DIAMEDIX IS-RF TEST SYSTEM

K974889 · Diamedix Corp. · DHR · Mar 6, 1998 · Immunology

Device Facts

• Record ID: K974889
• Device Name: DIAMEDIX IS-RF TEST SYSTEM
• Applicant: Diamedix Corp.
• Product Code: DHR · Immunology
• Decision Date: Mar 6, 1998
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.5775
• Device Class: Class 2

Indications for Use

The Diamedix Is-RF an Enzyme Immunoassay (EIA) for the detection and quantitative determination of RF-JgM antibodies in human serum as an aid in the diagnosis of rheumatoid arthritis. These reagents can be used either manually or in conjunction with the MAGO® Automated EIA Processor.

Device Story

Is-RF Test System is an ELISA for detecting and quantifying RF IgM-class antibodies in human serum. Purified human IgG is immobilized on microtiter wells; patient serum is added; RF-IgM binds to IgG. After washing, enzyme-labeled anti-human immunoglobulin conjugate is added, followed by substrate. Color intensity, measured photometrically, is proportional to antibody concentration. Used in clinical laboratories; performed manually or via MAGO Automated EIA Processor. Results aid clinicians in diagnosing rheumatoid arthritis. Benefits include standardized, quantitative assessment of RF-IgM levels compared to qualitative methods.

Clinical Evidence

Evaluation included 249 serum samples (200 normal, 49 clinical). Manual method: 98.5% sensitivity, 99.4% specificity. MAGO method: 98.5% sensitivity, 98.3% specificity. High linearity (R² > 0.95) and correlation between manual and MAGO methods (R² = 0.9911). Precision evaluated via intra-assay and inter-assay testing across three days; CVs generally <10%. No interference observed from ANA or prozone effects.

Technological Characteristics

ELISA-based immunoassay. Solid phase: microtiter wells coated with purified human IgG. Detection: enzyme-labeled anti-human immunoglobulin conjugate and substrate. Photometric measurement of color intensity. Compatible with manual processing or MAGO Automated EIA Processor. Standardized against WHO RF Reference preparation.

Indications for Use

Indicated for the detection and quantitative determination of RF-IgM antibodies in human serum as an aid in the diagnosis of rheumatoid arthritis in patients suspected of having the disease.

Regulatory Classification

Identification

A rheumatoid factor immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the rheumatoid factor (antibodies to immunoglobulins) in serum, other body fluids, and tissues. Measurement of rheumatoid factor may aid in the diagnosis of rheumatoid arthritis.

Predicate Devices

• RF Microassay

Submission Summary (Full Text)

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K974889

MAR - 6 1998

## 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: Diamedix Corporation 2140 N. Miami Avenue Miami, FL 33127

Contact Person: Phone Number: Fax Number:

Dr. Lynne Stirling 305-324-2354 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: K974889

### Applicant Information:

| Date Prepared: | Decmber 29, 1997 |
|----------------|-----------------------------------------|
| 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-RF Test System |
|----------------------|---------------------------|
| Common Name: | RF EIA Test |
| Classification Name: | RF Immunological Reagnets |

### Equivalent Device:

RF Microassay

Device Description: The Is-RF Test Kit System is an enzyme-linked immunosorbent assay (ELISA) for the detection and quantitation of RF IgM-class in human serum.

Intended Use: The assay is intended for use in detecting RF IgM antibodies in a single human serum sample. The results of the assay are to be used as an aid in the diagnosis of RA.

### Principle of the Procedure:

The Is-RF Test System is an enzyme-linked immunosorbent assay to detect RF-IgM in human serum. Purified human IgG is attached to a solid phase microtiter well. Diluted test sera are added to each well. If RF-IgM antibodies are present in the patient sample they will bind to the human IgG 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 prior step, the reaction is stopped and the color intesnity is measured photometrically producing an indirect measure of the specific antibody present in the patient sample.

