IS-RUBELLA IGG TEST SYSTEM

K981729 · Diamedix Corp. · LFX · Jan 28, 1999 · Microbiology

Device Facts

• Record ID: K981729
• Device Name: IS-RUBELLA IGG TEST SYSTEM
• Applicant: Diamedix Corp.
• Product Code: LFX · Microbiology
• Decision Date: Jan 28, 1999
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.3510
• Device Class: Class 2

Intended Use

The Diamedix Is-Rubella IgG Test Kit is an Enzyme Immunoassay (EIA) for the qualitative and quantitative determination of IgG antibodies in human serum to aid in the assessment of the patient's immunological response to infection with rubellaand in the determination of the immune status of individuals, including females of child-bearing age. The evaluation of acute and convalescent sera can aid in the diagnosis of recent or current infection with rubella. These reagents can be used either manually or in conjunction with the MAGO® Plus Automated EIA Processor.

Device Story

Is-Rubella IgG Test System is an ELISA for detecting IgG antibodies to rubella in human serum. Partially purified rubella antigen is immobilized on microtiter wells; patient serum is added; specific antibodies bind to antigen. After washing, enzyme-labeled anti-human immunoglobulin conjugate is added; substrate solution produces color intensity proportional to antibody concentration, measured photometrically. Used in clinical laboratories; performed manually or via MAGO Plus Automated EIA Processor. Results aid clinicians in assessing immune status and diagnosing recent/current rubella infection. Benefits include standardized, automated or manual assessment of rubella immunity, particularly for females of child-bearing age.

Clinical Evidence

Clinical performance evaluated using 376 prospective sera and 270 retrospective sera across three sites. Compared against marketed EIA methods. Relative sensitivity ranged from 97.1% to 100.0%; relative specificity ranged from 83.8% to 100.0%. Overall agreement was 96.3% to 99.6%. CDC serum panel testing showed 100% agreement for negative samples and 97.6% for positive samples. Precision studies (intra-assay, inter-assay, inter-site, lot-to-lot) demonstrated acceptable CVs. Linearity and correlation to WHO standard confirmed.

Technological Characteristics

Enzyme-linked immunosorbent assay (ELISA) using partially purified rubella antigen on solid-phase microtiter wells. Employs enzyme-labeled anti-human immunoglobulin conjugate and substrate for photometric detection. Compatible with manual processing or MAGO Plus Automated EIA Processor. Calibrated against WHO 1st International Standard for Anti-Rubella Immunoglobulin.

Indications for Use

Indicated for qualitative and quantitative detection of IgG antibodies to rubella in human serum. Used to assess immunological response to rubella infection and determine immune status in individuals, including females of child-bearing age. Aids in diagnosis of recent or current infection via paired sera evaluation.

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

• Incstar Rubella IgG "fast" ELISA Kit

Submission Summary (Full Text)

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K981729

JAN 28 1999

# Appendix E. 510(k) Summary of Safety and Effectiveness

The following section is included as required by the Safe Medical Device Act (SMDA) of 1990.

Name: Address:

i

Diamedix Corporation 2140 N. Miami Avenue Miami, FL 33127

Dr. Lynne Stirling Contact Person: Phone Number: 305-324-2354 Fax Number: 305-324-2585

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# 510(k) Summary of 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 807.92.

The assigned 510(k) number is: _______________________________________________________________________________________________________________________________________________

#### Applicant Information:

| Date Prepared: | May 14, 1998 |
|----------------|-----------------------------------------|
| Name: | Diamedix Corporation |
| Address: | 2140 N. Miami Avenue<br>Miami, FL 33127 |

| Contact Person: | Dr. Lynne Stirling |
|-----------------|--------------------|
| Phone Number: | 305-324-2354 |
| Fax Number: | 305-324-2585 |

#### Device Information:

Trade Name: Is-Rubella IgG Test System Common Name: Rubella IgG EIA Test Classification Name: Enzyme linked immunosorbent assay, rubella (866.3510)

#### Equivalent Device:

Incstar Rubella IgG "fast" ELISA Kit

Device Description: The Is-Rubella IgG Test System is an enzyme-linked immunosorbent assay (ELISA) for the qualitative and quantitative detection of IgG to rubella in human serum

Intended Use: The assay is intended for use in detecting IgG antibodies to rubella antigen in human serum. The results of the assay can be used as an aid in the assessment of the patient's immunological response to infection with rubella and in the determination of immune status of individuals, including females of child-bearing age. The evaluation of paired sera can aid in the diagnosis of current or recent infection.

Principle of the Procedure: The Is-Rubella IgG Test System is an enzyme-linked immunosorbent assay to detect IgG to rubella in human serum. Partially purified rubella antigen is attached to a solid phase microtiter well. Diluted test sera are added to each well. If antibodies which recognize the rubella antigen are present in the patient sample they will bind to the antigen on the well. After incubation, the wells are washed to remove unbound antibody. An enzyme labeled anti-human immunoglobulin (conjugate) is added to each test well. If antibody is present the enzyme-linked antibody will bind to it. After incubation, the wells are washed to remove unbound conjugate. A substrate solution is then added to each well. If enzyme is present from the prior step, the reaction is stopped and the color intensity is measured photometrically producing an indirect measure of the specific antibody present in the patient sample.

