N-GENEOUS WIDE RANGE CRP REAGENT AND CALIBRATOR SET

K040241 · Genzyme Corp. · DCK · Jun 25, 2004 · Immunology

Device Facts

• Record ID: K040241
• Device Name: N-GENEOUS WIDE RANGE CRP REAGENT AND CALIBRATOR SET
• Applicant: Genzyme Corp.
• Product Code: DCK · Immunology
• Decision Date: Jun 25, 2004
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.5270
• Device Class: Class 2

Intended 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).

Indications for Use

Indicated for the quantitative measurement of C-Reactive Protein (CRP) in human serum or plasma for in vitro diagnostic use. No specific patient population, age, or gender restrictions are stated.

Regulatory Classification

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)
• Dada Behring N Rheumatology Standard SL (K964527)

Submission Summary (Full Text)

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K040241

JUN 2 5 2004

510(k) PREMARKET NOTIFICATION

### 510(k) Summary of Safety and Effectiveness Information Upon Which An Equivalence Determination Could be Made

| Trade or Proprietary Name: | N-geneous™ Wide Range CRP Reagent<br>N-geneous™ Wide Range CRP Calibrator Set |
|----------------------------|---------------------------------------------------------------------------------------------------------------------------------------|
| Common or Usual Name: | C-Reactive Protein immunological test system<br>Calibrator for C-Reactive Protein |
| Classification Name: | C-Reactive Protein immunological test system<br>Calibrator, Primary |
| Manufacturer: | Genzyme Diagnostics<br>One Kendall Square<br>Cambridge, MA 02139-1562 |
| Contact Person: | Fred D. Lasky, Ph.D., Director, Regulatory Affairs [phone]<br>Robert Yocher, Vice President, Regulatory Affairs [phone] |

The use of the Genzyme N-geneous™ Wide Range CRP Reagent in the clinical laboratory setting is substantially equivalent to the Dade Behring N High Sensitive CRP method.

The Genzyme N-geneous™ Wide Range CRP Reagent is a two-reagent method for the quantitative measurement of CRP concentration from 0.04 to 320 mg/L in serum or plasma.

The test is an enhanced latex-agglutination turbidimetric immunoassay. Sample is added to a buffer solution and mixed with a suspension of mouse anti-human CRP monoclonal antibody, which is bound to latex. CRP binds to the latex-bound antibody, which agglutinates. The light scattering caused by the increase in particle size is used as a measure of CRP concentration. The amount of light scattering is proportional to the concentration of CRP in the sample.

N-geneous™ Wide Range CRP Calibrator Set is a stabilized human serum designed to be used to calibrate the N-geneous™ Wide Range CRP Reagent and is sold separately. The Ngeneous™ Wide Range CRP Calibrator Set is traceable to CRM470, available from theInstitute for Reference Materials and Measurements (IRMM), and certified by the European Commission, Community Bureau of Reference (BCR).

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Comparative performance studies were conducted using the N-geneous™ Wide Range CRP Reagent on the Hitachi 912 clinical analyzer and the Dade Behring N High Sensitive CRP method in which CRP was measured in 229 serum samples. The relationship between methods is:

N-geneous™ Wide Range CRP = 1.05 X (N High Sensitive CRP) – 0.31

Correlation coefficient (r) = 0.995

Precision studies were conducted using the N-geneous™ Wide Range CRP Reagent on the Hitachi 912 clinical analyzer. The studies were performed using sera that were stored frozen (-20°C) and thawed prior to use.

The mean, standard deviation (SD) and coefficient of variation (%CV) for within-run precision:

| Control | 1 | 2 | 3 | 4 | 5 |
|-------------|------|------|------|------|-----|
| Mean (mg/L) | 0.30 | 1.00 | 2.97 | 51.3 | 202 |
| SD (mg/L) | 0.02 | 0.02 | 0.04 | 0.61 | 3.0 |
| %CV | 5.5 | 1.8 | 1.3 | 1.2 | 1.5 |

The mean, standard deviation (SD) and coefficient of variation (%CV) for total precision:

| Control | 1 | 2 | 3 | 4 | 5 |
|-------------|------|------|------|------|-----|
| Mean (mg/L) | 0.30 | 1.00 | 2.97 | 51.3 | 202 |
| SD (mg/L) | 0.02 | 0.02 | 0.05 | 0.96 | 3.1 |
| %CV | 6.7 | 2.3 | 1.7 | 1.9 | 1.5 |

The N-geneous™ Wide Range CRP reagents yielded acceptable total precision.

These data demonstrate that the performance of the N-geneous™ Wide Range CRP Reagent in the clinical laboratory is substantially equivalent to the performance of a commercially available method.

