IMMAGE IMMUNOCHEMISTRY SYSTEMS HIGH SENSITIVITY CARDIAC C-REACTIVE PROTEIN (CCRP) REAGENT

K071002 · Beckman Coulter, Inc. · NQD · Jun 21, 2007 · Immunology

Device Facts

• Record ID: K071002
• Device Name: IMMAGE IMMUNOCHEMISTRY SYSTEMS HIGH SENSITIVITY CARDIAC C-REACTIVE PROTEIN (CCRP) REAGENT
• Applicant: Beckman Coulter, Inc.
• Product Code: NQD · Immunology
• Decision Date: Jun 21, 2007
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.5270
• Device Class: Class 2

Intended Use

High Sensitivity Cardiac C-Reactive Protein (CCRP) reagent, when used in conjunction with IMMAGE® 800 Immunochemistry Systems and Calibrator 5 Plus, is intended for the quantitative determination of C-Reactive protein in human serum or plasma by rate turbidimetry. CAL 5 Plus (Calibrator 5 Plus). when used in coniunction with Beckman Coulter reagents. is intended for use on IMMAGE® Immunochemistry Systems for the calibration of Anti-Streptolysin O (ASO), C-Reactive Protein (CRP) and Rheumatoid Factor (RF).

Device Story

The IMMAGE® 800 Immunochemistry System uses High Sensitivity Cardiac C-Reactive Protein (CCRP) reagent to perform quantitative determination of CRP in human serum or plasma. The device utilizes near-infrared particle immunoassay rate turbidimetry; anti-CRP antibody-coated latex particles bind to CRP in patient samples, forming insoluble aggregates. The rate of aggregate formation is measured, which is directly proportional to CRP concentration. The system is operated by laboratory personnel in a clinical setting. Results are used by clinicians to identify and stratify cardiovascular disease risk and to assess prognosis for recurrent events in patients with stable coronary disease or acute coronary syndrome. The system includes CAL 5 Plus, a frozen liquid serum matrix calibrator used to calibrate the assay.

Clinical Evidence

Bench testing only. Precision evaluated per CLSI EP5-A2 (N=80, CV 2.8-4.3%). Linearity assessed per CLSI EP6-A (r²=0.9992). Analytical sensitivity 0.06 mg/L; functional sensitivity 0.11 mg/L. Method comparison against predicate (N=157) showed Deming regression y=0.965x+0.334 (r=0.9962). Matrix comparison (serum vs plasma) showed high correlation (r>0.998).

Technological Characteristics

Near-infrared particle immunoassay rate turbidimetry. Reagent uses anti-CRP antibody-coated latex particles. System is a clinical chemistry analyzer. Calibration is single-point adjusted. CAL 5 Plus is a frozen liquid serum matrix.

Indications for Use

Indicated for use as an aid in the identification and stratification of individuals at risk for future cardiovascular disease. Also indicated for use in conjunction with traditional clinical laboratory evaluation of acute coronary syndromes as an independent marker of prognosis for recurrent events in patients with stable coronary disease or acute coronary syndrome. Aids in evaluation of stress, trauma, infection, inflammation, surgery, and associated diseases.

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 CardioPhase hsCRP (K033908)
• IMMAGE Immunochemistry Systems High Sensitivity CRPH Reagent (K010236)
• Beckman Cal 5 Plus (K926236/A)

Submission Summary (Full Text)

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K07/002

## Summary of Safety & Effectiveness Immage® 800 Immunochemistry Systems High Sensitivity Cardiac C-Reactive Protein (CCRP) Reagent

### 1.0 Submitted By:

Tara Viviani Senior Regulatory Affairs Specialist Beckman Coulter, Inc. 200 S. Kraemer Blvd., W-110 Brea, California 92822-8000 Telephone: [phone] FAX: [phone]

JUN 2 1 2007

### Date Submitted: 2.0

April 6, 2007

### 3.0 Device Name(s):

#### 3.1 Proprietary Names

Immage® Immunochemistry Systems High Sensitivity Cardiac C-Reactive Protein (CCRP) Reagent Beckman CAL 5 Plus

### Classification Name 3.2

C-Reactive Protein immunological test system (21 CFR § 866.5270) Calibrator, multi-analyte mixture (21 CFR § 862.1150)

