IMMULITE RUBELLA IGM,LKRM1, LKRM2, IMMULITE 2000 RUBELLA IGM, MODEL L2KRM2, L2KRM6

K012077 · Diagnostic Products Corp. · LFX · Jan 10, 2002 · Microbiology

Device Facts

• Record ID: K012077
• Device Name: IMMULITE RUBELLA IGM,LKRM1, LKRM2, IMMULITE 2000 RUBELLA IGM, MODEL L2KRM2, L2KRM6
• Applicant: Diagnostic Products Corp.
• Product Code: LFX · Microbiology
• Decision Date: Jan 10, 2002
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.3510
• Device Class: Class 2

Intended Use

IMMULITE® Rubella IgM – For in vitro diagnostic use with the IMMULITE Analyzer – for the qualitative detection of IgM antibodies to rubella virus in human serum or plasma (EDTA or heparinized), as an aid in the presumptive diagnosis of an acute or recent rubella infection, particularly in women of childbearing age. IMMULITE 2000® Rubella IgM - For in vitro diagnostic use with the IMMULITE 2000 Analyzer - for the qualitative detection of IgM antibodies to rubella virus in human serum or plasma (EDTA or heparinized), as an aid in the presumptive diagnosis of an acute or recent rubella infection, particularly in women of childbearing age.

Device Story

IMMULITE and IMMULITE 2000 Rubella IgM are automated chemiluminescent enzyme immunoassays. Input: human serum or plasma. Process: patient sample incubated with rubella antigen-coated polystyrene beads; rubella-specific IgM binds to antigen; centrifugal wash removes unbound serum; alkaline phosphatase-labeled anti-human IgM antibody added; second incubation; centrifugal wash; chemiluminescent substrate (phosphate ester of adamantyl dioxetane) added. Output: light emission measured by luminometer; photon output proportional to bound complex; qualitative result determined by comparison to established cutoff. Used in clinical laboratories; operated by trained personnel. Output assists clinicians in diagnosing acute or recent rubella infection.

Clinical Evidence

Clinical studies conducted at multiple sites compared IMMULITE/IMMULITE 2000 Rubella IgM against a commercially available EIA (Trinity Biotech CAPTIA Rubella-M). Studies included pregnant women and individuals with various conditions (total n=236 and n=233). Results showed high agreement: positive agreement 86.5%-100%, negative agreement 95.3%-99.3%, and overall agreement 93.6%-97.6%. Precision studies (within-run and total CVs) were performed across multiple sites and sample types (serum, EDTA, heparin), demonstrating acceptable reproducibility.

Technological Characteristics

Solid-phase, two-step chemiluminescent enzyme immunoassay. Solid phase: polystyrene bead. Energy source: chemiluminescent substrate (phosphate ester of adamantyl dioxetane). Analyzers: IMMULITE and IMMULITE 2000. Connectivity: automated analyzer integration. Sterilization: not specified. Software: automated analyzer firmware for signal processing and cutoff comparison.

Indications for Use

Indicated for qualitative detection of IgM antibodies to rubella virus in human serum or plasma (EDTA or heparinized) to aid in presumptive diagnosis of acute or recent rubella infection, particularly in women of childbearing age.

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

• Trinity Biotech™ CAPTIA Rubella-M (K885300)

Submission Summary (Full Text)

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# JAN 1 0 2002

K012077

## 510(k) Summary Safety and Effectiveness IMMULITE and IMMULITE 2000 Rubella IgM

This summary of safety and effectiveness information has been prepared in accordance with the requirements of SMDA 1990 and 21 CFR Part 807.92.

| Name: | Diagnostic Products Corporation |
|-----------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Address: | 5700 West 96th Street<br>Los Angeles, California 90045-5597 |
| Telephone Number: | [phone] |
| Facsimile Number: | [phone] |
| Contact Person: | Edward M. Levine, Ph.D.<br>Director of Clinical Affairs |
| Date of Preparation: | January 8, 2002 |
| Device Name: | IMMULITE® Rubella IgM |
| Trade: | IMMULITE® 2000 Rubella IgM |
| Catalog Number: | LKRM1(100 tests), LKRM2 (200 tests)<br>L2KRM2 (200 tests), L2KHQ6 (600 tests) |
| Common: | Reagent system for the qualitative detection of IgM<br>antibodies to rubella virus in human |
| Classification: | Class II device, 83-LFX (21CFR 866.3510) |
| Manufacturer: | Diagnostic Products Corporation<br>5700 West 96th Street<br>Los Angeles, CA 90045<br>(The Quality System of Diagnostic Products Corporation is<br>registered to ISO 9001:1994) |
| Establishment Registration<br>Number | DPC's Registration Number 2017183 |
| Substantially Equivalent<br>Predicate Device: | Trinity Biotech™ CAPTIA Rubella-M (K885300) |