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# Performance Characteristics

### A. Comparison Testing

A total of three hundred and seventy-six prospective (fresh) sera were tested for the presence of rubella IgG antibodies using the Diamedix Is-Rubella IgG Test Kit and two other marketed tests at two independent sites (site #1, Miami, FL and site #2, Salt Lake City, Utah). Site #3 (Diamedix Corp. ( Miami, FL) tested 270 retrospective (frozen) sera both manually and using the MAGO Plus Automated EIA Processor. In addition, all sites tested a panel of 100 retrospective selected negative and low positive sera provided by Diamedix. Site #1 also tested the CDC Rubella Reference Panel (See Section C. )

Site #1 tested 198 samples submitted for immune status screening. Samples were obtained from the S. Florida area. Table 1 compares the results obtained for the Is-Rubella IgG Test Kit and their currently used testing method.

Site #2 tested 178 samples submitted for ToRCH screening. Samples were obtained from the West region. Table 2 compares the results obtained for the Is-Rubella IgG Test Kit and their currently used testing method.

| TABLE 1<br>Is-Rubella IgG - Site #1 | | | TABLE 2<br>Is-Rubella IgG - Site #2 | | | | |
|-------------------------------------|-------------------------------------------------------------------------------------------------------------------------------|--------------------------------------|-------------------------------------|----------------------------|-------------------------------------------------------------------------------------------------------------------------------|--------------------------------------|-----------|
| | Positive | Negative | Equivocal | | Positive | Negative | Equivocal |
| Comp.<br>EIA 1<br>Positive | 165 [93] | 5 [2] | 8 [7] | Comp.<br>EIA 2<br>Positive | 127 [50] | 0 | 0 |
| Negative | 0 | 19 [7] | 1 [1] | Negative | 6 [3] | 31 [12] | 3 |
| | | | | Equivocal | 7 [3] | 2 [1] | 2 [2] |
| | 95% CI*<br>Relative Sensitivity 165/170 = 97.1%<br>Relative Specificity 19/19 = 100.0%<br>Overall Agreement** 184/189 = 97.4% | | | | 95% CI*<br>Relative Sensitivity 127/127 = 100.0%<br>Relative Specificity 31/37 = 83.8%<br>Overall Agreement** 158/164 = 96.3% | | |
| | | 93.3-99.0<br>82.4-100.0<br>93.9-99.1 | | | | 97.1-100.0<br>68.0-93.8<br>92.2-98.7 | |

For Site #1, further resolution of the discordant samples was performed by testing such samples in a referee EIA method. Four of the samples negative by the Is-Rubella IgG Test Kit and positive by the other EIA were negative by the referee method; the remaining sample was equivocal.

For Site #2, further resolution of the discordant samples was performed in a similar manner. Five of the six samples positive by the Is-Rubella IgG Test Kit and negative by the other EIA were positive by the referee method; the remaining sample was equivocal.

Site #3 (Diamedix Corp.) tested 270 samples (all frozen) by the manual method and 263 of these samples (seven being ONS) by the MAGO Plus method. Samples were obtained from S. Florida blood donors. Tables 3 and 4 compare the results obtained for the Is-Rubella IgG Test Kit and another marketed EIA method.

| TABLE 3<br>Is-Rubella IgG - Site #3 : Manual | | | | | TABLE 4<br>Is-Rubella IgG - Site #3 : | | | |
|----------------------------------------------|----------------------|-----------------|-----------|---------------------|---------------------------------------|----------------------|------------------|----|
| | Positive | Negative | Equivocal | | | Positive | Negative | |
| Other<br>EIA | Positive | 204 [73] | 4 [2] | 6 [5] | | Positive | 209 | 1 |
| | Negative | 0 | 49 [30] | 0 | Other<br>EIA | Negative | 0 | 43 |
| | Equivocal | 3 [1] | 3 [2] | 1 | | Equivocal | 3 | 1 |
| | Relative Sensitivity | 204/208 = 98.1% | | 95% CI*<br>95.1-99. | | Relative Sensitivity | 209/210 = 99.5% | |
| | Relative Specificity | 49/49 = 100.0% | | 92.7-100.0 | | Relative Specificity | 43/43 = 100.0% | |
| | Overall Agreement** | 253/257 = 98.4% | | 96.1-99.6 | | Overall Agreement** | 252/253 = 99.6 % | |

| TABLE 4 |
|-------------------------------------------|
| Measles-Rubella IgG - Site #3 : MAGO Plus |

= 100.0%

Equivocal

3

0 3

95% CI*

97.4-100.0

91.8-100.0

97.8-100.0

] denotes samples from females of childbearing age (18-45 years) [

* 95% Confidence Intervals (CI) calculated by the Exact Method

** Equivocal results were excluded from calculations

000278

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For Site #3 (manual testing), further resolution of the discordant sera revealed that of the Is-Rubella IgG Test Kit but positive in the other EIA two were negative and two were positive by a referee EIA method. For MAGO Plus testing, the sample that was negative in the Is-Rubella IgG Test Kit but positive in the other EIA was also negative by a referee EIA method.

