← Product Code [DCK](/submissions/IM/subpart-f%E2%80%94immunological-test-systems/DCK) · K040241

# N-GENEOUS WIDE RANGE CRP REAGENT AND CALIBRATOR SET (K040241)

_Genzyme Corp. · DCK · Jun 25, 2004 · Immunology · SESE_

**Canonical URL:** https://fda.innolitics.com/submissions/CH/subpart-f%E2%80%94immunological-test-systems/DCK/K040241

## Device Facts

- **Applicant:** Genzyme Corp.
- **Product Code:** [DCK](/submissions/IM/subpart-f%E2%80%94immunological-test-systems/DCK.md)
- **Decision Date:** Jun 25, 2004
- **Decision:** SESE
- **Submission Type:** Traditional
- **Regulation:** 21 CFR 866.5270
- **Device Class:** Class 2
- **Review Panel:** Immunology

## Indications for Use

The N-Geneous Wide Range CRP Reagent is intended for the quantitative measurement of C-Reactive Protein (CRP) concentration in serum or plasma. Measurement of CRP is useful for determining the existence of inflammatory lesions and to monitor treatment. The N-Geneous Wide Range CRP Calibrator is intended for the calibration of the N-Geneous Wide Range CRP assay.

## Device Story

N-geneous™ Wide Range CRP Reagent is a two-reagent, latex-agglutination turbidimetric immunoassay for quantitative CRP measurement in serum or plasma. Sample mixed with buffer and mouse anti-human CRP monoclonal antibody-coated latex particles; CRP-antibody binding causes agglutination. Increased particle size increases light scattering, measured by clinical analyzer (e.g., Hitachi 912) as proportional to CRP concentration. Used in clinical laboratories by technicians. Output is CRP concentration (0.04 to 320 mg/L). Provides clinicians with quantitative CRP levels to aid in diagnostic assessment. Calibrated using N-geneous™ Wide Range CRP Calibrator Set, traceable to CRM470.

## Clinical Evidence

No clinical data. Bench testing only. Performance validated via method comparison (n=229) against predicate, showing high correlation (r=0.995). Precision evaluated per NCCLS EP5-A (total CV 1.5–6.7%). Linearity assessed across 0.12–320 mg/L range. Functional sensitivity established at 0.12 mg/L (20% CV). Interference testing performed for endogenous substances and common drugs.

## Technological Characteristics

Two-reagent latex-agglutination turbidimetric immunoassay. Reagents: mouse anti-human CRP monoclonal antibody bound to latex. Calibrator: stabilized human serum. Traceability: CRM470 (IRMM/BCR). Analytical range: 0.04-320 mg/L. Designed for automated clinical chemistry analyzers (e.g., Hitachi 912).

## Regulatory Identification

A C-reactive protein immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the C-reactive protein in serum and other body fluids. Measurement of C-reactive protein aids in evaluation of the amount of injury to body tissues.

## Predicate Devices

- Dade Behring N High sensitivity CRP assay ([K991385](/device/K991385.md))
- Dada Behring N Rheumatology Standard SL ([K964527](/device/K964527.md))

## Submission Summary (Full Text)

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510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION
DECISION SUMMARY
DEVICE ONLY TEMPLATE

A. 510(k) Number:
K040241

B. Purpose for Submission:
Clearance of CRP assay

C. Analyte:
C-Reactive Protein (CRP)

D. Type of Test:
Turbidometric immunoassay

E. Applicant:
Genzyme, Inc.

F. Proprietary and Established Names:
N-Geneous Wide Range CRP Reagent
N-Geneous Wide Range CRP Calibrator

G. Regulatory Information:
1. Regulation section:
21 CFR § 866.5270, C-reactive protein immunological test system
862.1150, Calibrator
2. Classification:
Class II
3. Product Code:
DCK, C-reactive protein, antigen, antiserum, and control
JIS, Calibrator, primary
4. Panel:
Immunology (82)

H. Intended Use:
1. Intended use(s):
The N-Geneous Wide Range CRP Reagent is intended for the quantitative measurement of C-Reactive Protein (CRP) concentration in serum or plasma.

Measurement of CRP is useful for determining the existence of inflammatory lesions and to monitor treatment.

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The N-Geneous Wide Range CRP Calibrator is intended for the calibration of the N-Geneous Wide Range CRP assay.

2. **Indication(s) for use:**
See Intended Use section.

3. **Special condition for use statement(s):**
For in vitro diagnostic use.

Increases in CRP values are non-specific and should not be interpreted without a complete clinical history.

