Who is the manufacturer of Creatine Kinase?

Roche Diagnostics Operations (Rdo) filed the 510(k) submission for Creatine Kinase (K160570).

What is the FDA product code for Creatine Kinase?

JHS. It is classified under 21 CFR 862.1215 as a Class 2 device in the Clinical Chemistry panel.

What is the regulatory pathway for Creatine Kinase?

510(k) clearance (submission type: Traditional).

What are the predicate devices for Creatine Kinase?

COBAS INTEGRA Creatine Kinase (k951595).

Who can help prepare an FDA 510(k) submission like Creatine Kinase?

Innolitics — a medical-device software consultancy — provides regulatory and engineering support for FDA 510(k) submissions. See https://innolitics.com/services/510ks/ or contact https://innolitics.com/contact.

Creatine Kinase

K160570 · Roche Diagnostics Operations (Rdo) · JHS · May 25, 2016 · Clinical Chemistry

Device Facts

Record ID	K160570
Device Name	Creatine Kinase
Applicant	Roche Diagnostics Operations (Rdo)
Product Code	JHS · Clinical Chemistry
Decision Date	May 25, 2016
Decision	SESE
Submission Type	Traditional
Regulation	21 CFR 862.1215
Device Class	Class 2

Intended Use

Creatine kinase is an in vitro test for the quantitative determination of creatine kinase (CK) in human serum and plasma on Roche/Hitachi cobas c systems. The determination of CK and CK isoenzyme activities is utilized in the diagnosis and monitoring of myocardial infarction and myopathies such as the progressive Duchenne muscular dystrophy.

Device Story

Creatine Kinase assay; two-reagent (R1/R2) system for automated clinical chemistry analyzers (Roche/Hitachi cobas c 501). Input: human serum or plasma samples. Principle: CK activated by N-acetylcysteine catalyzes dephosphorylation of creatine phosphate; coupled reaction with hexokinase and G6PDH produces NADPH; photometric measurement of NADPH formation at 340nm/546nm proportional to CK activity. Used in clinical laboratories by trained personnel. Output: quantitative CK activity (U/L). Results assist clinicians in diagnosing/monitoring myocardial infarction and myopathies. Benefits: standardized, automated, high-throughput measurement of muscle/cardiac damage markers.

Clinical Evidence

Bench testing only. Precision evaluated per CLSI EP5-A2 (n=84 per pool, CVs 0.4-3.2%). Linearity confirmed 7-2000 U/L (R2 > 0.999). Detection limits (LoB/LoD/LoQ) established at 7 U/L. Interference testing performed for endogenous substances (hemolysis, lipemia, bilirubin) and common drugs; Cyanokit interference noted. Method comparison (n=132) against predicate showed high correlation (y = 1.021x + 5.88, r = 0.999). Matrix comparison (serum vs. plasma) showed equivalence.

Technological Characteristics

UV enzymatic assay; two-reagent system. Reagents include Imidazole buffer, NAC, HK, G6PDH, NADP+, and creatine phosphate. Sensing principle: photometric absorbance increase at 340nm/546nm. Form factor: liquid reagents for automated clinical chemistry analyzers (cobas c 501). Standardized against IFCC method. Connectivity: integrated with Roche/Hitachi cobas c systems.

Indications for Use

Indicated for quantitative determination of creatine kinase (CK) in human serum and plasma to aid in diagnosis and monitoring of myocardial infarction and myopathies, including Duchenne muscular dystrophy.

Regulatory Classification

Identification

A creatine phosphokinase/creatine kinase or isoenzymes test system is a device intended to measure the activity of the enzyme creatine phosphokinase or its isoenzymes (a group of enzymes with similar biological activity) in plasma and serum. Measurements of creatine phosphokinase and its isoenzymes are used in the diagnosis and treatment of myocardial infarction and muscle diseases such as progressive, Duchenne-type muscular dystrophy.

