ADVIA CHEMISTRY C-REACTIVE PROTEIN_2, (CRP_2) AND CALIBRATORS

{0}------------------------------------------------ ## 510(k) Summary # APR - 1 2008 | Submitter Information<br>Contact person: | Philip Liu<br>Manager, Regulatory Affairs & Compliance | |-----------------------------------------------------|----------------------------------------------------------------------------------------------------------------| | Address: | Siemens Healthcare Diagnostics<br>511 Benedict Avenue<br>Tarrytown, NY 10591 | | Phone: | 914-524-2443<br>914-524-2500 (fax) | | Date summary prepared: | February 18, 2008 | | Device Trade or Proprietary Names: | ADVIA® Chemistry C-Reactive Protein_2<br>(CRP_2) Assay<br>ADVIA® Chemistry C-Reactive Protein_2<br>Calibrators | | Device Common/Usual Name or<br>Classification Name: | C-Reactive Protein immunological test system<br>Calibrators | | Classification Number/Class: | DCN / Class II<br>JIX / Class II | This 510(k) summary of safety and effectiveness is being submitted in accordance with This 510(k) summary of satety and effect ctiveness is being subm The assigned 510(k) number is: _______________________________________________________________________________________________________________________________________________ #### Assay Predicate Device: | | Predicate Device | |---------------|--------------------------------------------------------------------------------------------------------------| | Device Name | ADVIA® Chemistry Systems C-Reactive Protein | | Common name | C-Reactive Protein Immunological Test System | | 510(k) Number | k992662 | | Manufacturer | Siemens Healthcare Diagnostics<br>(formerly Siemens Medical Solutions Diagnostics /<br>Bayer HealthCare LLC) | Siemens Healthcare Diagnostics (formerly Siemens Medical Solutions Diagnostics) ADVIA Chemistry C-Reactive Protein_2 Premarket Notification 510(K) ADVIA Chemistry C-Reactive Protein_2 Calibrator Premarket Notification 510(K) Attachment 1-510(k) Summary Revised {1}------------------------------------------------ ## Calibrator Predicate Device: | | Predicate Device | |---------------|--------------------------------------------------------------------------| | Device Name | ADVIA Chemistry wrCRP Calibrators | | Common name | C-Reactive Protein | | 510(k) Number | K022682 (Randox Labs, Ltd) | | Manufacturer | Siemens Medical Solutions Diagnostics<br>(formerly Bayer HealthCare LLC) | ### Device Description: The ADVIA Chemistry C-Reactive Protein_2 (CRP_2) assay is for in vitro diagnostic use in the quantitative determination of the concentration of C-Reactive Protein in human serum and plasma on the ADVIA® Chemistry systems. The ADVIA Chemistry C-Reactive Protein_2 Calibrators are used to calibrate this method. The proposed labeling indicates the ADVIA Chemistry CRP_2 reagents and Calibrators are for use on the family of ADVIA Chemistry Systems (1200 / 1650 / 1800 / 2400). The CRP_2 latex reagent is a suspension of uniform polystyrene latex particles coated with rabbit anti-CRP antibody. When serum or plasma containing CRP is mixed with the latex reagent, agglutination takes place resulting in an increase in the 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 C-Reactive Protein_2 Calibrators consist of six (6) levels of protein stabilized matrices containing varying concentrations of recombinant human CRP. The Calibrators have targeted expected values (lot specific) of 0, 5, 20, 40, 160, and 320 mg/L. The calibrators (1 mL/vial) and ready to use. Storage is at 2 - 8℃. ## Statement of Intended Use: The ADVIA Chemistry C-Reactive Protein_2 assay is for in vitro diagnostic use in the quantitative determination of the concentration of C-Reactive Protein in human serum and plasma (lithium heparin) on the ADVIA® Chemistry systems. Such measurements are used in the evaluation of infection, tissue injury, inflammatory disorders, and associated diseases. Increases in CRP values are non-specific for many disease processes and should not be interpreted without a complete clinical evaluation. The ADVIA Chemistry C-Reactive Protein_2 Calibrators are for in vitro diagnostic use in the calibration of ADVIA Chemistry Systems for the ADVIA Chemistry C-Reactive Protein_2 (CRP_2) method. {2}------------------------------------------------ # Comparisons to the Predicate Devices: ## Assay Similarities | | ADVIA Chemistry<br>C-Reactive Protein_2 (CRP_2)<br>( <i>new device</i> ) | ADVIA