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Description of Devices:

IMMULITE Rubella IgM and IMMULITE 2000 Rubella IgM are clinical devices for use with their respective IMMULITE and I IMMULITE 2000 Automated Immunoassay Analyzers.

## Intended Use of the Device:

IMMULITE® Rubella IgM – For in vitro diagnostic use with the IMMULITE Analyzer – for the qualitative detection of IgM antibodies to rubella virus in human serum or plasma (EDTA or heparinized), as an aid in the presumptive diagnosis of an acute or recent rubella infection, particularly in women of childbearing age.

IMMULITE 2000® Rubella IgM - For in vitro diagnostic use with the IMMULITE 2000 Analyzer - for the qualitative detection of IgM antibodies to rubella virus in human serum or plasma (EDTA or heparinized), as an aid in the presumptive diagnosis of an acute or recent rubella infection, particularly in women of childbearing age.

## Performance Equivalence:

Products Corporation (DPC) asserts that IMMULITE Rubella IgM and Diagnostic IMMULITE 2000 Rubella IgM produce substantially equivalent results to other commercially marketed Rubella IgM assays, such as Trinity Biotech™ CAPTIA Rubella-M (K885300). The IMMULITE and IMMULITE 2000 Rubella IgM assays and Trinity Biotech CAPTIA Rubella-M are intended strictly for in vitro diagnostic use for the presumptive diagnosis of acute (current in CAPTIA Rubella M) or recent rubella infection.

## Technology Comparison:

Provided below is a comparison of DPC's IMMULITE and IMMULITE 2000 Rubella IgM technology vs. the Trinity Biotech CAPTIA Rubella-M EIA technology.

IMMULITE Rubella IgM is a solid-phase, two-step chemiluminescent enzyme immunoassay. The solid phase, a polystyrene bead enclosed within an IMMULITE Test Unit, is coated with partially purified rubella 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, rubella-specific IgM in the sample binds to the rubella antigen-coated bead. Unbound serum is then removed by a centrifugal wash.

An alkaline phosphatase-labeled anti-human IgM antibody is introduced, and the Test Unit is incubated for approximately 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 a further 10 minutes.

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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 readings. The bound complex -- and thus also the photon output, as measured by the luminometer -- is related to the presence of rubella IgM in the sample. A qualitative result is then obtained by comparing the patient result to an established Cutoff.

IMMULITE 2000 Rubella IgM is a solid-phase, two-step chemiluminescent enzyme immunoassay. The solid phase, a polystyrene bead added to an IMMULITE 2000 Reaction Tube, is coated with partially purified rubella antigen.

Prediluted patient sample (1-in-20 dilution) and a protein-based buffer are simultaneously introduced into the Reaction Tube, and incubated for approximately 30 minutes at 37℃ with intermittent agitation. During this time, rubella-specific IgM in the sample binds to the rubella antigen-coated bead. Unbound serum is then removed by a centrifugal wash.

An alkaline phosphatase-labeled anti-human IgM antibody is introduced, and the Reaction Tube is incubated for approximately another 30-minute cycle. The unbound enzyme conjugate is removed by a centrifugal wash. Substrate is then added, and the Reaction Tube is incubated for a further 5 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 readings. The bound complex -- and thus also the photon output, as measured by the luminometer -- is related to the presence of rubella IgM in the sample. A qualitative result is then obtained by comparing the patient result to an established Cutoff.

