PAROS CRP

K022690 · Horiba, Ltd. · DCN · Dec 23, 2002 · Immunology

Device Facts

• Record ID: K022690
• Device Name: PAROS CRP
• Applicant: Horiba, Ltd.
• Product Code: DCN · Immunology
• Decision Date: Dec 23, 2002
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.5270
• Device Class: Class 2

Intended Use

The indications for use of the Paros CRP are for aiding in diagnosis and monitoring of inflammatory diseases. The primary utility is for screening for the presence of inflammatory disease, by measuring CRP on anti-coagulated whole blood samples, and thus eliminating the requirement for sample centrifugation. CRP measurement on serum samples is also possible. 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 inflammatory injury to body tissues.

Device Story

Benchtop in-vitro diagnostic system; measures C-Reactive Protein (CRP) levels in anti-coagulated whole blood or serum. Input: blood sample; process: three-phase immuno-turbidimetric reaction; phase 1: hemolysis via saponin-based reagent (R1); phase 2: incubation with interference-inhibiting reagent (R2); phase 3: incubation with anti-CRP antibody-coated latex beads (R3). Output: rate of turbidity change measured via 850nm LED optical sensor. Used in clinical laboratory settings by trained personnel. Output provides quantitative CRP concentration; aids clinicians in screening for inflammatory disease and monitoring inflammatory injury. Benefits patient by enabling whole blood testing, eliminating need for sample centrifugation.

Clinical Evidence

Bench testing only. Studies included precision (NCCLS EP5-A, total imprecision 0-2.6 CV%), linearity (0.2-10 mg/dl for whole blood; 0.2-7 mg/dl for serum), carry-over (0%), and sample stability (72 hours). Accuracy/bias assessment (NCCLS EP 9-A) demonstrated no significant bias and high correlation with Beckman Immage (R2=0.99 for whole blood, R=0.98 for serum). Interfering conditions (hemolysis, hyperbilirubinemia, etc.) and various pathological diagnoses were evaluated.

Technological Characteristics

Benchtop immuno-turbidimetric analyzer. Uses anti-CRP antibody-coated latex particles. Energy source: electrical. Sensing: 850nm LED light source and optical sensor. Reagents: R1 (saponin), R2 (interference inhibitor), R3 (latex beads). Connectivity: standalone. Sterilization: N/A (in-vitro diagnostic).

Indications for Use

Indicated for aiding in diagnosis and monitoring of inflammatory diseases in patients requiring CRP measurement via whole blood or serum samples.

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

• ABX / Horiba MICROS CRP (K002646)
• Beckman Coulter Immage IMMUNOCHEMISTRY SYSTEM (K981638)

Submission Summary (Full Text)

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DEC 2 3 2002

"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: KO 32690

- ABX Diagnostics Company: 34 Bunsen Drive Irvine CA92618 USA Phone: [phone] Fax: [phone] Contact Person: Ian Giles Date Prepared: May 20, 2002
Paros CRP Trade Name:

Common Name: In Vitro Diagnostic C-Reactive Protein Immunological Test System

Classification Name: C-Reactive Protein Immunological Test System

Device Classification: Class II

Regulation Number: 21 CFR (866.5270)

Substantial Equivalence:

The Paros CRP is substantially equivalent to the following devices:

- ABX / Horiba ™ MICROS CRP (K002646 October 2000) .
- Beckman Coulter Immage IMMUNOCHEMISTRY SYSTEM . (K981638 June 1998).

## Description:

The Paros CRP is a benchtop C-Reactive Protein Immunological Test System. It is a single parameter instrument (CRP only), with the ability to measure CRP on Whole Blood and Serum samples in-vitro. It employs the same measurement principles as the CRP measurement module of the ABX / Horiba ™MICROS CRP (K002646, October 2000). The Paros CRP does not have a cell counting module.

The CRP levels are measured in patients by reacting anti-CRP antibody coated latex particles with lyzed blood, and determining the rate of the turbidimetric reaction in the near infrared spectrum.

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Indications for Use:

The indications for use of the Paros CRP are for aiding in diagnosis and monitoring of inflammatory diseases. The primary utility is for screening for the presence of inflammatory disease, by measuring CRP on anti-coagulated whole blood samples, and thus eliminating the requirement for sample centrifugation. CRP measurement on serum samples is also possible.

Discussion of Performance Data Summary:

The determination of substantial equivalence is based on precision, linearity, stability and carry-over studies as well as an inter-procedural correlation study.

The data presented in this 510K Pre-market Notification demonstrate good precision as assessed by NCCLS EP5-A. Total Imprecision ranged from between 0 and 2.6 CV%.

Accuracy / bias assessment (NCCLS EP 9-A) showed no evidence of significant bias. Good correlation was demonstrated between the Paros CRP and the Beckman Immage for Whole Blood (R2=0.99). Similarly, the correlation for Serum samples between the Paros CRP and the Beckman Immage was excellent (R =0.98). For Whole blood samples, the linear regression formula of the trend line was Y-0.92X + 0.03. A comparison of the serum results showed linear regression trend line formula of: Y=0.95X.

Linearity assessment data supports a Whole Blood CRP linearity claim from 0.2 to 10 mg/d1; and for Serum samples, a linearity range between 0.2 and 7 mg / dl is supported.

The data shows linearity across the tested range for Whole Blood (Paros CRP result = 1.05 X Expected Target CRP value) R2=0.99; and serum: (Paros CRP result = 0.9X Expected Target CRP value) Re = 0.98.

