LIAISON HAV IgM, LIAISON Control HAV IgM

K160650 · DiaSorin, Inc. · LOL · Aug 25, 2016 · Microbiology

Device Facts

• Record ID: K160650
• Device Name: LIAISON HAV IgM, LIAISON Control HAV IgM
• Applicant: DiaSorin, Inc.
• Product Code: LOL · Microbiology
• Decision Date: Aug 25, 2016
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.3310
• Device Class: Class 2
• Attributes: Pediatric

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 plasma (sodium citrate, potassium EDTA, lithium and sodium heparin, and citrate dextrose (ACD)) 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 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 positive) are intended for use as assayed quality control samples to monitor the performance of the LIAISON® HAV IgM assay.

Device Story

LIAISON® HAV IgM is an in vitro chemiluminescent immunoassay (CLIA) for qualitative detection of IgM anti-HAV in human serum/plasma. Device uses magnetic particles coated with mouse monoclonal anti-human IgM and mouse monoclonal anti-HAV antibody conjugated to an isoluminol derivative. Process: 1) IgM antibodies in sample bind to solid phase; 2) Antibody conjugate reacts with added HAV antigen and bound IgM; 3) Unbound material washed; 4) Starter reagents added to induce flash chemiluminescence. Photomultiplier measures light signal (RLU) proportional to anti-HAV IgM concentration. Used in clinical laboratories on LIAISON® Analyzer. Results interpreted by clinicians alongside other serological/clinical data to diagnose acute/recent HAV infection. Benefits include rapid, automated detection of acute HAV infection.

Clinical Evidence

Cut-off verification study using 380 serum specimens: 121 prospective adult samples, 121 prospective pediatric samples (8 months to 20 years), and 138 retrospective acute HAV infection samples. Compared against predicate ETI-HA-IGMK Plus. Results: 100% negative percent agreement in prospective cohorts; 100% positive percent agreement in acute infection cohort. Seroconversion panel testing (n=5) showed equivalent detection timing to predicate. No clinical sensitivity/specificity study performed as this is a modification to a cleared device.

Technological Characteristics

Chemiluminescent immunoassay (CLIA). Solid phase: magnetic particles coated with mouse monoclonal anti-human IgM. Conjugate: mouse monoclonal anti-HAV antibody linked to isoluminol derivative. Energy source: LIAISON® Analyzer (photomultiplier detection). Sample types: serum, SST, sodium citrate, potassium EDTA, lithium/sodium heparin, ACD plasma. Connectivity: LIAISON® Analyzer. Software: Automated analysis of RLU signals.

Indications for Use

Indicated for qualitative detection of IgM anti-HAV in human serum/plasma to aid diagnosis of acute/recent HAV infection in individuals with signs/symptoms of acute hepatitis. Not for donor screening. Performance not established for immunocompromised/immunosuppressed patients.

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

• ETI-HA-IGMK Plus Kit (PMA #P890014)

Submission Summary (Full Text)

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Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is a stylized image of three human profiles facing to the right, stacked on top of each other.

August 25, 2016

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

Public Health Service

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

Re: K160650

Trade/Device Name: LIAISON® HAV IgM and LIAISON® Control HAV IgM Regulation Number: 21 CFR 866.3310 Regulation Name: Hepatitis A virus (HAV) serological assays Regulatory Class: II Product Code: LOL, JJX Dated: July 27, 2016 Received: July 28, 2016

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. 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 Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number [phone] or [phone] or at its Internet address

http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. 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

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number [phone] or [phone] or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours.

# Steven R. Gitterman -S

for Uwe Scherf M. Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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# Indications for Use

510(k) Number (if known) K160650

Device Name LIAISON® HAV IgM Assay LIAISON® Control HAV IgM

#### Indications for Use (Describe)

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 plasma (sodium citrate, potassium EDTA, lithium and sodium heparin, and citrate dextrose (ACD)) 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 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 positive) are intended for use as assayed quality control samples to monitor the performance of the LIAISON® HAV IgM assay.

Type of Use (Select one or both, as applicable)

| <span style="font-size:100%;"></span> <span style="font-size:100%;"> <svg height="15px" width="15px"> <path d="M2 2 L2 13 L13 13 L13 2 Z M3 3 L12 3 L12 12 L3 12 Z" fill="none" stroke="black" stroke-width="1"></path> <path d="M4 7 L6 9 L11 4" fill="none" stroke="black" stroke-width="2"></path> </svg> Prescription Use (Part 21 CFR 801 Subpart D)</span> |
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| <span style="font-size:100%;"></span> <span style="font-size:100%;"> <svg height="15px" width="15px"> <path d="M2 2 L2 13 L13 13 L13 2 Z M3 3 L12 3 L12 12 L3 12 Z" fill="none" stroke="black" stroke-width="1"></path> </svg> Over-The-Counter Use (21 CFR 801 Subpart C)</span> |

