For the quantitative detection of RF IgM-class antibodies in human serum by indirect enzyme immunoassayas an aid in the diagnosis of rheumatoid arthritis (RA). This test kit can be used either manually or in conjunction with the MAGO® Plus Automated EIA Processor.

Device Description

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

AI/ML Overview

Acceptance Criteria and Device Performance for Is-Rheumatoid Factor Test System

This document outlines the acceptance criteria and the results of studies demonstrating the performance of the Diamedix Is-Rheumatoid Factor Test System, an enzyme-linked immunosorbent assay (ELISA) for the detection and quantitation of IgM-class Rheumatoid Factor (RF) in human serum.

1. Acceptance Criteria and Reported Device Performance

The acceptance criteria for the Is-Rheumatoid Factor Test System were established through comparative studies against another commercially available EIA kit and nephelometry, as well as an assessment of linearity, cross-reactivity, precision, and expected values in normal and clinical populations.

Performance Characteristic	Acceptance Criteria (Implied)	Reported Device Performance
Relative Sensitivity	High agreement with predicate EIA device.	100% (89/89) compared to another EIA kit (95% CI: 95.9-100.0%)
Relative Specificity	High agreement with predicate EIA device.	100% (91/91) compared to another EIA kit (95% CI: 96.0-100.0%)
Overall Agreement	High agreement with predicate EIA device.	100% (190/190) compared to another EIA kit (95% CI: 98.1-100.0%)
Correlation with Nephelometry	Strong positive correlation (e.g., r > 0.90).	Correlation Coefficient (r) = 0.9672 (95% CI: 0.9384 to 0.9826) for 40 samples.
Comparison with Latex Agglutination	Demonstrate at least comparable sensitivity/specificity to latex agglutination, or better given the quantitative nature of the device.	- Normal Sera (40 samples): Specificity 100% (40/40 Negative) for both Latex and Is-RF. - Clinical Sera (18 samples): Sensitivity 50% (9/18 Positive) for Latex; Sensitivity 100% (18/18 Positive) for Is-RF. - Other Sera (13 samples): Latex 4/13 Positive; Is-RF 10/13 Positive. Higher sensitivity for Is-RF compared to Latex.
Linearity (WHO Standard)	High correlation coefficient (r) with serial dilutions.	Correlation Coefficient (r) = 0.9557.
Linearity (In-House Standard)	High correlation coefficient (r) with serial dilutions.	Correlation Coefficient (r) = 0.9634.
Lack of Cross-reactivity with other ANA	Minimal or no positive results from RF-negative samples containing other ANAs.	Out of 21 RF-negative samples with various ANAs (SSA, Sm, RNP, Scl-70, Jo-1, dsDNA, SSB), only one sample containing anti-SSB gave a very low positive result (21.2 IU/ml), all others were negative. This demonstrates minimal cross-reactivity.
Lack of Prozone/High-Dose Hook Effects	No evidence of prozone or high-dose hook effects across a range of RF concentrations.	No prozone or high-dose hook effects were evidenced in 8 sera (4 high concentrated, 2 mid-range, 2 negative) tested with serial dilutions.
Correlation of Manual and MAGO Plus Results	Strong positive correlation between manual and automated (MAGO Plus) testing.	Correlation Coefficient (r) = 0.9933 (95% CI: 0.9916 to 0.9946) for 303 normal and clinical serum samples.
Precision (Intra-assay and Inter-assay)	Acceptable coefficient of variation (%CV) for various RF levels, within generally accepted laboratory standards.	Manual: Intra-assay %CV generally < 10% for positive samples; inter-assay %CV generally < 7% for positive samples. Higher %CV for negative samples as expected due to values near zero. MAGO Plus: Intra-assay %CV generally < 12% for positive samples; inter-assay %CV generally < 8% for positive samples. Higher %CV for negative samples as expected due to values near zero.
Expected Values (Normal Population)	Low prevalence of RF in a normal healthy population.	- 118 normal healthy blood donors from S. Florida: 94.9% negative, 1.7% positive, 3.4% equivocal. - Overall prevalence: 1.69%.
Expected Values (Clinical Population)	High prevalence of RF in a population with diagnosed rheumatoid arthritis.	- 93 patients with diagnosed rheumatoid arthritis: 93.5% positive, 4.3% negative, 2.2% equivocal.