In addition to the samples tabulated above, each site tested the same panel consisting of approximately 50 negative and 50 low positive sera provided by diamedix. Table 5 shows the results of this testing compared to the predicate method.

| Other EIA | | | | | | | | | | Pos | | | Neg | | | Equ | | | Relative Sensitivity | Relative Specificity |
|----------------|----|---|---|---|----|---|---|---|---|-------|-----------|------|----------|-----|-----|-----|-----|-----|----------------------|----------------------|
| Is-Rubella IgG | | | | | | | | | | Pos | Pos | Pos | Neg | Neg | Neg | Equ | Equ | Equ | <i>95%CI</i> | <i>95% CI</i> |
| Site #1 | 52 | 0 | 1 | 0 | 43 | 2 | 0 | 1 | 1 | 100% | 93.2-100 | 100% | 91.8-100 | | | | | | | |
| Site #2 | 42 | 3 | 8 | 0 | 45 | 0 | 0 | 2 | 0 | 93.3% | 81.7-100 | 100% | 92.1-100 | | | | | | | |
| Site #3 | 46 | 4 | 3 | 0 | 45 | 0 | 0 | 2 | 0 | 92.0% | 80.0-97.8 | 100% | 92.1-100 | | | | | | | |

TABLE 5 : All Sites - Retrospective Panel of Negative and Weakly Positive Sera

NOTE : Please be advised that relative refers to the comparison of the assay's results to that of a similar assay. There was not an attempt to correlate the assay's results with disease presence or absence. No judgment can be comparison assay's accuracy to predict disease.

#### B. Correlation of Manual and MAGO Plus Results

The Is-Rubella IgG Test Kit has been developed for automated as well as manual use. To demonstrate the equivalence of the manual and MAGO Plus Procedures, the results of 193 samples tested assayed manually and by MAGO Plus were compared. Highly reactive samples that exceeded the reportable range and were excluded from this comparison. A scattergram and regression line of the results obtained with 95% confidence intervals is shown in Figure 1.

Image /page/3/Figure/7 description: This image is a scatter plot comparing MAGO PLUS IU/ml to MANUAL IU/ml. The data points are clustered around a regression line, indicating a positive correlation between the two variables. The equation of the regression line is Y = 1.6349 + 0.9947 X, and the correlation coefficient (r) is 0.9550, suggesting a strong positive linear relationship.

Image /page/3/Figure/8 description: The image shows the title of a figure. The title is "FIGURE 1 : Manual vs MAGO Plus Correlation". The title is written in a bold, sans-serif font.

#### C. CDC Serum Panel Data

)

The following information was obtained wth the Centers for Disease Control and Prevention (CDC) serum panel for rubella serology assays which was tested by the Is-Rubella IgG Test Kit both manually and using the MAGO Plus Automated Processor. For independent verification, this panel was also tested manually by outside site #1. The results are presented as a means to convey further information on the performance of this assay with a masked, characterized serum panel. Results were submitted to the CDC for their interpretation and evaluation. This does not imply an endorsement of the assay by the CDC.

The panel consists of 82% positive and 18% negative samples. The outside testing site correctly identified all samples (100% agreement). Of the results obtained by Diamedix, there was 100% (18 of 18) agreement with the negative results using both the manual and automated methods and 97.6% (80 of 82) agreement with the positive specimens using both the manual and automated methods.

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## C. Linearity

ﻤﺴﻠﺴﺔ

ﻟﻤﺴﺘﻘﻠﺔ

Several strongly positive serum samples were serially diluted and separate dilutions were assayed, in duplicate, in the Is-Rubella IgG Test Kit both manually and using the MAGO Plus Automated EIA Processor. Representative linear regression graphs and scattergrams of the mean results with 95% confidence intervals are presented in Figures 3 and 4 for one patient sample. The results demonstrate a high degree of linearity throughout the assay when samples are tested either manually or by MAGO Plus.

Image /page/4/Figure/2 description: The image contains two line graphs comparing manual linearity and MAGO Plus linearity. The graph on the left, labeled "FIGURE 2: Manual Linearity," shows a slope of 101.51, a Y-intercept of 0.54, and an R-squared value of 0.9933. The graph on the right, labeled "FIGURE 3: MAGO Plus Linearity," shows a slope of 168.47, a Y-intercept of -1.54, and an R-squared value of 0.9969. Both graphs plot dilution on the x-axis and IU/ml on the y-axis, with data points and trendlines indicating a positive correlation between dilution and IU/ml.

