IS-ANTI-SM TEST SYSTEM

K970220 · Diamedix Corp. · LLL · Apr 8, 1997 · Immunology

Device Facts

• Record ID: K970220
• Device Name: IS-ANTI-SM TEST SYSTEM
• Applicant: Diamedix Corp.
• Product Code: LLL · Immunology
• Decision Date: Apr 8, 1997
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.5100
• Device Class: Class 2

Intended Use

The assay is intended for use in detecting antibodies to Sm antigen in a single human serum sample. The results of the assay are to be used as an aid in the diagnosis of autoimmune disorders.

Device Story

Is-anti-Sm Test System is an ELISA for detecting IgG to Sm antigen in human serum. Purified Sm antigen is immobilized on microtiter wells; patient serum is added. If anti-Sm antibodies are present, they bind to the antigen. After washing, enzyme-labeled anti-human immunoglobulin conjugate is added, followed by a substrate. Enzyme-substrate reaction produces color intensity measured photometrically. The device is used in clinical laboratories; manual or automated (MAGO system) operation. Output is a semi-quantitative measurement (EU/ml) of specific antibody levels. Results assist clinicians in diagnosing autoimmune disorders by identifying presence of anti-Sm antibodies.

Clinical Evidence

Bench testing only. Evaluated using 150 samples (100 normal donors, 50 autoimmune patients). Manual method: 87% relative sensitivity, 100% relative specificity, 97% agreement. MAGO automated method: 85% relative sensitivity, 100% relative specificity, 96% agreement. Precision (intra/inter-assay CVs) and linearity demonstrated. Correlation between manual and MAGO methods was 0.99 (Pearson).

Technological Characteristics

Enzyme-linked immunosorbent assay (ELISA) using purified Sm antigen immobilized on microtiter wells. Photometric detection of colorimetric substrate conversion. Compatible with manual processing or MAGO automated system. Semi-quantitative output in EU/ml.

Indications for Use

Indicated for the detection and semi-quantitation of IgG antibodies to Sm antigen in human serum to aid in the diagnosis of autoimmune disorders.

Regulatory Classification

Identification

An antinuclear antibody immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the autoimmune antibodies in serum, other body fluids, and tissues that react with cellular nuclear constituents (molecules present in the nucleus of a cell, such as ribonucleic acid, deoxyribonucleic acid, or nuclear proteins). The measurements aid in the diagnosis of systemic lupus erythematosus (a multisystem autoimmune disease in which antibodies attack the victim's own tissues), hepatitis (a liver disease), rheumatoid arthritis, Sjögren's syndrome (arthritis with inflammation of the eye, eyelid, and salivary glands), and systemic sclerosis (chronic hardening and shrinking of many body tissues).

Predicate Devices

• Helix Diagnostics Enzyme Immunoassay Anti-Sm Antibody Test Kit

Submission Summary (Full Text)

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K970220

APR - 8 1997

# 510(k) Summary of Safety and Effectiveness

This summary of 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: January 15, 1997
Name: Diamedix Corporation
Address: 2140 N. Miami Avenue
Miami, FL 33127
Contact Person: Dr. Lynne Stirling
Phone Number: 305-324-2354
Fax Number: 305-324-2585

## Device Information:

Trade Name: Is-(immunosimplicity)-anti-Sm Test System
Common Name: Anti-Sm EIA Test
Classification Name: Extractable Antinuclear Antibody

## Equivalent Device:

Helix Diagnostics Enzyme Immunoassay Anti-Sm Antibody Test Kit

## Device Description:

The Is-anti-Sm Test Kit System is an enzyme-linked immunosorbent assay (ELISA) for the detection and semi-quantitation of IgG to Sm antigen in human serum.

## Intended use:

The assay is intended for use in detecting antibodies to Sm antigen in a single human serum sample. The results of the assay are to be used as an aid in the diagnosis of autoimmune disorders.

## Comparison to Predicate Device:

The Is-anti-Sm Test System is an enzyme-linked immunosorbent assay to detect IgG to Sm antigen in human serum. Purified Sm antigen is attached to a solid phase microtiter well. Diluted test sera are added to each well. If antibodies which recognize the Sm antigen are present in the patient sample, they will bind to the antigen in 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 substrate will be converted to produce a colored product. The reaction is stopped and the color intensity is measured photometrically providing an indirect measure of the specific antibody present in the patient sample.