2. Sample Sizes and Data Provenance

Relative Sensitivity and Specificity vs. Another EIA Test:
- Sample Size: 185 retrospective sera.
- Data Provenance: Not explicitly stated, but implies a collection from a clinical setting, likely within the US given the FDA submission. Retrospective.
Correlation with Nephelometry Results:
- Sample Size: 40 samples.
- Data Provenance: Not explicitly stated, but implies a collection from a clinical setting, likely within the US. Retrospective.
Comparison with Latex Agglutination:
- Sample Size: 71 sera (40 normal, 18 known clinical, 13 containing other autoantibodies).
- Data Provenance: Not explicitly stated, but implies a collection from a clinical setting, likely within the US. Retrospective.
Lack of Cross-reactivity with Other Antinuclear Antibodies:
- Sample Size: 21 RF-negative samples (5 SSA, 4 Sm, 5 RNP, 3 Scl-70, 4 Jo-1, 3 dsDNA, 1 SSB).
- Data Provenance: Not explicitly stated, but implies a collection from a clinical setting, likely within the US. Retrospective.
Lack of Prozone/High-Dose Hook Effects:
- Sample Size: 8 sera.
- Data Provenance: Not explicitly stated, but implies a collection from a clinical setting, likely within the US. Retrospective.
Correlation of Manual and MAGO Plus Results:
- Sample Size: 303 normal and clinical serum samples.
- Data Provenance: Not explicitly stated, but implies a collection from a clinical setting, likely within the US. Retrospective.
Precision:
- Sample Size: 6 serum samples of varying reactivity, plus kit Calibrator and controls.
- Data Provenance: Reference materials and likely internal samples for method validation.
Expected Values (Normal Population):
- Sample Size: 118 blood donors.
- Data Provenance: South Florida, USA; prospective collection (implied by "normal healthy population were assessed by testing sera").
Expected Values (Clinical Population):
- Sample Size: 93 sera from patients with a diagnosis of rheumatoid arthritis.
- Data Provenance: Not explicitly stated beyond "patients with a diagnosis of rheumatoid arthritis", but likely USA and retrospective.

3. Number of Experts Used to Establish Ground Truth and Their Qualifications

The studies described are for an in-vitro diagnostic (IVD) device that measures a biomarker (RF IgM). The "ground truth" for the test sets in this context is based on:

Established clinical diagnosis of Rheumatoid Arthritis (RA) for the clinical population. The number of experts or their qualifications for establishing these diagnoses are not specified in the document, as this is typically provided as pre-classified samples.
Pre-classification by other established assays: "another commercially available EIA kit for detecting RF," "nephelometry," and "latex agglutination test." These methods themselves serve as the reference standard or "ground truth" for comparative performance. The expertise involved in generating these reference results is inherent in the validation of those comparator methods.
Known normal healthy individuals: for the normal population. The "ground truth" for these samples is the absence of RA or high RF levels based on their healthy status.

No adjudication method using additional experts for these studies is described, as the comparison is primarily analytical against other assays or established clinical conditions.

4. Adjudication Method

Not applicable. The studies are analytical performance evaluations against other assays or established clinical classifications, not typically requiring external expert adjudication of results. The "ground truth" is derived from the established methods or patient diagnosis.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This is an in-vitro diagnostic device, not an imaging AI diagnostic device where MRMC studies are common to assess human reader performance with and without AI assistance. The device is intended to provide a quantitative measurement of RF, which is then interpreted by clinicians.

6. Standalone (Algorithm Only) Performance Study

Yes, the studies presented primarily represent "standalone" performance (algorithm only without human-in-the-loop performance) of the Is-Rheumatoid Factor Test System. The device directly measures RF IgM levels in serum, and its performance (sensitivity, specificity, correlation, precision, etc.) is evaluated without direct human interpretation of raw assay data. The results (IU/ml values) are then provided to healthcare professionals for interpretation in the context of a patient's clinical picture.

There is also a comparison between manual and MAGO Plus Automated EIA Processor results, demonstrating the equivalence of the automated process, which is also a standalone algorithmic process.