## 000242

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# Performance Charactistics

## A. Comparison Testing

The Diamedix Is-RF Test Kit was evaluated relative to another commercially available RF EIA test kit that is also standardized against the WHO RF Reference preparation. Two hundred sera from normal blood donors and 49 sera from clinical patients were tested by the Is-RF test kit and the comparative method. Testing was performed both manually and using the MAGO Automated Processor. Results are shown in Table 1.

| TABLE 1 | Manual | | | MAGO | | |
|-----------------------|-----------------------------------------------------|------|------------|------------------------------------------------------|------|------------|
| | # of Sera | % | 95% CI | # of Sera | % | 95% CI |
| Relative Sensitivity | 65/66 | 98.5 | 91.8-100.0 | 64/65 | 98.5 | 91.7-100.0 |
| Relative Specificiity | 173/174 | 99.4 | 96.8-100.0 | 176/179 | 98.3 | 95.2-99.7 |
| Overall Agreement | 238/240* | 99.2 | 97.9-99.9 | 240/244** | 98.4 | 95.2-99.7 |
| | * 9 equivocal results excluded<br>from calculations | | | ** 5 equivocal results excluded<br>from calculations | | |

For manual testing one sample was positive by the Is-RF and negative by the comparative method and one sample was negative in the Is-RF and positive by the comparative method. Both samples were negative by a referee method. For MAGO testing there were three samples that were positive in the Is-RF and negative in the comparative method and one sample that was negative in the Is-RF and positive by the comparative method. When the three samples that were positive by the Is-RF were tested by a referee method one was positive and two were negative. The sample that was negative in the Is-RF but positive by the comparative method was also negative in the referee method.

### B. Linearity

Figures 1 and 2 show typical examples of the Is-RF linearity. These figures depict the results of the in-house reference standard (which has been standardized against the WHO Reference) tested by the Is-RF after serial two-fold manual dilution in Sample Diluent. Separate dilutions were tested both manually and with MAGO. The results demonstrate a high degree of linearity for the Is-RF Test Kit throughout the reportable range of the assay.

Image /page/2/Figure/8 description: The image shows a scatter plot titled "Is-RF Secondary Standard". The x-axis is labeled "Dilution" and ranges from 0.0 to 1.0. The y-axis is labeled "Absorbance" and ranges from 0.0 to 2.0. The plot shows a positive correlation between dilution and absorbance, with an R-squared value of 0.9554.

FIGURE 1 - MANUAL LINEARITY

#### FIGURE 2 - MAGO LINEARITY

Image /page/2/Figure/10 description: The image shows a scatter plot titled "Is-RF Secondary Standard". The x-axis is labeled "Dilution" and ranges from 0.0 to 1.0. The y-axis is labeled "Absorbance" and ranges from 0.0 to 2.0. The plot shows a linear relationship between dilution and absorbance, with an R-squared value of 0.9650.

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## C. Precision

The precision of the Is-RF test kit was determined by testing six different sera and the kit calibrator and controls in triplicate in two runs on three different days. Precision was evaluated both manually and using the MAGO. The intraand interassay precision is shown in Tables 2 and 3.

