ABBOTT AXSYM RUBELLA IGM ANTIBODY ASSAY

K954318 · Abbott Laboratories · LFX · May 14, 1996 · Microbiology

Device Facts

• Record ID: K954318
• Device Name: ABBOTT AXSYM RUBELLA IGM ANTIBODY ASSAY
• Applicant: Abbott Laboratories
• Product Code: LFX · Microbiology
• Decision Date: May 14, 1996
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.3510
• Device Class: Class 2

Intended Use

The AxSYM Rubella IgM Antibody assay is a Microparticle Enzyme Immunoassay (MEIA) for the qualitative measurement of IgM antibodies to rubella virus in human serum and plasma (EDTA, heparin or sodium citrate) to aid in the diagnosis of primary or acute infection. The AxSYM Rubella IgM assay is not for use with cord blood or neonatal specimens.

Device Story

AxSYM Rubella IgM Antibody assay is an automated Microparticle Enzyme Immunoassay (MEIA) for qualitative detection of rubella-specific IgM in human serum/plasma. Device uses polystyrene microparticles coated with rubella virus antigen (strain HPV-77, Vero cell culture). Sample is processed on AxSYM analyzer; RF neutralization buffer is applied to all samples to mitigate interference. Immune complexes form between rubella antigens and patient IgM; goat anti-human IgM conjugated to alkaline phosphatase binds; MUP enzyme substrate produces signal. Output is qualitative result indicating presence of IgM antibodies. Used in clinical laboratory settings by trained personnel to aid diagnosis of primary or acute rubella infection. Results assist clinicians in confirming acute infection status.

Clinical Evidence

Clinical study at three sites compared AxSYM Rubella IgM to IMx Rubella IgM using 1300 samples (pregnant, non-pregnant, and IgM-positive individuals). Results: relative sensitivity 95.7%, relative specificity 99.4%, relative agreement 99.1%. Precision (CV) for positive controls/panel members ranged 6.9% to 12.6%. Discordant analysis performed using two additional EIA assays (Rubazyme M, RUBASTAT M).

Technological Characteristics

MEIA principle; polystyrene microparticle solid phase; rubella virus antigen (strain HPV-77) from Vero cell culture; goat anti-human IgM alkaline phosphatase conjugate; MUP enzyme substrate. Automated analyzer platform. RF neutralization buffer pretreatment.

Indications for Use

Indicated for qualitative detection of IgM antibodies to rubella virus in human serum and plasma to aid in diagnosis of primary or acute infection. Not for use with cord blood or neonatal specimens.

Regulatory Classification

Identification

Rubella virus serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to rubella virus in serum. The identification aids in the diagnosis of rubella (German measles) or confirmation of a person's immune status from past infections or immunizations and provides epidemiological information on German measles. Newborns infected in the uterus with rubella virus may be born with multiple congenital defects (rubella syndrome).

Special Controls

*Classification.* Class II. The special controls for this device are:(1) National Committee for Clinical Laboratory Standards': (i) 1/LA6 “Detection and Quantitation of Rubella IgG Antibody: Evaluation and Performance Criteria for Multiple Component Test Products, Speciment Handling, and Use of the Test Products in the Clinical Laboratory, October 1997,” (ii) 1/LA18 “Specifications for Immunological Testing for Infectious Diseases, December 1994,” (iii) D13 “Agglutination Characteristics, Methodology, Limitations, and Clinical Validation, October 1993,” (iv) EP5 “Evaluation of Precision Performance of Clinical Chemistry Devices, February 1999,” and (v) EP10 “Preliminary Evaluation of the Linearity of Quantitive Clinical Laboratory Methods, May 1998,” (2) Centers for Disease Control's: (i) Low Titer Rubella Standard, (ii) Reference Panel of Well Characterized Rubella Sera, and (3) World Health Organization's International Rubella Standard.

Predicate Devices

• Abbott IMx Rubella IgM Antibody assay (K954318)

Reference Devices

• Abbott Rubazyme M EIA
• BioWhittaker RUBASTAT M

Submission Summary (Full Text)

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Abbott Laboratories AxSYM Rubella IgM Antibody Assay [510(k)] Submission

# ATTACHMENT A

[510(k)] Summary of Safety and Effectiveness Information Supporting a Substantially Equivalent Determination and Certification of Search for Adverse Safety and Effectiveness

K954318

MAY 14 1996

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Abbott Laboratories AxSYM Rubella IgM Antibody Assay [510(k)] Submission

# [510(k)] Summary of Safety and Effectiveness Information Supporting a Substantially Equivalent Determination

The following information presented in the [510(k)] Submission for the AxSYM Rubella IgM Antibody assay constitutes data supporting a substantially equivalent determination:

# [510(k)] Summary of Device Performance

The AxSYM Rubella IgM Antibody assay is a Microparticle Enzyme Immunoassay (MEIA) for the qualitative measurement of IgM antibodies to rubella virus in human serum and plasma (EDTA, heparin or sodium citrate) to aid in the diagnosis of primary or acute infection. The AxSYM Rubella IgM assay is not for use with cord blood or neonatal specimens.

The predicate device for determination of substantial equivalence is Abbott's legally marketed IMx Rubella IgM Antibody assay; a Microparticle Enzyme Immunoassay (MEIA) for the qualitative measurement of IgM antibodies to rubella virus in human serum or plasma (EDTA, heparin or sodium citrate) to aid in the diagnosis of primary infection. The IMx Rubella IgM assay is not for use with cord blood or neonate specimens.