7. Type of Ground Truth Used

The type of ground truth used varies by study:

Clinical Diagnosis: For studies involving "clinical samples" or "patients with a diagnosis of rheumatoid arthritis," the ground truth is based on the diagnosis of rheumatoid arthritis.
Results from Predicate or Reference Assays:
- "another commercially available EIA kit for detecting RF"
- "nephelometry"
- "latex agglutination test"
- These comparator methods served as the reference standard for relative sensitivity, specificity, and correlation.
Known Healthy Status: For "normal samples" or "blood donors," the ground truth is their healthy status and presumed absence of elevated RF.
Known Autoantibody Status: For the cross-reactivity study, samples were "RF-negative samples (as determined by testing in an commercially available RF kit) containing various ANA," where the presence and specificity of other ANAs were the known ground truth.

8. Sample Size for the Training Set

This submission describes the validation studies for a diagnostic assay, not a machine learning algorithm that requires a "training set" in the conventional sense. The "development" or "optimization" of the assay kit components would involve internal studies, but these are not explicitly described as a distinct "training set" with specific sample sizes in this 510(k) summary. The provided sample sizes are for performance validation studies.

9. How the Ground Truth for the Training Set was Established

As noted above, this device is an IVD biochemical assay and not an AI/ML algorithm that leverages a "training set" in the typical manner. Therefore, the concept of establishing ground truth for a training set does not directly apply here. The "ground truth" mentioned in the validation studies (e.g., clinical diagnosis, results from other assays) is used for testing and validating the assay's performance, not for training an underlying model.

Summary

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9 2002 JUL

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: K021394

Applicant Information:

Date Prepared:	June 27, 2002
Name:	Diamedix Corporation
Address:	2140 N. Miami AvenueMiami. FL 33127

Contact Person:	Dr. Lynne Stirling
Phone Number:	305-324-2354
Fax Number:	305-324-2388

Device Information:

Trade Name:	Is-Rheumatoid Factor Test System
Common Name:	Rheumatoid Factor EIA Test
Classification Name:	RF Immunological Reagents

Equivalent Device:

Is-RF Test System

Device Description: The Is-Rheumatoid Factor 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 the quantitative detection of RF IgM-class antibodies in human serum by indirect enzyme immunoassay as an aid in the diagnosis of rheumatoid arthritis (RA). This test kit can be used either manually or in conjunction with the MAGO Plus Automated EIA processor.

Principle of the Procedure:

The Is-Rheumatoid Factor 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.

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SUMMARY OF SAFETY AND EFFECTIVENESS

Performance Charactistics

Comparisons with Other Methods

A. Relative Sensitivity and Specificity versus Another EIA Test

One hundred and eighty-five frozen retrospective sera were tested using the Is-Rheumatoid Factor Test Kit and another commercially available EIA kit for detecting RF. Based upon the results of this testing the relative sensitivity, relative specificity and overall agreement were calculated. The results obtained are summarized in TABLE 1 and reveal excellent agreement with no discordant/discrepant sample results.

TABLE 1

		Is-Rheumatoid Factor
OtherEIA		Positive	Negative	*Equivocal
	Positive	89	0	2
	Negative	0	91	1
	* Equivocal	2	0	0
	Relative SensitivityRelative SpecificityOverall Agreement	$89/89 = 100%$$91/91 = 100%$$190/190 = 100%$		**95% CI95.9-100.0%96.0-100.0%98.1-100.0%

Equivocal results were excluded from calculations ** 95% Confidence Intervals (CI) calculated by the Exact Method (11)

B. Correlation with Nephelometry Results

Forty samples containing varying levels of RF as determined by nephelometry were tested using the Is-Rheumatoid Factor Test Kit. Samples whose results exceeded the Calibrator value were diluted and results obtained were then multipled by the dilution factor. IU/ml values determined by both methods were then subjected to linear regression analysis. The correlation between IU/ml values determined by both methods is shown below.

Image /page/1/Figure/9 description: The image is a scatter plot titled "FIGURE 1: Correlation with Nephelometry". The x-axis is labeled "Is-Rheumatoid Factor IU/ml", and the y-axis is labeled "Nephelometry IU/ml". The scatter plot shows a positive correlation between the two variables. A line of best fit is drawn through the data, and the equation of the line is "Y = 44.8468 + 1.0658 X".

