TNL-ULTRA ASSAY FOR THE ADVIA CENTAUR SYSTEM

{0}------------------------------------------------ ## DEC 3 0 2005 ## 510(k) SUMMARY OF SAFETY AND EFFECTIVENESS Troponin I (TnI-Ultra) Assay for Bayer ADVIA Centaur® This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of the Safe Medical Device Act of 1990 and 21 CFR 807.92. The assigned 510(k) number is: #### 1. Intended Use For in vitro diagnostic use in the quantitative determination of cardiac troponin I in serum, heparinized or EDTA plasma using ADVIA Centaur® system. 1053020 Cardiac troponin I determinations aid in the diagnosis of acute myocardial infarction and in the risk stratification of patients with non-ST segment elevation acute coronary syndromes with respect to relative risk mortality, myocaridal infarction or increased probability of ischemic events requiring urgent revascularization procedures. The ADVIA Centaur® TnI-Ultra Calibrator is for the in vitro diagnostic use in the calibration of the TnI-Ultra assay on the ADVIA Centaur® system. #### 2. Predicate Devices | Product Name | Reagent REF | Calibrator REF | |-------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------|----------------| | ACS:180® and ADVIA<br>Centaur® Cardiac Troponin I<br>(cTnI) Assay | ACS:180<br>07572636 (50 test)<br>00370639 (300 test)<br>ADVIA Centaur<br>07640356 (100 tests)<br>0595168 (500 tests) | Kit component | #### 3. Device / Method | Product Name | Reagent REF | Calibrator REF | |-----------------------------------|----------------------------------------------|----------------| | ADVIA Centaur® TnI-Ultra<br>Assay | 02789602 (100 tests)<br>02790309 (500 tests) | Kit component | {1}------------------------------------------------ #### 4. Imprecision | ADVIA Centaur®<br>TnI-Ultra | | ADVIA Centaur® cTnI* | | ACS:180 cTnI* | | |-----------------------------|-----------------|----------------------|-----------------|------------------|-----------------| | Level<br>(ng/mL) | Total<br>CV (%) | Level<br>(ng/mL) | Total<br>CV (%) | Level<br>(ng/mL) | Total<br>CV (%) | | 0.1 | 4.6 | 0.94 | 6.6 | 0.8 | 7.5 | | 0.24 | 3.5 | 2.38 | 5.0 | 1.37 | 6.7 | | 0.85 | 2.7 | 3.72 | 3.0 | 15.73 | 5.0 | | 3.91 | 2.8 | 8.08 | 4.4 | 33.83 | 5.3 | | 14.47 | 3.4 | 13.29 | 3.9 | 43.01 | 5.8 | | 37.8 | 3.5 | 15.95 | 3.9 | | | | | | 43.62 | 3.6 | | | | ADVIA Centaur®<br>TnI-Ultra | Within-run<br>CV(%) | ADVIA Centaur® cTnI* | Within-run<br>CV(%) | |-----------------------------|---------------------|----------------------|---------------------| | Level<br>(ng/mL) | | Level<br>(ng/mL) | | | 0.1 | 3.2 | 0.94 | 4.6 | | 0.24 | 2.6 | 2.38 | 2.3 | | 0.85 | 1.6 | 3.72 | 2.6 | | 3.91 | 1.5 | 8.08 | 1.9 | | 14.47 | 1.5 | 13.29 | 1.4 | | 37.8 | 1.8 | 15.95 | 2.3 | | | | 43.62 | 2.4 | | ACS:180 cTnI* | | |------------------|---------------------| | Level<br>(ng/mL) | Within-run<br>CV(%) | | 0.8 | 4.4 | | 1.37 | 4.2 | | 15.73 | 2.2 | | 33.83 | 2.3 | | 43.01 | 3.0 | | * data from | | instructions for use The troponin I concentration at a total CV of 10% was determined to be 0.042 ng/mL. Functional Sensitivity (20% total C.V.) was calculated as <0.008 ng/mL for ADVIA Centaur® TnI-Ultra Assay. {2}------------------------------------------------ | Specimen type<br>Regression method | Comparative<br>System (X) | N | Regression<br>Equation | Sample<br>Range<br>(ng/mL) | |------------------------------------|---------------------------|-----|-------------------------------|----------------------------| | Serum Passing &<br>Bablok | Bayer<br>ADVIA<br>Centaur | 346 | $1.10X - 0.045$ | 0.1 