N LATEX RF KIT

K071247 · Dade Behring, Inc. · DHR · Aug 8, 2007 · Immunology

Device Facts

• Record ID: K071247
• Device Name: N LATEX RF KIT
• Applicant: Dade Behring, Inc.
• Product Code: DHR · Immunology
• Decision Date: Aug 8, 2007
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.5775
• Device Class: Class 2

Indications for Use

Quantitative determination of rheumatoid factors (RF) in human serum, lithium heparin and EDTA plasma on the BN™ II and BN ProSpec® Systems as an aid in the diagnosis of rheumatoid arthritis.

Device Story

N Latex RF Kit uses polystyrene particles coated with human immunoglobulin and sheep anti-human IgG. When mixed with patient serum, lithium heparin, or EDTA plasma samples containing RF, particles aggregate. Aggregation scatters light; intensity of scattered light is proportional to RF concentration. Used on BN™ II and BN ProSpec® Systems in clinical laboratory settings. Results are compared against known standards to quantify RF levels. Healthcare providers use these quantitative results as an aid in diagnosing rheumatoid arthritis.

Clinical Evidence

Bench testing only. Precision evaluated per CLSI EP5-A2 (repeatability/within-lab CVs 2.2-8.1%). Linearity confirmed across 10-640 IU/mL (r=1.00). Interference testing per CLSI EP7-A2 showed 89.7-100.7% recovery for bilirubin and hemoglobin. Method comparison (n=90) against predicate showed r=0.9757. Matrix comparison (n=111 for lithium heparin, n=33 for EDTA) showed high correlation (r≥0.992). No clinical sensitivity/specificity studies were performed.

Technological Characteristics

Particle-enhanced nephelometry. Reagents: polystyrene particles coated with human-γ-globulin/anti-human-γ-globulin immunocomplexes; polyethylene glycol/detergent supplement. Energy source: light scattering measurement. Analyzers: BN II and BN ProSpec systems. Standardized against N Rheumatology Standard SL and 1st British Standard 64/0023. Complies with CLSI EP5-A2 and EP7-A2 guidelines.

Indications for Use

Indicated for the quantitative determination of rheumatoid factors (RF) in human serum, lithium heparin, and EDTA plasma to aid in the diagnosis of rheumatoid arthritis.

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

• N Latex RF (K942328)

Submission Summary (Full Text)

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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

A. 510(k) Number:
k071247

B. Purpose for Submission:
New device

C. Measurand:
Rheumatoid factor (RF)

D. Type of Test:
Particle enhanced nephelometry

E. Applicant:
Dade Behring, Inc.

F. Proprietary and Established Names:
N Latex RF Kit

G. Regulatory Information:
1. Regulation sections:
21 CFR 866.5775 Rheumatoid factor immunological test system
2. Classifications:
Class II
3. Product codes:
DHR System, test, rheumatoid factor
4. Panel:
Immunology (82)

H. Intended Use:
1. Intended use(s):
Quantitative determination of rheumatoid factors (RF) in human serum, lithium heparin and EDTA plasma on the BN™ II and BN ProSpec® Systems as an aid in the diagnosis of rheumatoid arthritis.
2. Indication(s) for use:
Same as the Intended Use
3. Special conditions for use statement(s):
Prescription use
4. Special instrument requirements:
BN II or BN ProSpec Systems

I. Device Description:
The device consists of N RF Reagent: a suspension of polystyrene particles coated with an immunocomplex of human-γ-globulin/anti-human-γ-globulin from sheep; and N RF Supplement: an aqueous solution of polyethylene glycol containing detergent.

J. Substantial Equivalence Information:
1. Predicate device name(s):
Dade Behring N RF Latex
2. Predicate 510(k) number(s):
k942328

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3. Comparison with predicate:

| Similarities | | |
| --- | --- | --- |
| Item | New Device | Predicate |
| | N Latex RF Kit | N Latex RF |
| Indications for use | Aid in the diagnosis of rheumatoid arthritis | Same |
| Methodology | Nephelometry | Same |
| Capture | Immunocomplex of human-γ-globulin/sheep anti-human-γ-globulin | Same |
| Calibrator referenced to: | N Rheumatology Standard SL and 1st British Standard 64/0023 | Same |
| Reportable range | 10-640 IU/mL | Same |
| Differences | | |
| --- | --- | --- |
| Item | New Device | Predicate |
| Reagents | N RF Reagent – liquid and N RF Supplement Reagent - liquid | N RF Reagent – lyophilized and N RF Supplementary Reagent - liquid |
| Sample type | Serum | Serum, lithium heparin or EDTA plasma |
| Analyzer | BN Systems | BN II and BN ProSpec Systems |

K. Standard/Guidance Document Referenced (if applicable):
CLSI EP5-A2 Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline-Second Edition; and CLSI EP7-A2 Interference Testing in Clinical Chemistry; Approved Guideline-Second Edition

L. Test Principle:
Polystyrene particles coated with an immunocomplex consisting of human immunoglobulin and anti-human IgG from sheep are aggregated when mixed with samples containing RF. These aggregates scatter a beam of light passed through the sample. The intensity of the scattered light is proportional to the concentration of the protein in the sample. The result is evaluated by comparison with a standard of known concentration.