In addition, N-geneous™ Wide Range CRP Reagent is substantially equivalent to a currently marketed method, in that they measure the same analyte and have the same intended use. Additionally, they both use the same sample matrices and utilize mouse monoclonal antibody to CRP. Furthermore, they measure concentration by the magnitude of particle agglutination and light scatter, are in ready-to-use liquid format and both are traceable to CRM470 reference material. The N-geneous™ Wide Range CRP Reagent differs from the Dade Behring N High Sensitive CRP method in that the N-geneous™ Wide Range CRP Reagent utilizes a turbidimetric technique, whereas the Dade Behring N High Sensitive CRP

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is a nephelometric method. Also, the reportable range of the N-geneous™ Wide Range CRP Reagent is up to 320 mg/L before dilution is required, whereas the Dade Behring N High Sensitive CRP method requires additional on board sample dilution for concentrations above 11 mg/L. The N-geneous™ Wide Range CRP Reagent uses a set of five standards for calibration; the Dade Behring N High Sensitive CRP method has one calibrator.

N-geneous ™ Wide Range CRP Calibrator Set is substantially equivalent to a currently marketed calibrator, the Dade Behring N Rheumatology Standard SL in that they are both used to establish calibration of CRP methods to be used for measurement of CRP in serum or plasma. Both are human serum-base materials that are traceable to CRM470 available from the Institute for Reference Materials and Measurements (IRMM), and certified by the European Commission, Community Bureau of Reference (BCR).

In lieu of a 510(k) statement under 513(i) of the Act, this information is provided as a 510(k) summary for disclosure to any other persons/companies without the specific written authorization from Genzyme Corporation.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/3/Picture/1 description: The image shows the logo for the Department of Health & Human Services (HHS). The logo consists of a stylized eagle with three lines representing its body and wings. The eagle is facing to the right. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged in a circular pattern around the eagle.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Fred D. Lasky, Ph.D. Director, Regulatory Affairs Genzyme Corparation 500 Kendall Street Cambridge, MA 02142

## JUN 2 5 2004

k040241 Re: R040241
Trade/Device Name: N-geneous™ Wide Range CRP Reagent Kit Regulation Number: 21 CFR 866.5270 Regulation Name: C-reactive protein immunological test system Regulatory Class: Class II Product Code: DCK, JIS Dated: April 19, 2004 Received: April 21, 2004

Dear Dr. Lasky:

We have reviewed your Section 510(k) premarket notification of intent to market the device we nave reviewed your becaon 3 ro(x) premium is substantially equivalent (for the indications felerenced above and nave uctoringed law marketed predicate devices marketed in interstate for use stated in the encrosule) to regary manent date of the Medical Device Amendments, or to commerce prior to May 20, 1778, the exactions of the Federal Food, Drug, devices that have been recatismed in assessoval of a premarket approval application (PMA).
and Cosmetic Act (Act) that do not require approval of a premarket approval applica and Cosment Act (Act) that do not require approval es eneral controls provisions of the Act. The You may, merciole, market me devices, course requirements for annual registration, listing of general controls provisions of the fiel here here and prohibitions against misbranding and adulteration.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), If your device is classified (360 above) into e. Existing major regulations affecting your device it may be subject to sach additional controllar - Entistigation - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - can be found in Thic 21, Code of I concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean Please be advised that IDA s issualled of a baskuin complies with other requirements of the Act that FDA has made a decemmandir and Jointer Federal agencies. You must of any Federal statures and regulations administer or of limited to: registration and listing (21 comply with an the Act 3 requirements, morants 801 and good manufacturing practice CFK I art 807), labening (21 CF F 1 litt systems (QS) regulation (21 CFR Part 820).

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If you desire specific information about the application of labeling requirements to your device, or yeastions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at [phone]. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the I ou may of Small Manufacturers, International and Consumer Assistance at its toll-free number [phone] or [phone] or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.

Sincerely yours,

Robert L. Beckerh

Robert L. Becker, Jr., M.D., Ph. Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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# Indications for Use

510(k) Number (if known): K040241

Device Name: N-geneous™ Wide Range CRP Reagent Kit

Indications For Use:

#### Reagents:

For the quantitative measurement of C-Reactive Protein (CRP) concentration in serum or plasma.

For In Vitro Diagnostic Use

### Calibrator:

For the calibration of the N-geneousTM Wide Range CRP assay.

For In Vitro Diagnostic Use

Prescription Use' X (Part 21 CFR 801 Subpart D) AND/OR

Over-The-Counter Use (21 CFR 807 Subpart C)

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

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Alberts

**Division Sign-Off**

Office of In Vitro Diagno Device Evaluatio

510(k) K040241

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