The Trinity Biotech CAPTIA Rubella-M assay utilizes the Enzyme Immunoassay (EIA) technique for the detection of antibody to rubella virus. Goat antibody against human IgM is immobilized on the inner surface of microtitration wells. When diluted patient serum is incubated in the well a proportion of the total IgM is "captured" by the surface-bound antibody. Unbound serum components are rinsed away. Surface-bound rubella IgM is then specifically detected by incubation with a tracer pre-complex of rubella antigen, biotinylated rubella monoclonal antibody and horseradish peroxidase-streptavidin. Unbound complex is rinsed away. Surface bound enzyme labeled complex is identified by reaction with a substrate and the chromogen tetramethylbenzidine. The intensity of the colored reaction product is directly proportional to the amount of rubella IgM initially "captured" on the solid phase.

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## Expected Values

Individuals acutely infected with rubella virus will not exhibit detectable levels of IgM antibody in the early stages of infection. IgM antibodies to rubella virus are detected a few days after the onset of rash or vaccination. Peak IgM levels are reached in 3 to 6 weeks, then gradually decline over a period of months.

The prevalence of rubella infection can vary depending on a number of factors such as age, gender, vaccination history, geographic location, socio-economic status, race, type of test used, specimen collection and handling procedures and clinical and epidemiological history of individual patients.

## IMMULITE Rubella IgM

Studies with presumed healthy, asymptomatic subjects and individuals suspected of acute rubella infection were conducted at two clinical sites in the southern and northeastern United States. The study in the southern United States consisted of 236 specimens from 92 pregnant women and 144 individuals with various conditions. IMMULITE Rubella IgM tests on these samples yielded the following results:

| Subjects | Total<br>n | Positive | | Negative | | Indeterminate | |
|----------|------------|----------|-----|----------|-----|---------------|----|
| | | n | % | n | % | n | % |
| Pregnant | 92 | 5 | 6% | 84 | 91% | 3 | 3% |
| Various | 144 | 45 | 31% | 86 | 60% | 13 | 9% |
| All | 236 | 50 | 21% | 170 | 72% | 16 | 7% |

## Observed signal/cutoff ratios for all samples

Image /page/3/Figure/7 description: The image is a bar graph showing frequency on the y-axis and ratio on the x-axis. The frequency ranges from 0 to 120, while the ratio ranges from 0.0 to 5.0. The bar at ratio 0.5 has a frequency of approximately 110, while the bar at ratio 0.0 has a frequency of approximately 42.

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The study in the northeastern United States consisted of 233 specimens from 60 pregnant women The stady in the nermous conditions. IMMULITE Rubella IgM tests on these samples yielded the following results:

| Subjects | Total<br>n | Positive | | Negative | | Indeterminate | |
|----------|------------|----------|-----|----------|------|---------------|----|
| | | n | % | n | % | n | % |
| Pregnant | 60 | 0 | 0% | 60 | 100% | 0 | 0% |
| Various | 173 | 67 | 39% | 97 | 56% | 9 | 5% |
| All | 233 | 67 | 29% | 157 | 67% | 9 | 4% |

Observed signal/cutoff ratios for all samples

Image /page/4/Figure/3 description: The image is a bar graph showing frequency on the y-axis and ratio on the x-axis. The x-axis ranges from 0.0 to 5.0, and the y-axis ranges from 0 to 120. The bar at ratio 0.0 has a frequency of around 60, the bar at ratio 1.0 has a frequency of 100, and the bar at ratio 2.0 has a frequency of around 10.

#### IMMULITE 2000 Rubella IgM

Studies with presumed healthy, asymptomatic subjects and individuals suspected of acute rubella infection were conducted at one clinical sites in the southern United States. The study consisted of 236 specimens from 92 pregnant women and 144 individuals with various conditions. IMMULITE 2000 Rubella IgM tests on these samples yielded the following results:

| Subjects | Total<br>n | Positive | | Negative | | Indeterminate | |
|----------|------------|----------|-----|----------|-----|---------------|----|
| | | n | % | n | % | n | % |
| Pregnant | 92 | 13 | 14% | 73 | 79% | 6 | 7% |
| Various | 144 | 61 | 42% | 73 | 51% | 10 | 7% |
| All | 236 | 74 | 31% | 146 | 62% | 16 | 7% |

Observed signal/cutoff ratios for all samples

Image /page/4/Figure/8 description: This image is a bar graph that shows frequency on the y-axis and ratio on the x-axis. The x-axis ranges from 0.0 to 8.0. The y-axis ranges from 0 to 140. The bar at 0.0 has a frequency of approximately 120, while the bar at 1.0 has a frequency of approximately 60.

