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C-REACTIVE PROTEIN (LATEX) HIGH SENSITIVE TEST SYSTEM FOR COBAS INTEGRA INSTRUMENTS

Q: Who is the manufacturer of C-REACTIVE PROTEIN (LATEX) HIGH SENSITIVE TEST SYSTEM FOR COBAS INTEGRA INSTRUMENTS?

Roche Diagnostics Corp. filed the 510(k) submission for C-REACTIVE PROTEIN (LATEX) HIGH SENSITIVE TEST SYSTEM FOR COBAS INTEGRA INSTRUMENTS (K053603).

Q: What is the FDA product code for C-REACTIVE PROTEIN (LATEX) HIGH SENSITIVE TEST SYSTEM FOR COBAS INTEGRA INSTRUMENTS?

NQD. It is classified under 21 CFR 866.5270 as a Class 2 device in the Immunology panel.

Q: What is the regulatory pathway for C-REACTIVE PROTEIN (LATEX) HIGH SENSITIVE TEST SYSTEM FOR COBAS INTEGRA INSTRUMENTS?

510(k) clearance (submission type: Traditional).

Q: What are the predicate devices for C-REACTIVE PROTEIN (LATEX) HIGH SENSITIVE TEST SYSTEM FOR COBAS INTEGRA INSTRUMENTS?

Tina-quant® CRP (latex) HS Test System (K042485); Dade Behring N High Sensitivity CRP (K033908).

K053603 · Roche Diagnostics Corp. · NQD · Feb 9, 2006 · Immunology

Device Facts

Record ID	K053603
Device Name	C-REACTIVE PROTEIN (LATEX) HIGH SENSITIVE TEST SYSTEM FOR COBAS INTEGRA INSTRUMENTS
Applicant	Roche Diagnostics Corp.
Product Code	NQD · Immunology
Decision Date	Feb 9, 2006
Decision	SESE
Submission Type	Traditional
Regulation	21 CFR 866.5270
Device Class	Class 2

Intended Use

The CRP (Latex) High Sensitive Immmunoturbidimetric assay is for the in vitro quantitative determination of C-reactive protein (CRP) in human serum and plasma on Roche automated clinical chemistry analyzers. Measurement of CRP is of use for the detection and evaluation of inflammatory disorders and associated diseases, infection and tissue injury. Highly sensitive measurement of CRP may also be used as an aid in the assessment of the risk of future coronary heart disease. When used as an adjunct to other laboratory evaluation methods of acute coronary syndromes, it may also be an additional independent indicator of recurrent event prognosis in patients with stable coronary disease or acute coronary syndrome.

Device Story

Latex particle-enhanced immunoturbidimetric assay for quantitative measurement of C-reactive protein (CRP) in human serum or plasma. Human CRP agglutinates with latex particles coated with monoclonal anti-CRP antibodies; precipitate measured turbidimetrically on Roche COBAS Integra automated clinical chemistry analyzers. Used in clinical laboratory settings by trained personnel. Output is a quantitative CRP concentration (mg/L). Clinicians use results to evaluate inflammatory states, infection, tissue injury, and assess cardiovascular disease risk. High-sensitivity measurements aid in prognosis for patients with stable coronary disease or acute coronary syndromes. Results interpreted alongside patient history and other clinical findings.

Clinical Evidence

Bench testing only. Method comparison performed against predicate devices (K042485 and K033908). Passing-Bablok regression analysis (y=1.0548x + 0.0424; r=0.996) demonstrated correlation. Precision evaluated via within-run and between-run CVs; within-run CVs ranged 0.6-1.3%, between-run CVs 2.2-3.5%. Functional sensitivity (CV <10%) reported at 0.3 mg/L. Interference testing confirmed no significant interference from bilirubin, hemoglobin, triglycerides, or rheumatoid factors up to specified limits.