### 4.0 Predicate Device:

| Candidate(s) | Predicate | Manufacturer | Docket<br>Number |
|----------------------------------------------------------------------------|--------------------------------------------------------------------|--------------------------|------------------|
| IMMAGE Immunochemistry<br>Systems High Sensitivity<br>Cardiac CCRP Reagent | Dade Behring<br>CardioPhase hsCRP | Dade Behring<br>Inc.* | K033908 |
| IMMAGE Immunochemistry<br>Systems High Sensitivity<br>Cardiac CCRP Reagent | IMMAGE Immunochemistry<br>Systems High Sensitivity<br>CRPH Reagent | Beckman<br>Coulter, Inc | K010236 |
| Beckman CAL 5 Plus | Beckman Cal 5 Plus | Beckman<br>Coulter, Inc. | K926236/A |

*Dade Behring Inc. (Newark, DE)

#### 5.0 Description:

High Sensitivity Cardiac C-Reactive Protein (CCRP) reagent is intended for the quantitative determination of C-Reactive protein in human serum or plasma by rate turbidimetry. The IMMAGE® 800 Immunochemistry Systems CCRP reagent is based on the highly sensitive Near Infrared Particle Immunoassay rate methodology. An anti-CRP antibody-coated particle binds to CRP in the patient sample resulting in the formation of insoluble aggregates causing turbidity. The rate of aggregate formation is directly proportional to the concentration of CRP in the sample.

CAL 5 Plus (Calibrator 5 Plus) is a frozen liquid serum matrix intended for use on IMMAGE® Immunochemistry Systems for the calibration of Anti-Streptolysin O (ASO), C-Reactive Protein (CRP) and Rheumatoid Factor (RF).

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### 6.0 Intended Use:

High Sensitivity Cardiac C-Reactive Protein (CCRP) reagent, when used in conjunction with IMMAGE® 800 Immunochemistry Systems and Calibrator 5 Plus, is intended for the quantitative determination of C-Reactive protein in human serum or plasma by rate turbidimetry.

CAL 5 Plus (Calibrator 5 Plus). when used in coniunction with Beckman Coulter reagents. is intended for use on IMMAGE® Immunochemistry Systems for the calibration of Anti-Streptolysin O (ASO), C-Reactive Protein (CRP) and Rheumatoid Factor (RF).

### Clinical Significance:

Measurement of C-Reactive protein (CRP) aids in evaluation of stress, trauma, infection, inflammation, surgery, and associated diseases. Cardiac CRP assays are indicated for use as an aid in the identification and stratification of individuals at risk for future cardiovascular disease. When used in conjunction with traditional clinical laboratory evaluation of acute coronary syndromes, CRP may be useful as an independent marker of prognosis for recurrent events in patients with stable coronary disease or acute coronary syndrome.

### 7.0 Comparison to Predicate(s):

The following table shows similarities and differences between the predicates identified in Section 4.0 of this summary.

| | Similarities | |
|-----------------------------------|-----------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------|
| Immage<br>Cardiac CCRP<br>Reagent | Intended Use | Same as Behring<br>CardioPhase hsCRP |
| | Use of Latex<br>particle technology | Same as<br>Dade Behring CardioPhase hsCRP and Immage<br>CRPH |
| | Liquid stable<br>reagent | The formulation is identical to Immage CRPH<br>Reagent. |
| | Single point<br>adjusted<br>Calibration model | Same as IMMAGE CRPH Reagent |
| Beckman CAL<br>5 Plus | Formulation | Identical to Beckman CAL 5 Plus |
| | Differences | |
| Immage<br>Cardiac CCRP<br>Reagent | Antibody source | IMMAGE CCRP uses goat and mouse while the<br>Dade Behring Kit uses mouse only. |
| | Initial dilution range | The IMMAGE initial dilution range covers from 0.2<br>to 60.0 mg/L while the Dade Behring Kit covers<br>from 3.0 to 220 mg/L |
| | Extended dilution<br>range | The IMMAGE extended dilution range covers up to<br>1440.0 mg/L while the Dade Behring Kit covers the<br>range from 0.16 to 16000.0 mg/L |
| | Calibration model | IMMAGE High Sensitivity Cardiac CCRP uses a<br>different model equation for the predetermined<br>calibration curve than IMMAGE CRPH. |

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### 8.0 Summary of Performance Data:

The data in the Premarket Notification on safety and effectiveness supports a finding of substantial equivalence to chemistry test systems already in commercial distribution. Equivalence is demonstrated through method comparison, stability, linearity, and imprecision experiments.

| Candidate | Slope | Intercept | R | N | Predicate Method |
|---------------------------------------------------------------------|-------|-----------|--------|-----|-----------------------------------|
| IMMAGE High Sensitivity<br>Cardiac CCRP Reagent<br>(0.2 to 60 mg/L) | 0.965 | 0.334 | 0.9962 | 157 | Dade Behring<br>CardioPhase hsCRP |
| IMMAGE High Sensitivity<br>Cardiac CCRP Reagent<br>(0.2 to 10 mg/L) | 1.013 | -0.026 | 0.9939 | 98 | Dade Behring<br>CardioPhase hsCRP |

