SEKURE Creatine Kinase Assay

{0}------------------------------------------------ # Please wait... If this message is not eventually replaced by the proper contents of the document, your PDF viewer may not be able to display this type of document. You can upgrade to the latest version of Adobe Reader for Windows®, Mac, or Linux® by visiting http://www.adobe.com/go/reader_download. For more assistance with Adobe Reader visit http://www.adobe.com/go/acrreader. Windows is either a registered trademark of Microsoft Corporation in the United States and/or other countries. Mac is a trademark of Apple Inc., registered in the United States and other countries. Linux is the registered trademark of Linus Torvalds in the U.S. and other countries. {1}------------------------------------------------ This 510(k) Summary of Safety and Effectiveness is being submitted in accordance with the requirements of 21 CFR §807.92. This is a Traditional 510(k). K182702 The assigned 510(k) number: #### Applicant Information and Date [807.92 (a)(1)] | Applicant Name and Address: | SEKISUI DIAGNOSTICS P.E.I. INC.<br>70 Watts Avenue<br>Charlottetown, PE<br>Canada, C1E 2B9<br>Establishment Registration Number: 8020316 | |-----------------------------|------------------------------------------------------------------------------------------------------------------------------------------| | Application correspondent: | Jeanna MacLeod<br>Regulatory Affairs Specialist<br>902-628-0207<br>Jeanna.MacLeod@sekisui-dx.com | | Date Summary prepared: | April 10, 2019 | ## Device Name and Classification [807.92 (a)(2)] | Trade Name | Common Name | Classification Name | Classification | Product Code | |------------------------------|--------------------------------------|-------------------------------------------------------------------------|-----------------------------|--------------| | SEKURE Creatine Kinase Assay | Creatine Kinase Assay<br>or CK Assay | Creatine phosphokinase/<br>creatine kinase or<br>isoenzymes test system | Class II<br>21 CFR 862.1215 | CGS | #### Identification of Legally Marketed Predicate Devices [807.92 (a)(3)] | Predicate Device | Predicate 510(k) Number | |--------------------------|-------------------------| | Creatine Kinase-SL Assay | K973999 | {2}------------------------------------------------ # Device Description [807.92 (a)(4)] | Trade Name | Device Description | |-----------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | SEKURE<br>Creatine Kinase<br>Assay | The SEKURE Creatine Kinase Assay (CK Assay) is a spectrophotometric, coupled<br>enzyme assay for the quantitative measurement of creatine kinase (CK) activity.<br>The assay consists of two working reagents, a buffer solution (R1) and a substrate<br>reagent (R2). The SEKURE CK Assay employs the reverse reaction of CK, to<br>produce adenosine triphosphate (ATP). The reaction is coupled to hexokinase and<br>G6PDH which consumes ATP to generate NADPH. The rate of NADPH formation<br>is monitored at 340 nm and is directly proportional to CK activity.<br>Testing is performed on the SK500 in conjunction with calibrator and controls<br>which are provided separately. | | SK500 Clinical<br>Chemistry<br>Analyzer | The SK500 Analyzer is manufactured as Clinical Chemistry Analyzer Tokyo Boeki<br>Medisys Inc. Biolis 50i Superior. "SK500" is the Sekisui Diagnostics labelled name<br>for the Tokyo Boeki Medisys Inc. Biolis 50i Superior instrument. | # Intended Use [807.92 (a)(5)] For the in vitro quantitative measurement of creatine kinase activity in serum and plasma on the SK500 Clinical Chemistry System. Measurements of creatine kinase are used in the diagnosis and treatment of myocardial infarction and muscle diseases such as progressive, Duchenne-type muscular dystrophy. | | | | | Technological Similarities and Differences to the Predicate [807.92 (a)(6)] | |--|--|--|--|-----------------------------------------------------------------------------| |--|--|--|--|-----------------------------------------------------------------------------| | Characteristic | Predicate Device | New Device | |--------------------|--------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | Intended Use | Creatine Kinase-SL Assay<br>For the <i>in vitro</i> quantitative<br>measurement of creatine kinase activity<br>in serum. | SEKURE Creatine Kinase Assay<br>Similar<br>For the <i>in vitro</i> quantitative<br>measurement of creatine kinase activity<br>in serum and plasma on the SK500<br>Clinical Chemistry System. | | Platform | Hitachi 717 Analyzer (K953239) | SK500 Clinical Chemistry Analyzer | | Methodology | Colorimetric (NADPH), Enzymatic<br>(coupled hexokinase-G6PD) | SAME | | Specimen type | Serum | Similar<br>Serum and lithium heparin plasma | | Measuring interval | 2-1500 