Chemistry<br>C-Reactive Protein (CRP)<br>( <i>predicate device</i> ) | |-----------------|--------------------------------------------------------------------------|----------------------------------------------------------------------------| | Intended Use | Quantitative determination of C-<br>Reactive Protein | Quantitative determination of C-<br>Reactive Protein | | Specimen Type | Human serum or plasma (lithium<br>heparin) | Human serum | | Calibration | Multi-point (6) | Multi-point (6) | | Reaction Type | Turbidimetric Endpoint | Turbidimetric Endpoint | | Reagents | Two liquid reagents, ready to use | Two liquid reagents, ready to use | | Standardization | CRM-470 | CRM-470 | ## Assay Differences | | ADVIA Chemistry<br>C-Reactive Protein_2 (CRP_2)<br>( <i>new device</i> ) | ADVIA Chemistry<br>C-Reactive Protein (CRP)<br>( <i>predicate device</i> ) | |-----------------------------|--------------------------------------------------------------------------|----------------------------------------------------------------------------| | Assay Principle | Latex turbidimetric immunoassay | Polyethylene glycol assisted<br>turbidimetric immunoassay | | Read<br>Wavelength | 571 nm | 340/ 694 nm | | Calibrators | ADVIA Chemistry CRP_2<br>Calibrators | ADVIA Chemistry CRP Calibrators | | Analytical Range<br>(mg/L)* | 4 to Calibrator 6<br>(Cal 6 target 304– 336) | 5 to Calibrator 6<br>(Cal 6 target 195 – 205) | | Expected Values | <10 mg/L** | <10 mg/L** | ** Tletz NW. Clinical Guide to Laboratory Tests, 4th Edition ## Callbrator Simllarities | | ADVIA Chemistry<br>C-Reactive Protein_2 Calibrators<br>( <i>new device</i> ) | ADVIA Chemistry<br>Wide Range C-Reactive Protein<br>Calibrators<br>( <i>predicate device</i> ) | |---------------------------|-------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------| | Intended Use | For <i>in vitro</i> diagnostic use in the<br>calibration of ADVIA Chemistry<br>systems for the CRP_2 method | For <i>in vitro</i> diagnostic use in the<br>calibration of ADVIA Chemistry<br>systems for the wrCRP method | | Matrix | Liquid, ready to use | Liquid, ready to use | | Calibrator Levels | 6 | 6 | | Calibrator<br>Ingredients | Recombinant human CRP in a<br>stabilized protein matrix; contains<br>sodium azide | Recombinant human CRP in a<br>stabilized protein matrix; contains<br>sodium azide | | Shelf Life | 18 months | 18 months | | Standardization | CRM-470 | CRM-470 | Slemens Healthcare Diagnostics (formerly Slemens Medical Solutions Diagnostics) ADVIA Chemistry C-Reactive Protein_2 Premarket Notification 510(k) ADVIA Chemistry C-Fleactive Attachment 1- 510(k) Summary Revised {3}------------------------------------------------ ## Calibrator Differences | | ADVIA Chemistry<br>C-Reactive Protein_2 Calibrators<br>(new device) | ADVIA Chemistry<br>Wide Range C-Reactive Protein<br>Calibrators<br>(predicate device) | |---------------------------------|---------------------------------------------------------------------|---------------------------------------------------------------------------------------| | Expected Values | Lot specific:<br>0, 5, 20, 40, 160, and 320 mg/L | Lot specific:<br>0, 2.5, 10, 20, 80, and 160 mg/L | | Open Vial<br>(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 (total), interfering substances, analytical range, and method comparison results. All of the evaluation studies gave acceptable results compared to the predicate devices. These studies support that the ADVIA Chemistry C-Reactive Protein_2 assay is substantially equivalent to the ADVIA Chemistry C-Reactive Protein assay that is currently marketed. | | ADVIA Chemistry<br>C-Reactive Protein_2 | ADVIA Chemistry<br>C-Reactive Protein | | |--------------|-----------------------------------------|---------------------------------------|--------------| | | ADVIA 1650 | ADVIA 1650 | | | Level (mg/L) | Total CV (%) | Level (mg/L) | Total CV (%) | | 31 | 1.3 | 5 | 13.6 | | 56 | 1.1 | 42 | 4.6 | | 83 | 1.5 | | | | 221 | 1.5 | | | #### Imprecision #### Correlation ## (y = ADVIA Chemistry C-Reactive Protein_2, x = comparison method/system) | Specimen type,<br>System (y) | Comparison System (x) | N | Regression<br>Equation | Sy.x<br>(mg/L) | r | Sample<br>Range<br>(mg/L) | |------------------------------|-----------------------|----|------------------------|----------------|-------|---------------------------| | Serum, ADVIA<br>1650 | ADVIA 1650 CRP | 47 | $Y = 0.99x - 2.8$ | 9.8 | 0.990 | 5 - 199 | Siemens Healthcare Diagnostics (formerly Siemens Medical Solutions Diagnostics) Clemono Frountibure Protein_2 Premarket Notification 510(K) ADVIA ChemIstry C-Reactive Protein_2 Calibrator Premarket Notification 510(k) Attachment 1- 510(k) Summary Revised {4}------------------------------------------------ | Interfering Substance | Interferent<br>Conc. (mg/dL) | CRP conc.