CARESIDE CK

{0}------------------------------------------------ 4/19/99 **CARESIDE, Inc.** Page 10 # 510(K) SUMMARY: CARESIDE™ CK SAFETY AND IV. EFFECTIVENESS ### I. Applicant Information - A. Applicant Name - Applicant/Manufacturer Address B. - C. Telephone Number - D. Contact Person - E. FAX Number - F. e-Mail Address - Date 510(k) Summary prepared G. ### II. Device Information - A. Device Name (Trade) - Device Name (Classification) B. - C. Device Classification # CARESIDE, Inc. 6100 Bristol Parkway Culver City, CA 90230 310-338-6767 Kenneth B. Asarch, Pharm.D., Ph.D. 310-338-6789 AsarchK@CARESIDE.com January 29, 1999 # CARESIDE™ CK Creatine phosphokinase/creatine kinase or isoenzymes test system Clinical chemistry panel CK test system Regulation Number: 21 CFR 862.1215 Regulatory Class II Classification Number: 75JFX None applicable - D. Special controls and performance standards ### III. Substantial Equivalence Claim - General equivalency claim A. 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. CK in vitro diagnostic products, in both dry film and other formats, are already on the U.S. market, including CK products that utilize enzymatic coupling to convert the reaction product, ATP, to a colored dye. ### B. Specific equivalency claim This CARESIDE™ CK test is substantially equivalent in principle, intended use, and clinical performance to the currently marketed Vitros slides for the quantitative measurement of CK for use on the Vitros DTSC module of the Vitros DT II system. | Name of Predicate Device: | Johnson and Johnson's (formerly Eastman Kodak, Inc.) Vitros CK DT Slides for use on the<br>Vitros DTSC module of the Virtos DT II system<br>(formerly Eastman Kodak's DT 60 II). | |-------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | Predicate Device 510K number: | K912844/A | | Product Code: | 75JFX | {1}------------------------------------------------ ### IV. Device Description CARESIDE™ CK cartridges are used with the CARESIDE, Inc. CARESIDE Analyzer™ to The CARESIDE™ CK measure CK activity in whole blood, serum or plasma specimens. cartridge, a single use disposable in vitro diagnostic test cartridge, delivers a measured volume of serum or plasma to a dry film to initiate the measurement of CK activity. The film cartidge (patent pending) contains all reagents necessary to measure CK activity. #### Explanation of Device Function A. Fach CARESIDE™ CK cartridge consists of a CK-specific multi-layer reagent film mounted in a plastic base with a hinged lid. The user introduces the specimen into the cartridge sample deposition well, closes the lid and inserts the cartridge into the 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. 8.5 µL microliters of sample remains in the metering passage. Any excess sample flows into an overflow well. The sample is automatically dispensed onto the multi-layer reagent film. The spreading and substrate layer distributes the specimen which in turn catalyzes the reaction of creatine phosphate with ADP to form creatine and ATP. In the reagent layer, glucose-6phosphate (G-6-P) is formed by the hexokinase catalyzed reaction of glucose with ATP. G-6-P then reduces NAD+ to NADH in a glucose 6-phosphate dehydrogenase (G6PDH) catalyzed reaction. NADH then reduces NTB to diformazan dye in a diaphorase catalyzed reaction. The color intensity of the resulting reddish dye, as measured by the amount of reflected light at 570 nanometers directly relates to the CK activity of the specimen. ## Test Reaction Sequence: Creatine phosphate + ADP - CPK -> Creatine + ATP Hexokinase > ADP + G-6-P ATP + Glucose Mg+2 G-6-P + NAD* -- Gepul-> 6-phosphogluconic acid + NADH + H* NTB + NADH -- Diaphorase > Diformazan dye + NAD* As the cartridges spin, a photodiode measures reflectance of light emitted by a wavelength-specific light emitting diode (LED) over a fixed time period. The analyzer uses the reflectance measurements and the lot-specific standard curve to calculate CK activity. {2}------------------------------------------------ ### B. Test Summary Creatine kinase (CK), also known as creatine phosphokinase, is an enzyme consisting of two sub-units (termed B and M) that catalyzes the reversible phosphorylation of creatine by adenosine-triphosphate (ATP) to creatine phosphate and adenosine-diphosphate (ADP). Only the CK dimer has enzymatic activity. Thus, total active CK is the combination of CKBB, CKMB and CKMM isoenzymes. These are also referred to as CK-1, CK-2 and CK-3 respectively, according to their differential mobility on an electrophoretic gel. CK is distributed in various organs; the highest activities are found in skeletal muscle, heart, and brain. Considerably lower activities are present in the urinary bladder, stomach, ileum, colon, and uterus. The CK content of liver, erythrocytes, and kidney is less that 1% of the amount found in skeletal muscle. Measurement of total CK activity is important in the diagnosis of cardiac and skeletomuscular disorders, and is increased after muscle trauma, intramuscular injections, exercise, and in other conditions. CK level is also increased after acute alcohol intoxication, surgery-induced muscle injury, drug overdoses and poisoning, trauma to muscle or brain, hypothermia, hyperthermia, Reye's syndrome, infectious diseases, and hypothyroidism. Abnormal CK activities have been described in all forms of muscular dystrophy as well as polymyositis, dermatomyositis, and other myopathies. Many non-affected carriers of muscular dystrophy have abnormal CK activity in the blood. which provides a method for identifying such carriers. ### V. Intended Use - A. Intended Use The CARESIDE™ CK cartridge is intended for in vitro diagnostic use in conjunction with the CARESIDE Analyzer™ to quantitatively measure CK activity in whole blood, serum or plasma. #### B. Indications for Use For in vitro diagnostic use with the CARESIDE Analyzer™ to quantitatively measure CK activity from anti-coagulated whole blood, plasma, or serum specimens to aid