U/L | Similar<br>11-1500 U/L | {3}------------------------------------------------ # Summary of Non-Clinical Performance Data [807.92 (b)(1)] ## Precision Testing was conducted as per CLSI EP05-A3 using two lots of SEKURE CK reagents on one SK500 instrument. Two levels of sera controls, one level of pooled serum, and three levels of pooled plasma were assayed in duplicate in two runs per day for twenty (20) days. The CK activity data (U/L) are summarized in the following table. | Lot | Sample | N | Mean CK | Repeatability | | Within Laboratory | | |-------|------------------|----|---------|---------------|-----|-------------------|-----| | | | | (U/L) | SD | %CV | SD | %CV | | Lot 1 | Serum Control 1 | 80 | 145.3 | 1.6 | 1.1 | 2.5 | 1.7 | | | Serum Control 2 | 80 | 438.1 | 3.2 | 0.7 | 6.0 | 1.4 | | | Serum High Pool | 80 | 772.2 | 5.3 | 0.7 | 13.4 | 1.7 | | | Plasma Low Pool | 80 | 155.9 | 1.9 | 1.2 | 3.4 | 2.2 | | | Plasma Med Pool | 80 | 372.3 | 3.1 | 0.8 | 7.7 | 2.1 | | | Plasma High Pool | 80 | 576.5 | 3.4 | 0.6 | 20.0 | 3.5 | | Lot 2 | Serum Control 1 | 80 | 143.3 | 1.7 | 1.2 | 2.4 | 1.7 | | | Serum Control 2 | 80 | 436.9 | 3.3 | 0.8 | 5.3 | 1.2 | | | Serum High Pool | 80 | 773.9 | 4.8 | 0.6 | 13.8 | 1.8 | | | Plasma Low Pool | 80 | 153.5 | 2.0 | 1.3 | 3.3 | 2.1 | | | Plasma Med Pool | 80 | 370.6 | 2.6 | 0.7 | 7.2 | 1.9 | | | Plasma High Pool | 80 | 574.2 | 3.8 | 0.7 | 20.4 | 3.6 | Analytical Sensitivity # Limit of Blank (LoB) and Limit of Detection (LoD) Limit of Blank and Limit of Detection testing was based on guidance from the CLSI guidance document EP17-A2. Testing was completed by analyzing low level samples (saline blanks and dilutions of pooled serum or plasma in saline) in quadruplicate for three days producing a total of 60 measurements of each level. All samples were assayed on two lots of CK reagents and one SK500 analyzer. The LoB and LoD were determined individually for each reagent lot, dilution level, and matrix type; the maximal values are claimed for the SEKURE CK Assay. | Parameter | CK Activity | |-----------|-------------| | LoB | 3 U/L | | LoD | 5 U/L | {4}------------------------------------------------ # Limit of Quantitation (LoQ) Limit of Quantitation testing was based on guidance from the CLSI guidance document EP17-A2. Eight linear serum samples and eight linear plasma samples were assayed in five runs over three days to give 40 replicates. All samples were assayed on two lots of CK reagents and one SK500 analyzer. The LoQ was determined as the lowest CK value at which the %CV was determined individually for each reagent lot and each matrix type; the maximal value is claimed as the LoQ for the SEKURE CK Assay. The LoQ claimed is 11 U/L. # Linearity/Assay Reportable Range A linearity study was performed based on guidance from the CLSI guidance document EP06-A. Linearity testing for serum was conducted using eight dilutions of pooled serum to generate a CK activity range from 0 - 1650 U/L. Linearity testing for plasma was conducted using ten dilutions and admixtures of pooled plasma to generate a CK activity range from 3 - 2700 U/L. All samples were run in quadruplicate on two lots of SEKURE CK reagents and one SK500. The sample observed mean values were within ± 10% or ± 3 U/L of the sample theoretical values across all sample concentrations. The serum and plasma linearity data support the measuring range claim up to 1500 U/L for the SEKURE CK Assay. # Traceability, Stability, Expected Values (controls calibrators or methods) ## Value Assignment Calibration and control material are provided separately. Sekisui DC-Cal Multi-Analyte Calibrator (Cat. SE-035, Product Code JIX, 510(k) Exempt) and DC-Trol Multi-Analyte Controls (Parts SM-052 and SM-056. Product Code JJY, 510(k) Exempt) are recommended for use with the SEKURE Creatine Kinase Assay. The CK activity value assignment for DC-Cal is traceable to an IFCC reference method. ## Stability Product stability has been previously established as 18 months at 2-8°C. The product stability is verified by annual long-term stability testing conducted at half-expiry (9 months) and one-month past expiry (19 months). Onboard Stability of SEKURE CK on the SK500 analyzer was demonstrated to be 30 days. Calibration stability for CK using the DC-Cal Multi-Analyte calibrator on the SK500 was determined to be 30 days. ## Analytical Specificity An interference study was performed based on the CLSI EP07-A2 guideline to assess common or known substances that could interfere with the CK Assay. Interference testing was conducted using two lots of SEKURE CK reagents. All interferents were tested according to the paired difference method with CK activity levels of 180 and 415 U/L and a minimum of seven interferent concentrations in replicates