CARESIDE CREATININE

{0}------------------------------------------------ Mar. 1999 10:040M P7 Exigent Diagnostics, Inc. Page 13 CareSide™ Creatinine Premarket Notification MAR 3 0 1998 revised on March 23, 1998 ## CareSide™ Creatinine Safety and 510(k) Summary: V. Effectiveness #### I. Applicant Information - A. Applicant Name - Applicant/Manufacturer Address B, - C. Telephone Number - D. Contact Person - E. FAX Number - F. e-Mail Address - G. Date 510(k) Summary prepared #### Device Information 11. - Device Name (Trade) A. - Device Name (Classification) B. - Device Classification C. # CareSide™ Creatinine asarchk@worldnet.att.net Exigent Diagnostics, Inc. Kenneth B. Asarch, Pharm.D., Ph.D. 6100 Bristol Parkway Culver City, CA 90230 310-338-6767 310-338-6789 February 11, 1998 Creatinine test system Clinical chemistry panel Creatinine test system Regulation Number: 21 CFR 862.1225 Regulatory Class II Classification Number: 75JFY Tier 1 None applicable - D. Device Tier - Special controls and E. performance standards #### III. Substantial Equivalence Claim - A. General equivalency claim The ability to monitor analyte-specific biochemical reactions in dry film and other formats is widely recognized and has gained widespread acceptance for use in chemistry assays. Creatinine in vitro diagnostic products, in both dry film and other formats, are already on the U.S. market, including creatinine products which utilize creatinine deaminasc catalyzed generation of ammonia by reaction non-enzymatically with bromophenol blue indicator dye. #### B. Specific equivalency claim This CareSide™ Creatinine test is substantially equivalent in principle, intended use, and clinical performance to the currently marketed Vitros slides for the quantitative measurement of Creatinine on the Vitros DT 60 II. | Name of Predicate Device: | Johnson and Johnson's (formerly Eastman Kodak,<br>Inc.) Vitros CREA Slides (blank corrected method)<br>for Johnson and Johnson's Vitros DT 60 (formerly<br>Eastman Kodak's DT 60 II). | |-------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | Predicate Device 510K number: | K912844/A | | Product Code: | 75JLA | {1}------------------------------------------------ Exigent Diagnostics, Inc. Page 13a CareSide™ Creatinine Premarket Notification revised on March 23, 1998 #### Device Description IV. CareSide™ Creatinine cartridges are used with the Exigent Diagnostics CareSide™ Analyzer to measure creatinine concentration in anti-coagulated whole blood, plasma or serum specimens. The CareSide™ Creatinine cartridge, a single use disposable in vitro diagnostic test cartridge, aids in specimen separation and delivers a measured volume of plasma or serum to a dry film to initiate the measurement of creatinine concentration. The film cartridge (patent pending) contains all reagents necessary to measure creatinine concentration. When used in conjunction with the CareSideTM BUN cartridge on the CareSide™ Analyzer, the analyzer calculates a BUN to creatinine ratio. #### Explanation of Device Function A. Each Exigent Diagnostics CareSide™ Creatinine cartridge consists of a creatininespecific multi-layer reagent film mounted in a plastic base with a hinged lid. The user introduces the anti-coagulated whole blood, serum, or plasma specimen into the cartridge deposition well, closes the lid and inserts the cartridge into the sample Exigent Diagnostics CareSide™ Analyzer. Once loaded, the CareSide™ analyzer scans the cartridge barcode, brings the cartridge and the contained specimen to 37°C, and spins the cartridge to move the sample from the sample deposition well into the cartridge channels and chambers. As the cartridge continues to spin, the blood cells are separated from the plasmalserum and the cells accumulate in the separation well. Ten microliters of plasma (or serum, as applicable) remain in the metering passage. Any excess sample flows into an overflow well. The ten microliters of plasma (or serum, as applicable) is automatically dispensed onto the multi-layer reagent film. The spreading layer distributes the sample evenly on the film and filters large molecular weight components such as protein and dye fragments before the specimen enters the ammonia removal layer. Endogenous ammonia is removed by the enzymatic conversion to L-glutamic acid through the action of glutamate dehydogenase (GLDH) in the presence of a-ketoglutaric acid and NADPH. A separation layer prevents mixing the former