Predicate Devices

COBAS INTEGRA Creatine Kinase (k951595)

Related Devices

K983070 — CK · Abbott Laboratories · Feb 16, 1999
K981218 — CREATINE KINASE (CK) · Abbott Laboratories · May 1, 1998
K021332 — WIENER LAB. CK-NAC UV UNITEST, WIENER LAB. CK-NAC UV AA, WIENER LAB. CK-NAC UV AA, WIENER LAB.NAC UV AA LIQUIDA · Wiener Laboratories Saic · Jul 3, 2002

Submission Summary (Full Text)

{0}------------------------------------------------ Image /page/0/Picture/1 description: The image is a black and white logo for the U.S. Department of Health & Human Services. The logo features the department's symbol, which consists of three stylized human profiles facing to the right, arranged in a cascading manner. The symbol is encircled by the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" in a circular arrangement. Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002 May 25, 2016 ROCHE DIAGNOSTICS OPERATIONS (RDO) NOEL MENCIAS REGULATORY AFFAIRS CONSULTANT 9115 HAGUE ROAD INDIANAPOLIS MD 46250 Re: K160570 Trade/Device Name: Creatine Kinase Regulation Number: 21 CFR 862.1215 Regulation Name: Creatine phosphokinase/creatine kinase or isoenzymes test system Regulatory Class: II Product Code: JHS Dated: February 26, 2016 Received: February 29, 2016 Dear Noel Mencias: 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. 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 Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050. {1}------------------------------------------------ If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. 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 the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance. You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. Sincerely yours. # Katherine Serrano -S 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 {2}------------------------------------------------ # Indications for Use 510(k) Number (if known) k160570 Device Name Creatine Kinase Indications for Use (Describe) Creatine Kinase is an in vitro test for the quantitative determination of creatine kinase (CK) in human serum and plasma on Roche/Hitachi cobas c systems. The determination of CK and CK isoenzyme activities is utilized in the diagnosis and monitoring of myocardial infarction and myopathies such as the progressive Duchenne muscular dystrophy. Type of Use (Select one or both, as applicable) | <div> <svg fill="none" height="16" viewbox="0 0 16 16" width="16" xmlns="http://www.w3.org/2000/svg"> <path d="M14.9414 2.94141L2.94141 14.9414M14.9414 14.9414L2.94141 2.94141" stroke="black" stroke-linecap="round" stroke-linejoin="round" stroke-width="1.5"></path> </svg> Prescription Use (Part 21 CFR 801 Subpart D) </div> | |--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | <div> <svg fill="none" height="16" viewbox="0 0 16 16" width="16" xmlns="http://www.w3.org/2000/svg"> <rect height="15" rx="1.5" stroke="black" width="15" x="0.5" y="0.5"></rect> </svg> Over-The-Counter Use (21 CFR 801 Subpart C) </div> | ## CONTINUE ON A SEPARATE PAGE IF NEEDED. This section applies only to requirements of the Paperwork Reduction Act of 1995. ### *DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.* The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to: > Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov "An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number." {3}------------------------------------------------ # 510(k) Summary This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of 21 CFR 807.92. | Submitter Name | Roche Diagnostics Operations (RDO) | |----------------------------|------------------------------------------------------------------| | Address | 9115 Hague Road | | | Indianapolis, IN, 46250, USA | | | Noel B. Mencias | | Contact | Phone: (317) 521-3172 | | | FAX: (317) 521-2324 | | | Email: noel.mencias@roche.com | | Date Prepared | February 26, 2016 | | Proprietary Name | Creatine Kinase | | Common Name | Creatine Kinase | | Classification Name | Creatine phosphokinase/creatine kinase or isoenzymes test system | | Product Codes | JHS, 21 CFR § 862.1215 | | Predicate Devices | Creatine Kinase, K951595 | | Establishment Registration | 1823260, Roche Diagnostics Corporation | {4}------------------------------------------------ #### 1. DEVICE DESCRIPTION The Creatine Kinase assay is a two reagent assay for the quantitative determination of creatine kinase (CK) in human serum and plasma on automated clinical chemistry analyzers. Photometrically measured NAPDP formation is directly proportional to CK activity in a human sample. #### 2. INDICATIONS FOR USE Creatine Kinase is an in vitro test for the quantitative determination of creatine kinase (CK) in human serum and