of five on each reagent lot. Testing was performed using serum only, plasma data is expected to be similar. Significant interference was identified as a percent difference greater than 10% from control. {5}------------------------------------------------ | Potential Interferent | Highest Tested Concentration at which no significant<br>interference was observed | | | | |------------------------|-----------------------------------------------------------------------------------|-------------|--|--| | | Conventional Units | SI Units | | | | Conjugated Bilirubin | 40 mg/dL | 475 umol/L | | | | Unconjugated Bilirubin | 40 mg/dL | 684 umol/L | | | | Hemoglobin | 200 mg/dL | 31 umol/L | | | | Intralipid | 1000 mg/dL | 11.3 mmol/L | | | | Ascorbic Acid | 3 mg/dL | 170 umol/L | | | The interference study results are summarized in the following table: #### Summary of Method Comparison #### Method Comparison with Predicate Device Method comparison testing was conducted based on CLSI EP09-A3 on using two lots of SEKURE CK reagents on one SK500 instruments and two lots of SEKURE CK reagent on the Hitachi 717 (predicate). A set of 112 serum specimens were tested in duplicate over five or more operating days. The CK activity of the samples ranged from 23 to 1413 U/L. The regression was generated using first replicate data from the candidate method and mean sample values from the predicate method and is summarized in the following table. | Deming Regression | Lot 1 | Lot 2 | |-------------------------|--------|--------| | y Intercept (U/L) | 2.4 | 2.3 | | Correlation Coefficient | 0.9998 | 0.9997 | | Bias | -2.7% | -2.2% | | Slope | 0.964 | 0.970 | #### Matrix Comparison Matrix comparison testing was conducted to evaluate the suitability of lithium heparin with the SEKURE CK Assay on the SK500. A set of 75 matched serum and lithium heparin plasma specimens were assayed in duplicate using two lots of CK reagents on the SK500. The CK activity ranged from approximately 35 to 1500 U/L. The regression was generated using first replicate data from plasma and mean sample values from serum and is summarized in the following table. {6}------------------------------------------------ | Deming Regression | Lot 1 | Lot 2 | |-------------------------|--------|--------| | Slope | 1.013 | 1.015 | | y Intercept (U/L) | -1.8 | -3.4 | | Correlation Coefficient | 0.9991 | 0.9991 | | Mean Bias (%) | 0.9 | 0.7 | ## Clinical studies (clinical sensitivity, clinical specificity, other clinical supportive data) #### Not Applicable #### Expected values/Reference Range The IFU for the SEKURE CK Assay includes the following statement on reference intervals: Males: 46-171 U/L (37°C) Females: 34-145 U/L (37°C) (Rifai, N .; Horvath, A.R .; Wittwer, C., (Eds). Tietz Textbook of Clinical Chemistry and Molecular Diagnostics, Sixth Edition. Elsevier, St. Louis, Missouri (2018), p. 409-11) These values are suggested guidelines. It is recommended that each laboratory establish the normal range for the area in which it is located. ## Proposed Labeling The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10 #### Conclusion The submitted information in this premarket notification is complete and supports a substantial equivalence decision. {7}------------------------------------------------ Image /page/7/Picture/0 description: The image shows the logo for the U.S. Food & Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA logo on the right. The FDA logo is in blue and includes the letters "FDA" followed by the words "U.S. FOOD & DRUG ADMINISTRATION". April 17, 2019 SEKISUI DIAGNOSTICS P.E.I. INC. Jeanna MacLeod Regulatory Affairs Specialist 70 Watts Avenue Charlottetown, PEI C1E 2B9 Canada Re: K182702 Trade/Device Name: SEKURE Creatine Kinase Assay Regulation Number: 21 CFR 862.1215 Regulation Name: Creatine phosphokinase/creatine kinase or isoenzymes test system Regulatory Class: Class II Product Code: CGS Dated: March 20, 2019 Received: March 21, 2019 # Dear Jeanna MacLeod: We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above 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 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) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading. If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. 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 that FDA has made 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 comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part {8}------------------------------------------------ 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.html; good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm. For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100). Sincerely, for Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health Enclosure