The Sample Stability Study showed reproducibility of results over the entire 72 hour assessment period. At a level of 0.2 mg / dl, the % difference in results can be attributed to the fact that there is a single decimal point on the CRP result, and to the level of CRP testing. All other results showed <10% deviation from the baseline measurement.

There was Zero % Carry-over in this study.

Potential Interfering Clinical Conditions were investigated. Samples with hyperbilirubinemia, hemolysis, hypergammaglobulinemia, and hyperlipemia were included in the bias assessment study. Pathological diagnoses in the bias assessment study included: Multiple Myeloma, Rheumatoid Arthritis, Giant Cell Arteritis, Polymyalgia Rheumatica, Polymyositis, non-specific arthropathies, and somatic carcinomas.

Prepared By: Dr Ian Giles ABX Diagnostics

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The principles of immuno-turbidimetry on the MICROS CRP and PAROS CRP are summarized below:

Image /page/2/Figure/1 description: This image shows a diagram of a three-phase process. In phase 1, whole blood cells and antigens are mixed with R1, resulting in hemolysis. In phase 2, the product of phase 1 is mixed with R2, resulting in zero interference. In phase 3, the product of phase 2 is mixed with R3, which consists of latex beads coated with antibodies, and the resulting mixture is analyzed by a sensor using a light source LED at 850nm.

# Principles of CRP Measurement on Whole Blood.

:

- Phase 1 : Hemolysis, using reagent R1 ; R1 contains saponin as active principle.
- Phase 2 : Incubation of the hemolysate with R2, which inhibits potential interference during the incubation with the specific R3 reagent.
- Phase 3 : Incubation with latex beads coated with anti-CRP antibodies. The recognition of CRP by anti-CRP antibodies induces bead aggregation. This increases the turbidity (opacity) of the incubation medium. The rate of change in turbidity is measured by using a light source (850nm LED) and an optical sensor.

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# 1. MICROS CRP SPECIFICATIONS

MICROS CRP technical specifications are summarized in Table 3.

# MICROS CRP SPECIFICATIONS

]

| Parameters | |
|---------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| CBC/DIFF Mode | 18 parameters (16 for the US) with graphics for<br>RBC, PLT and WBC populations<br>RBC, HGB, HCT, MCH, MCHC, RDW<br>PLT, MPV, PDW*, THT*<br>LYM, MON, NEU (% and #) |
| CRP Mode | 19 parameters (17 for USA) with graphics for<br>RBC, PLT and WBC populations<br>RBC, HGB, HCT, MCH, MCHC, RDW<br>PLT, MPV, PDW*, THT*<br>LYM, MON, NEU (% and #)<br>CRP |
| Reagents | |
| CBC/DIFF Mode | Three reagents :<br>ABX MINIDIL LMG, ABX ALPHALYSE, ABX<br>MINICLEAN |
| CRP Mode | Six reagents :<br>ABX MINIDIL LMG, ABX ALPHALYSE, ABX<br>MINICLEAN<br>CRP-100 (CRP-R1, CRP-R2, CRP-R3) |
| Quality Control | Calibrator (Hematology) : Minocal<br>Control Blood : Minotrol 16 (L, H, M)<br>CRP Calibrator : CRPCAL<br>CRP Control : CRPTROL (L, H) |
| Principles of Measurement | Spectrophotometry (HGB)<br>Impedance (CBC/DIFF) |

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Image /page/4/Picture/0 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle with three stripes extending from its back, representing the department's commitment to health, services, and people. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged in a circular pattern around the logo.

# DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

Food and Drug Administrati 2098 Gaither Road Rockville MD 20850

Horiba, Ltd. c/o Dr. Ian Giles ABX Scientific Affairs Manager ABX Diagnostics 34 Bunsen Drive Irvine, CA 92618

Re: k022690

Trade/Device Name: Paros CRP Regulation Number: 21 CFR 866.5270 Regulation Name: C-reactive protein immunological test system Regulatory Class: Class II Product Code: DCN Dated: November 20, 2002 Received: November 22, 2002

Dear Dr. Giles:

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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## Page 2

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). 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 [phone] or [phone] or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.

Sincerely yours,

Steven Sutman

Steven I. Gutman, M.D., M.B.A. Director Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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# INDICATIONS FOR USE STATEMENT

S10(k) Number (if known): K O22690

Device Name: Paros CRP

Indications For Use: Indications for Use:

The indications for use of the Paros CRP are for aiding in diagnosis and monitoring of inflammatory diseases. The primary utility is for screening for the presence of inflammatory disease, by measuring CRP on anti-coagulated whole blood samples, and thus eliminating the requirement for sample centrifugation. CRP measurement on serum samples is also possible.

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 inflammatory injury to body tissues.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

| Prescription Use | <div> <span style="text-decoration: overline;">✓</span> </div> |
|----------------------|----------------------------------------------------------------|
| (Per 21 CFR 801.109) | |

OR

| Over-The-Counter Use | |
|--------------------------|--|
| (Optional Format 1-2-96) | |

| (Division Sign-Off) | <span style="text-decoration: overline;">J. Reeve for J. Bautista</span> |
|-----------------------------------------|--------------------------------------------------------------------------|
| Division of Clinical Laboratory Devices | |

| 510(k) Number | <span style="text-decoration: overline;">KC022690</span> |
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