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### Performance Characteristics

## Clinical Performance

In a clinical study in the southern United States, a total of 236 frozen samples from apparently healthy male and female subjects, pregnant women and patients suspected of being rubella IgM positive were tested by IMMULITE Rubella IgM and by a commercially available enzyme immunoassay (Kit A - Trinity Biotech CAPTIA Rubella M). The IMMULITE Rubella IgM results were compared to the results of Kit A.

Comparison for all subjects

| | IMMULITE Rubella IgM | | |
|------------------------------------------------------------|----------------------|----------|----------|
| Kit A | Positive | Indeterm | Negative |
| Positive | 45 | 12 | 7 |
| Indeterm | 3 | 4 | 8 |
| Negative | 2 | 0 | 155 |
| Positive Agreement: 86.5% (45/52, 95% CI: 74.2% - 94.4%) | | | |
| Negative Agreement: 98.7% (155/157, 95% CI: 95.5% - 99.9%) | | | |
| Agreement: 95.7% (200/209, 95% CI: 92.0% - 98.0%) | | | |

Comparison for pregnant subjects:

| IMMULITE Rubella IgM | | | |
|---------------------------------------------------------|-----|-----|-----|
| Kit A | Pos | Ind | Neg |
| Pos | 3 | 2 | 1 |
| Ind | 1 | 1 | 6 |
| Neg | 1 | 0 | 77 |
| Positive Agreement: 75.0% (3/4, 95% CI: 19.4% - 99.4%) | | | |
| Negative Agreement: 98.7% (77/78, 95% CI: 93.1% - 100%) | | | |
| Agreement: 97.6% (80/82, 95% CI: 91.5% - 99.7%) | | | |

In another clinical study in the northeastern United States, a total of 233 frozen samples from apparently healthy male and female subjects, pregnant women and patients suspected of being rubella IgM positive were tested by IMMULITE Rubella IgM and Kit A. The IMMULITE Rubella IgM results were compared to the results of Kit A.

Comparison for all subjects

| IMMULITE Rubella IgM | | | |
|-----------------------------------------------------------|----------|----------|----------|
| Kit A | Positive | Indeterm | Negative |
| Positive | 66 | 6 | 8 |
| Indeterm | 0 | 1 | 13 |
| Negative | 1 | 2 | 136 |
| Positive Agreement: 89.2% (66/74, 95% CI: 79.8% - 95.2%) | | | |
| Negative Agreement: 99.3% (136/137, 95% CI: 96.0% - 100%) | | | |
| Agreement: 95.7% (202/211, 95% CI: 92.1% - 98.0%) | | | |

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All 60 samples from pregnant subjects were negative by both IMMULITE Rubella IgM and Kit A, yielding a negative agreement of 100% (95% CI 94%-100%) for this group of subjects.

In the clinical study in the southern United States, the samples were also tested by IMMULITE mine enimbal baday in the IMMULITE 2000 Rubella IgM results were compared to the results of Kit A.

Comparison for all subjects

| IMMULITE 2000 Rubella IgM | | | |
|------------------------------------------------------------|----------|----------|----------|
| Kit A | Positive | Indeterm | Negative |
| Positive | 59 | 5 | 0 |
| Indeterm | 8 | 2 | 5 |
| Negative | 7 | 9 | 141 |
| Positive Agreement: 100% (59/59, 95% CI: 93.9% - 100%) | | | |
| Negative Agreement: 95.3% (141/148, 95% CI: 90.5% - 98.1%) | | | |
| Agreement: 96.6% (200/207, 95% CI: 93.2% - 98.6%) | | | |

Comparison for pregnant subjects

| Kit A | Pos | Indeterm | Neg |
|----------------------------------------------------------|-----|----------|-----|
| Pos | 5 | 1 | 0 |
| Ind | 3 | 0 | 5 |
| Neg | 5 | 5 | 68 |
| Positive Agreement: 100% (5/5, 95% CI: 47.8% - 100%) | | | |
| Negative Agreement: 93.2% (68/73, 95% CI: 84.7% - 97.7%) | | | |
| Agreement: 93.6% (73/78, 95% CI: 85.7% - 97.7%) | | | |