Image /page/1/Figure/10 description: The image shows statistical data including the intercept, slope, coefficient of determination, correlation coefficient, and confidence interval. The intercept is 44.8468, and the slope is 1.0658. The coefficient of determination is 0.9355, and the correlation coefficient r is 0.9672. The 95% confidence interval for r ranges from 0.9384 to 0.9826.

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C. Comparison with Latex Agglutination

The performance of the Is-Rheumatoid Factor Test Kit was also compared to that of the latex agglutination test which is another commonly used method for detecting RF. A total of 71 sera were tested by both methods. These consisted of 40 normal samples, 18 known clinical samples and 13 samples containing other autoantibodies with or without RF. The results are summarized in TABLE 2 below.

Sample Type	#	Latex Results	Is- Results	Comments
Normal Sera	40	40/40 Negative	40/40 Negative	Specificity: Latex & Is- 100%
Clinical Sera	18	9/18 Positive	18/18 Positive	Sensitivity: Latex 50%Sensitivity: Is- 100%
Other Sera	13	4/13 Positive	10/13 Positive	Other ELISA 9/13 Positive

				TABLE 2 : Comparison with a Latex Agglutination Test
--	--	--	--	------------------------------------------------------	--

It should be note that the screening dilution for the latex is 1:20. A positive result at this dilution is considered equivalent to 60 IU/ml. Therefore, all samples less than 60 IU/ml by either ELISA or nephelometry were negative by latex.

D. Linearity

To assess the linearity of the Is-Rheumatoid Factor Test Kit several highly positive samples were serially diluted using Sample Diluent and each dilution was then tested in the assay system. In addition to this testing, the WHO Standard anhouse Reference Standard, both assigned values of 100 IU/ml, were also serially diluted and each dilution then tested with the assay system. FIGURES 2 and 3 show the titration of these materials. The Correlation Coefficients of the other samples were in close agreement with those shown below.

Image /page/2/Figure/7 description: The image shows the title of a figure. The title is "FIGURE 2 : Linearity of WHO Standard". The text is in bold font.

Image /page/2/Figure/8 description: The image shows a scatter plot with a linear regression line. The equation of the line is Y = 17.8458 + 90.8827X. The plot shows the relationship between dilution and IU/ml. The image also includes the intercept (17.8458), slope (90.8827), coefficient of determination (0.9133), and correlation coefficient (0.9557).

Image /page/2/Figure/9 description: The image shows the title of a figure. The title is "FIGURE 3 : Linearity of In-House Standard". The title is written in a bold, sans-serif font. The text is centered on the image.

Image /page/2/Figure/10 description: The image shows a scatter plot with a linear regression line. The equation of the line is Y = 13.0647 + 95.2950 X. The plot shows the relationship between dilution and IU/ml, and the equation parameters are listed as Intercept 13.0647 and Slope 95.2950. The coefficient of determination is 0.9282, and the correlation coefficient r is 0.9634.

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E. Lack of Crossreactivity with Other Antinuclear Antibodies

Antinuclear antibodies (ANA) have been found in 14 to 28% of patients with RA and are usually found in patients with more advanced disease (1). Several RF-negative samples (as determined by testing in an commercially available RF kit) containing various ANA were evaluated to ensure lack of interference from these antibodies in RF-negative sera. These results are shown in TABLE 3 and show that only one sample containing anti-SSB gave a very low positive result.

# of Samples	Primary ANASpecificity	Is-Rheumatoid FactorIU/ml values	Interp
5	SSA	1.8, 1.9, 4.4, 1.3, 1.4	5/5 NEG
4	Sm	9.1, 1.7, 1.6, 1.3	4/4 NEG
5	RNP	4.0, 0.9, 1.2, 0.8, 1.6	5/5 NEG
3	Scl-70	0.8, 1.6, 3.2	3/3 NEG
4	Jo-1	1.9, 2.6, 2.7, 1.8	3/3 NEG
3	dsDNA	1.6, 3.8, 3.7	3/4 NEG
1	SSB	21.2	1/1 POS

TABLE 3 : Crossreactivity Results

F. Lack of Prozone/High-Dose Hook Effects

The lack of interference from prozone/high-dose hook effects was determined by testing several sera, serially diluted and undiluted in the Is-Rheumatoid Factor test Kit. A total of 8 sera were evaluated, 4 contained the highest concentrations available as established by nephelometry, 2 contained levels in the mid range and 2 were in the negative range. No prozone or high-dose hook effects were evidenced by any of the results obtained from the samples tested in the assay system.