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Summary of Safety and Effectiveness

## Performance Characteristics

### A. Comparison Testing

The Diamedix Is-anti-Sm Test Kit was evaluated relative to another commercially available anti-Sm ELISA test kit using 100 sera from normal blood donors and 50 sera from autoimmune patients. The results are summarized in Table 1 below.

| Table 1 | Manual | | | MAGO | | |
| --- | --- | --- | --- | --- | --- | --- |
| | Number of Sera | % | 95% Confidence | Number of Sera | % | 95% Confidence |
| Relative Sensitivity | 34/39 | 87 | 73-96 | 35/41 | 85 | 71-94 |
| Relative Specificity | 107/107 | 100 | 97-100 | 107/107 | 100 | 97-100 |
| Agreement | 141/146* | 97 | 92-99 | 142/148** | 96 | 92-99 |

* Two equivocal and two borderline samples were excluded from the calculations.
** Two borderline samples were excluded from the calculations.

Five sera negative by Is-anti-Sm (manual) and positive by the comparative method were negative when tested by a third method. Six sera negative by Is-anti-Sm (MAGO) and positive by the comparative method were negative when tested by a third method. All discordant sera were from patient samples.

### B. Linearity

Figures 1 and 2 show typical examples of Is-anti-Sm Test Kit linearity. The figures depict the results of the Calibrator tested by Is-anti-Sm after serial two-fold manual dilutions in Sample Diluent. Separate dilutions were tested both manually and with MAGO. The results demonstrate a high degree of linearity for Is-anti-Sm Test Kit throughout the testing range.

Figure 1 Manual Linearity

Figure 2 MAGO Linearity

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C. Precision Testing

The precision of the Is-anti-Sm Test Kit was determined at Diamedix by testing six different sera and kit Calibrator and controls in two runs on three different days. The intra- and interassay precision is shown in Table 2 below.

| SERUM | Overall MEAN EU/ml | MANUAL | | MAGO | |
| --- | --- | --- | --- | --- | --- |
| | | INTRA-CV% | INTER-CV% | INTRA-CV % | INTER-CV % |
| 1 (NEG) | 1.6 | 8.2 | 7.1 | 19.7 | 23.5 |
| 2 (NEG) | 1.6 | 9.2 | 25.0 | 10.2 | 13.3 |
| 3 (POS) | 56.0 | 3.2 | 3.5 | 3.9 | 4.5 |
| 4 (POS) | 38.4 | 5.5 | 5.7 | 3.4 | 7.9 |
| 5 (POS) | 80.7 | 3.9 | 4.6 | 2.1 | 3.4 |
| 6 (POS) | 93.9 | 2.8 | 3.6 | 2.7 | 5.3 |
| CAL | 104.3 | 2.8 | 4.2 | 3.7 | 6.7 |
| POS CTRL | 52.6 | 3.1 | 4.2 | 5.2 | 7.6 |
| NEG CTRL | 0.8 | 12.1 | 25.0 | 47.2 | 50.0 |

D. Crossreactivity

Twenty-four sera positive for the six autoimmune specificities were tested in Is- anti-Sm Test Kit. The results are shown in Table 3.

Table 3 Crossreactivity

| Sample | Is anti-Sm | Interp | Specificity |
| --- | --- | --- | --- |
| 1 | 2.2 | NEG | SSA |
| 2 | 2.6 | NEG | SSA |
| 3 | 1.4 | NEG | SSA |
| 4 | 1.3 | NEG | SSA |
| 5 | 2.0 | NEG | SSB |
| 6 | 2.2 | NEG | SSB |
| 7 | 2.1 | NEG | SSB |
| 8 | 1.5 | NEG | SSB |
| 9 | 78.2 | POS | Sm |
| 10 | 66.4 | POS | Sm |
| 11 | 103.6 | POS | Sm |
| 12 | 103.1 | POS | Sm |
| 13 | 7.1 | NEG | RNP |
| 14 | 3.8 | NEG | RNP |
| 15 | 10.2 | NEG | RNP |
| 16 | 2.1 | NEG | RNP |
| 17 | 2.8 | NEG | Jo-1 |
| 18 | 4.0 | NEG | Jo-1 |
| 19 | 3.4 | NEG | Jo-1 |
| 20 | 2.6 | NEG | Jo-1 |
| 21 | 1.6 | NEG | Scl-70 |
| 22 | 2.0 | NEG | Scl-70 |
| 23 | 2.3 | NEG | Scl-70 |
| 24 | 1.9 | NEG | Scl-70 |

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# E. Expected Values

The expected values in the normal population were determined by assaying 100 normal donor sera collected in South Florida. Figures 3 and 5 show the distribution of Sm results in the normal population performed manually and on MAGO respectively.

The distribution of EU/ml values for 50 clinically characterized sera along with the 100 normal donor sera are shown in Figures 4 and 6 performed manually and on MAGO respectively.

Figure 3 Manual Normals

Figure 4 Manual Expected Values

Figure 5 MAGO Normals

Figure 6 MAGO Expected Values

# F. Correlation of Manual and MAGO Results

Numerical comparison of EU/ml values, between manual and MAGO results for 150 samples in the Is-anti-Sm Test Kit showed a correlation of 0.99 (Pearson).

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