LIAISON EA IGG

K060204 · DiaSorin, Inc. · LSE · Oct 18, 2006 · Microbiology

Device Facts

• Record ID: K060204
• Device Name: LIAISON EA IGG
• Applicant: DiaSorin, Inc.
• Product Code: LSE · Microbiology
• Decision Date: Oct 18, 2006
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.3235
• Device Class: Class 1
• Attributes: 3rd-Party Reviewed

Intended Use

The LIAISON® EA IgG assay and LIAISON® EA IgG Controls use chemiluniescent immunoassay (CLIA) technology on the LIAISON Analyzer for the qualitative determination of IgG antibodies to Epstein-Barr virus early antigen-diffuse [EA(D)] in human serum. This assay can be used as an aid in the clinical laboratory diagnosis of Epstein-Barr viral Syndrome in patients with signs and symptoms of EBV infection such as infectious mononucleosis (IM).

Device Story

The LIAISON® EA IgG is an indirect chemiluminescence immunoassay (CLIA) performed on the LIAISON® Analyzer. It utilizes magnetic particles coated with 47-kDa recombinant EA(D) antigen and an isoluminol-antibody conjugate. Input: human serum samples. Process: samples are incubated with magnetic particles; EA(D) antibodies bind to the solid phase; isoluminol-antibody conjugate is added; unbound material is washed away; starter reagents induce a flash chemiluminescence reaction. Output: relative light units (RLU) measured by a photomultiplier, indicating the presence of EA(D) IgG antibodies. Used in clinical laboratories by trained personnel. Results assist clinicians in diagnosing Epstein-Barr viral syndrome in patients with symptoms like infectious mononucleosis. The device aids in patient management by providing serological evidence of EBV infection.

Clinical Evidence

Clinical performance was evaluated using 70 retrospective samples from acute EBV patients and 823 prospective samples from patients referred for EBV testing. In retrospective samples, the device showed 100% positive agreement (70/70) with reference serological profiles. In prospective samples, negative agreement was 98.4% (62/63) for seronegative subjects and 56.9% for past infection cases. Precision testing across three sites showed a mean total %CV of 11.2%. Cross-reactivity was evaluated against 222 samples; 11 samples (including CMV, VZV, HIV, and Hepatitis B) showed positive or equivocal results.

Technological Characteristics

Indirect chemiluminescence immunoassay (CLIA). Solid phase: magnetic microparticles coated with 47-kDa recombinant EA(D) polypeptide. Conjugate: mouse monoclonal anti-human IgG-isoluminol derivative. Energy source: electrical (LIAISON® Analyzer). Form factor: automated benchtop analyzer. Connectivity: standalone system. Software: embedded firmware for automated processing and signal quantification. Sterilization: N/A (reagents).

Indications for Use

Indicated for the qualitative determination of IgG antibodies to Epstein-Barr virus early antigen-diffuse [EA(D)] in human serum as an aid in the clinical laboratory diagnosis of Epstein-Barr viral Syndrome such as infectious mononucleosis (IM). Not for use in immunocompromised/immunosuppressed patients, cord blood, neonates, infants, or for diagnosis of nasopharyngeal carcinoma, Burkitt's lymphoma, or other EBV-associated lymphomas. Prescription use only.

Regulatory Classification

Identification

Epstein-Barr virus serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to Epstein-Barr virus in serum. The identification aids in the diagnosis of Epstein-Barr virus infections and provides epidemiological information on diseases caused by these viruses. Epstein-Barr viruses are thought to cause infectious mononucleosis and have been associated with Burkitt's lymphoma (a tumor of the jaw in African children and young adults) and postnasal carcinoma (cancer).

