RAICHEM RHEUMATOID FACTOR SPIA

K970373 · Henage Diagnostics, Inc. · DHR · Apr 17, 1997 · Immunology

Device Facts

• Record ID: K970373
• Device Name: RAICHEM RHEUMATOID FACTOR SPIA
• Applicant: Henage Diagnostics, Inc.
• Product Code: DHR · Immunology
• Decision Date: Apr 17, 1997
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.5775
• Device Class: Class 2

Intended Use

A latex agglutination assay intended for the quantitative turbidimetric detection of Rheumatoid IgM antibodies in human serum and plasma. When used according to instructions, the assay is useful in establishing the presence of rheumatoid factor and as an aid in the diagnosis and management of rheumatoid arthritis.

Device Story

Rheumatoid Factor SPIA™ is a latex agglutination assay for quantitative detection of Rheumatoid Factor (RF) IgM antibodies in human serum and plasma. Input: patient serum/plasma samples. Principle: latex microspheres coated with human and rabbit IgG aggregate in presence of RF; aggregation reduces suspension turbidity; change in optical density measured. Output: quantitative RF concentration determined via comparison to standard curve. Used in clinical laboratories; performed manually or adapted for automated systems (e.g., Roche COBAS-MIRA). Results assist clinicians in diagnosing and managing rheumatoid arthritis.

Clinical Evidence

Bench testing and comparative clinical study. Precision evaluated via inter-assay and intra-assay reproducibility studies (n=6 samples). Comparative study (n=335) against predicate (hemagglutination) and third-party EIA method. Results: Relative analytical sensitivity 95.4% (95% CI: 90.8%–97.8%); relative analytical specificity 100% (95% CI: 98.0%–100%).

Technological Characteristics

Latex agglutination turbidimetric assay. Materials: latex microspheres coated with human and rabbit IgG. Sensing principle: optical density change proportional to RF concentration. Connectivity: manual or automated (e.g., COBAS-MIRA). Calibration: traceable to W.H.O. International Reference Preparation.

Indications for Use

Indicated for the quantitative detection of Rheumatoid Factor IgM antibodies in human serum and plasma to aid in the diagnosis and management 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

• Hemagen® RF Kit (HA method) (K855221/A)

Reference Devices

• COBAS-MIRA Analyzer (K851172)
• Hemagen® RF Kit (EIA method) (K962386)

Submission Summary (Full Text)

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K970373
April 17, 1997

510(k) Summary

1. Submitter's Name/Contact Person
Joseph M. Califano Manager, Regulatory Affairs

Address
Hemagen Diagnostics, Inc.
34-40 Bear Hill Road
Waltham, MA, 02154

Phone: [phone]
Fax: [phone]

Date Prepared
30 Jan 1997

2. Device Name
Trade Name: Rheumatoid Factor SPIA™
Common Name: RF (Rheumatoid Factor)
Classification Name: System, Test, Rheumatoid Factor

3. Predicate Device
Hemagen ® RF Kit (HA method) {510 (k) Docket No. K 855221/A}

3a. Methods
I. Manual: Described in Laboratory Diagnostic Procedures in the Rheumatic Diseases, 3rd Ed. (1985) Chap. 4 Rheumatoid Factors, Techniques of Analysis by McDuffie, F.C.
II. Automated System: COBAS-MIRA Analyzer. {510 (k) Docket No. k 851172}
III. Third Party Test: Hemagen ® RF Kit (EIA method) {510 (k) Docket No. K 962386}

4. Description of Device
Raichem's Rheumatoid Factor SPIA™ latex agglutination assay is a quantitative turbidimetric assay for the detection of Rheumatoid Factor IgM antibodies in human serum and plasma.

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## 4. Description of Device

Ralchem's Rheumatoid Factor SPIA™ latex agglutination assay is a quantitative turbidimetric assay for the detection of Rheumatoid Factor IgM antibodies in human serum and plasma.

In this assay, latex microspheres coated with human and rabbit IgG are diluted in a reaction buffer designed to allow aggregation without rapid settling of Rheumatoid Factor complexed microparticles. As aggregates form, the suspension becomes less cloudy, resulting in less light being absorbed. The change in optical density is proportional to the amount of RF present in the suspension.

A quantitative determination of the amount of RF present in a serum/plasma sample is made by comparison to a standard curve.

## 5. Intended Use of Device

A latex agglutination assay intended for the quantitative turbidimetric detection of Rheumatoid IgM antibodies in human serum and plasma. When used according to instructions, the assay is useful in establishing the presence of rheumatoid factor and as an aid in the diagnosis and management of rheumatoid arthritis.