| Is-RF Precision (Manual) | | | | | | | | | | | | |
|--------------------------|-------------------|-----|-----|-------|-----|-----|-------|-----|-----|-------------------|-----|-----|
| TABLE 2 | Intra-assay (n=6) | | | | | | | | | Interassay (n=18) | | |
| | Day 1 | | | Day 2 | | | Day 3 | | | | | |
| SERUM | Mean | SD | %CV | Mean | SD | %CV | Mean | SD | %CV | Mean | SD | %CV |
| A (Neg) | 1.4 | 0.4 | N/A | 1.2 | 0.3 | N/A | 1.4 | 0.1 | N/A | 1.4 | 0.3 | N/A |
| B (Neg) | 0.4 | 0.1 | N/A | 0.4 | 0.1 | N/A | 0.6 | 0.1 | N/A | 0.5 | 0.1 | N/A |
| C (Pos) | 37.7 | 2.8 | 7.4 | 39.7 | 2.9 | 7.2 | 41.9 | 4.0 | 9.6 | 39.8 | 3.6 | 9.0 |
| D (Pos) | 54.5 | 2.8 | 5.2 | 56.7 | 2.8 | 5.0 | 60.6 | 3.4 | 5.6 | 57.3 | 3.9 | 6.7 |
| E (Pos) | 80.4 | 2.4 | 3.0 | 82.7 | 4.1 | 4.9 | 87.8 | 1.5 | 1.7 | 83.6 | 4.2 | 5.0 |
| F (Pos) | 113.3 | 4.7 | 4.1 | 113.8 | 7.1 | 6.2 | 113.4 | 3.9 | 3.4 | 113.5 | 5.1 | 4.5 |
| Cal. | 110.4 | 5.5 | 5.0 | 114.2 | 6.1 | 5.4 | 107.5 | 4.4 | 4.1 | 110.7 | 5.8 | 5.2 |
| Pos. | 46.7 | 2.6 | 5.7 | 48.9 | 3.5 | 7.2 | 47.7 | 3.8 | 7.9 | 47.7 | 3.3 | 6.9 |
| Neg. | 0.7 | 0.2 | N/A | 0.6 | 0.1 | N/A | 0.8 | 0.2 | N/A | 0.7 | 0.2 | N/A |

Is-RF Precision (Manual)

| | | | C | |
|---|----|---|---|--|
| 1 | AB | 1 | 1 | |

Is-RF Precision (MAGO)

| Intra-assay (n=6) | | | | | | | | | Interassay (n=18) | | | |
|-------------------|-------|-----|-----|-------|-----|-----|-------|-----|-------------------|-------|-----|-----|
| SERUM | Day 1 | | | Day 2 | | | Day 3 | | | Mean | SD | %CV |
| | Mean | SD | %CV | Mean | SD | %CV | Mean | SD | %CV | | | |
| A (Neg) | 1.7 | 0.3 | N/A | 1.4 | 0.4 | N/A | 1.3 | 0.4 | N/A | 1.4 | 0.4 | N/A |
| B (Neg) | 0.8 | 0.3 | N/A | 0.6 | 0.6 | N/A | 0.5 | 0.4 | N/A | 0.6 | 0.4 | N/A |
| C (Pos) | 37.7 | 1.1 | 2.9 | 39.2 | 1.3 | 3.3 | 40.8 | 3.2 | 7.8 | 39.2 | 2.4 | 6.0 |
| D (Pos) | 56.9 | 2.1 | 3.6 | 59.3 | 1.9 | 3.2 | 63.4 | 2.6 | 4.1 | 59.8 | 3.5 | 5.8 |
| E (Pos) | 87.7 | 1.8 | 2.1 | 88.1 | 4.5 | 5.1 | 90.7 | 5.1 | 5.6 | 88.8 | 4.0 | 4.5 |
| F (Pos) | 115.9 | 3.5 | 3.0 | 113.5 | 3.5 | 3.1 | 116.1 | 3.6 | 3.1 | 115.1 | 3.5 | 3.1 |
| Cal. | 111.9 | 3.5 | 3.1 | 111.9 | 4.0 | 3.6 | 113.4 | 2.6 | 2.3 | 112.4 | 3.3 | 2.9 |
| Pos. | 49.2 | 1.8 | 3.7 | 48.6 | 2.2 | 4.5 | 49.6 | 2.3 | 4.6 | 49.2 | 2.0 | 4.2 |
| Neg. | 1.4 | 0.4 | N/A | 1.2 | 1.0 | N/A | 0.6 | 0.6 | N/A | 1.1 | 0.7 | N/A |

### D. Crossreactivity/Interference

Antinuclear antibodies (ANA) have been found in 14 to 28% of patients with RA and are usually found in patient with more advanced disease (1). Several RF-negative samples containing various ANA were evaluated to ensure lack of interference from these antibodies in RF-negative sera. These results are shown in Table 4 In addition, no prozone interference was encountered when testing high titered sera.

