CARESIDE TOTAL PROTEIN

{0}------------------------------------------------ EB 4 1998 Exigent Diagnostics, Inc. Page 13 CareSide™ Total Protein Premarket Notification revised on January 30, # CARESIDE™ TOTAL 510(K) SUMMARY: V. SAFETY AND EFFECTIVENESS Exigent Diagnostics, Inc. Kenneth B. Asarch, Pharm.D., Ph.D. Regulation Number: 21 CFR 862.1635 6100 Bristol Parkway 310-338-6767 310-338-6789 January 30, 1998 Culver City, CA 90230 asarchk@worldnet.att.net CareSide™ Total Protein Total Protein test system Clinical chemistry panel Total Protein test system Regulatory Class II None applicable Tier I ## Applicant Information ﻟﺴﻨﺔ - Applicant Name A. - Applicant/Manufacturer Address B. - Telephone Number C. - Contact Person D. - FAX Number E. - e-Mail Address ר. - Date 510(k) Summary prepared G. # 11. Device Information - Device Name (Trade) A. - Device Name (Classification) B. - Device Classification C. - Device Tier D. Special controls and E. performance standards ### Substantial Equivalence Claim 111. - 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. Total Protein in vitro diagnostic products, in both dry film and other formats, are already on the U.S. market including total protein products which utilize the biuret reaction (reaction of protein peptide bonds with cupric ion in alkaline environment). #### B. Specific equivalency claim This CareSide™ Albumin product is substantially equivalent in principle, intended use, and clinical performance to the currently marketed Vitros slides for the quantitative measurement of total protein on the Vitros DT 60 II. | Name of Predicate Device: | Johnson and Johnson's Vitros Total Protein Slides<br>(formerly Eastman Kodak, Inc.). | |-------------------------------|--------------------------------------------------------------------------------------| | Predicate Device 510K number: | K912844/A | | Product Code: | 75CEK | {1}------------------------------------------------ Exigent Diagnostics, Inc. Page 13a CareSide™ Total Protein Premarket Notification revised on January 30, 1998 #### Device Description IV. CareSide™ Total Protein cartridges are used with the Exigent Diagnostics CareSide™ Analyzer to measure total protein concentration in whole blood, plasma or serum specimens. The CareSide™ Total Protein cartridge, a single use disposable in vitro diagnostic test carridge, aids in specimen separation and delivers a measured volume of plasma or serum to a dry film to initiate the measurement of total protein concentration. The film cartridge (patent pending) contains all reagents necessary to measure total protein concentration. When used in conjunction with the CareSide™ Albumin cartidge on the CareSide™ Analyzer, the analyzer calculates globulin (as the difference between the total protein and albumin concentrations) and the albumin/globulin ratio (A/G ratio). # Explanation of Device Function A. Each Exigent Diagnostics CareSide™ Total Protein cartridge consists of a total protein specific multi-layer reagent film mounted in a plastic base with a hinged lid. The user introduces the whole blood, sorum, or plasma specimen into the carridge sample deposition well, closes the lid and inserts the cartridge into the Exigent Diagnostics CareSide™ Analyzer. Once loaded, the CareSide™ analyzer scans the cartridge barcode, brings the cartridge and the contained specimen to 37℃, and spins the cartridge to move the sample from the sample deposition well into the cartridge channels and chambers. As the carridge continues to spin, the blood cells are separated from the plasma/serum 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 scrum, as applicable) is automatically dispensed onto the multi-layer reagent film. The spreading and substrate layer distributes the sample evenly on the film and diffuses into the reagent layer where protein in the specimen reacts with copper ion in an alkaline environment to form a purple dye. # Test Reaction Sequence: Protein + Cupric ion -> purple dye As the carridges spin, photodiodes measure reflectance of light emitted by wavelengthspecific light emitting diodes (LEDs) at a fixed time. The analyzer uses the reflectance measurements and the lot-specific standard curve to calculate total protein concentration. #### B. Test Summary The majority of proteins found in the blood, except for immunoglobulins and protein hormones, are synthesized in the liver by hepatocytes and enter the bloodstream through the hepatic sinusoids. Functions of protein in the blood include maintenance of osmotic pressure, transport, defense, coagulation, fibrinolysis, buffering, and other special functions. The amount and proportions of blood proteins can be altered in some diseases. Severe hypoproteinemia (primarily albumin). < 6.0 g/dL, can be seen in dietary insufficiency, maldigestion, or malabsorption. Severe liver and renal disease such as glomerular nephritis, nephrotic syndrome, and severe proximal tubular disease can also cause decreased total protein levels. Edema can result in a fall in serunt or plasma protein levels ( . 