## D. Correlation to WHO Standard

The Is-Rubella IgG Test Kit has been calibrated against the WHO 1st International Standard for Anti-Rubella Immunoglobulin (code RUBI-1-94). To demonstrate the accuracy of the quantitative procedure, several dilutions of the WHO Standard were prepared and assayed manually in triplicate versus the Is-Rubella IgG Test Kit standard curve. The linear regression graph and scattergram of the mean results with 95% Confidence Intervals is shown in Figure 4.

Image /page/4/Figure/5 description: The image is titled "FIGURE 4: WHO IU/ml vs Is-Rubella IgG IU/ml". The image contains the equation Y = 24080 + 07327 X. The number 80 is also present in the image.

Image /page/4/Figure/6 description: This image is a scatter plot that shows the relationship between Is-Rubella IgG IU/ml and WHO IU/ml. The x-axis represents WHO IU/ml, and the y-axis represents Is-Rubella IgG IU/ml. The plot includes a regression line with the equation Y = 2.4080 + 0.7327 X, and the coefficient of determination (R^2) is 0.9846, indicating a strong positive correlation between the two variables.

#### E. Quantitative Data

Serum pairs were obtained by preparing multiple two-fold dilutions of several strongly positive sera. Ratios for dilutions representing a four-fold difference in antibody level were evaluated as a serum pair both manually and using the MAGO Plus. Overall, it was estimated that a 2.8 told (mean 4.8-fold ) increase in Is-Rubella IgG IU/ml values corresponded to a four-fold titer increase in rubella IgG antibody levels.

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## F. Cross-Reactivity Data

Sera containing IgG antibodies to viruses potentially cross-reactive to rubella have been tested in the Is-Rubella IgG Test Kit. Forty-nine sera negative for IgG antibodies to rubella IgG Test Kit as well as in another marketed test but positive for one or more viruses were evaluated. The data in the following table suggest that no cross-reactivity should be expected with the Is-Rubella IgG Test Kit from these analytes.

| TABI | | 1 | | t<br>0 |
|------|--|---|--|--------|
|------|--|---|--|--------|

| Analyte | Rubella IgG | VZV IgG | HSV IgG | CMV IgG | Toxoplasma IgG | EBV IgG | Parvovirus B19 IgG | Measles IgG |
|-----------------------|-------------|---------|---------|---------|----------------|---------|--------------------|-------------|
| No.of Pos.<br>Samples | 0 | 42 | 48 | 43 | 5 | 48 | 12 | 47 |

### G. Precision

)

Seven serum samples, spanning the reportable range, as well as the 10 IU/ml Standard and kit Low Positive and Negative Controls were tested quantitatively and values calculated from IU/ml results. Sites #1 and #2 tested samples in triplicate in three separate runs on three different days. Site #3 (Diamedix Corp.) tested samples in triplicate in two separate runs on three different days both manually and using the MAGO Plus Automated EIA Processor. Note that for MAGO Plus (Table 10) the 50 IU/ml Standard was replaced with an additional weakly positive sample. Tables 7-13 show the intra- and interassay precision for each site, the inter-site precision for manual and MAGO Plus.

TABLE 7 : Site #1- Intra-Assay and Interassay Precision

| SERUM | INTRA-ASSAY DAY 1 | | | INTRA-ASSAY DAY 2 | | | INTRA-ASSAY DAY 3 | | | INTERASSAY (n=9) | | |
|--------|-------------------|------|-------|-------------------|------|-------|-------------------|------|-------|------------------|------|-------|
| | MEAN<br>IU/ml | SD | CV% | MEAN<br>IU/ml | SD | CV% | MEAN<br>IU/ml | SD | CV% | MEAN<br>IU/ml | SD | CV% |
| A | 0.1 | 0.10 | N/A | 0.0 | 0.00 | N/A | 0.0 | 0.06 | N/A | 0.0 | 0.07 | N/A |
| B | 0.3 | 0.06 | N/A | 0.1 | 0.06 | N/A | 0.3 | 0.00 | N/A | 0.3 | 0.10 | N/A |
| C | 20.9 | 0.95 | 4.55 | 20.8 | 3.07 | 14.76 | 21.9 | 2.32 | 10.59 | 21.2 | 2.05 | 9.67 |
| D | 25.8 | 1.76 | 6.82 | 18.3 | 0.51 | 2.79 | 21.2 | 1.56 | 7.36 | 21.8 | 3.48 | 15.96 |
| E | 42.4 | 0.65 | 1.53 | 39.5 | 3.86 | 9.77 | 34.9 | 2.65 | 7.59 | 38.9 | 4.03 | 10.36 |
| F | 42.7 | 4.12 | 9.65 | 41.9 | 4.43 | 10.57 | 37.2 | 2.23 | 5.99 | 40.6 | 4.11 | 10.12 |
| G | 23.1 | 4.04 | 17.49 | 20.5 | 2.76 | 13.46 | 20.0 | 2.00 | 10.00 | 21.2 | 3.00 | 14.15 |
| 10 STD | 10.9 | 1.88 | 17.25 | 14.1 | 2.87 | 20.35 | 10.3 | 2.43 | 23.59 | 11.8 | 2.73 | 23.14 |
| 50 STD | 50.5 | 1.19 | 2.36 | 55.9 | 3.30 | 5.90 | 45.9 | 0.06 | 0.13 | 50.8 | 4.67 | 9.19 |
| LPC | 24.5 | 0.06 | 0.24 | 26.5 | 0.91 | 3.43 | 21.0 | 1.11 | 5.29 | 24.0 | 2.51 | 10.46 |
| NC | 2.7 | 0.06 | N/A | 2.8 | 0.06 | N/A | 2.2 | 0.06 | N/A | 2.6 | 0.25 | N/A |