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#### 5.0 510(k) SUMMARY

| SUBMITTED BY: | Carol A. DePouw<br>Regulatory Affairs Specialist<br>DiaSorin Inc.<br>1951 Northwestern Avenue<br>Stillwater, MN 55082-0285<br>Phone [phone]<br>Fax [phone]<br>Email: [e-mail] |
|----------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| NAME OF DEVICE: | |
| Trade Name: | LIAISON® HAV IgM,<br>LIAISON® Control HAV IgM |
| Common Names/Descriptions: | Hepatitis A Test (Antibody and IgM Antibody)<br>and Controls |
| Classification Names: | Hepatitis A Virus (HAV) Serological assays<br>21 CFR 866.3310 Class II Special Controls<br>Microbiology<br>Single (Specified) analyte controls (assayed<br>and unassayed); Class I reserved;<br>21 CFR 862.1660: Clinical Chemistry |
| Product Code: | LOL, JJX |
| PREDICATE DEVICES | DiaSorin Inc. ETI-HA-IGMK Plus Kit<br>(PMA #P890014) |

#### DEVICE DESCRIPTION:

#### INTENDED USE:

The LIAISON® HAV IqM 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 plasma (sodium citrate, potassium EDTA, lithium and sodium heparin and citrate dextrose (ACD)) 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.

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The LIAISON® Control HAV IgM (negative and positive) are intended for use as assayed quality control samples to monitor the performance of the LIAISON® HAV laM assav.

The method for qualitative determination of HAV IgM is an KIT DESCRIPTION: 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.

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.

### REASON FOR SUBMISSION:

The purpose of this 510(k) Submission is to present the proposed modifications to the DiaSorin LIAISON® HAV IgM and the LIAISON® Control HAV IgM (K082050).

Description of modifications to the LIAISON® HAV IgM and the LIAISON® Control HAV IgM:

1. Proprietary changes to the monoclonal antibodies and conjuqate.

2. Extension of stability claims for the calibration curve, on-board and open use storage.

- 3. Addition of sample types and sample stabilities.
- 4. Change from buffer based controls to serum based controls.

# PERFORMANCE DATA:

The following studies were conducted to demonstrate that the modifications to the LIAISON® HAV IgM assay confirm the substantial equivalence to the predicate device and raise no new questions of safety and effectiveness. Studies not pertaining to the modifications may be found in the original 510(k) K082050.

#### COMPARATIVE STUDIES:

Five commercially available HAV seroconversion panels were tested using the LIAISON® HAV IgM and the FDA-approved comparator assay to determine sensitivity of the assay. The results are summarized in Table 1.

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| Panel ID | LIAISON® HAV IgM | | Comparator Assay | | Difference<br>in days<br>from last<br>reactive<br>result |
|--------------------------|--------------------------------------------------------|-------------------------------------------------|--------------------------------------------------------|-------------------------------------------------|----------------------------------------------------------|
| | Post-bleed<br>day of<br>earliest<br>reactive<br>result | Post-bleed<br>day of last<br>reactive<br>result | Post-bleed<br>day of<br>earliest<br>reactive<br>result | Post-bleed<br>day of last<br>reactive<br>result | |
| 0615-0026 seroconversion | 14 | 27 | 14 | 27 | 0 |
| PHT902 seroconversion | 16 | 21 | 16 | 21 | 0 |
| PHT903 seroconversion | 38 | 108 | 38 | 108 | 0 |
| RP004 seroconversion | 6 | 62 | 6 | 62 | 0 |
| RP013 seroconversion | 8 | 189 | 8 | 189 | 0 |

#### Table 1

The sensitivity of the LIAISON® HAV IgM was equivalent to the comparator assay in the five seroconversion panels tested.

### REPRODUCIBILITY:

A 5 day reproducibility/precision study was conducted at three external laboratories. The CLSI document EP15-A3 was consulted in the preparation of the testing protocol. A coded panel comprised of 6 frozen serum samples was prepared by DiaSorin S.p.A. The coded panel was prepared by either spiking or diluting samples as necessary to contain negative, low positive and mid positive samples.