In three clinical sites, the AxSYM Rubella IgM Antibody assay was compared to the Abbott IMx Rubella IgM Antibody assay using 1300 samples from pregnant women, non-pregnant individuals and individuals positive for IgM antibodies to rubella. The AxSYM Rubella IgM Antibody assay was shown to have a relative sensitivity of 95.7%, relative specificity of 99.4% and a relative agreement of 99.1%. Percent CV's on positive panel members and positive controls was 6.9% to 12.6%.

Further evaluation of 11 discordant specimens was performed using two additional legally marketed assays (Abbott Rubazyme M EIA and BioWhittaker RUBASTAT M). Of the seven specimens positive by AxSYM and negative by EIA, two were found to be positive, four were found to be negative and one was found to be equivocal for IgM antibody. Of the four specimens negative by AxSYM and positive by EIA, one was found to be negative and three were found to be equivocal for IgM antibody. Specimens giving equivocal results using AxSYM and/or EIA were not included in the calculation of relative agreement, relative sensitivity and relative specificity.

In conclusion, the AxSYM Rubella IgM Antibody assay is substantially equivalent to the Abbott IMx Rubella IgM Antibody assay for the detection of IgM antibodies to rubella virus in human serum and plasma (EDTA, heparin or sodium citrate) specimens to aid in the diagnosis of primary or acute infection.

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Abbott Laboratories AxSYM Rubella IgM Antibody Assay [ 510(k)] Submission

## [510(k)] Summary Of Technological Comparison

The AxSYM Rubella IgM Antibody Assay and the IMx Rubella IgM Antibody assay are Substantially Equivalent in that:

1. Both are in vitro immunologic test methods.
2. Both are intended for use in the detection of IgM antibody to rubella virus in human serum or plasma (EDTA, heparin or sodium citrate).
3. Both are based on the formation of immune complexes between rubella virus antigens and antibody.
4. Both use a polystyrene microparticle solid phase.
5. Both are qualitative assays.
6. Both use a solid phase coated with antigen from rubella virus strain HPV-77.
7. Both use antigen produced in Vero cell culture.
8. Both use goat anti-human IgM antibody conjugated to alkaline phosphatase.
9. Both use MUP as the enzyme substrate.
10. Both use an automated instrument.

The AxSYM Rubella IgM Antibody Assay and the IMx Rubella IgM Antibody assay Differ in that:

1. The AxSYM Rubella IgM Antibody assay is an automated microparticle enzyme immunoassay performed with the AxSYM, a random and continuously accessed automated immunoassay analyzer. The IMx Rubella IgM Antibody assay is an automated microparticle enzyme immunoassay performed with the IMx automated immunoassay analyzer.
2. The IMx Rubella IgM Antibody assay requires that all positive samples be treated (RF neutralized) with human IgG microparticles and retested due to the potential for RF interference. The AxSYM Rubella IgM Antibody assay pretreats all samples with an RF neutralization buffer and does not require additional treatment and testing of positive samples.

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Abbott Laboratories AxSYM Rubella IgM Antibody Assay [510(k)] Submission

Comparison of Methods

| Assay Characteristics | AxSYM Rubella IgM | IMx Rubella IgM |
| --- | --- | --- |
| Assay Type | Qualitative | Qualitative |
| Antibody Measured | Specific IgM | Specific IgM |
| Assay Principle | MEIA | MEIA |
| Solid Phase | Polystyrene microparticles | Polystyrene microparticles |
| Solid Phase Coating | Rubella virus antigen strain HPV-77 grown in Vero cells | Rubella virus antigen strain HPV-77 grown in Vero cells |
| Conjugate | Goat anti-human IgM conjugated to alkaline phosphatase | Goat anti-human IgM conjugated to alkaline phosphatase |
| Specimen | Human serum and plasma (EDTA, heparin or sodium citrate) | Human serum and plasma (EDTA, heparin or sodium citrate) |
| Automation | Performed on automated instrument | Performed on automated instrument |
| Relative Sensitivity | 95.7% | 95.4% |
| Relative Specificity | 99.4% | 99.4% |

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Abbott Laboratories AxSYM Rubella IgM Antibody Assay [510(k)] Submission

# Certification of search for adverse safety and effectiveness

The undersigned certifies to the best of his knowledge and belief that reasonable search of all information known or otherwise presently available to Abbott Laboratories has been conducted. The scope of the search was as follows:

Accuracy/Clinical Utility/Reproducibility/Safety of Rubella Immunoassays
Biohazard of Rubella Antigen
Adverse Effects and Safety of Sodium Azide

The searches were performed by Abbott Laboratories Information Services Department for the undersigned individual on March 2, 1995.

Dialog® Information Service was used for database searches. A list of databases is included on the following page in this section.

Conclusion: No adverse safety and effectiveness data was found in the search provided the product is used as intended for in vitro diagnostic use.


Richard M. Fleming
Associate Scientist
CRG Business Unit
Abbott Laboratories
One Abbott Park Road
Abbott Park, IL 60064

Databases Searched:

## Database File Name

5: BIOSIS PREVIEWS® 1969-1995/Feb W2
72: EMBASE 1985-1995/ISS 06
73: EMBASE 1974-1995/ISS 05
144: PASCAL 1973-1994/Aug
154: MEDLINE (R) 1985-1995/Apr W2
155: MEDLINE® 1966-1995/Apr W2
156: TOXLINE(R) 1965-1995/Jan
336: REG TOX EFF CHEM SUB 1994/Oct
434: SCISEARCH(R) 1974-1995/Jan W5

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