reaction with the next layer in which the enzymc creatinine deiminase (CD) acts on creatinine in the presence of water to form ammonia gas and N-methylhydantoin. The ammonia gas crosses the gas penneation layer to enter the detection layer where it reacts with bromophenol blue to form a blue dye. Test Reaction Sequence: NH3 + a-ketoglutaric acid + NADPH - 040 > L-glutamic acid + NADP* Creatinine + H2O -- > N-Inethylhydantoin + NI3 Bromophenol blue + NH3 -> Blue dye As the cartridges spin, photodiodes measure reflectance of light emitted by waveleugthspecific light emitting diodes (LEDs) at a fixed time. The analyzer uses the reflectance measurements and the lot-specific standard curve to calculate creatinine concentration. #### Test Summary B. Creatinine is produced during muscle contraction when the high-energy compound phosphocreatine degrades into creatine, which subsequently dehydrates into circulating creatinine. Creatinine levels in blood serve as an indicator of total muscle mass and activity, and of renal function. Decreased levels of creatinine are seen in cases of muscular dystrophy. Increased creatinine levels arc found in cases of kidney disease and urinary tract obstruction. Creatinine concentration in blood is closely correlated with the kidney's glomerular filtration rate (GFR), and the creatinine clearance rate is used as an estimate of the GFR. The creatinine clearance rate, estimated from the blood creatinine concentration, is used to determine or to adjust the dosage of certain drugs which are excreted via glomerular filtration in the kidneys. {2}------------------------------------------------ Exigent Diagnostics, Inc. Page 13b CareSide™ Creatinine Premarket Notification revised on March 23, 1998 #### V. Intended Use #### ん. Intended Use The CareSide™ Creatinine cartridge is intended for in vitro diagnostic use in conjunction with the Exigent Diagnostics CareSide™ Analyzer to quantitatively measure creatinine cooncentration in anti-coagulated whole blood, plasma or serum by laboratory professionals. When used in conjunction with the Exigent Diagnostics CareSide™ BUN test cartridge on the Exigent Diagnostics CareSide™ Analyzer, the creatinine product may be used to calculate a BUN to creatinine ratio. The CareSide™ Creatinine test aids in the diagnosis and treatment of renal diseases. #### Indications for Use B. This product is indicated for use with patients with various renal diseases. #### Technological Characteristics VI. - A. Similarities | | CareSide™ Creatinine | Vitros Creatinine DT Slides | |-------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------| | Intended Use | Primarily to aid in the diagnosis<br>and treatment of renal diseases. | Same | | Indications | For in vitro diagnostic use.<br>For professional use only. | Same | | Measurement | Quantitative | Same | | Method Principle | Dry film based creatinine<br>deiminase conversion of<br>creatinine to ammonia and<br>reaction with ammonia<br>indicating dye. Chromogen<br>quantitated by reflectance<br>measurement after fixed time. | Same except that endogenous<br>creatinine is measured and<br>subtracted rather than<br>enzymatically eliminated. | | Specimen dilution | Not required | Same | | Materials Source | Creatinine deiminase<br>(Bacillus sp)<br>Indicator - Bromocresol blus<br>(synthetic) | Creatinine deiminase<br>(source unknown)<br>Indicator - Bromocresol blus<br>(synthetic) | | Detector | Reflectance (570 nm) | Reflectance (605 nm) | | Test time | Approximately 4 minute warm-<br>up (on-board) plus 5 minute test<br>time. | 15 minutes slide warm-up (off-<br>line) plus 5 minutes test time. | | Reference Method | HPLC | HPLC | | Sample Type | Serum, plasma, anti-coagulated<br>whole blood (wb) [wb applied<br>sample, plasma test sample] | serum, plasma | | Specimen volume | 10 µl test volume<br>(85 ± 15 µl applied volume) | 10 µl | | Calibration | Calibration information bar-<br>coded on each cartridge.