In a study at DPC, IMMULITE 2000 Rubella IgM was compared to IMMULITE Rubella IgM on 223 samples:

| IMMULITE | Positive | Indeterm | Negative |
|-----------------------------------------------------------|----------|----------|----------|
| Positive | 19 | 0 | 0 |
| Indeterm | 1 | 0 | 0 |
| Negative | 1 | 3 | 199 |
| Positive Agreement: 100% (19/19, 95% CI: 82.4% - 100%) | | | |
| Negative Agreement: 99.5% (199/200, 95% CI: 97.2% - 100%) | | | |
| Agreement: 99.5% (218/219, 95% CI: 97.5% - 100%) | | | |

Indeterminate results were excluded from calculations.

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#### Performance Data

Precision (Serum): Precision studies for IMMULITE Rubella IgM assay were conducted at three different sites: in-house at DPC (Site 1) and at two sites in the southern and northeasten United States (Sites 2 and 3). At Site 1, samples were assayed in duplicate over the course of 20 Onled blates (Stees 2 and of 40 runs and 80 replicates. (See "Site 1" table). At Sites 2 and 3, samples were assayed in triplicate over the course of 5 days, one run per day, for a total of 5 runs and 15 replicates. (See "Site 2" and "Site 3" tables). The means, within-run and total CVs were calculated by the Analysis of Variance. Results are expressed as a signal-to-cutoff ratio. Precision statistics are summarized below.

| | Within-Run | | | Total | |
|---|------------|-------|------|-------|------|
| | Mean | SD | CV | SD | CV |
| 1 | 4.01 | 0.270 | 6.7% | 0.348 | 8.7% |
| 2 | 1.49 | 0.070 | 4.7% | 0.098 | 6.5% |
| 3 | 1.08 | 0.048 | 4.4% | 0.075 | 7.0% |
| 4 | 0.669 | 0.054 | 8.1% | 0.064 | 9.6% |
| 5 | 0.122* | — | — | — | — |

## IMMULITE Rubella IgM Precision - Serum (ratio): Site 1

* Consistently at a very low ratio

#### IMMULITE Rubella IgM Precision - Serum (ratio): Site 2

| | Mean | Within-Run | | Total | |
|---|--------|------------|-------|-------|-------|
| | | SD | CV | SD | CV |
| 1 | 3.20 | 0.207 | 6.5% | 0.203 | 6.3% |
| 2 | 1.43 | 0.062 | 4.3% | 0.060 | 4.2% |
| 3 | 1.06 | 0.049 | 4.6% | 0.066 | 6.2% |
| 4 | 0.690 | 0.080 | 11.6% | 0.081 | 11.7% |
| 5 | 0.229* | – | – | – | – |

*Consistently at a very low ratio

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| | Mean | Within-Run | | | Total | |
|---|--------|------------|-------|-------|-------|--|
| | | SD | CV | SD | CV | |
| 1 | 3.10 | 0.128 | 4.1% | 0.116 | 3.7% | |
| 2 | 1.45 | 0.062 | 4.3% | 0.059 | 4.1% | |
| 3 | 1.08 | 0.048 | 4.4% | 0.056 | 5.2% | |
| 4 | 0.720 | 0.106 | 14.7% | 0.111 | 15.4% | |
| 5 | 0.192* | - | - | - | - | |

#### IMMULITE Rubella IgM Precision - Serum (ratio): Site 3

* Consistently at a very low ratio

Precision (Serum): Precision studies for IMMULITE 2000 Rubella IgM assay were conducted at two different sites: in-house at DPC (Site 1) and in the southern United States (Site 2). At both sites, samples were assayed in triplicate over the course of 5 days, one run per day, for a total of 5 runs and 15 replicates. (See "Site 1" and "Site 2" tables). The means, within-run and total CVs were calculated by the Analysis of Variance. Results are expressed as a signal-to-cutoff ratio. Precision statistics are summarized below.