<br>(mg/L) | Effect<br>(% change) | |------------------------|------------------------------|---------------------|----------------------| | Hemoglobin | 1000 mg/dL | 5 | 0.7 | | Lipids (Intralipid) | 1000 mg/dL | 5 | - 0.7 | | Lipids (Triglycerides) | 1000 mg/dL | 5 | 0.5 | | Bilirubin, free | 60 mg/dL | 5 | 1.8 | | Bilirubin, conjugated | 60 mg/dL | 5 | 2.0 | | Rheumatoid Factor | 200 IU/mL | 4 | 8.4 | ## Interfering Substances (ADVIA Chemistry C-Reactive Protein_2 on ADVIA 1650) #### Analytical Range - Serum/Plasma | Platform | ADVIA Chemistry C-Reactive Protein_2 | |------------|--------------------------------------| | ADVIA 1650 | 4 to Calibrator 6 (304-336) mg/L | #### Conclusions: The ADVIA Chemistry C-Reactive Protein_2 assay is substantially equivalent to other products in commercial distribution intended for similar use. Most notably, it is substantially equivalent to the currently marketed Siemens Healthcare Diagnostics (formerly Bayer HealthCare LLC) ADVIA Chemistry C-Reactive Protein (k992662) assay. The ADVIA® Chemistry C-Reactive Protein _2 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). {5}------------------------------------------------ Image /page/5/Picture/0 description: The image shows the logo for the Department of Health & Human Services. The logo consists of a stylized caduceus symbol, which is a staff with two snakes coiled around it, and the text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" arranged in a circular pattern around the symbol. The text is in all caps and is relatively small compared to the caduceus symbol. Public Health Service Food and Drug Administration 2098 Gaither Road Rockville MD 20850 Siemens Medical Solutions Diagnostics c/o Philip Liu, Ph.D. Manager, Regulatory Affairs and Compliance 511 Benedict Avenue Tarrytown, NY 10591 Re: k072658 Trade/Device Name: ADVIA® Chemistry C-Reactive Protein_2 (CRP_2) Assay ADVIA® Chemistry C-Reactive Protein_2 Calibrators Regulation Number: 21 CFR 866.5270 Regulation Name: C-reactive protein immunological test system Regulatory Class: Class II Product Code: DCN, JIX Dated: February 19, 2008 Received: February 21, 2008 APR - 1 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 the Code of Federal Regulations, Title 21, Parts 800 to 898. 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 Part 801); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The {6}------------------------------------------------ Page 2 - 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) 276-0450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at 240-276-3474. For questions regarding the reporting of device adverse events (Medical Device Reporting (MDR)), please contact the Division of Surveillance Systems at 240-276-3464. 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 (240) 276-3150 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html. Sincerely yours, Clara Beckerf Robert L. Becker, Jr., M.D., Ph.D. Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health Enclosure {7}------------------------------------------------ # Indications for Use 510(k) Number (if known): k072658 ## Device Name: ADVIA CHEMISTRY C-Reactive Protein 2 Assay ADVIA CHEMISTRY C-Reactive Protein 2 Calibrators Indications For Use: The ADVIA CHEMISTRY C-Reactive Protein_2 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) on the ADVIA Chemistry systems. Such measurements are used in the evaluation of infection, tissue injury, inflammatory disorders, and associated diseases. Increases in CRP values are non-specific for many disease processes and should not be interpreted without a complete clinical evaluation. The ADVIA Chemistry C-Reactive Protein_2 Calibrators are for in vitro diagnostic use in the calibration of ADVIA Chemistry systems for the C-Reactive Protein 2 (CRP 2) 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 Diagnostic Devices (OIVD) Mana M. Chen Division Sign Off Division Stan-Off Office of In Vitro Diagnostic Device Evaluation and Safety Page 1 of 1 510(k) K072657