4. **Special instrument Requirements:**
Clinical chemistry analyzers (testing performed on Roche Hitachi 912 analyzer)

I. **Device Description:**
The N-Geneous Wide Range CRP assay consists of two wet reagents. Reagent 1 is a buffering solution and Reagent 2 contains latex beads coated with mouse monoclonal anti-human CRP antibodies. The assay is for use on general clinical chemistry analyzers.

J. **Substantial Equivalence Information:**
1. **Predicate device name(s):**
Dade Behring N High sensitivity CRP assay
Dada Behring N Rheumatology Standard SL
2. **Predicate K number(s):**
K991385
K964527
3. **Comparison with predicate:**

|  Similarities  |   |   |
| --- | --- | --- |
|  Item | Device | Predicate  |
|  Intended Use | Quantitative measurement of CRP in serum or plasma | Quantitative measurement of CRP in serum or plasma  |
|  Sample Matrix | Serum or plasma | Serum or plasma  |
|  Antibody | Mouse monoclonal anti-human CRP | Mouse monoclonal anti-human CRP  |
|  Differences  |   |   |
|  Item | Device | Predicate  |
|  Assay Range | 0.12 to 320 mg/L | 0.175 to 11 mg/L  |
|  Antibody substrate | Latex beads | Polystyrene beads  |
|  Number of calibrators | 5 | 1  |

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# K. Standard/Guidance Document Referenced (if applicable):

NCCLS Guideline EP9-A - Method Comparison and Bias Estimation Using Patient Samples

NCCLS Guideline EP5-A - Evaluation of Precision Performance of Clinical Chemistry Devices

NCCLS Guideline EP6-A - Evaluation of the Linearity of Quantitative Analytical Methods

NCCLS Guideline EP7-A - Interference Testing in Clinical Chemistry

NCCLS Guideline C28-A - How to Define and Determine Reference Intervals in the Clinical Laboratory

# L. Test Principle:

Sample is mixed with the buffer solution and the anti-CRP antibody-coated beads. CRP in the sample binds the antibody-coated beads and agglutinates. The light scattering caused by an increase in particle size is measured. The amount of light scattering is proportional to the concentration of CRP in the sample.

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

1. Analytical performance:

a. Precision/Reproducibility:

Device imprecision was evaluated according to NCCLS EP5-A. Spiked serum samples were run in duplicate twice per day for 20 days (units = mg/L).

|  Control | Mean | Within Run |   | Total  |   |
| --- | --- | --- | --- | --- | --- |
|   |   |  SD | % CV | SD | % CV  |
|  1 | 0.30 | 0.02 | 5.5 | 0.02 | 6.7  |
|  2 | 1.00 | 0.02 | 1.8 | 0.02 | 2.3  |
|  3 | 2.97 | 0.04 | 1.3 | 0.05 | 1.7  |
|  4 | 51.3 | 0.61 | 1.2 | 0.96 | 1.9  |
|  5 | 202 | 3.0 | 1.5 | 3.1 | 1.5  |

b. Linearity/assay reportable range:

The useable range of this device is $0.12 - 320\mathrm{mg / L}$ (the Limit of Quantification to the upper end of the linear range).

Linearity was assessed using two separate sets of samples to cover the range (range covered = 0.6 – 337 mg/L). Two sets of CRP-stripped serum samples were spiked with human CRP to values of 55 or 360 mg/L. The two spiked samples were then mixed with the same (unspiked) CRP-stripped serum matrix to result in a set of samples with predicted CRP concentrations that covered the assay range. The samples were assayed and the results were compared to the concentrations calculated from the dilution factors of the original samples. Results are summarized below (units = mg/L).

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|  Set | Expected | Observed | Bias to Expected | Bias to Observed  |
| --- | --- | --- | --- | --- |
|  A | 0.00 | 0.01 | 0.01 | ---  |
|  A | 56.19 | 53.98 | -2.21 | -4 %  |
|  A | 112.38 | 110.49 | -1.89 | -2 %  |
|  A | 224.75* | 224.75 | --- | ---  |
|  A | 337.13 | 337.27 | 0.14 | 0 %  |
|  B | 0.00 | 0.02 | 0.02 | ---  |
|  B | 0.55 | 0.63 | 0.08 | 14 %  |
|  B | 1.11 | 1.24 | 0.13 | 12 %  |
|  B | 5.54 | 5.50 | -0.04 | -1 %  |
|  B | 11.07 | 10.33 | -0.74 | -7 %  |
|  B | 22.14 | 20.41 | -1.73 | -8 %  |
|  B | 27.68 | 26.34 | -1.33 | -5 %  |
|  B | 33.21 | 32.72 | -0.49 | -1 %  |
|  B | 44.28 | 44.51 | 0.23 | 1 %  |
|  B | 55.35* | 55.35 | --- | ---  |

*Sponsor assumed 100% recovery for these samples

The results above indicate that the assay is linear across the measuring range of the assay.