G. Correlation of Manual and MAGO Plus Results

The Is-Rheumatoid Factor Test Kit has been developed for both automated as well as manual use. To demonstrate the equivalence of the manual and MAGO Plus procedures, the results of 303 normal and clinical serum samples tested for RF by both the manual and MAGO Plus methods were plotted. A scattergram and regression line of the results obtained with 95% confidence intervals is shown in FIGURE 6. The data indicate excellent correlation with a Correlation Coefficiient (r)=0.9933.

Image /page/3/Figure/8 description: This image is a scatter plot comparing MAGO Plus IU/ml to MANUAL IU/ml. The x-axis represents MANUAL IU/ml, ranging from 0 to 160, while the y-axis represents MAGO Plus IU/ml, ranging from -20 to 180. A linear regression line is plotted on the scatter plot, with the equation Y = 0.0724 + 1.1636X.

FIGURE 4 : Manual vs MAGO Plus Correlation

Intercept = 0.0724
Slope = 1.1636
Coefficient of determination = 0.9866
Correlation Coefficient r = 0.9933
95% CI for r = 0.9916 to 0.9946

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H. Precision

To assess the precision of the Is-Rheumatoid Factor Test Kit six serum samples of varying reactivity as well as the kit Calibrator and controls were tested in two runs per day for three days. Precision was assessed both manually and using the MAGO Plus Automated EIA Processor. Results are summarized in TABLES 4 and 5.

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)	0.7	0.21	30.00	1.0	0.10	10.00	0.8	0.05	6.25	0.8	0.16	20.00
B (Neg)	0.4	0.33	>50.00	0.7	0.09	12.86	0.5	0.05	10.00	0.5	0.23	46.00
C (Pos)	34.1	1.25	3.67	35.1	2.94	8.38	34.2	1.94	5.67	34.5	2.08	6.03
D (Pos)	57.6	1.80	3.13	60.0	1.50	2.50	57.9	2.05	3.54	58.5	2.01	3.44
E (Pos)	82.2	1.93	2.35	84.9	3.57	4.20	79.6	1.57	1.97	82.2	3.23	3.93
F (Pos)	98.4	2.18	2.22	102.3	2.07	2.02	96.7	1.86	1.92	99.1	3.10	3.13
Cal.	98.8	2.03	2.05	101.6	1.25	1.23	98.4	1.16	1.18	101.0	3.98	3.94
Pos.	41.6	1.43	3.44	46.5	0.44	0.95	43.2	1.44	3.33	43.8	2.39	5.46
Neg.	0.7	0.18	25.71	0.9	0.05	5.78	0.6	0.09	15.00	0.7	0.16	22.86

TABLE 4 : Manual Intra-Assay and Interassay Precision for Is-Rheumatoid Factor

TABLE 5: MAGO Plus Intra-Assay and Interassay Precision for Is-Rheumatiod Factor

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)	0.9	0.26	28.89	0.9	0.95	>50.00	0.2	0.18	>50.00	0.6	0.65	>50.00
B (Neg)	0.3	0.25	>50.00	0.4	0.40	>50.00	0.4	0.63	>50.00	0.4	0.43	>50.00
C (Pos)	33.7	3.75	11.13	34.9	1.67	4.79	35.1	2.00	5.70	34.5	2.56	7.42
D (Pos)	69.6	1.18	1.70	70.3	3.05	4.34	69.9	1.96	2.80	69.9	2.09	2.99
E (Pos)	87.0	4.42	5.08	85.0	1.91	2.25	85.7	3.26	3.80	85.9	3.27	3.81
F (Pos)	102.0	1.84	1.80	101.2	2.52	2.49	101.6	2.91	2.86	101.6	2.33	2.29
Cal.	108.1	3.38	3.13	102.0	2.76	2.71	103.9	4.24	4.08	104.7	4.21	4.02
Pos.	43.3	7.29	16.84	40.5	2.54	6.27	40.2	2.02	5.02	41.3	4.56	11.04
Neg.	0.4	0.40	>50.00	0.7	0.60	>50.00	0.2	0.48	>50.00	0.4	0.50	>50.00

