RAICHEM CO2 REAGENT

{0}------------------------------------------------ JUN 2 4 1998 K982056 Page 1 of 4 # CO2 XL Reagent # Special 510(k): Device Modification Summary #### Submitter's Name/Contact Person l. Melissa A. Saner/Manager ### Address Raichem Division of Hemagen Diagnostics Inc. # 2022395 Formerly: Reagents Applications, Inc. 8225 Mercury Court San Diego, CA 92129 Phone: 619-569-8009 Fax: 619-569-6208 ## Date Prepared June 1, 1998 #### ll. Device Name Trade Name: Common Name: Classification Name: Device Classification: Regulation Number: Panel: CO2 XL Reagent Carbon Dioxide Bicarbonate/carbon dioxide Test System ll 21 CFR 862.1160 Chemistry (75) CDT #### 111. Predicate (Cleared) Device CO2 Reagent: 510(k) Docket No. K854544 Manufactured By: Raichem Division of Hemagen Diagnostics Inc. (Reagents Applications, Inc.) Submitted Bv: Reagents Applications, Inc. #### IV. Description of Modified Device This reagent is intended for the quantitative in vitro enzymatic determination of CO2 in serum or plasma on manual or automated systems. The method used in the present procedure is based on the following reactions. Carbon dioxide, in the form of bicarbonate ions, reacts with phosphoenolpyruvate (PEP) to form oxaloacetate and phosphate. This reaction is catalyzed by the enzyme phosphoenolpyruvate carboxylase (PEPC). PEP + HCO3- - PERC > oxaloacetate + H2PO4 This reaction is coupled with a second enzymatic reaction. Oxaloacetate, in the presence of malate dehydrogenase (MDH), is converted to malate, by reduced nicotinamide adenine dinucleotide (NADH). In this reaction one molecule of NADH is oxidized for each molecule of oxaloacetate present. oxaloacetate + NADH + H - MDH > malate + NAD The decrease in absorbance resulting from the oxidation of NADH is proportional to the original concentration of CO2 in the sample. {1}------------------------------------------------ Raichem wishes to market an extended stability formulation modification of the predicate device. Slight variations in the concentrations of ingredients were made to achieve an extended reconstituted stability of one year at 2 to 8 °C. The assay procedure and timing of the assay is the same as that of the predicate device. #### Intended Use of Modified Device V. This reagent is intended for the quantitative in vitro enzymatic determination of CO₂ in serum or plasma on manual or automated systems. The measurement of serum or plasma CO2 content is useful in the assessment of disturbances of acid-base balance in respiratory or metabolic acidosis and alkalosis. #### VI. Substantial Equivalence # Modified Device This reagent is intended for the quantitative in vitro enzymatic determination of CO₂ in serum or plasma on manual or automated systems. The method used in the present procedure is based on the following reactions. Carbon dioxide, in the form of bicarbonate ions, reacts with phosphoenolpyruvate (PEP) to form oxaloacetate and phosphate. This reaction is catalyzed by the enzyme phosphoenolpyruvate carboxylase (PEPC). PEP + HCO3 - PEPC > oxaloacetate + H2PO4 This reaction is coupled with a second enzymatic reaction. Oxaloacetate, in the presence of malate dehydrogenase (MDH), is converted to malate, by reduced nicotinamide adenine dinucleotide (NADH). In this reaction one molecule of NADH is oxidized for each molecule of oxaloacetate present. oxaloacetate + NADH + H - MOR > malate + NAD The decrease in absorbance resulting from the oxidation of NADH is proportional to the original concentration of CO2 in the sample. # Predicate (Cleared) Device Raichem CO2 Reagent is intended for the quantitative in vitro enzymatic determination of CO2 content in serum or plasma. The following enzymatic reactions are involved in the assay: Carbon dioxide (in the form of bicarbonate ions) reacts with phosphoenolpyruvate (PEP) to form oxaloacetate and phosphate. This reaction is catalyzed by the enzyme phosphoenolpyruvate carboxylase (PEPC). PEP + HCO3 - PEPC > oxaloacetate + H2PO4 This reaction is coupled with another enzymatic reaction in which oxaloacetate, in the presence of malate dehydrogenase (MDH), is converted to malate, by reduced nicotinamide adenine dinucleotide (NADH). In this reaction one molecule of NADH is oxidized for each molecule of oxaloacetate present. oxaloacetate + NADH + H - MDH > malate + NAD The decrease in absorbance resulting from the oxidation of NADH is proportional to the original concentration of CO2 in the sample. # Summary The intended use and the fundamental scientific technology of the device remain the same. The CO2 XL Reagent (modified device) is substantially equivalent to the predicate (cleared) device. {2}------------------------------------------------ #### Performance Data VII. ### Precision ## Manual Assay | Within Run | | | |---------------|------|------| | Mean (mmol/L) | 15.7 | 23.2 | | SD | 0.7 | 0.4 | | CV (%) | 4.3 | 1.8 | | N | 10 | 10 | | Total | | | | Mean (mmol/L) | 15.3 | 23.2 | | SD | 0.9 | 0.5 | | CV (%) | 5.7 | 2.3 | | N | 20 | 20 | ### Hitachi 717 Precision studies were performed in 52 runs over a period of 26 days following the NCCLS EP5-T2 Tentative Guideline. | | ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ | | <br>Status C. Parcel<br>------<br><br>1.6 AMERICA | | |----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------|---------------------------------------------------|-------------------------------------------------------| | .