IMMULITE CMV IGG

K950672 · Diagnostic Products Corp. · LFZ · Jun 17, 1996 · Microbiology

Device Facts

• Record ID: K950672
• Device Name: IMMULITE CMV IGG
• Applicant: Diagnostic Products Corp.
• Product Code: LFZ · Microbiology
• Decision Date: Jun 17, 1996
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.3175
• Device Class: Class 2
• Attributes: Pediatric

Intended Use

IMMULITE CMV IgG is designed for the qualitative detection of IgG antibodies to cytomegalovirus (CMV) in human serum. It is intended strictly for in vitro diagnostic use as an aid in the determination of serological status to CMV

Device Story

IMMULITE CMV IgG is a solid-phase, two-step, chemiluminescent enzyme immunoassay used with the IMMULITE Automated Immunoassay Analyzer. Input: human serum sample. Process: sample and protein buffer incubated with CMV antigen-coated polystyrene bead; unbound serum removed via centrifugal wash; alkaline phosphatase-labeled anti-human IgG antibody added and incubated; unbound conjugate removed via centrifugal wash; chemiluminescent substrate (phosphate ester of adamantyl dioxetane) added. Operation: hydrolysis of substrate by alkaline phosphatase yields unstable intermediate emitting light. Output: photon output measured by luminometer, compared to stored Master Cutoff to provide qualitative result. Used in clinical laboratory settings by trained technicians. Benefits: aids in determining CMV serological status, supporting screening of blood for transfusion and donor organ selection.

Clinical Evidence

Clinical performance evaluated via comparison to CDC proficiency panel (n=100), BioWhittaker CYTOMEGELISA II IgG (n=202), and Abbott IMx CMV IgG (n=200). Results showed 100% agreement with CDC panel. Agreement with CYTOMEGELISA II was 98.5% (97.9% sensitivity, 100% specificity). Agreement with IMx was 99.5% (100% sensitivity, 98.7% specificity).

Technological Characteristics

Solid-phase, two-step chemiluminescent enzyme immunoassay. Components: polystyrene bead coated with CMV antigen, alkaline phosphatase-labeled anti-human IgG conjugate, phosphate ester of adamantyl dioxetane substrate. Automated processing via IMMULITE Analyzer. Detection principle: photon emission from chemiluminescent substrate hydrolysis proportional to bound CMV IgG. Qualitative result determined by comparison to stored Master Cutoff.

Indications for Use

Indicated for the qualitative detection of IgG antibodies to cytomegalovirus (CMV) in human serum to determine serological status. Applicable to humans of all ages, including neonates and immunocompromised individuals (e.g., cancer patients, organ recipients, AIDS patients).

Regulatory Classification

Identification

Cytomegalovirus serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to cytomegalovirus in serum. The identification aids in the diagnosis of diseases caused by cytomegaloviruses (principally cytomegalic inclusion disease) and provides epidemiological information on these diseases. Cytomegalic inclusion disease is a generalized infection of infants and is caused by intrauterine or early postnatal infection with the virus. The disease may cause severe congenital abnormalities, such as microcephaly (abnormal smallness of the head), motor disability, and mental retardation. Cytomegalovirus infection has also been associated with acquired hemolytic anemia, acute and chronic hepatitis, and an infectious mononucleosis-like syndrome.

Predicate Devices

• BioWhittaker CYTOMEGELISA II IgG
• Abbott Laboratories' IMx® CMV IgG

Submission Summary (Full Text)

{0}

Diagnostic Products Corporation
IMMULITE® CMV IgG
JUN 17 1996
K950672

# Attachment 9

## 510 (k) Summary

## Safety and Effectiveness

Page 35 of 35

{1}

Diagnostic Products Corporation
5700 West 96th Street
Los Angeles, CA 90045
Tel: [phone]
Fax: [phone]

# DPC

# 510 (k) Summary Safety and Effectiveness

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR Part 807.92.

| Name: | Diagnostic Products Corporation |
| --- | --- |
| Address: | 5700 West 96th Street
Los Angeles, California 90045 |
| Telephone Number: | [phone] |
| Contact Person: | Kenneth B. Asarch, Pharm.D., Ph.D. |
| Date of Preparation: | February 10, 1995 |
| Device Name: | |
| Trade: | IMMULITE® CMV IgG |
| Catalog Number: | LKCVZ (50 tests); LKCV2 (200 tests) |
| Common: | Reagent system for the determination of cytomegalovirus IgG antibodies in human serum. |
| Classification: | Class II device (866.3175) |
| Manufacturer: | Diagnostic Products Corporation
5700 West 96th Street
Los Angeles, California 90045 |
| Establishment Registration #: | DPC's Registration # is 2017183 |
| Substantially Equivalent Predicate Device: | BioWhittaker CYTOMEGELISA II IgG
Abbott Laboratories' IMx® CMV IgG |
| Description of Device: | IMMULITE CMV IgG is a clinical device for use with the IMMULITE Automated Immunoassay Analyzer. |
| Intended Use of the Device: | IMMULITE CMV IgG is designed for the qualitative detection of IgG antibodies to cytomegalovirus (CMV) in human serum. It is intended strictly for in vitro diagnostic use as an aid in the determination of serological status to CMV |

Diagnostic Products Corporation IMMULITE® CMV IgG

{2}

# Summary and Explanation of the Test:

Cytomegalovirus (CMV), a member of the Herpesvirus group is found throughout the world. Humans of all ages are susceptible and infection is spread through sexual contact, direct exposure to infected body fluids, blood transfusions and organ transplants. Infection can be severe in patients with congenital or acquired cellular immune defects, including cancer patients, organ recipients and AIDS patients. The majority of infections are asymptomatic, however, CMV infections can be severe in neonates and immunocompromised individuals.

