Who can help prepare an FDA 510(k) submission like ADVIA CHEMISTRY CARDIOPHASE HIGH SENSITIVITY C-REACTIVE PROTEIN (HSCRP), CALIBRATORS?

Innolitics — a medical-device software consultancy — provides regulatory and engineering support for FDA 510(k) submissions. See https://innolitics.com/services/510ks/ or contact https://innolitics.com/contact.

ADVIA CHEMISTRY CARDIOPHASE HIGH SENSITIVITY C-REACTIVE PROTEIN (HSCRP), CALIBRATORS

Q: Who is the manufacturer of ADVIA CHEMISTRY CARDIOPHASE HIGH SENSITIVITY C-REACTIVE PROTEIN (HSCRP), CALIBRATORS?

Siemens Healthcare Diagnostics, Inc. filed the 510(k) submission for ADVIA CHEMISTRY CARDIOPHASE HIGH SENSITIVITY C-REACTIVE PROTEIN (HSCRP), CALIBRATORS (K081294).

Q: What is the FDA product code for ADVIA CHEMISTRY CARDIOPHASE HIGH SENSITIVITY C-REACTIVE PROTEIN (HSCRP), CALIBRATORS?

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 ADVIA CHEMISTRY CARDIOPHASE HIGH SENSITIVITY C-REACTIVE PROTEIN (HSCRP), CALIBRATORS?

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

K081294 · Siemens Healthcare Diagnostics, Inc. · NQD · Jul 29, 2008 · Immunology

Device Facts

Record ID	K081294
Device Name	ADVIA CHEMISTRY CARDIOPHASE HIGH SENSITIVITY C-REACTIVE PROTEIN (HSCRP), CALIBRATORS
Applicant	Siemens Healthcare Diagnostics, Inc.
Product Code	NQD · Immunology
Decision Date	Jul 29, 2008
Decision	SESE
Submission Type	Traditional
Regulation	21 CFR 866.5270
Device Class	Class 2

Intended Use

The ADVIA Chemistry CardioPhase™ High Sensitivity C-Reactive Protein assay is for in vitro diagnostic use in the quantitative determination of the concentration of C-Reactive Protein (CRP) in human serum and plasma (lithium heparin and potassium EDTA) on the ADVIA Chemistry systems. In acute phase response, increased levels of a number of plasma proteins, including CRP, are observed. Measurement of CRP is useful for the detection and evaluation of infection, tissue injurv, inflammatory disorders, and associated diseases. High sensitivity CRP (hsCRP) measurements may be used as an independent risk marker for the identification of individuals at risk for future cardiovascular disease. Measurement of hsCRP, 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. The ADVIA Chemistry CardioPhase™ High Sensitivity C-Reactive Protein Calibrators are for in vitro diagnostic use in the calibration of ADVIA Chemistry systems for the CardioPhase High Sensitivity C-Reactive Protein method.

Device Story

Assay uses latex-enhanced immuno-turbidimetric method to measure CRP concentration in human serum/plasma. Polystyrene latex particles coated with anti-CRP antibodies agglutinate upon contact with CRP; resulting turbidity measured at 571 nm. Calibration curve generated using six-level recombinant human CRP calibrators. Used in clinical laboratory settings on ADVIA Chemistry systems; operated by laboratory technicians. Output is quantitative CRP concentration (mg/L). Clinicians use results to assess inflammatory states, identify cardiovascular disease risk, and determine prognosis for patients with coronary syndromes. Benefits include standardized, high-sensitivity detection of CRP to aid clinical decision-making.

Clinical Evidence

Bench testing only. Performance evaluated via imprecision (within-run CV 0.8-3.2%, total CV 1.2-4.2%), method comparison (N=167, Passing Bablok Y=1.00x+0.01, r=0.998), and interference studies (hemoglobin, lipids, bilirubin, rheumatoid factor). Analytical range 0.16-10.0 mg/L. Results demonstrate substantial equivalence to predicate.