### 6.(A) Technological Characteristics

#### Proposed Device

Ralchem's Rheumatoid Factor SPIA™ latex agglutination assay is a quantitative turbidimetric assay. The amount of RF present is proportional to the change in optical density in the suspension. The RF IgM antibody concentration is quantified by comparison to a standard curve. This assay is performed manually following clinically accepted methodologies. The assay is designed to enable users to readily adapt it for use with automated systems such as the Roche COBAS MIRA Analyzer.

#### Predicate Device

The Hemagen® RF(HA) Kit is a hemagglutination based assay. The device utilizes the method of agglutination of specifically sensitized human erythrocytes by patient serum containing rheumatoid factor. The resultant level of agglutination is used to determine the presence or absence of rheumatoid factor.

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## 6.(B) Performance Data

### I. Precision

To evaluate precision, inter-assay and intra-assay studies were conducted with the Raichem Rheumatoid Factor SPIA™ on an automated system {COBAS-MIRA}

### A. Inter-assay reproducibility

Six different serum samples were assayed twice a day on four different days.

| SAMPLE | Mean IU/mL | Std. Dev | % CV | Mean Delta | Std. Dev | % CV |
| --- | --- | --- | --- | --- | --- | --- |
| 1 | 95.4 | 5.0 | 5.3 | 0.111 | 0.007 | 6.4 |
| 2 | 80.3 | 5.3 | 6.6 | 0.097 | 0.007 | 7.7 |
| 3 | 67.9 | 9.9 | 14.6 | 0.087 | 0.010 | 11.8 |
| 4 | 45.9 | 9.5 | 20.7 | 0.071 | 0.010 | 13.8 |
| 5 | < 20 | N/A | N/A | 0.037 | 0.003 | 9.4 |
| 6 | < 20 | N/A | N/A | 0.036 | 0.005 | 15.0 |

### B. Intra-assay reproducibility

Six different serum samples were assayed 20 consecutive times in a single run.

| SAMPLE | Mean IU/mL | Std. Dev | % CV | Mean Delta | Std. Dev | % CV |
| --- | --- | --- | --- | --- | --- | --- |
| 1 | 56 | 3.7 | 6.7 | 0.080 | 0.004 | 5.4 |
| 2 | 48 | 3.2 | 6.6 | 0.070 | 0.004 | 5.3 |
| 3 | 28 | 2.8 | 10.0 | 0.047 | 0.003 | 7.1 |
| 4 | 23 | 2.7 | 11.5 | 0.041 | 0.004 | 9.6 |
| 5 | < 20 | N/A | N/A | 0.015 | 0.005 | 31.4 |
| 6 | < 20 | N/A | N/A | 0.011 | 0.003 | 31.5 |

### II. Verification of the RF Calibrator

The RF Calibrator{120 IU/mL} supplied with the assay is the same as the High Calibrator supplied with the Hemagen® Rheumatoid Factor Kit (EIA method) (Refer to 510 (k) Docket No. 962386). The kit calibrators were compared to the World Health Organization International Reference Preparation of Rheumatoid Arthritis Serum. It was demonstrated that there is a high degree of correlation that exists between the kit calibrators and the W.H.O. Standard.

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# III. Comparison Testing

The Ralchem Rheumatoid Factor SPIA™ and the Hemagen® RF Hemagglutination Kit were used to assay serum specimens from rheumatoid arthritis patients, patients with autoimmune diseases, and normal apparently healthy donors.

## A. Comparison with an automated method (COBAS-MIRA)

Table 1.1 Disease State Specimens (combined) n =335

| Predicate Device | | | | |
| --- | --- | --- | --- | --- |
| Proposed Device | Positive | Negative | Equivocal | Total |
| Positive | 141 | 3^{1} | 0 | 144 |
| Negative | 9^{1} * | 180 | 2^{1} * | 191 |
| Total | 150 | 183 | 2 | 335 |

1. The discrepant and equivocal samples were evaluated by a third party EIA method

| EIA | | |
| --- | --- | --- |
| Proposed Device | Positive | Negative |
| Positive | 3 | 0 |
| Negative | 7 | 4 |

Table 1.2 Disease State Specimens (combined), n =335

| Predicate Device | | | |
| --- | --- | --- | --- |
| Proposed Device | Positive | Negative | Total |
| Positive | 144 | 0 | 144 |
| Negative | 7 | 184 | 191 |
| Total | 151 | 184 | 335 |
| Relative analytical sensitivity = 95.4 % (144/151), 0.95_{INTERVAL} = 90.8 % to 97.8 % | | | |
| Relative analytical specificity = 100 % (184/184), 0.95_{INTERVAL} = 98.0 % to 100 % | | | |

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