| TABLE 4 | | | |
|----------|----------------|--------|------------------|
| Sample # | Is-RF<br>IU/ml | Interp | ANA Specificity |
| 1 | 1.6 | NEG | Scl-70, SSA |
| 2 | 1.4 | NEG | Scl-70, SSA |
| 3 | 2.0 | NEG | Jo-1, SSA,Sm/RNP |
| 4 | 11.6 | NEG | Jo-1, Sm/RNP |
| 5 | 3.6 | NEG | SSA, SSB |
| 6 | 10.6 | NEG | SSA, SSB |
| 7 | 4.2 | NEG | SSA, Sm/RNP |
| 8 | 2.4 | NEG | SSA, Sm/RNP |
| 9 | 0.6 | NEG | SSA |
| 10 | 0.6 | NEG | SSA |
| 11 | 1.8 | NEG | Sm/RNP |
| 12 | 1.4 | NEG | Sm/RNP |
| 13 | 1.0 | NEG | SSA, SSB, dsDNA |
| 14 | 5.6 | NEG | SSA, dsDNA |

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### E. Expected Values

The expected value in the normal population is negative. However, apparently healthy asymptomatic individuals may have and The expected value in the normal population is north, appeases with age and is similar in males and These individuals usually have tow theirs. The theoched of the normal S. Florida donor population performed manually temales. Highles 3 and 3 show de distribution of 10 100 the normals gave positive values; for MAGO testing the positive frequency was 9.0%.

The distribution of IU/ml values for 49 sera from clinical patients is shown in Figures 4 and 6 performed The usuloudon of TOrin Values For 19 octa increase of the for RF using either testing method.

Image /page/4/Figure/3 description: The image contains four plots comparing the results of manual and MAGO methods for normals and clinical patients. Figure 3 shows the manual method results for normals, with the x-axis representing the number of sera and the y-axis representing IU/ml. Figure 4 shows the manual method results for clinical patients, with the x-axis representing the number of sera and the y-axis representing IU/ml. Figure 5 shows the MAGO method results for normals, and Figure 6 shows the MAGO method results for clinical patients.

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## F. Correlation of Manual and Mago Results

Correlation of manual and MAGO IU/ml values for 249 samples tested in the Is-RF Test Kit yielded an R² value of 0.9911 as shown in Figure 7.

Image /page/5/Figure/2 description: The image is a scatter plot titled "FIGURE 7". The x-axis is labeled "Is-RF Manual (IU/ml)" and ranges from 0.0 to 150.0. The y-axis is labeled "Is-RF Test-MAGO (IU/ml)" and ranges from 0.0 to 200.0. The data points are clustered around a straight line, and the R-squared value is 0.9911.

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Image /page/6/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle with three stripes forming its body and wings. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" are arranged in a circular pattern around the eagle.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Lynne Stirling, Ph.D. Diamedix® Corporation 2140 North Miami Avenue Miami, Florida 33127

MAR - 6 1999

Re : K974889 Trade Name: Diamedix Is-RF Test System Regulatory Class: II Product Code: DHR Dated: December 29, 1997 Received: December 30, 1997

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 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 requirement, 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 Failure to comply with the GMP regulation may result in assumptions. 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.

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Page 2

Under the Clinical Lahoratory 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 Butman

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 (if known):_K974889

Device Name:

Indications For Use:

Indications for Use :The Diamedix Is-RF an Enzyme Immunoassay (EIA) for the detection and quantitative determination of RF-JgM antibodies in human serum as an aid in the diagnosis of rheumatoid arthritis. These reagents can be used either manually or in conjunction with the MAGO® Automated EIA Processor.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Ctetin E. Mayfin

(Division Sign-Off)
Division of Clinical Laboratory Devices K974889
510(k) Number

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

Over-The-Counter Use__________________________________________________________________________________________________________________________________________________________

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