To test the dilution recovery of high samples, 5 patient samples with CRP values ranging from 200 to  $360\mathrm{mg / L}$  were diluted up to 5X with saline and measured in quadruplicate. The sponsor states that expected results were recovered for all samples (expected is defined as within  $+ / - 10\%$ ).

# c. Traceability (controls, calibrators, or method):

The device is calibrated by a set of 5 calibrators (sold separately) with targeted CRP concentrations of 3, 6, 30, 170, and  $360\mathrm{mg / L}$ . The calibrator is traceable to CRM470. A master calibrator is prepared and value assigned by multiple measurements of multiple lots using the device. The calibrators are traceable to this master calibrator and are value assigned using the device. Stability testing is described.

# d. Detection limit:

Functional sensitivity, defined as the lowest concentration at which the assay performs with  $20\%$  CV, was assessed by measuring 4 serum samples 15 times in each of 3 runs (for  $\mathrm{n} = 45$  for each sample). By this method, the functional sensitivity of this assay is said to be  $0.12\mathrm{mg / L}$  (derived by extrapolation of plot of concentration vs.  $\%$  CV). Results are summarized below (units  $= \mathrm{mg / L}$ ).

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|  Mean CRP Concentration | SD | % CV  |
| --- | --- | --- |
|  0.32 | 0.024 | 7.7 %  |
|  0.15 | 0.022 | 14.5 %  |
|  0.10 | 0.025 | 24.9 %  |
|  0.08 | 0.021 | 25.7 %  |

The analytical sensitivity was defined as the lowest concentration distinguishable from zero. Saline was run 20 times on the assay and the mean plus two standard deviations was calculated as 0.04 mg/L.

e. Analytical specificity:

Interference of endogenous substances was evaluated by testing for the effect of hemoglobin (up to 1000 mg/dL), ascorbic acid (up to 500 mg/dL), bilirubin (up to 60 mg/dL), Intralipid (up to 3%), Rheumatoid factor (153 – 1711 IU/mL), and HAMA (100 – 194 ng/mL) on serum samples containing a nominal concentration of 3 mg/L. The only interference observed was a bias of >0.3 mg/L at Intralipid concentrations > 0.8 % (~2400 mg/dL triglyceride equivalent). Interference was defined as a result +/- 10 % of the control. This information is in the package insert.

To test exogenous interferences (defined as a result +/- 10 % of the control), 27 common drugs were tested for their effect on a serum sample with a nominal CRP concentration of 3 mg/L. No interferences were seen. The list of tested drugs and their concentrations can be found in the package insert.

f. Assay cut-off:

Not applicable

2. Comparison studies:

a. Method comparison with predicate device:

Serum samples (n=229) ranging from 0.2 to 198 mg/L were measured using the device and comparing those measurement to those made with the predicate device. Samples that had CRP concentrations above the measuring range of the predicate device were diluted before measurement and then multiplied by the dilution factor per the predicate labeling. Results are summarized below.

All Samples: Device = 1.05(Predicate) – 0.31; r = 0.995
Standard Error: 0.012 (slope) and 0.263 (intercept)
95% CI: 1.03 – 1.07 (slope) and -0.83 – 0.21 (intercept)

Samples <0.5: Device = 1.02(Predicate) + 0.08
95% CI: 0.86 – 1.17 (slope) and 0.03 – 0.13 (intercept)

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Samples <10.0: Device = 0.94(Predicate) + 0.1; r = 0.995

Samples >50: Device = 1.10(Predicate) - 12.9
95% CI: 0.92 – 1.29 (slope) and -40.9 – 15.2 (intercept)

b. Matrix comparison:

Samples from 18 patients were collected as matched serum, Na heparin plasma, Li heparin plasma, and EDTA plasma samples. Samples were measured in quadruplicate and results were compared. There were no significant differences observed between sample types.

Sample stability was assessed and no significant bias was observed when samples were held at 25°C, 2-8°C, or -20°C for 5, 13, or 36 days. No significant bias was observed when samples were subjected to two freeze-thaw cycles for either serum or plasma.

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

4. Clinical cut-off: Not applicable

5. Expected values/Reference range:

The sponsor references a study of 22,403 apparently healthy individuals and cites CRP ranges (5th -95th percentiles) of 0.19 – 9.14 mg/L for women and 0.28 – 8.55 mg/L for men.

The sponsor states that they performed a small study of 50 apparently healthy men and women (25 of each). They state that their results are in line with their referenced study.

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

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**Source:** [https://fda.innolitics.com/submissions/CH/subpart-f%E2%80%94immunological-test-systems/DCK/K040241](https://fda.innolitics.com/submissions/CH/subpart-f%E2%80%94immunological-test-systems/DCK/K040241)

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