Technological Characteristics

Latex particle-enhanced immunoturbidimetric assay. Reagents: R1 (TRIS buffer, BSA, mouse immunoglobulins, stabilizers) and R2 (latex particles coated with mouse anti-CRP antibodies in glycine buffer). Standardized to CRM 470. Measuring range 0-20 mg/L (up to 300 mg/L with dilution). Automated analysis on COBAS Integra systems. No high-dose hook effect up to 1000 mg/L.

Indications for Use

Indicated for in vitro quantitative determination of CRP in human serum and plasma to detect/evaluate inflammatory disorders, infection, and tissue injury. Also indicated as an aid in assessing risk of future coronary heart disease and as an independent prognostic indicator for recurrent events in patients with stable coronary disease or acute coronary syndrome.

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

Tina-quant® CRP (latex) HS Test System (K042485)
Dade Behring N High Sensitivity CRP (K033908)

Related Devices

K081294 — ADVIA CHEMISTRY CARDIOPHASE HIGH SENSITIVITY C-REACTIVE PROTEIN (HSCRP), CALIBRATORS · Siemens Healthcare Diagnostics, Inc. · Jul 29, 2008
K073277 — ROCHE-CREACTIVE PROTEIN (LATEX) · Roche Diagnostics Corp. · Mar 6, 2008
K003400 — CRP HS TEST SYSTEM · Roche Diagnostics Corp. · May 10, 2001
K030545 — CRP-LATEX (II)X2 SEIKEN ASSAY KIT · Denka Seiken Co., Ltd. · Jun 2, 2003

Submission Summary (Full Text)