Predicate Devices

• DiaSorin ETI-EA-G Kit (K992191)

Submission Summary (Full Text)

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K060204

## 6.0 510(k) SUMMARY

OCT 1 8 2006

David M. Ikeda Requlatory Affairs/Quality Systems Manager DiaSorin Inc. 1951 Northwestern Avenue P.O. Box 285 Stillwater, MN 55082-0285 Phone [phone] Fax [phone] E-mail: [e-mail]

LIAISON® EA IgG / LIAISON® Control EA IgG

Immunoassay for the detection of IgG antibodies to

NAME OF DEVICE: Trade Name:

SUBMITTED BY:

Common Names/Descriptions:

Classification Names:

Product Code:

PREDICATE DEVICE:

EBV early antigen-diffuse [EA(D)]

EPSTEIN-BARR VIRUS, OTHER

DiaSorin ETI-EA-G Kit (K992191)

DEVICE DESCRIPTION:

INTENDED USE: The DiaSorin LIAISON® EA IgG kit uses chemiluminescence immunoassay (CLIA) technology on the LIAISON® Analyzer for the qualitative detection of specific IgG antibodies to Epstein-Barr virus early antigen-diffuse [EA(D)] in human serum. This assay uses a 47-kDa recombinant antigen expressed in E. coll DH-1 cells. When used in conjunction with other EBV markers, this assay can be used as an aid in the clinical laboratory diagnosis of Epstein-Barr viral Syndrome in patients with signs and symptoms of EBV infection such as infectious mononucleosis (IM). LIAISON® Control EA IgG kit is used in conjunction with LIAISON® EA IgG immunoassay for monitoring substantial reagent failure.

LSE

KIT DESCRIPTION: The method for qualititative determination of specific IgG to Epstein-Barr virus early antigen-diffuse (EA(D) recombinant polypeptide] is an indirect chemiluminescence immunoassay (CLIA). All assay steps (with the exception of magnetic particle resuspension) and incubations are performed by the LIAISON® Analyzer. The principal components of the test are magnetic particles (solid phase) coated with EA(D) recombinant polypeptide and a conjugate of mouse monoclonal antibody to human IgG linked to an isoluminol derivative (isoluminol-antibody conjugate). During the first incubation, EA(D) antibodies present in calibrators, samples or controls bind to the solid phase. During the second incubation, the antibody conjugate reacts with EA(D) antibodies that are already bound to the solid phase. After each incubation, 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

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photomultiplier as relative light units (RLU) and is indicative of the presence of EA(D) IgG antibodies present in calibrators, samples or controls.

## PERFORMANCE DATA:

COMPARATIVE CLINICAL TRIALS: The clinical trials were conducted at two external US laboratories and at DiaSorin. Testing was performed on repository and prospective samples as defined below. The samples were tested by LIAISON® EA IgG and comparison assay (DiaSorin ETI-EA-G ELISA Kit), at the trial sites per the manufacturers' instructions for use.

Prospective Samples: Subjects Sent to the Laboratory for EBV Testing:

| LIAISON®<br>EA IgG | DiaSorin ETI-EA-G | | Total |
|---------------------------|-------------------|----------|-------|
| | Positive | Negative | |
| Positive (≥11.0 U/mL) | 297 | 20 | 317 |
| Equivocal (9.0-10.9 U/mL) | 17 | 12 | 29 |
| Negative (<9.0 U/mL) | 15 | 462 | 477 |
| Total | 329 | 494 | 823 |

| Percent Agreement | Exact 95% confidence interval | |
|-------------------|-------------------------------|--------------|
| Positive | 90.3% (297/329) | 86.6 – 93.3% |
| Negative | 93.5% (462/494) | 91.0 – 95.5% |
| Overall | 92.2% (759/823) | 90.2 – 94.0% |

Retrospective Samples: VCA IgM-positive Samples

| LIAISON®<br>EA IgG | DiaSorin ETI-EA-G | | |
|-------------------------------|-------------------|----------|-------|
| | Positive | Negative | Total |
| Positive (≥11.0<br>U/mL) | 70 | 0 | 70 |
| Equivocal (9.0-<br>10.9 U/mL) | 0 | 0 | 0 |
| Negative (<9.0<br>U/mL) | 0 | 0 | 0 |
| Total | 70 | 0 | 70 |

.

