory | | Reproducibility<br>(Total) | |
|-----------------------|---------|-----|-------------------------------|------|-------------|------|-----------------------|------|----------------------------|------|
| | | | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| Negative<br>Control | 175186* | 144 | 3012 | 1.7% | 6194 | 3.5% | 3757 | 2.1% | 7846 | 4.5% |
| Positive<br>Control | 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.

{6}------------------------------------------------

# 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