to 34.8 | | Linear Regression | Bayer<br>ADVIA<br>Centaur | 346 | $1.26X - 0.52$<br>$r = 0.975$ | 0.1 to 34.8 | | Serum Passing &<br>Bablok | ACS:180 | 334 | $1.2X - 0.032$ | 0.1 to 30.9 | | Linear Regression | ACS:180 | 334 | $1.4X - 0.51$<br>$r = 0.967$ | 0.1 to 30.9 | ## 5. Correlation (Y= ADVIA Centaur® TnI-Ultra, X = Comparative System) In order to demonstrate equivalence between devices, the following correlations were generated using clinically significant troponin doses less than 4.0 ng/mL only. | Specimen type<br>Regression method | Comparative<br>System (X) | N | Regression<br>Equation | Sample<br>Range<br>(ng/mL) | |------------------------------------|---------------------------|-----|----------------------------|----------------------------| | Serum Passing &<br>Bablok | Bayer<br>ADVIA<br>Centaur | 229 | 1.08X - 0.02 | 0.1 to 4.0 | | Linear Regression | Bayer<br>ADVIA<br>Centaur | 229 | 1.04X + 0.04<br>r = 0.946 | 0.1 to 4.0 | | Serum Passing &<br>Bablok | ACS:180 | 230 | 1.17X - 0.006 | 0.1 to 4.0 | | Linear Regression | ACS:180 | 230 | 1.13X + 0.068<br>r = 0.943 | 0.1 to 4.0 | Further comparison of clinical utility was done by comparing doses from ADVIA Centaur TnI-Ultra to ACS:180 and ADVIA Centaur cTnI. The WHO criteria cut-off of 0.9 ng/mL was used for this evaluation. | | ADVIA Centaur cTnI | | |--------------------------|--------------------|-------------| | ADVIA Centaur TnI- Ultra | < 0.9 ng/mL | ≥ 0.9 ng/mL | | < 0.9 ng/mL | 101 | 2 | | ≥ 0.9 ng/mL | 7 | 261 | | Concordance = 97.6% | | | {3}------------------------------------------------ | | ACS:180 cTnI | | |---------------------|--------------|-------------| | | < 0.9 ng/mL | ≥ 0.9 ng/mL | | < 0.9 ng/mL | 101 | 2 | | ≥ 0.9 ng/mL | 20 | 236 | | Concordance = 93.9% | | | ## 6. Interfering substances | | Interference<br>Concentration | Recovery<br>(ng/mL) | | % | |-----------------------------------|-------------------------------|---------------------|----------|-----------| | Interference | | Expected | Observed | Deviation | | Hemoglobin | 500 mg/dL | 1.17 | 1.15 | -1.7 | | Lipemia | 1000 mg/dL | 1.06 | 1.05 | -0.9 | | Icterus<br>Conjugated bilirubin | 20 mg/dL | 0.85 | 0.81 | -4.7 | | Icterus<br>Unconjugated bilirubin | 20 mg/dL | 1.16 | 1.07 | -7.8 | | Human immunoglobulin | 12 g/dL | 1.10 | 1.04 | -5.4 | #### 7. Analytical Range 0.008 ng/mL to 50 ng/mL. # 8. Minimum Detectable Concentration | ADVIA Centaur®<br>TnI-Ultra<br>(ng/mL) | ADVIA Centaur® TnI<br>(ng/mL) | |----------------------------------------|-------------------------------| | 0.008 | 0.07 | ## 9. 99th Percentile Distribution and Functional Sensitivity Based on 648 serum samples from apparently healthy donors, the upper 99th percentile Troponin I value is 0.044 ng/mL. {4}------------------------------------------------ ## 10. Expected Results The AMI cutoff value of ≥ 0.9 ng/mL is based on the data for the Bayer HealthCare The AMI Culori Vardo of = 0.5 hg mg mg Ma Centaur® TnI-Ultra method is equivalent. | Method | % Sensitivity | % Specificity | |-----------------------------|---------------|---------------| | ACS:180 cTnI | 97.3 | 97.0 | | No. Patients (n) | 112 | 166 | | 95% Confidence Interval | 92.4 - 99.4 | 93.1 - 99.0 | | Alternate troponin I method | 96.4 | 93.4 | | No. Patients (n) | 112 | 166 | | 95% Confidence Interval | 91.1 - 99.0 | 88.5 - 96.7 | December 28, 2005 Date Andres Holle Manager Regulatory Affairs Bayer Corporation 511 Benedict Avenue Tarrytown, New York 10591-5097 914-524-3494 {5}------------------------------------------------ DEPARTMENT OF HEALTH & HUMAN SERVICES Public Health Service Image /page/5/Picture/2 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized caduceus symbol, which features three diagonal lines that resemble a human figure. The caduceus is surrounded by a circular border with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" written around it. The text is in all capital letters and is evenly spaced around the circle. Food and Drug Administration 2098 Gaither Road Rockville MD 20850 #### DEC 3 0 2005 Mr. Andres Holle Manager Regulatory Affairs Bayer Corporation 511 Benedict Avenue Tarrytown, NY 10591-5097 Re: k053020 R055020 Trade/Device Name: Troponin I Ultra Assay and Calibrator for the ADVIA Centaur® System Regulation Number: 21 CFR 862.1215 Regulation Name: Creatine phosphokinase/creatine kinase or isoenzymes test system Regulatory Class: Class II Product Code: MMI, JIT Dated: October 21, 2005 Received: October 28, 2005 Dear Mr. Holle: We have reviewed your Section 510(k) premarket notification of intent to market the device we nave reviewed your 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 for use stated in the encreated 776, the enactment date of the Medical Device Amendments, or to conimered prior of may 2011-11-11) 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). and Cosmetic Flor (110) that the device, subject to the general controls provisions of the Act. The r va may, attrols 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 r may 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 r reaso be action and 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 or any 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). {6}------------------------------------------------ Page 2 - This letter will allow you to begin marketing your device as described in your Section 510(k) I mis letter will anow you to begin mailieding of substantial equivalence of your device to a legally promatic. Inclineation: "The PDF 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, If you desire specific infortion and advertising of your device, please contact the Office of In of questions on the promotion and Safety at (240) 276-0484. Also, please note the v Itto Diagnostic Developmenting by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Tou may obtain other general ers, 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 Guts 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 {7}------------------------------------------------ # Indications for Use 510(k) Number (if known): KD530 00 Device Name: Troponin I Ultra Assay and Calibrator for the ADVIA Centaur® System Indications For Use: The ADVIA Centaur® Tnl-Ultra (Tnl-Ultra) method is for in vitro diagnosic use in the The ADVIA Centadi Thi-Olira (Thi Ultra) moment serum and heparinized and Cardiac troponin I determinations aid in the diagnosis of acute EDTA plasma. EDTA plasma. Galulac troponin T decommination of patients with non-ST segment myocardial Tiffanction and In the Thor Stratinediter of elative risk mortality, myocardian elevation actie coronaly syndromes with respective to requiring urgent revascularization procedures. The ADVIA Centaur® Tnl-Ultra Calibrator is for the in vitro diagnostic use in the The ADVIA Centaur Thi-Ultra Galbrator 15 The Prescription Use (Part 21 CFR 801 Subpart D) (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) Cogcurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD) Int. Ultra Division Sign-Off Office of in Vitro Diagnostic Device. Evaluation and Safety Page 1 of 51062 k05302d