Technological Characteristics

Latex-enhanced immuno-turbidimetric assay. Reagents: two liquid, ready-to-use reagents. Calibrators: six-level recombinant human CRP in stabilized protein matrix. Sensing: turbidimetric measurement at 571 nm. Standardization: IRMM CRM 470. Platform: ADVIA Chemistry systems.

Indications for Use

Indicated for quantitative determination of C-Reactive Protein (CRP) in human serum and plasma (lithium heparin or potassium EDTA) to detect/evaluate infection, tissue injury, inflammatory disorders, and associated diseases. Also indicated as an independent risk marker for future cardiovascular disease and as a prognostic marker for recurrent events in patients with stable coronary disease or acute coronary syndromes.

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

CardioPhase™ High Sensitivity C-Reactive Protein (hsCRP) on the BNII Systems (K033908)
ADVIA Chemistry wrCRP (K022682)

Related Devices

K103557 — DIAZYME HS CRP ASSAY KIT / CALIBRATOR SET / CONTROL SET · Diazyme Laboratories · Apr 27, 2011
K053603 — C-REACTIVE PROTEIN (LATEX) HIGH SENSITIVE TEST SYSTEM FOR COBAS INTEGRA INSTRUMENTS · Roche Diagnostics Corp. · Feb 9, 2006
K030545 — CRP-LATEX (II)X2 SEIKEN ASSAY KIT · Denka Seiken Co., Ltd. · Jun 2, 2003
K023269 — HEMOSIL C-REACTIVE PROTEIN - HIGH SENSITIVITY AND HIGH SENSITIVITY CONTROLS · Instrumentation Laboratory CO · Dec 23, 2002
K032663 — QUANTEX CRP HIGH SENSITIVITY STANDARD MULTIPOINT, QUANTEX CRP HIGH SENSITIVITY CONTROLS VE CONTROLS 1/2 · Instrumentation Laboratory CO · Dec 19, 2003

Submission Summary (Full Text)