in the diagnosis and treatment of patients with myocardial infarction and muscle diseases such as progressive, Duchenne-type muscular dystrophy. It is intended professional laboratory use: not for point of care or physician office laboratory use. {3}------------------------------------------------ - ## VI. Technological Characteristics - A. Similarities | | CARESIDE™ CK | Vitros CK DT Slides | |-------------------|------------------------------------------------------------------|----------------------------------------------------------| | Intended Use | Primarily to aid in the diagnosis | Diagnosis of skeletal muscle | | | and treatment of patients with | disease, myocardial infarction, | | | with myocardial infarction | and cerebrovascular accidents. | | | and muscle diseases such as | | | | progressive, Duchenne-type | | | | muscular dystrophy. | | | Indications | For in vitro diagnostic use. | For in vitro diagnostic use | | | For professional laboratory: | | | | for point of care or<br>not | | | | physician office laboratory use. | | | Measurement | Quantitative | Same | | Method Principle | Reflectometry of enzymatically<br>coupled production of dye from | Same | | | CK reaction product. | | | Specimen dilution | Not required | Same | | | | | | Materials | Creatine phosphate, | Glycerophosphate oxidase,<br>peroxidase, gycerol kinase, | | | nitrotetrazorium blue, ADP, | creatine phosphate, | | | glucose, hexokinase, glucose- | N-acetylsysteine, magnesium | | | 6-phosphate dehydrogenase | acetate, glycerol, ADP. | | | (G6PDH), NAD*, diaphorase<br>Reflectance (570 nm) | | | Detector | | Reflectance (680 nm) | | Test time | Approximately<br>4-minute<br>warm-up (on-board)<br>plus | 15 minutes slide warm-up | | | 4 minute test time. | (off-line) plus 5 minutes test<br>time. | | Sample Type | Anti-coagulated<br>whole blood, | Plasma or serum | | | plasma, or serum | | | Specimen volume | 8.5 ul test volume | 10 µl | | | (85 ± 15 ul applied volume) | | | Calibration | Calibration<br>information | Run Vitros DT II calibrators | | | bar-coded on each cartridge. | whenever a new slide lot is | | | Calibration information<br>may | used or when necessary. | | | change with each lot. | | | Quality Control | 2 levels | Same | | Reporting Units | U/L | Same | | Reaction Temp. | 37°C | Same | ### B. Differences | | CARESIDE™ CK | Vitros CK DT Slides | |------------------------|--------------|---------------------| | Accurate<br>pipetting | Not required | Required | | Reagent<br>pre-warming | Not required | Required | {4}------------------------------------------------ -- -- : ・・・ ## C. Comparative Performance Characteristics | | CARESIDE™ CK | Vitros CK DT Slides | |----------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------| | Detection limit | 20 U/L | 20 U/L | | Reportable range | 20 to 1600 U/L | 20 to 1600 U/L | | Accuracy | Mean recovery 101% | Not provided | | Precision | Total CV, 168 U/L, 10% | Total CV, 175 U/L, 3% | | Reference Method | Kinetic determination with<br>enzymatically coupled<br>spectrophotometric detection of<br>creatine. | Not provided | | Method<br>comparison | CARESIDE™ CK = 1.03 (Trace) – 22.4 U/L, r = 0.98 | | | Linearity | Linearity yielded slope and<br>correlation coefficient within<br>acceptable limits. | Not provided | | Interference | No significant interference<br>observed at tested<br>concentration of interferent:<br>Ascorbic Acid, 10 mg/dL<br>Bilirubin, 20 mg/dL<br>Triglycerides 2000 mg/dL | Elevated carbon dioxide<br>(> 40mmol/L) may decrease<br>CK results. | D. Conclusion > The nonclinical and clinical data provided demonstrate that the CARESIDE™ CK product is as safe, effective, and performs as well as or better than the legally marketed predicate device. {5}------------------------------------------------ Image /page/5/Picture/1 description: The image is a black and white logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle with three lines forming its body and wings. The eagle is enclosed within a circle, and the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged around the upper half of the circle. Public Health Service APR 1 9 1995 Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850 Kenneth B. Asarch, Pharm. D., Ph.D. Vice President, Quality Systems/ Regulatory Affairs Careside Inc. 6100 Bristol Parkway Culver City, California 90230 K990439 Re: Trade Name: CARESIDE™ CK Regulatory Class: II Product Code: JHS Dated: January 29, 1999 Received: February 11, 1999 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 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). 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 concerning your device in the Federal Register. Please note: 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. {6}------------------------------------------------ Page 2 Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770) 488-7655. 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 regulation (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 premarket notification"(21 CFR 807.97). 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 "http://www.fda.gov/cdrl/dsma/dsmamain.html". Sincerely yours, Steven Dutman 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 {7}------------------------------------------------ CARESIDE, Inc. Page 16 ## INDICATIONS FOR USE VI. 510(k) Number: Device Name: K 990439 CARESIDE™ CK Indications for use: For in vitro diagnostic use with the CARESIDE Analyzer™ to quantitatively measure CK from anti-coagulated whole blood, plasma, or serum specimens to aid in the diagnosis and treatment of patients with myocardial infarction and muscle diseases such as progressive, Duchenne-type muscular dystrophy. Sean Cooper (Division Sign-Off) Division of Clinical Laboratory Devices K99 0439 510(k) Number (PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED) Concurrence of CDRH, Office of Device Evaluation (ODE) Prescription Use (Per 21 CFR 801.109) OR Over-The-Counter Use (Optional Format 1-2-96)