#### IMMULITE 2000 Rubella IgM Precision - Serum (ratio): Site 1

| | | Within-Run | | | Total | |
|---|--------|------------|-------|--|-------|-------|
| | Mean | SD | CV | | SD | CV |
| 1 | 5.40 | 0.450 | 8.3% | | 0.420 | 7.8% |
| 2 | 1.81 | 0.116 | 6.4% | | 0.117 | 6.5% |
| 3 | 1.24 | 0.105 | 8.5% | | 0.092 | 7.4% |
| 4 | 0.810 | 0.122 | 15.1% | | 0.111 | 13.7% |
| 5 | 0.166* | | | | | |

* Consistently at a very low ratio

## IMMULITE 2000 Rubella IgM Precision - Serum (ratio): Site 2

| | Within-Run | | | Total | |
|---|------------|-------|-------|-------|-------|
| | Mean | SD | CV | SD | CV |
| 1 | 4.00 | 0.195 | 4.9% | 0.32 | 8.0% |
| 2 | 1.58 | 0.042 | 2.7% | 0.108 | 6.8% |
| 3 | 1.05 | 0.053 | 5.0% | 0.065 | 6.2% |
| 4 | 0.860 | 0.144 | 16.7% | 0.174 | 20.2% |
| 5 | 0.277* | - | - | - | - |

*Consistently at a very low ratio

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Precision (Plasma): Precision studies for IMMULITE Rubella IgM and IMMULITE 2000 Rubella IgM assays on plasma samples (EDTA and heparin) were conducted at DPC by testing samples in triplicate over the course of 3 days, two runs per day, for a total of 6 runs and 18 replicates. The means, within-run and total CVs were calculated by the Analysis of Variance. Results are expressed as a signal-to-cutoff ratio. Precision statistics are summarized below.

| | Mean | Within-Run | | Total | |
|---|-------|------------|-------|-------|-------|
| | | SD | CV | SD | CV |
| 1 | 0.128 | 0.044 | 34.4% | 0.047 | 36.7% |
| 2 | 0.78 | 0.057 | 7.3% | 0.064 | 8.2% |
| 3 | 1.12 | 0.062 | 5.5% | 0.071 | 6.3% |
| 4 | 1.62 | 0.099 | 6.1% | 0.112 | 6.9% |

#### IMMULITE Rubella IgM Precision - EDTA (ratio):

#### IMMULITE 2000 Rubella IgM Precision - EDTA (ratio):

| | Mean | Within-Run | | Total | |
|---|------|------------|-------|-------|-------|
| | | SD | CV | SD | CV |
| 1 | 0.17 | 0.048 | 27.6% | 0.045 | 25.9% |
| 2 | 0.91 | 0.053 | 5.8% | 0.048 | 5.3% |
| 3 | 1.32 | 0.063 | 4.8% | 0.063 | 4.8% |
| 4 | 1.88 | 0.076 | 4.0% | 0.083 | 4.4% |

#### IMMULITE Rubella IgM Precision - Heparin (ratio):

| | Mean | Within-Run | | Total | |
|---|------|------------|-------|-------|-------|
| | | SD | CV | SD | CV |
| 1 | 0.42 | 0.114 | 27.1% | 0.142 | 33.8% |
| 2 | 0.91 | 0.137 | 15.1% | 0.167 | 18.4% |
| 3 | 1.21 | 0.115 | 9.5% | 0.125 | 10.3% |
| 4 | 1.62 | 0.2 | 12.3% | 0.183 | 11.3% |

#### IMMULITE 2000 Rubella IgM Precision - Heparin (ratio):

| | Mean | Within-Run | | | Total | |
|---|------|------------|-------|--|-------|-------|
| | | SD | CV | | SD | CV |
| 1 | 0.50 | 0.079 | 15.8% | | 0.084 | 16.8% |
| 2 | 1.19 | 0.095 | 8.0% | | 0.088 | 7.4% |
| 3 | 1.47 | 0.148 | 10.1% | | 0.130 | 8.8% |
| 4 | 1.94 | 0.172 | 8.9% | | 0.148 | 7.6% |

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Crossreactivity: A study was conducted to evaluate whether the measurement of rubella IgM antibody is affected by closely related microorganisms. Ninety-one seronegative sera and one seropositive serum containing antibodies to Varicella Zoster Virus (n=3), Measles (n=10), Cytomegalovirus (CMV) (n=10), Herpes Simplex Virus (n=10), Toxoplasma (n=10), mycloplasma pneumoniae (n=10), Epstein-Barr Virus (n=10), Syphilis (n=10) and Parvovirus (n=10) and rheumatoid factor (n=9) were tested by IMMULITE and IMMULITE 2000 Rubella IgM. All 91 rubella IgM negative samples yielded negative results. A single rubella IgM positive serum with antibodies to measles virus was positive with the IMMULITE and IMMULITE 2000 Rubella IgM assay. This sample was further tested by a commercially available rubella IgM assay and yielded a positive result.