TABLE 8 : Site #2 - Intra-Assay and Interassay Precision

| SERUM | INTRA-ASSAY<br>DAY 1 | | | INTRA-ASSAY<br>DAY 2 | | | INTRA-ASSAY<br>DAY 3 | | | INTERASSAY (n=9) | | |
|--------|----------------------|------|-------|----------------------|------|-------|----------------------|------|-------|------------------|------|-------|
| | MEAN<br>IU/ml | SD | CV% | MEAN<br>IU/ml | SD | CV% | MEAN<br>IU/ml | SD | CV% | MEAN<br>IU/ml | SD | CV% |
| A | 0.3 | 0.06 | N/A | 0.3 | 0.12 | N/A | 0.5 | 0.00 | N/A | 0.4 | 0.12 | N/A |
| B | 0.5 | 0.06 | N/A | 0.4 | 0.06 | N/A | 0.4 | 0.12 | N/A | 0.4 | 0.11 | N/A |
| C | 17.2 | 1.25 | 7.27 | 17.1 | 2.19 | 12.81 | 16.0 | 2.10 | 13.13 | 16.8 | 1.75 | 10.42 |
| D | 14.3 | 0.98 | 6.85 | 14.0 | 1.57 | 11.21 | 12.8 | 0.25 | 1.95 | 13.7 | 1.16 | 8.47 |
| E | 50.6 | 3.16 | 6.25 | 31.8 | 1.85 | 5.82 | 43.2 | 0.59 | 1.37 | 41.9 | 8.43 | 20.12 |
| F | 28.0 | 1.45 | 5.18 | 26.3 | 2.24 | 8.52 | 25.2 | 2.50 | 9.92 | 26.5 | 2.20 | 8.30 |
| G | 14.2 | 1.82 | 12.82 | 12.5 | 1.27 | 10.16 | 10.6 | 1.93 | 18.21 | 12.5 | 2.13 | 17.04 |
| 10 STD | 9.7 | 0.06 | 0.62 | 10.6 | 0.85 | 8.02 | 9.7 | 0.25 | 2.58 | 10.0 | 0.63 | 6.30 |
| 50 STD | 45.2 | 0.66 | 1.46 | 46.2 | 0.64 | 1.39 | 45.8 | 3.53 | 7.71 | 45.7 | 1.87 | 4.09 |
| LPC | 21.1 | 0.44 | 2.09 | 24.2 | 2.36 | 9.75 | 22.0 | 3.12 | 14.18 | 22.4 | 2.39 | 10.67 |
| NC | 2.7 | 0.06 | N/A | 2.3 | 0.85 | N/A | 2.9 | 0.28 | N/A | 2.6 | 0.44 | N/A |

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TABLE 9 : Site #3-Intra-Assay and Interassay Precision (Manual)

-

-

| SERUM | INTRA-ASSAY DAY 1 | | | INTRA-ASSAY DAY 2 | | | INTRA-ASSAY DAY 3 | | | INTERASSAY (n=18) | | |
|--------|-------------------|------|-------|-------------------|------|------|-------------------|------|-------|-------------------|------|-------|
| | MEAN IU/ml | SD | CV% | MEAN IU/ml | SD | CV% | MEAN IU/ml | SD | CV% | MEAN IU/ml | SD | CV% |
| A | 0.0 | 0.05 | N/A | 0.1 | 0.08 | N/A | 0.2 | 0.16 | N/A | 0.1 | 0.13 | N/A |
| B | 0.2 | 0.04 | N/A | 0.2 | 0.04 | N/A | 0.2 | 0.20 | N/A | 0.2 | 0.11 | N/A |
| C | 14.2 | 0.99 | 6.97 | 14.6 | 1.23 | 8.42 | 14.3 | 6.12 | 42.80 | 14.4 | 3.43 | 23.82 |
| D | 15.1 | 1.13 | 7.48 | 14.3 | 1.38 | 9.65 | 15.8 | 3.94 | 24.94 | 15.1 | 2.44 | 16.16 |
| E | 37.4 | 1.93 | 5.16 | 35.8 | 2.63 | 7.35 | 35.3 | 7.52 | 21.30 | 36.1 | 4.54 | 12.58 |
| F | 33.9 | 2.18 | 6.43 | 34.6 | 2.33 | 6.73 | 28.4 | 4.18 | 14.72 | 32.3 | 4.04 | 12.51 |
| G | 20.3 | 2.32 | 11.43 | 19.8 | 1.49 | 7.53 | 15.9 | 2.44 | 15.35 | 18.6 | 2.85 | 15.32 |
| 10 STD | 9.2 | 0.48 | 5.22 | 9.4 | 0.26 | 2.77 | 12.5 | 1.83 | 14.64 | 10.4 | 1.88 | 18.08 |
| 50 STD | 53.3 | 3.35 | 6.29 | 51.1 | 2.12 | 4.15 | 53.9 | 9.17 | 17.01 | 52.8 | 5.55 | 10.51 |
| LPC | 24.7 | 3.62 | 14.66 | 24.6 | 1.11 | 4.51 | 30.4 | 4.90 | 16.12 | 26.6 | 4.38 | 16.47 |
| NC | 2.8 | 0.12 | N/A | 2.8 | 0.12 | N/A | 3.1 | 0.33 | N/A | 2.9 | 0.24 | N/A |