4.0 g/dL). Hyperproteinemia ( 10 to 15% increase) can be a symptom in monoclonal gammopathies as well as in dehydration. {2}------------------------------------------------ Exigent Diagnostics, Inc. Page 13b CarcSide™ Total Protein Premarket Notification revised on January 30, 1998 # Intended Use V. # Intended Use A. The CareSide™ Total Protein product is intended for in vitro diagnostic use when used rice Careside™ Total Proceit processer » Analyzer to measure total protein concentration with the Exigunt Diagnostion serum specimens. When used in conjunction with the Exigent Diagnostics CareSide™ Albumin cartridge on the CareSide™ Analyzer, the total protein device may be used to calculate globulin concentration and albumin/globulin ratio from albumin and total protein results. The CareSide™ Total Protein test aids in the diagnosis and treatment of a varicty of diseases involving liver, kidney, or bone marrow as well as various metabolic or nutritional disorders. #### Indications for Use B. This product is indicated for use with patients with a variety of diseases involving liver, kidney, or bone marrow as well as various metabolic or nutritional disorders. # Technological Characteristics VI. #### Similarities A. | | CareSide™ Total Protein | Vitros TP DT Slides | |-------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------| | Intended Use | Primarily to aid in the diagnosis and treatment of a variety of diseases involving liver, kidney, or bone marrow as well as various metabolic or nutritional disorders. | Same | | Indications | For <i>in vitro</i> diagnostic use.<br>For professional use only. | Same | | Measurement | Quantitative | Same | | Reportable range | 2.0 to 11 g/dL | 2.0 to 11 g/dL | | Method Principle | Dry film based reaction of protein with cupric ion in an alkaline environment | Same | | Specimen dilution | Not required | Same | | Materials Source | Cupric sulfate (synthetic) | Cupric tartrate (synthetic) | | Detector | Reflectance (570 nm) | Reflectance (555 nm) | | Test time | Approximately 4 minute warm-up (on-board) plus 4 minute test time. | 15 minutes slide warm-up (off-line) plus 5 minutes test time. | | Reference Method | Biuret | Same | | Sample Type | Serum, plasma, whole blood (wb) [wb applied sample, plasma test sample] | serum, plasma | | Specimen volume | 10 μl test volume<br>(85 ± 15 μl applied volume) | 10 μl | | Calibration | Calibration information bar-coded on each cartridge.<br>Calibration information may change with each lot. | | | Quality Control | 2 levels | Same | | Reporting Units | g/dL or g/L | Same | | Reaction<br>temperature | 37 °C | Same | {3}------------------------------------------------ Exigent Diagnostics, Inc. Page 13c CareSide™ Total Protein Premarket Notification revised on January 30, 1998 # B. Differences | | CareSide™ Total Protein | Vitros TP DT Slides | |--------------------------|-------------------------|--------------------------------------------------------------------------| | Direct blood<br>specimen | Yes, whole blood | No, requires separation of<br>whole blood prior to sample<br>application | | Accurate<br>pipetting | Not required | Required | | Reagent pre-<br>warming | Not required | Required | # Comparative Performance Characteristics C. | | CareSide™ Total Protein | Vitros TP DT Slides | |------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------| | Detection limit | 2 g/dL | 2 g/dL | | Reportable range | 2.0 to 11 g/dL | 2.0 to 11 g/dL | | Accuracy | Mean recovery 105% | Not provided | | Precision | Total CV, 6.0 g/dL 7.2% | Total CV, 4.5 g/dL 2.5% | | Method<br>comparison | CareSide™ = 0.9 (Vitros Total Protein DT) + 0.56, r=0.93 | | | Lincarity | Mean deviation approx 1%,<br>r² ≥0.99 | Not provided | | Interference | No significant interference observed at tested concentration of interferent:<br>Ascorbic Acid, 20 mg/dL<br>Bilirubin, 20 mg/dL<br>Hemoglobin, 250 mg/dL<br>Triglycerides 1500 mg/dL | Not provided | | Specimen Types<br>& Anticoagulants | No clinically significant difference between heparinized whole blood, serum, heparin plasma, and EDTA plasma. | No clinically significant difference between serum and and heparin plasma. Whole blood is unsuitable. | | Expected Values | 6.3 to 8.4 g/dL<br>(combined male and female)<br>Central 95% interval | 6.3 to 8.2 g/dL<br>(combined male and female)<br>Central 95% interval | # D. Conclusion The nonclinical and clinical data provided demonstrate that the CareSide™ Total Protein I the hollenmour and entired. and performs as well as or better than the legally marketed predicate device. {4}------------------------------------------------ Image /page/4/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle with three tail feathers, representing the department's commitment to health, human services, and well-being. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" are arranged in a circular pattern around the eagle. Food and Drug Administration 2098 Gaither Road Rockville MD 20850 # FEB 4 1998 Kenneth B. Asarch, Ph.D. . VP Quality Systems and Regulatory Affairs Exigent Diagnostics Inc. 6100 Bristol Parkway Culver City, California 90230 K980042 Re : CareSide™ Total Protein Regulatory Class: II Product Code: CEK December 30, 1997 Dated: 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 The general controls provisions of the Act 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 In addition, FDA may publish further announcements action. concerning your device in the Federal Reqister. 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. {5}------------------------------------------------ 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 The FDA described in your 510 (k) premarket notification. 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 diaqnostic 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 "http://www.fda.gov/cdrh/dsmamain.html". Sincerely yours, Steven Litman 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 # VII. INDICATIONS FOR USE 510(k) Number: To be assigned CareSide Total Protein Device Name: Indications for use: For in vitro diagnostic use with Exigent Diagnostics CareSide™ Analyzer to measure total protein from whole blood, heparinized plasma or serum specimens by professionals to aid in the diagnosis and treatment of a variety of diseases involving the liver, kidney, or bone marrow as well as other metabolic or nutritional disorders. y (Division Sign-Off) Division of Clinical 510(k) Number