{0}------------------------------------------------ # 510(k) Summary | Submitter information Contact person: | Philip Liu Manager, Regulatory Affairs & Compliance | |-----------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | Address: | Siemens Healthcare Diagnostics Inc. 511 Benedict Avenue Tarrytown, NY 10591 | | Phone: | 914-524-2443 914-524-2500 (fax) | | Date summary prepared: | May 1, 2008 | | Device Trade or Proprietary Names: | ADVIA® Chemistry CardioPhase High Sensitivity C-Reactive Protein (hsCRP) Assay ADVIA® Chemistry CardioPhase High Sensitivity C-Reactive Protein (hsCRP) Calibrators | | Device Common/Usual Name or Classification Name: | Cardiac C-Reactive Protein, Antigen, Antiserum, and Control Calibrators | | Classification Number/Class: | NQD / Class II JIX / Class II | This 510(k) summary of safety and effectiveness is being submitted in accordance with the requirements of 21 CFR 807.92. | The assigned 510(k) number is: | K081294 | |--------------------------------|---------| |--------------------------------|---------| ### Assay Predicate Devices: | | Predicate Device | |---------------|---------------------------------------------------------------------------------| | Device Name | CardioPhase™ High Sensitivity C-Reactive Protein (hsCRP) on the BNII Systems | | Common name | High Sensitivity C-Reactive Protein (hsCRP) | | 510(k) Number | K033908 | | Manufacturer | Siemens Healthcare Diagnostics (formerly Dade Behring, Inc.) | Siemens Healthcare Diagnostics ADVIA Chemistry CardioPhase High Sensitivity C-Reactive Protein Premarket Notification 510(k) ADVIA Chemistry CardioPhase High Sensitivity C-Reactive Protein Calibrators Premarket Notification 510(k) 510(k) Summary Page 1 of 6 {1}------------------------------------------------ ### Calibrator Predicate Device: | | Predicate Device | | |---------------|------------------------------------------------------------------------------------|--| | Device Name | ADVIA Chemistry wrCRP | | | Common name | C-Reactive Protein Calibrators | | | 510(k) Number | K022682 (Randox Labs, Ltd) | | | Manufacturer | Siemens Healthcare Diagnostics (formerly Siemens Medical Solutions Diagnostics) | | ## Device Description: The ADVIA Chemistry CardioPhase™ High Sensitivity C-Reactive Protein assay is for in vitro diagnostic use in the quantitative determination of the concentration of C-Reactive Protein (CRP) in human serum and plasma on the ADVIA Chemistry systems. The CardioPhaseTM hsCRP latex reagent is a suspension of uniform polystyrene latex particles coated with anti-CRP antibody. When serum or plasma containing CRP is mixed with the latex reagent, agglutination takes place resulting in an increase in turbidity. This turbidity is measured at 571 nm. The CRP concentration in serum or plasma is determined from a calibration curve that is generated with the calibrators. The ADVIA® Chemistry CardioPhase™ High Sensitivity C-Reactive Protein Calibrators consist of six (6) levels of protein stabilized matrices containing varying concentrations of recombinant human CRP. The Calibrators have targeted values (lot specific) of 0, 0.53, 1.05, 1.58, 5.25, and 10.50 mg/L. The calibrators (1 mL/vial) are liquid and ready to use. Storage is at 2 - 8℃. # Statement of Intended Use: The ADVIA Chemistry CardioPhase™ High Sensitivity C-Reactive Protein assay is for in vitro diagnostic use in the quantitative determination of the concentration of C-Reactive Protein (CRP) in human serum and plasma (lithium heparin and potassium EDTA) on the ADVIA Chemistry systems. In acute phase response, increased levels of a number of plasma proteins, including CRP, are observed. Measurement of CRP is useful for the detection and evaluation of infection, tissue injurv, inflammatory disorders, and associated diseases. High sensitivity CRP (hsCRP) measurements may be used as an independent risk marker for the identification of individuals at risk for future cardiovascular disease. Measurement of hsCRP, 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. The ADVIA Chemistry CardioPhase™ High Sensitivity C-Reactive Protein Calibrators are for in vitro diagnostic use in the calibration of ADVIA Chemistry systems for the CardioPhase High Sensitivity C-Reactive Protein method. {2}------------------------------------------------ ### Comparisons to the Predicate Device: # Assay Similarities | | ADVIA Chemistry CardioPhase™ High Sensitivity C-Reactive Protein (hsCRP) ( new device ) | Siemens Healthcare CardioPhase™ High Sensitivity CRP on the BNII Systems (formerly Dade Behring) ( predicate device ) | |-----------------|---------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------| | Intended Use | For in vitro diagnostic use in the quantitative determination of C- Reactive Protein | For in vitro diagnostic use in the quantitative