The LIAISON® Control HAV IgM (negative and positive) were also included in the 5 day study. The LIAISON® HAV IgM Negative Control as well as negative panel sample (HAVM-P00) read below the detectable limit of the curve <<0.10; therefore, standard deviation (SD) and %CVs were calculated using the Relative Light Units (RLU's) for each respective sample

#### Results

The 5 day results are summarized in Table 2 (combined sites). The mean Index value, standard deviation, and coefficient of variation (%CV) of the results were computed for each of the tested specimens for intra- run, run to run, between site, and Total across sites.

| | | Intra-Run | | Run to Run | | Between Site | | Total | |
|----------------|------|-----------|-------|------------|------|--------------|------|-------|-------|
| Sample ID | mean | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| HAVM Negative* | 334 | 18.70 | 5.6 | 7.45 | 2.2% | 8.28 | 2.5 | 21.80 | 6.5% |
| HAVM Positive | 2.22 | 0.26 | 11.7% | 0.05 | 2.2% | 0.05 | 2.3% | 0.26 | 11.8% |
| HAVM-P00 | 535 | 20.50 | 3.8% | 16.10 | 3.0% | 0.00 | 0.0% | 26.00 | 4.9% |
| HAVM-P01* | 1.48 | 0.12 | 8.4% | 0.01 | 0.7% | 0.03 | 2.1% | 0.13 | 8.6% |
| HAVM-P04 | 0.60 | 0.07 | 11.0% | 0.01 | 1.7% | 0.01 | 1.2% | 0.07 | 11.2% |
| HAVM-P14 | 1.18 | 0.08 | 6.6% | 0.02 | 1.9% | 0.02 | 1.3% | 0.08 | 6.7% |
| HAVM-P15 | 2.42 | 0.21 | 8.6% | 0.03 | 1.3% | 0.03 | 1.2% | 0.21 | 8.8% |
| HAVM-P16 | 5.62 | 0.48 | 8.5% | 0.00 | 0.0% | 0.31 | 5.5% | 0.57 | 10.1% |

#### Table 2: Combined Sites

*RLU used in calculations

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#### STABILITY STUDIES: REAGENTS

| LIAISON® HAV IgM | |
|------------------------------------|-----------|
| Study | Stability |
| Calibration Curve | 4 weeks |
| Open Use storage On-board Analyzer | 8 weeks |
| Open Use storage at 2-8°C | 8 weeks |

| LIAISON® Control HAV IgM | |
|---------------------------|-----------|
| Study | Stability |
| Open Use storage at 2-8°C | 4 weeks |

#### SAMPLE EQUIVALENCY AND STABILITY STUDIES:

Sample sets of matched serum/multiple plasma were used in the study to evaluate the risk of potential unspecific reaction related to the use of different sample matrix.

Forty (40) matched sets of samples were assayed. The samples were collected as serum, serum in serum separator tubes, and plasma in anticoagulants Sodium Citrate, Potassium EDTA, Lithium and Sodium heparin and Citrate Dextrose (ACD). The serum specimen in the set was assumed as the reference. Samples belonging to each set were tested in triplicate with one LIAISON® HAV IgM reagent lot on one instrument in a single run.

Results of the SST tube and all plasma samples were compared to serum by Passing and Bablok regression and Bland Altman agreement.

All slopes were between 0.90-1.10, and the bias was within ± 10%.

Human serum, SST serum, Sodium Citrate Plasma, Potassium EDTA Plasma, Lithium Heparin Plasma, Sodium Heparin Plasma, or ACD Plasma are acceptable sample types for use in the LIAISON® HAV IgM assay.

#### SAMPLE STABILITY:

Studies were performed to evaluate the stability of samples at different sample storage conditions. The results are provided in the table below.

| <b>Specimen</b> | |
|----------------------------|------------------|
| <b>Study</b> | <b>Stability</b> |
| Room Temperature (15-30°C) | 2 days |
| Refrigerated (2-8°C) | 7 days |
| Freeze/Thaw Cycles | 5 cycles |

#### CUT-OFF VERIFICATION:

A verification study was performed to ensure that the original cut-off values were appropriate for the modified LIAISON® HAV IgM.

The user may continue to use the following cut-off values for interpretation of patient results.

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| Index | Results | Interpretation |
|-------------------|------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| < 0.90 | Negative<br>(No further testing) | No detectable IgM antibodies to HAV were found.<br>A negative result generally indicates that the patient has not<br>been infected. If clinical exposure to HAV is suspected<br>despite a negative finding, a second sample should be<br>collected and tested no less than one to two weeks later. |
| ≥ 0.90 and < 1.10 | Equivocal<br>(Retest in duplicate) | Equivocal samples should be retested in duplicate by the<br>LIAISON® HAV IgM assay to confirm the initial result.<br>Samples which are reactive (≥ 1.10) on both repeat tests<br>should be considered reactive. Samples which are negative<br>(< 0.90) on both repeat tests should be considered negative.<br>A second sample should be collected and tested no less<br>than one to two weeks later when at least one of the repeat<br>results is equivocal or if the duplicates of the repeat results<br>are reactive and negative.* |
| ≥ 1.10 | Reactive<br>(No further testing) | Indicates the presence of detectable IgM antibodies to HAV.<br>A reactive result generally indicates that the patient has an<br>acute HAV infection. A reactive anti-HAV IgM result does not<br>rule out other hepatitis infections. |

# CONCLUSION:

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