{0}------------------------------------------------ K 053603 ______________________________________________________________________________________________________________________________________________________________________________ FEB 9 2006 ## 510(k) Summary | Introduction | According to the requirements of 21 CFR 807.92, the following information provides sufficient detail to understand the basis for a determination of substantial equivalence. | |----------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | Submitter name, address, contact | Roche Diagnostics 9115 Hague Road Indianapolis, IN 46250 317-521-3723 | | | Contact Person: Theresa M. Ambrose Date Prepared: January 18, 2006 | | Device Name | Proprietary name: C-Reactive Protein (Latex) High Sensitive test system for COBAS Integra instruments [CRP (latex) HS] Common name: hsCRP test system | | | Classification name: Cardiac C-reactive Protein, Antigen, Antiserum, and Control | | Predicate devices | The CRP (latex) HS Test System for COBAS Integra instruments is substantially equivalent to the currently marketed Roche Tina-quant® CRP (latex) HS Test System cleared under K042485. For purposes of cardiac risk assessment, the CRP (latex) HS system is also equivalent to the Dade Behring N High Sensitivity CRP (K033908) | | Device Description | The CRP (latex) HS Test System is a latex particle-enhanced immunoturbidimetric test for the quantitative measurement of C-reactive protein in human serum or plasma. Human CRP agglutinates with latex particles coated with monoclonal anti-CRP antibodies. The precipitate is determined turbidimetrically. The calibrator is the Calibrator for automated systems (C.f.a.s). Proteins; and the recommended control materials are CRP T Control N and Precinorm Protein. | {1}------------------------------------------------ ## 510(k) Summary, Continued | Intended use | The CRP (Latex) High Sensitive Immmunoturbidimetric assay is for the in vitro quantitative determination of C-reactive protein (CRP) in human serum and plasma on Roche automated clinical chemistry analyzers. Measurement of CRP is of use for the detection and evaluation of inflammatory disorders and associated diseases, infection and tissue injury. Highly sensitive measurement of CRP may also be used as an aid in the assessment of the risk of future coronary heart disease. When used as an adjunct to other laboratory evaluation methods of acute coronary syndromes, it may also be an additional independent indicator of recurrent event prognosis in patients with stable coronary disease or acute coronary syndrome. | |--------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | Comparison to predicate device | The below table compares the CRP (Latex) HS for COBAS Integra instruments with the predicate device, Tina-Quant® CRP (Latex) HS (K042485) | {2}------------------------------------------------ 510(k) Summary, Continued Substantial eq | | Substantial equivalence: comparison table | | | |-----------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | Characteristic | CRP (Latex) HS for COBAS Integra instruments | Predicate device Tina-Quant® CRP (Latex) HS (K042485) | Predicate device | | Intended Use/ Indications for Use | Same as K042485 | The Tina-quant® CRP (Latex) High Sensitive Immmunoturbidimetric assay is for the in vitro quantitative determination of C-reactive protein (CRP) in human serum and plasma on Roche automated clinical chemistry analyzers. Highly sensitive measurement of CRP is of use for the detection and evaluation of inflammatory disorders and associated diseases, infection and tissue injury. Measurement of CRP may also be used as an aid in the assessment of the risk of future coronary heart disease. When used as an adjunct to other laboratory evaluation methods of acute coronary syndromes, it may also be an additional independent indicator of recurrent event prognosis in patients with stable coronary disease or acute coronary syndrome.. | N High Sensitivity CRP is an in vitro diagnostic reagent for the quantitative determination of C-reactive protein (CRP) in human serum, and heparin and EDTA plasma by means of particle- enhanced immunonephelometry using BN Systems. In acute phase response, increased levels of a number of plasma proteins, including C-reactive protein, are observed. Measurement of CRP is useful for the detection and evaluation of infection, tissue injury, inflammatory disorders, and associated diseases. Measurements may also be used as an aid in the identification of individuals at risk for future cardiovascular disease. High sensitivity CRP (hsCRP) measurements, when used in conjunction with traditional clinical laboratory evaluation of acute coronary syndromes, may be useful as an independent marker of prognosis for recurrent events, in patients with stable coronary disease or acute coronary syndromes | | Characteristic | CRP (Latex) HS for COBAS Integra instruments | Predicate device Tina-Quant® CRP (Latex) HS (K042485) | Predicate device Dade-Behring N High Sensitivity CRP (K033908) | | Assay principle | Same as K042485 | Latex particle-enhanced immunoturbidimetric test | Particle-enhanced agglutination with nephelometric detection | | Instrument | COBAS Integra family of analyzers (Integra 400/ 700/ 800) | Roche/Hitachi family of analyzers | Dade-Behring BN Systems (nepholometric systems) | | Reagent Stability | Unopened kit: up to the stated expiration date at 2-8 °C On board the analyzer (opened and refrigerated): 12 weeks | Unopened kit: up to the stated expiration date at 2-8 °C On board the analyzer (opened and refrigerated): 90 days | Unopened kit: up to the stated expiration date at 2-8 °C Opened: 4 weeks at stored in closed vial. Do not freeze | | Reagent composition | Same active ingredients and antibody as K042485 | R1: TRIS buffer with bovine serum albumin, immunoglobulins (mouse), preservative, stabilizers R2: Latex particles coated with anti-CRP (mouse) in glycine buffer; preservatives; stabilizers | Suspension of polystyrene particles coated with mouse monoclonal antibodies to CRP; preservatives | | Sample type | Same as K042485 | Human serum and plasma | Human serum, and heparin and EDTA plasma | | Traceability/ standardization | Standardized to Tina-Quant® CRP (Latex) HS which is standardized to reference preparation CRM 470 (RPPHS 91/0619) (same as both predicates) | IFCC/BCR/CAP reference preparation CRM 470 (RPPHS 91/0619) | IFCC/BCR/CAP reference preparation CRM 470 (RPPHS 91/0619) | | Characteristic | CRP (Latex) HS for COBAS Integra instruments | Predicate device Tina-Quant® CRP (Latex) HS (K042485) | Predicate device Dade-Behring N High Sensitivity CRP (K033908) | | Measuring range | 0-20 mg/L without dilution 0-300 mg/L with postdilution | 0.1 – 20 mg/L without dilution 0.1 – 300 mg/L extended range with dilution and rerun | 0.175 – 1100 mg/L with dilution | | Lower Detection Limit | 0.1 mg/L | 0.03 mg/L | 0.175 mg/L | | Within-run precision (%CV) | Control material • 0.9% at 3.3 mg/L • 0.7% at 8.0 mg/L Human serum • 1.3% at 1.6 mg/L • 0.6% at 11.4 mg/L | Control material • 0.43% at 4.27 mg/L • 0.41% at 11.62 mg/L Human serum • 1.34% at 0.55 mg/L • 0.28% at 12.36 mg/L | Control material • 2.5% at 0.5 mg/L • 3.8% at 1.3 mg/L • 2.1% at 2.1 mg/L • 2.6% at 14 mg/L • 3.9% at 24 mg/L • 5.7% at 56 mg/L | | Between-run precision (%CV) | Control material • 3.5% at 3.3 mg/L • 2.2% at 8.0 mg/L Human serum • 3.1% at 1.5 mg/L • 2.3% at 11.4 mg/L | Control material • 2.70% at 4.34 mg/L • 3.45% at 11.90 mg/L Human serum • 5.70% at 0.52 mg/L • 2.51% at 10.98 mg/L | Control material • 3.1% at 0.5 mg/L • 3.8% at 1.1 mg/L • 3.4% at 2.1 mg/L • 4.0% at 15 mg/L • 2.3% at 26 mg/L • 4.4% at 62 mg/L | | Characteristic | CRP (Latex) HS for COBAS Integra instruments | Predicate device Tina-Quant® CRP (Latex) HS (K042485) | Predicate device Dade-Behring N High Sensitivity CRP (K033908) | | Functional Sensitivity (CV <10%) | 0.3 mg/L | 0.11 mg/L | Not available. | | Limitations: interferences | No significant interference up to: • 10 g/L bilirubin • 0.6 g/L hemoglobin • 5 g/L triglyceride at 2 mg/L CRP • Rheumatoid factors < 1200 IU/mL | No significant interference up to: • I index of 60 (60 mg/dL bilirubin) • H index of 1000 (1000 mg/dL hemoglobin) • L index of 1000 at CRP > 5mg/L (lipemia; intralipid) • L index of 800 at CRP > 4mg/L • L index of 500 at CRP > 2 mg/L • Rheumatoid factors < 1200 IU/mL | No interference from: • Bilirubin up to 230 mg/L • Hemoglobin up to 36 g/L • Triglycerides up to 7.4 g/L Highly lipemic samples that cannot be clarified by centrifugation (10 min at 15000 X G) must not be tested. | | | No high dose hook effect up to 1000 mg/L CRP | No high dose hook effect up to 1000 mg/L | Particles that are formed in incompletely clotted serum or plasma or due to protein denaturation must be removed by centrifugation prior to testing. | | | In rare cases, monoclonal gammopathy may lead to false CRP values. | In rare cases, gammopathy, in particular IgM Waldenstrom's macroglobinemia may cause unreliable results | | | | Erroneous results may be obtained in samples taked from patients who have been treated with monoclonoal mouse | | | | Predicate devices (continued) | | | | | Characteristic | Predicate device CRP (Latex) HS for COBAS Integra instruments | Predicate device Tina-Quant® CRP (Latex) HS (K042485) | Predicate device Dade-Behring N High Sensitivity CRP (K033908) | | Result Interpretation | Same as K042485 | For diagnostic purposes, results should always be assessed in conjunction with the patient's medical history and other findings. Increases in CRP values are non- specific and should not be interpreted without a complete clinical history. When using CRP to assess the risk of coronary heart disease, measurements should be made on metabolically stable patients and compared to previous values. Optimally, the