CMV is the most common congenital infection, infecting between 0.5 and 2.5 percent of newborn infants. Five percent of these will develop classic cyromegalic inclusion disease with jaundice, pneumonia and central nervous system disorder. Infected infants may be asymptomatic at birth, but can develop neurological problems later in life.

Between 40 and 100 percent of people have detectable antibody, with the prevalence highest in developing countries. Serological screening of blood used for transfusion can limit the transmission of infection. In addition, transplantation of organs from donors seronegative for CMV antibodies appears to limit the incidence of acute infection in the recipient.

# Summary and Explanation of the Device:

IMMULITE® CMV IgG is a solid-phase, two-step, chemiluminescent enzyme immunoassay. The solid phase, a polystyrene bead enclosed within an IMMULITE® Test Unit, is coated with a CMV antigen.

Prediluted patient sample (1-in-21 dilution) and a protein-based buffer are simultaneously introduced into the Test Unit, and incubated for approximately 30 minutes at 37°C with intermittent agitation. During this time, CMV IgG in the sample binds to the CMV antigen-coated bead. Unbound serum is then removed by a centrifugal wash.

An alkaline phosphatase-labeled anti-human IgG antibody is introduced, and the Test Unit is incubated for another 30-minute cycle. The unbound enzyme conjugate is removed by a centrifugal wash. Substrate is then added, and the Test Unit is incubated for an additional 10 minutes.

The chemiluminescent substrate, a phosphate ester of adamantyl dioxetane, undergoes hydrolysis in the presence of alkaline phosphatase to yield an unstable intermediate. The continuous production of this intermediate results in the sustained emission of light, thus improving precision by providing a window for multiple reading. The bound complex - and thus the photon output, as measured by the luminometer - is directly related to the presence of CMV IgG in the sample. A qualitative result is then obtained by comparing the patient result to a stored Master Cutoff.

# Performance Equivalence - Technology Comparison:

Diagnostic Products Corporation (DPC) asserts that IMMULITE® CMV IgG is substantially equivalent to the CYTOMEGELISA II IgG kit marketed by BioWhittaker Inc. (Walkersville, MD), and the IMx® CMV IgG kit marketed by Abbott Laboratories (Abbott Park, IL).

Each product is designed for the detection of IgG antibodies to cytomegalovirus (CMV) in human serum. Each product is intended strictly for in vitro diagnostic use as an aid in the determination of serological status to CMV.

Diagnostic Products Corporation IMMULITE® CMV IgG

{3}

# Performance Equivalence - Technology Comparison (continued):

IMMULITE® CMV IgG is a chemiluminescent enzyme immunoassay, CYTOMEGELISA II IgG is an enzyme-linked immunosorbent assay (ELISA), and IMx CMV IgG is a microparticle enzyme immunoassay (MEIA). The technology in DPC's IMMULITE CMV IgG is identical to technology used in previously cleared and commercially marketed IMMULITE® products.

In the CYTOMEGELISA II IgG assay, purified CMV antigen is attached to the surface of microplate wells. Diluted patient serum is added to the wells, and the CMV IgG specific antibody, if present, binds to the antigen. All unbound antibody is washed away and enzyme-conjugated anti-human IgG is added. The enzyme conjugate binds to the antibody-antigen complex. Excess enzyme conjugate begins a hydrolytic reaction. After a specified time, the enzyme reaction is stopped. The intensity of the color generated is proportional to the amount of CMV IgG specific antibody in the sample. The results are read by a spectrophotometer, producing an indirect measurement of the CMV IgG specific antibody in the serum.

In the IMx CMV IgG assay, the patient sample and diluent buffer are added to predilution well of a reaction cell. CMV coated microparticles and the diluted sample are added to an incubation well. The CMV antibody binds to the CMV coated microparticles, forming an antigen-antibody complex. Diluent buffer is added to the reaction mixture and an aliquot of the antigen-antibody complex is transferred to the glass fiber matrix. The microparticles bind irreversibly to the glass fiber matrix. The matrix is washed to remove unbound materials. The anti-human IgG/alkaline phosphatase conjugate is dispensed onto the matrix and binds to the antigen-antibody complex. Finally, the matrix is washed to remove unbound materials, the substrate, 4-Methylumbelliferyl Phosphate, is added to the matrix, and the fluorescent product is measured by the optical assembly.

# Performance Equivalence - Method Comparison:

The clinical performance of the IMMULITE CMV IgG procedure was compared to a CMV proficiency panel obtained from the United States Centers for Disease Control and Prevention (CDC), the CYTOMEGELISA II IgG assay, and the IMx CMV IgG assay. A summary of the results is shown in the table below.

| | IMMULITE vs. CDC | IMMULITE vs. CYTOMEGELISA II IgG | IMMULITE vs. IMx CMV IgG |
| --- | --- | --- | --- |
| Agreement | 100.0% | 98.5% | 99.5% |
| Sensitivity | 100.0% | 97.9% | 100.0% |
| Specificity | 100.0% | 100.0% | 98.7% |
| n = | 100 | 202 | 200 |

# Conclusion:

The conclusions drawn from the clinical and nonclinical studies demonstrate that the device is safe, effective, and performs as well as, or better, than the current legally marketed devices.

Kenneth B. Asarch, Pharm.D., Ph.D.
Director of Regulatory Affairs

2/10/95
Date

Diagnostic Products Corporation IMMULITE® CMV IgG
Page 3 of 3