determination of C- Reactive Protein | | Specimen Type | Human serum or plasma (lithium heparin, potassium EDTA) | Human serum or plasma (lithium heparin, potassium EDTA) | | Calibration | Multi-point (6) | Reference curves generated by multi- point calibration | | Standardization | IRMM Reference Material CRM 470 | IRMM Reference Material CRM 470 | | Expected Values | Healthy individuals ≤ 3 mg/L | Healthy individuals ≤ 3 mg/L | | | Risk for cardiovascular disease prediction*: Low < 1 mg/L Average 1-3 mg/L High > 3 mg/L | Relative risk/average hsCRP: Low <1 mg/L Average 1.0-3.0 mg/L High >3.0 mg/L | *AHA/CDC Scientific Statement # Assay Differences | | ADVIA Chemistry CardioPhase™ High Sensitivity C-Reactive Protein (hsCRP) ( new device ) | Siemens Healthcare CardioPhase™ High Sensitivity CRP on the BNII Systems (formerly Dade Behring) ( predicate device ) | |----------------------------|---------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------| | Assay Principle | Latex-enhanced immuno-turbidimetric assay | Particle enhanced immuno- nephelometry on the BN system | | Calibrator | ADVIA Chemistry CardioPhase™ High Sensitivity C-Reactive Protein Calibrators | N Rheumatology Standard SL N Diluent | | Reagents | Two liquid reagents, ready to use | Ready to use reagent | | Analytical Range (mg/L) | 0.16 – 10.0 mg/L | 0.10 – 20 mg/L | . {3}------------------------------------------------ # Calibrator Similarities | | ADVIA Chemistry CardioPhase High Sensitivity C-Reactive Protein Calibrators ( new device ) | ADVIA Chemistry Wide Range C-Reactive Protein Calibrators ( predicate device ) | |---------------------------|----------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------| | Intended Use | For in vitro diagnostic use in the calibration of ADVIA Chemistry systems for the Cardiophase hsCRP method | For in vitro diagnostic use in the calibration of ADVIA Chemistry systems for the wrCRP method | | Matrix | Liquid, ready to use | Liquid, ready to use | | Calibrator Levels | 6 | 6 | | Calibrator Ingredients | Recombinant human CRP in a stabilized protein matrix; contains sodium azide | Recombinant human CRP in a stabilized protein matrix; contains sodium azide | | Shelf Life | 18 months | 18 months | | Standardization | CRM-470 | CRM-470 | # Calibrator Differences | | ADVIA Chemistry CardioPhase High Sensitivity C-Reactive Protein Calibrators (new device) | ADVIA Chemistry Wide Range C-Reactive Protein Calibrators (predicate device) | |---------------------------------|---------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------| | Expected Values | Lot specific: 0, 0.53, 1.05, 1.58, 5.25, and 10.50 mg/L | Lot specific: 0, 2.5, 10, 20, 80, and 160 mg/L | | Open Vial (capped) Stability | 60 days stored @2-8°C | 28 days stored @2-8°C | ### Performance: Substantial equivalence was demonstrated by testing several performance characteristics including imprecision, method comparison, interfering substances, serum/plasma equivalency, and analytical range. The following tables summarize the precision (within run), interfering substances, analytical range, and method comparison results. All of the evaluation studies gave acceptable results compared to the predicate device (this predicate device was used in clinical studies supporting an indication for cardiovascular use). These studies support that the ADVIA Chemistry CardioPhase™ High Sensitivity C-Reactive Protein assay is substantially equivalent to the Siemens Healthcare CardioPhase™ High Sensitivity CRP on the BNII Systems that is currently marketed. {4}------------------------------------------------ #### Imprecision | ADVIA Chemistry CardioPhase hsCRP | | | Siemens Healthcare (former Dade Behring) CardioPhase hsCRP | | |--------------------------------------|----------------------|-----------------|------------------------------------------------------------------|----------------------| | ADVIA 1650 | | | BNII | | | Level (mg/L) | Within run CV (%) | Total CV (%) | Level (mg/L) | Within run CV (%) | | 0.21 | 3.2% | 4.2% | 0.5 | 2.5% | | 1.04 | 1.1% | 1.2% | 1.3 | 3.8% | | 3.12 | 0.8% | 1.3% | 2.1 | 2.1% | | 10.27 | 1.4% | 1.6% | 14 | 2.6% | | | | | 24 | 3.9% | #### Correlation #### (y = ADVIA Chemistry CardioPhase hsCRP, x = comparison method/system) | Specimen type, System (y) | Comparison System (x) | N | Regression Equation | Sy.x (mg/L) | r | Sample Range (mg/L) | |------------------------------|-----------------------------------------------------|-----|---------------------------------------|----------------|-------|---------------------------| | Serum, ADVIA 1650 | former Dade Behring CardioPhase hsCRP on BNII | 167 | Passing Bablok: $Y = 1.00x + 0.01$ | N/A | N/A | 0.17 - 9.05 | | Serum, ADVIA 1650 | former Dade Behring CardioPhase hsCRP on BNII | 167 | Least Squares: $Y = 