plasma on Roche/Hitachi cobas c systems. The determination of CK and CK isoenzyme activities is utilized in the diagnosis and monitoring of myocardial infarction and myopathies such as the progressive Duchenne muscular dystrophy. Measurements of creatine phosphokinase and its isoenzymes are used in the diagnosis and treatment of myocardial infarction and muscle diseases such as progressive, Duchenne-type muscular dystrophy. #### TECHNOLOGICAL CHARACTERISTICS 3. The Creatine Kinase assay is a UV test for the quantitative determination of creatine kinase (CK) in human serum and plasma on Roche/Hitachi cobas c systems. The CK is activated by Nacetylcysteine (NAC). In a primary reaction, the activated CK catalyzes the dephosphorylation of creatine phosphate. In a coupled reaction, catalyzed by hexokinase (HK), glucose is phoshorylated by the ATP formed in the primary reaction to form D-glucose-6-phosphate (G6P). Finally D-glucose-6-phosphate dehydrogenase (G6PDH) catalyzes the oxidation of G6P by NADP to form D-6-phosphogluconate and NADPH. The rate of NADPH formation is directly proportional to catalytic CK activity. It is determined by measuring the increase in absorbance at 340nm (main) and 546nm (sub). Roche Diagnostics claims substantial equivalence to COBAS INTEGRA Creatine Kinase cleared in K951595 on the COBAS INTEGRA analyzer. The reagent was applied to cobas c 501 (c 501) following the 2003 FDA Policy document "Replacement Reagent and instrument family Policy." A comparison of the similarities and differences between the candidate device and the {5}------------------------------------------------ predicate device is provided in the following table. There are no prior submissions for the candidate device. | Assay Comparison Similarities | | | | |---------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--| | Feature | Predicate Device: COBAS INTEGRA Creatine Kinase (K951595) | Candidate Device: Creatine Kinase | | | Intended Use | The COBAS INTEGRA Creatine Kinase (CK) contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative determination of the catalytic activity of CK (EC 2.7.3.2: adenosine triphosphate: creatine N- phosphotransferase) in serum and plasma (test CKL, 0-039). | In vitro test for the quantitative determination of creatine kinase (CK) in human serum and plasma on Roche/Hitachi cobas c systems. | | | Sample Types | Serum and plasma, free from hemolysis. Acceptable anticoagulants are heparin and EDTA. | Serum: Non hemolyzed serum is the specimen of choice and also recommended by IFCC. Plasma: Li-Heparin, K2-, K3-EDTA. | | | Test Principle | The CK is activated by N-acetylcysteine (NAC). In a primary reaction the activated CK catalyzes the dephosphorylation of creatine phosphate. In a coupled reaction catalyzed by hexokinase (HK) glucose is phoshorylated by the ATP formed in the primary reaction to form D-glucose-6- phosphate (G6P). Finally D-glucose-6- phosphate dehydrogenase (G6PDH) catalyzes the oxidation of G6P by NADP to form D-6-phosphogluconate and NADPH. The rate of NADPH formation is directly proportional to catalytic CK activity. It is determined by measuring the increase in absorbance at 340nm. | The CK is activated by N-acetylcysteine (NAC). In a primary reaction the activated CK catalyzes the dephosphorylation of creatine phosphate. In a coupled reaction catalyzed by hexokinase (HK) glucose is phoshorylated by the ATP formed in the primary reaction to form D-glucose-6- phosphate (G6P). Finally D-glucose-6- phosphate dehydrogenase (G6PDH) catalyzes the oxidation of G6P by NADP to form D-6-phosphogluconate and NADPH. The rate of NADPH formation is directly proportional to catalytic CK activity. It is determined by measuring the increase in absorbance at 340nm (main) and 546nm (sub). | | | Reagent Shelf Life Stability | + 2 to +8 ℃ until expiration date | 2-8 ℃ until expiration date | | | Reagent On-Board Stability | On-board in use at +8ºC: 4 weeks | On-board in use and refrigerated on the analyzer: 8 weeks | | | Table 1: | Substantial Equivalence – Assay Similarities | | | | |----------|----------------------------------------------|--|--|--| |----------|----------------------------------------------|--|--|--| {6}------------------------------------------------ | Assay Comparison Similarities | | | |--------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | Feature | Predicate Device: COBAS INTEGRA Creatine Kinase (K951595) | Candidate Device: Creatine Kinase | | Sample Stability | CK activity in serum remains stable for 24h at +22 °C or 10 days at +4 °C and -20 °C. | Stability in serum: 2 days at 20-25 °C 7 days at 4-8 °C 4 weeks at -20 °C Stability in EDTA/heparin plasma: 2 days at 15-25 °C 7 