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# M. Performance Characteristics (if/when applicable):

# 1. Analytical performance:

# a. Precision/Reproducibility:

Precision testing was performed on a BN II System in accordance with CLSI EP5-A2. Specimens at each level were analyzed in duplicate, twice a day, for 20 days. The repeatability, between-run and within-lab $\% \mathrm{CVs}$ were calculated by the analysis of variance method.

| Sample | Mean IU/mL | Repeatability %CV | Between Run %CV | Within Lab %CV |
| --- | --- | --- | --- | --- |
| Control SL/1 | 69.3 | 2.2 | 5.2 | 5.7 |
| Control SL/2 | 170.2 | 2.2 | 3.1 | 3.8 |
| Serum pool low 1 | 27.9 | 2.7 | 5.4 | 7.9 |
| Serum pool low 2 | 81.3 | 2.2 | 4.8 | 5.3 |
| Serum pool high 1 | 582.7 | 5.1 | 4.8 | 7.7 |
| Serum pool high 2 | 600.8 | 5.3 | 5.8 | 8.1 |

# b. Linearity/assay reportable range:

Linearity across the assay range (approximately 10 to $640~\mathrm{IU / mL}$ ) was confirmed by testing an internal, high standard. The standard was serially diluted with System Diluent down to the lower measuring range (693.2 down to $10.8~\mathrm{IU / mL}$ ) on a BN II Analyzer. Each dilution was tested in replicates of three. Data were analyzed using linear regression analysis. The slope was 1.021, intercept 0.665 and $\mathbf{r} = 1.00$ .

Linearity

Hook Effect: The possibility of hook effect occurring was evaluated with a

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serum sample above the assay range. The sample was serially diluted and analyzed on the BN II analyzer and demonstrated no hook effect up to 3967 IU/mL.

c. Traceability, Stability, Expected values (controls, calibrators, or methods): The calibrator is standardized against the N Rheumatology Standard SL and 1st British Standard 64/0023.

d. Detection Limit/Analytical Sensitivity: The analytical sensitivity of the assay was determined by the lower limit of the reference curve (approximately 10 IU/mL).

e. Analytical specificity: Interference testing was performed according to CLSI EP7-A2 to determine the effect of bilirubin (0.6 g/L) and hemoglobin (10/g/L). Testing was conducted by running a serum sample without the interferant and comparing it to the value obtained from the same sample to which the potential interferant had been added. For each spiked sample, the % recovery was determined. Percent recoveries ranged from 92.3 to 100.7% in the bilirubin spiked samples and from 89.7 to 95.6% for hemoglobin

f. Assay cut-off: Testing of serum from 253 adult European blood donors resulted in a 97.5th percentile of 15.9 IU/mL.

2. Comparison studies:

a. Method comparison with predicate device: Serum samples from 90 subjects were tested on the BN II analyzer.


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| Parameter: | | 95% confidence interval |
| --- | --- | --- |
| N = 90 (15.8 – 598.8 IU/mL) | | |
| Slope | 1.098 | 1.0505, 1.1560 |
| Intercept | -12.94 | -19.7692, -8.6201 |
| Pearson correlation coefficient | r=0.9757 (r²=0.9520) | |

For samples with results <100 IU/mL:


| Parameter: | | 95% confidence interval |
| --- | --- | --- |
| N=43 (20 – 78.3) | | |
| Slope | 0.9916 | 0.8310, 1.1713 |
| Intercept | -6.8057 | -17.4694, 1.5805 |
| Pearson correlation coefficient | r=0.8709 (r²=0.7584) | |

b. Matrix comparison:

A comparison was performed with matched specimens of serum, lithium heparin (n=111) and EDTA (n=33) plasma. Passing-Bablok regression analyses showed the following:

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Serum vs. lithium heparin plasma

| Parameter: | | 95% confidence interval |
| --- | --- | --- |
| N = 111 (14.5 – 533 IU/mL) | | |
| Slope | 0.963 | 0.949, 0.977 |
| Intercept | 0.928 | -0.767, 2.221 |
| Pearson correlation coefficient | r=0.992 (r²=0.984) | |

Serum vs. EDTA plasma (n=33)

| Parameter: | | 95% confidence interval |
| --- | --- | --- |
| N = 33 (19.1 – 527 IU/mL) | | |
| Slope | 0.957 | 0.923, 0.998 |
| Intercept | -12.94 | -3.670, 1.659 |
| Pearson correlation coefficient | r=0.997 (r²=0.994) | |

c. Behring ProSpec analyzer (k001647) compared to the BN II analyzer
The Performance Study Protocol included method comparison and precision. Between run %CVs ranged from 1.1 to 5.3% and within lab ranged from 2.2 to 6.3%. The linearity studies showed a slope of 0.98 and r = 1.0. The two instruments were compared by testing 86 samples ranging from 18.7 to 510.3 IU/mL. The comparison showed the following: y = 1.1 – 13.4, r = 0.99. Established acceptance criteria were met.

3. Clinical studies:
a. Clinical Sensitivity: Not determined
b. Clinical specificity: Not determined
c. Other clinical supportive data (when a. and b. are not applicable): Not applicable

4. Clinical cut-off: Not determined

5. Expected values/Reference range:
The expected value in the normal population is negative. However, apparently healthy asymptomatic individuals may have RF, usually of low titer. The incidence of false positive increases with age and is similar in females and males.

N. Proposed Labeling:
The labeling is sufficient and satisfies the requirements of 21 CFR Part 809.10.

O. Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.