TABLE 10 : Site #3- Intra-assay and Interassay Precision (MAGO Plus)

| SERUM | INTRA-ASSAY DAY 1 | | | INTRA-ASSAY DAY 2 | | | INTRA-ASSAY DAY 3 | | | INTERASSAY (n=18) | | |
|--------|-------------------|------|-------|-------------------|------|-------|-------------------|------|-------|-------------------|------|-------|
| | MEAN IU/ml | SD | CV% | MEAN IU/ml | SD | CV% | MEAN IU/ml | SD | CV% | MEAN IU/ml | SD | CV% |
| A | 0.2 | 0.08 | N/A | 0.2 | 0.10 | N/A | 0.2 | 0.10 | N/A | 0.2 | 0.09 | N/A |
| B | 0.4 | 0.06 | N/A | 0.2 | 0.10 | N/A | 0.3 | 0.05 | N/A | 0.3 | 0.12 | N/A |
| C | 16.8 | 2.46 | 14.64 | 15.4 | 2.93 | 19.03 | 19.6 | 2.87 | 16.67 | 17.2 | 3.17 | 18.43 |
| D | 15.3 | 1.65 | 10.78 | 12.7 | 1.45 | 11.42 | 16.0 | 2.68 | 14.64 | 14.6 | 2.38 | 16.30 |
| E | 39.6 | 2.47 | 6.24 | 35.6 | 2.51 | 7.05 | 39.8 | 3.00 | 7.54 | 38.3 | 3.18 | 8.30 |
| F | 37.7 | 1.98 | 7.69 | 38.1 | 3.23 | 8.48 | 34.4 | 3.37 | 9.80 | 36.7 | 3.43 | 9.35 |
| G | 17.1 | 2.90 | 8.36 | 16.6 | 1.80 | 10.84 | 18.1 | 1.26 | 6.96 | 17.3 | 1.55 | 8.96 |
| H | 14.2 | 1.43 | 13.94 | 15.4 | 3.21 | 20.84 | 17.5 | 1.23 | 7.03 | 15.6 | 2.59 | 16.60 |
| 10 STD | 17.0 | 2.19 | 12.88 | 14.1 | 0.89 | 6.31 | 18.6 | 1.23 | 6.61 | 16.5 | 2.39 | 14.48 |
| LPC | 33.3 | 1.20 | 3.60 | 27.7 | 3.13 | 11.30 | 36.3 | 1.57 | 4.33 | 32.4 | 4.19 | 12.93 |
| NC | 4.2 | 0.28 | N/A | 4.1 | 0.24 | N/A | 4.9 | 0.12 | N/A | 4.4 | 0.41 | N/A |

TABLE 11 : Inter-Site Precision (manual)

| SERUM | Site #1 | Site #2 | Site #3 | INTERSITE | | |
|--------|---------------|---------------|---------------|---------------|------|-------|
| | MEAN<br>IU/ml | MEAN<br>IU/ml | MEAN<br>IU/ml | MEAN<br>IU/ml | SD | CV% |
| A | 0.0 | 0.4 | 0.1 | 0.2 | 0.21 | N/A |
| B | 0.3 | 0.4 | 0.2 | 0.3 | 0.10 | N/A |
| C | 21.2 | 16.8 | 14.4 | 17.5 | 3.45 | 19.71 |
| D | 21.8 | 13.7 | 15.1 | 16.9 | 4.33 | 25.62 |
| E | 38.9 | 41.9 | 36.1 | 39.4 | 3.63 | 9.21 |
| F | 40.6 | 26.5 | 32.3 | 33.1 | 7.09 | 21.42 |
| G | 21.2 | 12.5 | 18.6 | 17.4 | 4.47 | 25.69 |
| 10 STD | 11.8 | 10.0 | 10.4 | 10.7 | 0.95 | 8.88 |
| 50 STD | 50.8 | 45.7 | 52.8 | 49.8 | 3.66 | 7.35 |
| LPC | 24.0 | 22.4 | 26.6 | 24.3 | 2.12 | 8.72 |
| NC | 2.6 | 2.6 | 2.9 | 2.7 | 0.17 | N/A |