average of hsCRP results repeated two weeks apart should be used for risk assessment. Measurements should be compared to previous values. For risk assessment persistently unexplained values about 10 mg/L should be evaluated for non-cardiovascular origins. Testing for risk assessment should not be performed while there is indications of infection, systemic inflammation, or trauma | Increases in CRP values are non- specific and should not be interpreted without a complete clinical history. | {3}------------------------------------------------ ## 510(k) Summary, Continued Predicate devices (continued {4}------------------------------------------------ ## 510(k) Summary, Continued, Continue Predicate devices (continued {5}------------------------------------------------ 510(k) Summary, Continued, Continue Predicate devices (continued {6}------------------------------------------------ # 510(k) Summary, Continued, Continue {7}------------------------------------------------ | Continued 1 400 | |-----------------------------------------------------------------------| | 1 1 1 1 C Both, CO II facts, II do 1 1 1 1 | | 1 1 10 11 244-48 11-12-15 | | 1 1 510 | | | redicate devices (continue | Characteristic | CRP (Latex) HS for COBAS Integra instruments | Predicate device Tina-Quant® CRP (Latex) HS (K042485) | Predicate device Dade-Behring N High Sensitivity CRP (K033908) | |-----------------|-------------------------------------------------|---------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------| | Expected values | Same as K042485 | Adults: < 5.0 mg/L Neonates 0-3 weeks: 0.1 – 4.1 mg/L Children (2 months-15 years) 0.1 – 2.8 mg/L | Relative risk/average hsCRP: Low < 1 mg/L Average 1.0-3.0 mg/L High >3.0 mg/L | | | | For CVD risk assessment: relative risk Low < 1 mg/L Average 1.0-3.0 mg/L High >3.0 mg/L | | | Comparison | | y = Integra CRP (Latex) hs x = Tina-Quant® CRP (latex) hs | y= Integra CRP (latex) hs x= Dade-Behring N High Sensitivity CRP | | | | Passing-Bablok results: y=1.0548x + 0.0424. T = 0.956; r = 0.996 | | he new test system has imilar interferes, comparable standards and alibrators, an comparable in absolute values, which are cleared for indications including cariat sk assess nalytical validation experiments were performed in order to establish the performance characteristics ethod comparison was performed between this method and the predicate dev Performance evaluation {8}------------------------------------------------ DEPARTMENT OF HEALTH & HUMAN SERVICES Image /page/8/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle with three stripes forming its wing. The eagle is facing right. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged in a circular pattern around the eagle. Public Health Service Food and Drug Administratio 2098 Gaither Road Rockville MD 20850 Ms. Theresa M. Ambrose Regulatory Principal Roche Diagnostics Corporation 9115 Hague Rd. Indianapolis, IN 46250 FEB & 2006 Re: k053603 > Trade/Device Name: C-Reactive Protein (Latex) High Sensitive Test System For Cobas Integra Instruments Regulation Number: 21 CFR8866.5270 Regulation Name: C-reactive protein immunological test system Regulatory Class: Class II Product Code: NQD Dated: December 22, 2005 Received: December 23, 2005 Dear Ms. Ambrose: 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 (OS) regulation (21 CFR Part 820). {9}------------------------------------------------ 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 (240) 276-0484. 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 (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html. Sincerely yours, Alberto Gutierrez Alberto Gutierrez, Ph.D. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health Enclosure {10}------------------------------------------------ ## Indications for Use 510(k) Number (if known): K053603 ## Device Name: C-Reactive Protein (Latex) High Sensitive Test System For Cobas Integra Instruments Indications For Use: The CRP (Latex) High Sensitive Immunoturbidimetric assay is for the in vitro quantitative determination of C-reactive protein (CRP) in human serum and plasma on Roche automated clinical chemistry analyzers. Measurement of CRP is of use for the detection and evaluation of inflammatory disorders and associated diseases, infection and tissue injury. Highly sensitive measurement of CRP may also be used as an aid in the assessment of the risk of future coronary heart disease. When used as an adjunct to other laboratory evaluation methods of acute coronary syndromes, it may also be an additional independent indicator of recurrent event prognosis in patients with stable coronary disease or acute coronary syndrome. Prescription Use × (Part 21 CFR 801 Subpart D) AND/OR Over-The-Counter Use (21 CFR 801 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) Ann Chappell Division Sign-Off Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety Page 1 of 1 510(k)_ lc 053603