1.01x - 0.01$ | 0.13 | 0.998 | 0.17 - 9.05 | #### Interfering Substances #### (ADVIA Chemistry CardioPhase High Sensitivity C-Reactive Protein on ADVIA 1650) | Interfering Substance | Interferent Conc. (mg/dL) | CRP conc. (mg/L) | Effect (% change) | |-----------------------|------------------------------|---------------------|----------------------| | Hemoglobin | 500 mg/dL | 0.43 | - 9% | | Lipids (Intralipid) | 1000 mg/dL | 0.52 | - 7% | | Bilirubin, free | 30 mg/dL | 0.53 | 4% | | Bilirubin, conjugated | 30 mg/dL | 0.51 | 0 | | Rheumatoid Factor | 1040 IU/mL | 3.15 | 8% | #### Analytical Range (Serum/Plasma) | Platform | ADVIA Chemistry CardioPhase High Sensitivity C-Reactive Protein | |------------|-----------------------------------------------------------------| | ADVIA 1650 | 0.16 to 10 mg/L | Siemens Healthcare Diagnostics ADVIA Chemistry CardioPhase High Sensitivity C-Reactive Protein Premarket Notification 510(k) ADVIA Chemistry CardioPhase High Sensitivity C-Reactive Protein Calibrators Premarket Notification 510(k) 510(k) Summary {5}------------------------------------------------ ### Conclusions: The ADVIA Chemistry CardioPhase High Sensitivity C-Reactive Protein assay is substantially equivalent to other products in commercial distribution intended for similar Most notably, it is substantially equivalent to the currently marketed Siemens use. Healthcare Diagnostics (formerly Dade Behring) CardioPhase High Sensitivity CRP on the BNII Systems (this predicate device was used in clinical studies supporting an indication for cardiovascular use). The ADVIA® Chemistry CardioPhase High Sensitivity C-Reactive Protein Calibrators are substantially equivalent to other products in commercial distribution intended for similar use. Most notably, it is substantially equivalent to the currently marketed ADVIA Chemistry Wide Range C-Reactive Protein Calibrators (k022682). {6}------------------------------------------------ Image /page/6/Picture/1 description: The image shows the logo for the Department of Health & Human Services - USA. The logo features a stylized eagle with three lines representing its wings and body. The eagle is facing right. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular fashion around the eagle. Food and Drug Administration 2098 Gaither Road Rockville MD 20850 JUL 2 9 2008 Siemens Healthcare Diagnostics Inc. c/o Philip Liu Manager, Regulatory Affairs & Compliance 511 Benedict Avenue Tarrytown, NY 10591 Re: k081294 Trade/Device Name: ADVIA® Chemistry CardioPhase High Sensitivity C-Reactive Protein (hsCRP) Assay, ADVIA Chemistry CardioPhase High Sensitivity C-Reactive Protein Calibrators Regulation Number: 21CFR Sec .- 866.5270 Regulation Name: C-Reactive Protein Immunological Test System. Regulatory Class: Class II Product Code: NQD, JIX Dated: May 5, 2008 Received: May 7, 2008 Dear Dr. Liu: 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 {7}------------------------------------------------ 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 logally marketed predicate device results in a classification for your device of July , 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) 276-0490. Also, please othe 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 the (800) 638-2041 or (240) 276-3150 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. Jean 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 {8}------------------------------------------------ # Indications for Use 510(k) Number (if known): Device Name(s): ### ADVIA CHEMISTRY CardioPhase™ High Sensitivity C-Reactive Protein Assay ADVIA CHEMISTRY CardioPhase™ High Sensitivity C-Reactive Protein Calibrators Indications For Use: The ADVIA Chemistry CardioPhase High Sensitivity C-Reactive Protein assay is for in vitro diagnostic use in the quantitative determination of the concentration of C-Reactive Protein (CRP) in human serum and plasma (lithium heparin or potassium EDTA) on the ADVIA Chemistry systems. In acute phase response, increased levels of a number of plasma proteins, including CRP, are observed. Measurement of CRP is useful for the detection and evaluation of infection, tissue injury, inflammatory disorders, and associated diseases. High sensitivity CRP (hsCRP) measurements may be used as an independent risk marker for the identification of individuals at risk for future cardiovascular disease. Measurement of hsCRP, 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. The ADVIA Chemistry CardioPhase High Sensitivity C-Reactive Protein Calibrators are for in vitro diagnostic use in the calibration of ADVIA Chemistry systems for the CardioPhase High Sensitivity C-Reactive Protein method. 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 Djagnostic Devices (OIVD) and Page 1 of 1 Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety K081294