Interference: Coniugated or unconjugated bilirubin: no effect up to 20 mg/dL Lipemia: no effect of triglycerides up to 3000 mg/dL Hemoglobin: no effect up to 539 mg/dL

Anti-coagulants: Twenty-eight blood samples drawn into plain, heparinized and EDTA vacutainer tubes were assayed by the IMMULITE 2000 Rubella IgM assay. Results (in S/CO ratio) from the anticoagulant tubes were compared with those from the serum tubes in regression analyses:

| Regressions: | $Heparin = 0.94 \times (Serum) + 0.04$ | r = 0.993 |
|---------------------|----------------------------------------|-----------|
| | $EDTA = 0.95 \times (Serum) + 0.01$ | r = 0.992 |
| Means (S/CO ratio): | Serum = 0.85 | |
| | Heparin = 0.83 | |
| | EDTA= 0.82 | |

Gel Barrier: Twenty-eight blood samples drawn into plain and SST vacutainer tubes were assayed by the IMMULITE 2000 Rubella IgM assay. Results (in S/CO ratio) from the SST tubes were compared with those from the serum tubes in a regression analysis:

| Regressions: | $SST = 0.92 \times (Serum) + 0.01$ | r = 0.993 |
|---------------------|------------------------------------|-----------|
| Means (S/CO ratio): | Serum = 0.85 | |
| | SST = 0.80 | |

## Conclusion:

The data presented in this summary of safety and effectiveness is the data that the Food and Drug Administration used in granting DPC substantial equivalence for the IMMULITE Rubella IgM and IMMULITE 2000 Rubella IgM assays.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/11/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized depiction of a human figure, represented by three curved lines that suggest a profile. The figure is enclosed within a circular border, and the text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" is arranged around the upper half of the circle. The logo is presented in black and white.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

JAN 1 0 2002

Edward M. Levine, Ph.D. Director of Clinical Affairs Diagnostic Products Corporation 5700 West 96th Street Los Angeles, CA 90045-5597

> k012077 Trade/Device Name: IMMULITE® and IMMULITE® 2000 Rubella IgM Regulation Number: 21 CFR 866.3510 Regulation Name: Rubella virus serological reagents Regulatory Class: Class II Product Code: LFX Dated: November 30, 2001 Received: December 3, 2001

Dear Dr. Levine:

Re:

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.

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 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); good manufacturing practice requirements as set forth in the quality systems (OS) 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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This letter will allow you to begin marketing your device as described in your 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 advice for your device on our labeling regulation (21 CFR Part 801 and ' additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at [phone]. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at [phone]. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 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,

Steven Autman

Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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#### 510(k) Number: K012077 IMMULITE® Rubella IgM and Device Name: IMMULITE® 2000 Rubella IgM

Indications For Use:

IMMULITE® Rubella IgM - For in vitro diagnostic use with the IMMULITE Analyzer - for the qualitative detection of IgM antibodies to rubella virus in human serum or plasma (EDTA or heparinized), as an aid in the presumptive diagnosis of an acute or recent rubella infection, particularly in women of childbearing age.

IMMULITE 2000 Rubella IgM - For in vitro diagnostic use with the IMMULITE 2000 Analyzer - for the qualitative detection of IgM antibodies to rubella virus in human serum or plasma (EDTA or heparinized), as an aid in the presumptive diagnosis of an acute or recent rubella infection, particularly in women of childbearing age.

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Concurrence of CDRH, Office of Device Evaluation (ODE)

Woody Dubris

cal Laboratory Dev 01207

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**Prescription Use**
(Per 21 CFR 801.109)

OR

Over-The-Counter Use

(Optional Format 1-2-96)