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| | Percent Agreement | Exact 95% confidence interval |
|----------|-------------------|-------------------------------|
| Positive | 100.0% (70/70) | 94.9 - 100.0% |
| Negative | N.C.* (0/0) | N.C.* |
| Overall | 100.0% (70/70) | 94.9 - 100.0% |

REPRODUCIBILITY: Reproducibility studies were performed at 3 sites using a coded panel comprised of 9 frozen repository serum samples. The serum panel was prepared to represent from low- to mid-positive analyte level. The same coded panel was tested at all sites, in three replicates per run for ten runs. Results expressed in U/mL are summarized in the following table.

| ID# | N | mean<br>(U/mL) | within<br>run<br>S.D. | within<br>run<br>%CV | between<br>run<br>S.D. | between<br>run<br>%CV | between<br>site<br>S.D. | between<br>site<br>%CV | overall<br>S.D. | overall<br>%CV |
|------|----|----------------|-----------------------|----------------------|------------------------|-----------------------|-------------------------|------------------------|-----------------|----------------|
| EAS1 | 90 | 47.6 | 1.78 | 3.71 | 4.56 | 8.65 | 2.46 | 5.16 | 4.78 | 10.04 |
| EAS2 | 90 | 99.1 | 6.10 | 6.06 | 9.24 | 8.60 | 4.64 | 4.68 | 10.82 | 10.92 |
| EAS3 | 90 | 112.3 | 7.50 | 7.07 | 15.81 | 13.19 | 2.84 | 2.53 | 17.26 | 15.36 |
| EA1 | 90 | 18.2 | 0.93 | 5.17 | 1.56 | 5.50 | 1.37 | 7.52 | 1.85 | 10.15 |
| EA2 | 90 | 20.4 | 0.63 | 3.17 | 2.27 | 5.87 | 2.31 | 11.33 | 2.34 | 11.45 |
| EA3 | 90 | 47.4 | 2.07 | 4.60 | 4.87 | 5.18 | 5.09 | 10.75 | 5.28 | 11.15 |
| EA4 | 90 | 35.9 | 1.58 | 4.60 | 4.02 | 6.02 | 4.08 | 11.35 | 4.30 | 11.99 |
| EA5 | 90 | 52.4 | 2.03 | 3.88 | 4.54 | 3.55 | 5.01 | 9.56 | 4.94 | 9.43 |
| EA6 | 90 | 18.1 | 0.60 | 3.38 | 1.72 | 4.12 | 1.86 | 10.27 | 1.80 | 9.91 |

INTERFERENCE: Controlled studies of potentially interfering substances showed that the assay performance was not affected by hemolysis (at 1000 mg/dL hemoglobin), lipemia (at 3000 mg/dL triglycerides), icterus (at 20 mg/dL bilirubin).

CROSS-REACTIVITY: The cross-reactivity studies for the LIAISON® EA IgG assay were designed to evaluate potential interference from IgG immunoglobulins directed against other Epstein-Barr virus antibodies (VCA, EBNA), closely-related members of the herpes virus family (HSV-1/2, HSV-2, VZV, CMV), from other organisms that may cause symptoms similar to EBV (Toxoplasma gondii, rubella virus) and from other conditions that may result from atypical immune system activity (rheumatoid factor (RF), antinuclear antibodies (ANA)). In addition, potential interference from human anti-mouse antibodies (HAMA) was evaluated.

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| Organism / condition | Number of<br>Samples | Positive or<br>equivocal<br>LIAISON® EA<br>IgG Result |
|--------------------------|----------------------|-------------------------------------------------------|
| EBV VCA IgG | 3 | (0/3) |
| EBV VCA IgG/EBNA<br>IgG | 4 | (0/4) |
| CMV IgG | 27 | (2/27) |
| VZV IgG | 6 | (0/6) |
| HSV-1/2 IgG | 21 | (1/21) |
| HSV-2 IgG | 1 | (0/1) |
| Toxoplasma gondii<br>IgG | 17 | (4/17) |
| Rubella virus IgG | 87 | (8/87) |
| RF | 2 | (0/2) |
| ANA | 10 | (0/10) |
| HAMA | 5 | (0/5) |
| Total | 183 | (15/183) |