<br>Calibration information may<br>change with each lot. | Run Vitros DT II calibrators<br>whenever a new slide lot is<br>used or when necessary. | | Quality Control | 2 levels | Same | | Reporting Units | mg/dL or µmol/L | Same | | Reaction Temp. | 37 °C | Same | {3}------------------------------------------------ Exigent Diagnostics, Inc. Page 13c CareSide™ Creatinine Premarket Notification revised on March 23, 1998 #### B. Differences | | CareSide™ Creatinine | Vitros Creatinine DT Slides | |--------------------------|-------------------------------------|--------------------------------------------------------------------------| | Direct blood<br>specimen | Yes, anti-coagulated whole<br>blood | No, requires separation of<br>whole blood prior to sample<br>application | | Reportable range | 0.2 to 16 mg/dL | 0.01 to 15 mg/dL | | Accurate<br>pipetting | Not required | Required | | Reagent pre-<br>warming | Not required | Required | ### Comparative Performance Characteristics C. | | CareSide™ Creatinine | Vitros Creatinine DT Slides | |---------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------| | Detection limit | 0.2 mg/dL | Not provided | | Reportable range | 0.2 to 16 mg/dL | 0.01 to 15 mg/dL | | Accuracy | Mean recovery 99% | Not provided | | Precision | Total CV, 9 mg/dL, 4.2% | Total CV, 10 mg/dL, 3.3% | | Method comparison | CareSide™ = $1.08 (Vitros Creatinine DT) - 0.38, r=0.99$ | | | Linearity | Mean deviation approx 4%,<br>r>0.99 | Not provided | | Interference | No significant interference observed at tested concentration of interferent:<br>Ammonium PO₄, 500 μM<br>Ascorbic Acid, 10 mg/dL<br>Bilirubin, 20 mg/dL<br>5-fluorocytosine, 80 μg/mL<br>Glucose, 600 mg/dL<br>Hemoglobin, 500 mg/dL<br>Triglycerides 3000 mg/dL<br>Urea Nitrogen (BUN), 100 mg/dL | Not provided | | Specimen Types & Anticoagulants | No clinically significant difference between heparinized whole blood, serum, heparin plasma, and EDTA plasma. | No clinically significant difference between serum and heparin plasma. Whole blood is unsuitable. | | Expected Values | 0.4 to 0.9 mg/dL (female)<br>0.6 to 1.3 mg/dL (male)<br>Central 95% interval | 0.5 to 1.2 mg/dL (female)<br>0.7 to 1.4 mg/dL (male)<br>Central 95% interval | #### D. Conclusion The nonclinical and clinical data provided demonstrate that the CareSide™ Creatinine product is as safe, effective, and performs as well as or better than the legally marketed predicate device. {4}------------------------------------------------ Image /page/4/Picture/1 description: The image contains the text "Public Health Service". The text is black and is centered horizontally. The background is white. Image /page/4/Picture/2 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo features a stylized eagle or bird-like symbol with three curved lines forming its body and wings. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the bird symbol. The text is in all caps and is in a sans-serif font. Food and Drug Administration 2098 Gaither Road Rockville MD 20850 MAR 3 0 1998 Kenneth B. Asarch, Ph.D. Vice President Quality Systems and Regulatory Affairs Exigent Diagnostics Inc. 6100 Bristol Parkway Culver City, California 90230 K980043 Re : CareSide™ Creatinine Regulatory Class: II Product Code: JFY Dated: December 30, 1997 Received: January 6, 1998 Dear Dr. Asarch: We have reviewed your Section 510(k) notification of intent to market the device referenced above and we have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to 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). 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 (Premarket Approval), 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 895. A substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic QS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements Please note: concerning your device in the Federal Register. this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations . {5}------------------------------------------------ Paqe 2 This letter will allow you to begin marketing your device as described in your 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 advice for your device on our labeling requlation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its internet address "dsmo@fdadr.cdrh.fda.qov". Sincerely yours, Steven Autman Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health Enclosure {6}------------------------------------------------ Exigent Diagnostics, Inc. Page 15 CareSide™ Creatinine Promarket Notification Revised on March 23, 1998 # VII. Indications for Use - 510(k) Number: To be assigned CareSide™ Creatinine Device Name: For in vitro diagnostic use with Exigent Diagnostics CareSide Analyzer to Indications for use: measure creatinine in whole blood, plasma or serum specimens by professionals to aid in the diagnosis and treatment of renal diseases. (Division Sign-Off) Division of Clinical Laboratory Devices 510(k) Number K980043 /Prescription use