<br>1<br>Monte<br>------------------------------------------------------------------------------------------------------------------------------------------------------------------------------<br>-----------<br>------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ | ------ | -------------<br>Acres Andrews A<br>LAND STATE<br>11 - 10 - 10 - 10 - 10 - 10 - | <br><br>Chicago | Section 4<br>Amount of the comments of the<br>------- | | ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------<br><br>------------------------------------------------------------------------------------------------------------------------------------------------------------------------------<br>----------------<br> | ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ | | | | | | | | 1 | | # Comparison Testing ### Comparison with Raichem CO2 Reagent (510(k) No. K854544) | Number of sample pairs | 65 | |-------------------------------------------------|-------------------| | Range of results (mmol/L): | 4 - 40 | | Correlation Coefficient : | 0.993 | | Regression Equation: | y = 0.988x + 0.43 | | Note: where x = CO2 Reagent, y = CO2 XL Reagent | | # Automated Method (Hitachi 717) Comparison with Raichem CO2 Reagent (510(k) No. K854544) on Hitachi 717 following the NCCLS EP9-A Approved Guideline | Number of sample pairs | 107 | |-------------------------------------------------|--------------------| | Range of results (mmol/L): | 7 - 46 | | Correlation Coefficient : | 0.998 | | Regression Equation: | y = 0.976x + 0.487 | | Note: where x = CO2 Reagent, y = CO2 XL Reagent | | # Interfering Substances Interference from bilirubin, hemolysis, and lipemia was evaluated in accordance with NCCLS EP7-P. Bilirubin: No significant interference observed up to 20 mg/dL of bilirubin. Hemolysis (Hemoglobin): No significant interference observed up to 500 mg/dL of hemoglobin. Lipemia: No significant interference observed up to 3000 mg/dL of triglycerides. {3}------------------------------------------------ # Summary The product performance has been evaluated by both manual and automated analyzer methods. The results of the comparative studies support the claim that the Raichem CO2 XL Reagent (modified device) is substantially equivalent to the predicate (cleared) device. The safety and effectiveness information upon which the substantial equivalence determination is based has been enclosed with this submission. This has been prepared in accordance with the requirements of the SMDA 1990 and 21 CFR Sections 807.87. {4}------------------------------------------------ ### DEPARTMENT OF HEALTH & HUMAN SERVICES Image /page/4/Picture/2 description: The image shows the logo for the Department of Health & Human Services - USA. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the top half of the circle. The bottom half of the circle contains a stylized image of an eagle. JUN 2 4 Food and Drug Administration 2098 Gaither Road Rockville MD 20850 Melissa A. Saner Manaqer RAICHEM Division of Hemagen Diagnostics 8225 Mercury Court San Diego, CA 92111 K982056 Re : Trade Name: CO2 XL Reagent Application Requlatory Class: II Product Code: CDT June 2, 1998 Dated: Received: June 9, 1998 Dear Ms. Saner: 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 acvice in babbantosure) 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 Requlations, 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. {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 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 at (301) 443-6597, or at its internet address "http://www.fda.gov/cdrh/dsmamain.html". Sincerely yours, Steven Butman Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health {6}------------------------------------------------ Device Name: CO2 XL Reagent Indication(s) For Use The use of this reagent is indicated for the measurement of CO2 levels in serum or plasma on manual or automated systems. The measurement of serum or plasma CO2 content is useful in the assessment of disturbance of acid base balance in respiratory or metabolic acidosis and alkalosis # (PLEASE DO NOT WRITE BELOW THIS LINE) Concurrence of CDRH, Office of Device Evaluation (ODE) Clive Xuri (Division Sign-Off) (Division of Clinical Laboratory Devices 1982056 510(k) Number. Prescription Use V (Per 21 CFR 801.109) OR Over-The-Counter-Use