Fifteen specimens out of 183 total specimens tested from the cross-reaction panel relumed
positive or equivocal results in the LIAISON® EA lgG assay. were-poeitive. There-was somalos the necessionity samples, were aguivanal, by HAIOAN Coannot be excluded. Five of the fifteen discordant included in the colouictions Lion For Locking EA IgG. Equivocal results by LIAISON® EA IgG are semples, sellected and non-agreement since it was not possible to acquire tollow-up samples collected one to two weeks later as recommended. Since the highest rate of the Enclain Ramaines (There with conditions caused by organisms taxonomically unrelated to the Epstein-Barr virus (Toxoplasma gondii and rubella virus), the apparent cross-reactivity may be due to performance differences between the two EA IgG test methods. In fact, the observed that obtained with the presentive with the can inchieds (11.8%) with these samples is similar to that obtained with the prospective clinical samples (93.5% negative sample startenen),

The recombinant EA(D) antigen used in the assay is expressed in E. coli DH-1 cells. The performance characteristics of this device with samples containing antibodies against E. coli have not been established.

WARNING: Assay interference due to circulating antibodies against HIV and Hepatitis A, Hepatitis B and Hepatitis C viruses has not been evaluated. The and repail.ls A, establishing cross-reactivity performance with these infectious agents.

## CONCLUSION

The LIAISON® EA IgG assay showed equivalent performance to the corresponding FDAcleared assay. The DiaSorin LIAISON® EA lgG assay demonstrated agreement with the comparison method higher then 92% among prospectively collected samples and 100% agreement among retrospective selected samples. The results demonstrated that LIAISON® EA IgG assay can be used with the LIAISON® Analyzer for the qualitative detection of IGG antibodies to EA(D) recombinant polypeptide and can be intended for use as an aid in the clinical laboratory diagnosis of Epstein-Barr viral Syndrome in patients with signs and symptoms of EBV infection such as infectious mononucleosis (IM)

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Image /page/4/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle with three tail feathers, representing the department's commitment to health, human services, and well-being. The eagle is positioned to the right of the department's name, which is arranged in a circular pattern around the logo. The text reads "DEPARTMENT OF HEALTH & HUMAN SERVICES . USA".

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Mr. Don Kafader Director of Regulatory Affairs DiaSorin Inc. 1951 Northwestern Ave. P.O. Box 285 Stillwater, MN 55082

OCT 1 8 2006

Re: k060204

> Trade/Device Name: DiaSorin LIAISON® EA IgG Assay Regulation Number: 21 CFR 866.3235 Regulation Name: Epstein-Barr virus Serological Reagents Regulatory Class: Class I Product Code: LSE Dated: October 6, 2006 Received: October 13, 2006

Dear Mr. Kafader:

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, istis 1.0.1 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 Begister.

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).

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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 a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at [phone]. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number [phone] or [phone] or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.

Sincerely yours,

Sally, axtom

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

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## Indications for Use

510(k) Number (if known): K060204

LIAISON® EA IgG Assay and LIAISON® EA IgG Controls Device Name:

Indications For Use: The LIAISON® EA IgG assay and LIAISON® EA IgG Controls use chemiluniescent immunoassay (CLIA) technology on the LIAISON Analyzer for the qualitative determination of IgG antibodies to Epstein-Barr virus early antigen-diffuse [EA(D)] in human serum. This assay can be used as an aid in the clinical laboratory diagnosis of Epstein-Barr viral Syndrome in patients with signs and symptoms of EBV infection such as infectious mononucleosis (IM).

Prescription Use × (Part 21 CFR 801 Subpart D)

AND/OR

Over-The-Counter Use (21 CFR 801 Subpart C)

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Sali atta
Division Sign

Office of In Vitro Diagnostic D» Evaluation and S & J

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