TABLE 12 : Lot-to-Lot Precision (manual)

| SERUM | Lot 31107<br>INTERASSAY | | | Lot 41307<br>INTERASSAY | | | Lot 50707<br>INTERASSAY | | | LOT-TO-LOT<br>INTERASSAY | | |
|--------|-------------------------|------|-------|-------------------------|------|-------|-------------------------|------|-------|--------------------------|------|-------|
| | MEAN | SD | CV% | MEAN | SD | CV% | MEAN | SD | CV% | MEAN | SD | CV% |
| | IU/ml | | | IU/ml | | | IU/ml | | | IU/ml | | |
| A | 0.1 | 0.05 | N/A | 0.1 | 0.10 | N/A | 0.1 | 0.13 | N/A | 0.1 | 0.00 | N/A |
| B | 0.2 | 0.07 | N/A | 0.2 | 0.22 | N/A | 0.2 | 0.11 | N/A | 0.2 | 0.00 | N/A |
| C | 13.9 | 1.54 | 11.08 | 13.0 | 1.45 | 11.15 | 14.4 | 3.43 | 23.82 | 13.8 | 0.71 | 5.14 |
| D | 13.4 | 1.86 | 13.88 | 13.6 | 2.12 | 15.59 | 15.1 | 2.44 | 16.16 | 14.0 | 0.93 | 6.64 |
| E | 35.2 | 3.36 | 9.55 | 33.2 | 4.21 | 12.68 | 36.1 | 4.54 | 12.58 | 34.8 | 1.48 | 4.25 |
| F | 33.3 | 1.91 | 5.74 | 33.5 | 1.81 | 5.40 | 32.3 | 4.04 | 12.51 | 33.0 | 0.64 | 1.94 |
| G | 16.9 | 1.82 | 10.77 | 20.4 | 2.24 | 10.98 | 18.6 | 2.85 | 15.32 | 18.6 | 1.75 | 9.41 |
| 10 STD | 9.1 | 0.50 | 5.49 | 9.0 | 0.80 | 8.89 | 10.4 | 1.88 | 18.08 | 9.5 | 0.78 | 8.21 |
| 50 STD | 50.2 | 3.79 | 7.55 | 49.7 | 3.29 | 6.62 | 52.8 | 5.55 | 10.51 | 50.9 | 1.66 | 3.26 |
| LPC | 21.0 | 1.75 | 8.33 | 24.6 | 3.14 | 12.76 | 26.6 | 4.38 | 16.47 | 24.1 | 2.84 | 11.78 |
| NC | 2.8 | 0.21 | N/A | 3.0 | 0.34 | N/A | 2.9 | 0.24 | N/A | 2.9 | 0.10 | N/A |

Image /page/6/Picture/8 description: The image shows the number 000282 in a clear, sans-serif font. The numbers are evenly spaced and of uniform size, creating a symmetrical appearance. The image is simple and focuses solely on the numerical sequence.

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#### TABLE 13 : Lot-to-Lot Precision (Mago Plus)

| SERUM | Lot 31107<br>INTERASSAY | | | Lot 41307<br>INTERASSAY | | | Lot 50707<br>INTERASSAY | | | LOT-TO-LOT<br>INTERASSAY | | |
|--------|-------------------------|------|-------|-------------------------|------|-------|-------------------------|------|-------|--------------------------|------|-------|
| | MEAN<br>IU/ml | SD | CV% | MEAN<br>IU/ml | SD | CV% | MEAN<br>IU/ml | SD | CV% | MEAN<br>IU/ml | SD | CV% |
| A | 0.3 | 0.16 | N/A | 0.2 | 0.10 | N/A | 0.2 | 0.09 | N/A | 0.2 | 0.06 | N/A |
| B | 0.3 | 0.14 | N/A | 0.4 | 0.60 | N/A | 0.3 | 0.12 | N/A | 0.3 | 0.06 | N/A |
| C | 19.7 | 1.96 | 9.95 | 17.0 | 1.76 | 10.40 | 17.2 | 3.17 | 18.43 | 18.0 | 1.50 | 8.30 |
| D | 20.3 | 2.45 | 12.07 | 16.3 | 2.79 | 17.12 | 14.6 | 2.38 | 16.30 | 17.1 | 2.93 | 17.10 |
| E | 42.3 | 3.67 | 8.68 | 36.7 | 2.60 | 7.08 | 38.3 | 3.18 | 8.30 | 39.1 | 2.88 | 7.40 |
| F | 34.0 | 6.64 | 19.53 | 34.1 | 1.45 | 4.25 | 36.7 | 3.43 | 9.35 | 34.9 | 1.53 | 4.38 |
| G | 16.6 | 1.48 | 8.92 | 17.1 | 1.78 | 10.41 | 17.3 | 1.55 | 8.96 | 17.0 | 0.36 | 2.12 |
| H | 18.9 | 2.60 | 13.76 | 13.3 | 1.65 | 12.41 | 15.6 | 2.59 | 16.60 | 15.9 | 3.27 | 20.57 |
| 10 STD | 18.7 | 1.14 | 6.10 | 15.9 | 2.08 | 13.08 | 16.5 | 2.39 | 14.48 | 17.0 | 1.47 | 8.65 |
| LPC | 33.5 | 1.90 | 5.67 | 29.0 | 3.99 | 13.76 | 32.4 | 4.19 | 12.93 | 31.6 | 2.35 | 7.44 |
| NC | 4.4 | 0.43 | N/A | 3.7 | 0.36 | N/A | 4.4 | 0.41 | N/A | 4.2 | 0.40 | N/A |