## Method Comparison Study Results

# IMMAGE High Sensitivity Cardiac CCRP Reagent Imprecision Results

| Sample | Mean (mg/dL) | S.D. (mg/dL) | %C.V. | N |
|---------|--------------|------------------------|-------|----|
| | | Within-Run Imprecision | | |
| Level 1 | 0.807 | 0.0229 | 2.8 | 80 |
| Level 2 | 13.56 | 0.4109 | 3.0 | 80 |
| Level 3 | 51.538 | 1.7181 | 3.3 | 80 |
| | | Total Imprecision | | |
| Level 1 | 0.807 | 0.0279 | 3.5 | 80 |
| Level 2 | 13.56 | 0.4248 | 3.1 | 80 |
| Level 3 | 51.538 | 2.1933 | 4.3 | 80 |

## Beckman CAL 5 Plus Stability Testing Summary

| Stress<br>Temperature | Duration of<br>Incubation | Predicted<br>Stability | Beckman Stability<br>Claim* |
|-----------------------|---------------------------|------------------------|-----------------------------|
| 32°C | 40 days | 32 months | 24 months |
| 37°C | 24 days | 33 months | 24 months |
| 41°C | 15.5 days | 32 months | 24 months |

* expiration dating placed on the packaging based in date of manufacture

This summary of safety and effectiveness is being submitted in accordance with the requirements of the Safe Medical Device Act of 1990 and the implementing regulation 21 CFR 807.92.

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Image /page/3/Picture/1 description: The image shows the logo for the Department of Health & Human Services - USA. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is an abstract image of an eagle.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Beckman Coulter, Inc. Diagnostics Development Center c/o Ms. Tara Viviani Sr. Regulatory Affair Specialist 200 S. Kraemer Boulevard, W-110 P.O. Box 8000 Brea, CA 92822-8000

JUN 2 1 2007

Re: k071002

> Trade/Device Name: Immage® Immunochemistry Systems High Sensitivity Cardiac C-Reactive Protein (CCRP), Cal 5 Plus (Calibrator 5 Plus) Regulation Number: 21 CFR 862.1150 Regulation Name: Calibrator Regulatory Class: Class II Product Code: NQD, JIX Dated: April 06, 2007 Received: April 09, 2007

Dear Ms. Viviani:

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 Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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 Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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This letter will allow you to begin marketing your device as described in your Section 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 information about the application of labeling requirements to your device. or questions 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 Division of Small Manufacturers, International and Consumer Assistance at its toll-free number [phone] or [phone] or at its Internet address at http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours.

Jean M. Cooper, M.S., D.V.M.

Yéan M. Cooper, M.S., D.V.M. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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510(k) Number (if known): K071002

Device Name: Immage® Immunochemistry Systems High Sensitivity Cardiac C-Reactive Protein (CCRP) Beckman CAL 5 Plus

# Reagent:

Indications for Use:

High Sensitivity Cardiac C-Reactive Protein (CCRP) reagent, when used in conjunction with IMMAGE® 800 Immunochemistry Systems and Calibrator 5 Plus, is intended for the quantitative determination of C-Reactive protein in human serum or plasma by rate turbidimetry.

## Clinical Significance:

Measurement of C-Reactive protein (CRP) aids in evaluation of stress, trauma, infection, inflammation, surgery, and associated diseases. Cardiac CRP assays are indicated for use as an aid in the identification and stratification of individuals at risk for future cardiovascular disease. When used in conjunction with traditional clinical laboratory evaluation of acute coronary syndromes, CRP may be useful as an independent marker of prognosis for recurrent events in patients with stable coronary disease or acute coronary syndrome.

### Calibrator:

Indications for use:

CAL 5 Plus (Calibrator 5 Plus), when used in conjunction with Beckman Coulter reagents, is intended for use on IMMAGE® Immunochemistry Systems for the calibration of Anti-Streptolysin O (ASO), C-Reactive Protein (CRP) and Rheumatoid Factor (RF).

Prescription Use (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)

Carol C. Benam
ion Sign-Off

**ion Sign-Off**

Office of In Vitro Diagnostic Device
Evaluation and Safety

K07/002

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Beckman Coulter, Inc., Section 510(k) Notification IMMAGE® System High Sensitivity Cardiac C-Reactive Protein (CRPH) Reagent, Immage CCRP510k_Summary UPDATED.doc, April 2007

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