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Expected Values

The prevalence of RF may vary depending on a number of factors such as age, gender, geographical location, race, type of test used and clinical history of individual patients. The expected value in the normal population is negative. However, a small but variable percentage of apparently healthy asymptomatic individuals may have RF. These individuals usually have low titers. The incidence of false positives tends to increase with age and is similar in males and females.

In the present study the expected values for a normal healthy population were assessed by testing sera from one hundred and eighteen S. Florida blood donors in the Is-Rheumatoid Factor Test Kit. One hundred and twelve sera (94.9%) were negative, two sera (1.7%) were positive and four sera (3.4%) were equivocal. The age distribution and prevalences for this population are shown in TABLE 6. Note that similar results were obtained for both manual and MAGO Plus testing.

The expected values for a clinical population were assessed by testing ninety-three sera from patients with a diagnosis of rheumatoid arthritis in the Is-Rheumatoid Factor Test Kit. For this population eighty-seven sera (93.5%) were positive, four (4.3%) were negative and two (2.2%) were equivocal.

Histograms showing the distribution of values for both the normal and clinical populations are shown in FIG-URES 5 and 6.

	Number of Donors	Prevalence
Total Number	118	1.69%
Geographic Location	South Florida : 118
Age
10-19	5	0.0%
20-29	25	4.0%
30-39	61	1.6%
40-49	20	0.0%
50-59	7	0.0%

TABLE 6: Age Distribution and Prevalence of Rheumatoid Factor in a Normal S. Florida Population

Image /page/5/Figure/7 description: The image contains two histograms, labeled as Figure 5 and Figure 6, which display the distribution of IgM-RF values. Figure 5 shows the distribution in a normal population, where the majority of values are concentrated near 0 IU/ml, with a frequency of approximately 100. Figure 6 illustrates the distribution in a clinical population, where the values are more spread out between 0 and 160 IU/ml, with the highest frequency of approximately 18 around 140 IU/ml.

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Image /page/6/Picture/1 description: The image is a black and white logo for the U.S. Department of Health & Human Services. The logo features a stylized depiction of three human profiles facing right, arranged in a row and connected by flowing lines that resemble hair or fabric. The profiles are positioned within a circular border that contains the text "DEPARTMENT OF HEALTH & HUMAN SERVICES-USA" in a sans-serif font.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

9 2002 JUL

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

Re: K021394

Trade/Device Name: Diamedix Is-Rheumatoid Factor Test System Regulation Number: 21 CFR § 866.5775 Regulation Name: Rheumatoid Factor Immunological Test System Regulatory Class: II Product Code: DHR Dated: May 1, 2002 Received: May 2, 2002

Dear Dr. Stirling:

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 (QS) 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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Page 2

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 (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. 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 (800) 638-2041 or (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsma/dsmamain.html".

Sincerely yours,

Steven Dutman

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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Page of of

510(k) Number (if known): KOO |399

DEVICE NAME : Is-Rheumatoid Factor Test System

Indications for Use :For the quantitative detection of RF IgM-class antibodies in human serum by indirect enzyme immunoassayas an aid in the diagnosis of rheumatoid arthritis (RA). This test kit can be used either manually or in conjunction with the MAGO® Plus Automated EIA Processor.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

J Reeves for Sr. Altaie

(Division Sign-Off)
Division of Clinical Laboratory Devices/
510(k) Number K021394

Prescription Use (Per 21 CFR 801.109) Over-The-Counter Use__________________________________________________________________________________________________________________________________________________________

(Optional Format 1-2-96)

Regulation Number and Section

§ 866.5775 Rheumatoid factor immunological test system.

(a)
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.(b)
Classification. Class II (performance standards).