# Expected Values

)

The incidence of rubella IgG antibodies varies among populations depending on vaccination practices. In a recent national survey of military recruits the seronegativity rate was 17.4% for males and 12.8% for females.

In the present studies sera from 100 healthy South Florida donors (52 female and 48 male) were evaluated in the Is-Rubella IgG Test Kit. Of the 100 samples, 89 (89%) were found to be positive, 9 (9%) were negative and 2 (2%) were equivocal. Age distribution, geographic location and prevalence is provided in Table 14. Histograms demonstrating the distribution of IU/ml values are shown in Figures 5 and 6.

Thirty-seven of the female donors were of child-bearing age (18-45 years). Of the sera from these donors, 29 (79%) were positive, 6 (16%) were negative and 2 (5%) were equivocal. A total of 45 sera from pregnant females (15 from each trimester) were also tested in the Is-Rubella IgG Test Kit. Forty one (92%) were negative, 2 (4%) were negative and 2 (4%) were equivocal for anti-rubella IgG. In addition, a total of 294 samples from females of childbearing age were identified in the outside and in-house clinical studies (these included the 45 sera from pregnant females already referenced). Of these samples, 223 (76%) were positive, 56 (19%) were negative and 15 (5%) were equivocal for antirubella IgG when evaluated in the Is-Rubella IgG Test Kit.

| | Number of Donors | Prevalence |
|------------------------------------------|------------------|------------|
| Total Number | 100 | 89.0% |
| Geographic Location:<br>South-Eastern US | 100 | 89.0% |
| Age | | |
| 10-19 | 13 | 92.3% |
| 20-29 | 23 | 73.9% |
| 30-39 | 40 | 92.5% |
| 40-49 | 13 | 92.3% |
| 50-59 | 5 | 100.0% |
| 60-69 | 6 | 100.0% |

| 6 | | | ﺎ<br>1 |
|---|---|--|--------|
| | 1 | | |

Image /page/7/Figure/8 description: The image contains two bar charts, labeled as Figure 5 and Figure 6. Figure 5 shows the Is-Rubella IgG Positive Population, with the x-axis representing IU/mL levels in ranges (0-10, 11-20, 21-30, 31-40, 41-50, and >50) and the y-axis representing frequency, with the >50 range having the highest frequency. Figure 6 shows the Is-Rubella IgG Negative Population, with the x-axis representing IU/mL levels in ranges (1-2, 3-4, 5-6, and 7-10) and the y-axis representing frequency, with the 1-2 range having the highest frequency. Both charts provide a visual comparison of the distribution of Is-Rubella IgG levels in positive and negative populations.

{8}------------------------------------------------

Image /page/8/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" arranged around the perimeter. Inside the circle is an abstract symbol resembling an eagle or a stylized human figure, composed of three curved lines.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

JAN 28 1999

Lynne Stirling, Ph.D. Vice President, Regulatory Affairs Diamedix Corporation 2140 North Miami Ave. Miami, FL 33127

Re: K981729 Trade Name: Is-Rubella IgG Test System Regulatory Class: III Product Code: LFX Dated: November 23, 1998 Received: November 24, 1998

Dear Dr. Stirling:

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we 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). 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 (Premarket Approval), 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 895. A substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic QS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations.

{9}------------------------------------------------

Page 2

Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at [phone].

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" (21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll free number [phone] or at [phone] or at its internet address "http://www.fda.gov/cdrh/dsmamain.html"

Sincerely yours,

Steven Sutman

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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# Appendix G. Indications for Use Statement

# INDICATIONS FOR USE STATEMENT

510(K) NUMBER : ______________________________________________________________________________________________________________________________________________________________

# DEVICE NAME : Is-Rubella IgG Test System

Indications for Use : The Diamedix Is-Rubella IgG Test Kit is an Enzyme Immunoassay (EIA) for the qualitative and quantitative determination of IgG antibodies in human serum to aid in the assessment of the patient's immunological response to infection with rubellaand in the determination of the immune status of individuals, including females of child-bearing age. The evaluation of acute and convalescent sera can aid in the diagnosis of recent or current infection with rubella. These reagents can be used either manually or in conjunction with the MAGO® Plus Automated EIA Processor.

Woody Dubois

(Division Sign Off)
Division of Clinical Laboratory Devices
510(k) Number K981729

PRESCRIPTION USE *X*