days at 2-8 °C 4 weeks at (-15)-(-25) °C | | Measuring Range | 0 - 2000 U/L (0 -33.4 µkat/L) | 7 - 2000 U/L (0.12-33.4 µkat/L) | | Traceability | Traceable to IFCC | This method has been standardized against the IFCC Method for Creatine Kinase | | Calibrator | Calibrator (human) | Calibrator for automated systems (C.f.a.s.) (k101456) | | Calibration frequency | Each lot | After reagent lot change and as required following quality control procedures | | Controls | Control Serum N (human) Control Serum P (human) | Precinorm U plus/Precipath U Plus (k042389) Precinorm CK-MB/Precipath CK-MB (k062972) PreciControl ClinChem Multi 1 and 2 (k102016) | | Lower Limits of Measurement | LDL = 0 U/L | LoB = 7 U/L (0.12 µkat/L) LoD = 7 U/L (0.12 µkat/L) LoQ = 7 U/L (0.12 µkat/L) | | Reagent Composition | 3 Reagents R1 liquid, and R2 and SR granulates R1: Buffer in vial A (15.8 mL). R2: Enzyme granulate in vial B (0.5 g for 12.3 mL). R3 = SR: Creatine phosphate granulate in vial C (0.7 g for 5 mL). | 2 Reagents R1 Imidazole buffer: 123 mmol/L, pH 6.5 (37 °C); EDTA: 2.46 mmol/L; Mg2+: 12.3 mmol/L; ADP: 2.46 mmol/L; AMP: 6.14 mmol/L; diadenosine pentaphosphate: 19 µmol/L; NADP+ (yeast): 2.46 mmol/L; N- acetylcysteine: 24.6 mmol/L; HK (yeast): ≥ 36.7 µkat/L; G6PDH (E. coli): ≥ 23.4 µkat/L; preservative; stabilizers; additives. R2 CAPSO* buffer: 20 mmol/L, pH 8.8 (37 °C); glucose: 120 mmol/L; EDTA: 2.46 mmol/L; creatine phosphate: 184 mmol/L; preservative; stabilizers. *CAPSO:3(-cyclohexylamine)-2-hydroxy- 1-propanesulfonic acid | {7}------------------------------------------------ {8}------------------------------------------------ #### NON-CLINICAL PERFORMANCE EVALUATION 4. The following performance data were provided in support of the substantial equivalence determination: Detection Limitaccording to CLSI EP17-A2 Precision according to CLSI EP5-A2 Linearity according to CLSI EP6-A Matrix Comparison - Anticoagulants Interferences- H, L and I Indices Interference - Drugs Method Comparison to Predicate All performance specifications were met. Cyanokit (Hydroxocobalamin) at therapeutic concentrations was found to interfere with the test. #### 4.1. Detection Limits according to CLSI EP17-A2 LoB, LoD, and LoQ studies were performed based upon CLSI EP17-A2. LoB: The concentration at which there is a 95% probability that a sample is analyte-free. For determination of LoB one analyte free sample was measured with three lots in 10-fold determination in 6 runs, distributed over 3 days, on one c 501 analyzer. In total, 60 measurements were obtained per lot. Data analysis is based on determination of the 95th percentile of the 60 measured values. LoD: Defined as the concentration, at which there is a 95% probability that a sample contains analyte. For determination of LoD five samples with low-analyte concentration (approximately up to 4 times the LoB) will be measured with three lots in two-fold determination in 6 runs, distributed over 3 days, on one c 501 analyzer. In total 60 measurements will be obtained per lot. {9}------------------------------------------------ LoO: The lowest analyte concentration that can be quantitatively determined with a stated acceptable precision and trueness under stated experimental conditions. A low Level Sample Set was prepared by diluting 5 human serum samples with an analyte free diluent (0.9% NaCl). The Low level Sample Set was tested in 5 replicates per sample on 5 days, one run per day on one cobas c 501 analyzer LoB and LoD Results Table 2: | | Result (U/L) | Claim (U/L) | |-----------------------------|--------------|-------------| | Limit of Blank (LoB) | 0.3 | 7 | | Limit of Detection (LoD) | 1.0 | 7 | | Limit of Quantitation (LoQ) | 3.3 | 7 | #### Precision according to CLSI EP5-A2 4.2. Precision experiments are performed in accordance with CLSI Guideline EP5-A2. Two aliquots per run, two runs per day for ≥ 21 days were performed on the same analyzer using 3 lots of reagent. Repeatability (within run precision) and intermediate precision (within lab precision) were calculated. The samples were randomized in each run separately. For each sample, the following are calculated: mean, repeatability and intermediate precision as CV and SD values, and the upper 95% confidence interval for SD and CV values. | Specimen | Mean (U/L) | SD (U/L) | CV (%) | |--------------------------------|------------|----------|--------| | Human Serum 1 | 18.7 | 0.6 | 3.0 | | Human Serum 2 | 137 | 0.8 | 0.6 | | Human Serum 3 | 477 | 3.0 | 0.6 | | Human Serum 4 | 946 | 5.3 | 0.6 | | Human Serum 5 | 1816 | 9.4 | 0.5 | | PreciControl ClinChem Multi 1 | 154 | 0.9 | 0.6 | | PreciControl ClinChem Multi 2 | 301 | 1.3 | 0.4 | #### Table 3: Repeatability Summary {10}------------------------------------------------ | Specimen | Mean (U/L) | SD (U/L) | CV (%) | |-------------------------------|------------|----------|--------| | Human Serum 1 | 18.7 | 0.6 | 3.2 | | Human Serum 2 | 137 | 1.1 | 0.8 | | Human Serum 3 | 477 | 3.1 | 0.6 | | Human Serum 4 | 946 | 5.8 | 0.6 | | Human Serum 5 | 1816 | 10 | 0.6 | | PreciControl ClinChem Multi 1 | 154 | 1.7 | 1.1 | | PreciControl ClinChem Multi 2 | 301 | 2.6 | 0.9 | Table 4: Intermediate Precision Summary #### Linearity according to CLSI EP6-A 4.3. Linearity was assessed according to CLSI EP6-A with one batch of reagent, in one run, and with samples measured in triplicate. Two separate dilution series differing by sample type (serum and plasma) were prepared with 14 concentrations. Dilutions were made using 0.9% NaCl. In a first step, a linearity check was performed with first order (linear) regression and then with higher order models (quadratic and cubic). The linear regression was not forced through the origin. The linear regression was weighted. | Table 5: | Linearity results | | |----------|-------------------|--| |----------|-------------------|--| | Sample type | Linear Regression | |-------------|--------------------------------------------------------------| | Serum | y=1.001x-0.646 Pearson correlation coefficient (R)=0.9999 | | Plasma | y=1.002x-1.205 Pearson correlation coefficient (R)=0.9999 | #### Matrix Comparison - Anticoagulants 4.4. The effect of the presence of anticoagulants on analyte recovery was determined by method comparison, obtained from samples drawn into serum and different types of plasma collection tubes (K2 EDTA, K3 EDTA, Li Heparin, and Gel Separation). For each of the four tube types, 30 tubs were filled completely. {11}------------------------------------------------ Method comparison was executed by using the serum data as the reference. Slope, Intercept and Correlation were calculated. | Anticoagulant | Regression | |--------------------------------|---------------------------------| | Serum vs. Serum Gel Separation | $y = 0.998x + 0.010, r = 0.999$ | | Serum vs. Li-heparin | $y = 1.00x - 1.994, r = 0.998$ | | Serum vs. K2-EDTA | $y = 0.993x - 2.016, r = 0.998$ | | Serum vs. K3-EDTA | $y = 0.981x - 2.671, r = 0.999$ | Matrix Comparison Table 6: #### 4.5. Interferences - H, L and I Indices The effects of interference by hemoglobin, lipemia (Intralipid), Bilirubin on the CK test system are determined on the cobas c 501 analyzer using pooled human serum samples spiked with varying levels of interferent. The resulting sample series (10 dilution steps per sample) were tested in triplicate and the median values used to calculate % recovery, by comparing the measured concentration to the expected concentration (which is the CK concentration when no interferent was added). | Table 7: | Interference – H, L, I Indices | |----------|--------------------------------| |----------|--------------------------------| | Interferent | No interference up to | Claim | |-------------|------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | Hemolysis | Level 1: 103 H Index Level 2: 130 H Index | No significant interference up to an H index of 100 (approximate hemoglobin concentration: 62.1 umol/L or 100 mg/dL). The level of interference may be variable depending on the exact content of erythrocytes. | | Lipemia | Level 1: 1356 L Index Level 2: 1143 L Index | No significant interference up to an L index of 1000. There is poor correlation between the L index (corresponds to turbidity) and triglycerides concentration. Highly lipemic specimens (L index > 1000) may cause high absorbance flagging. Choose diluted sample treatment for automatic rerun. | {12}------------------------------------------------ | Interferent | No interference up to | Claim | |------------------------|--------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | Unconjugated Bilirubin | Level 1: 67 I Index Level 2: 67 I Index | No significant interference up to an I index of 60 for conjugated and unconjugated bilirubin (approximate conjugated and unconjugated bilirubin concentration: 1026 µmol/L or 60 mg/dL) | | Conjugated Bilirubin | Level 1: 68 Index Level 2: 76 I Index | | #### Interferences – Drugs 4.6. Two sample pools containing a low and high concentration of CK were used. These sample pools were divided into an appropriate number of aliquots. One aliquot is not spiked with the drugs and it was used as the reference sample for CK concentration. The CK concentration in the sample was determined with n = 3 measurements on a cobas c 501 analyzer. The other sample aliquots, with either the high or low CK concentrations, were spiked with the respective amount of drug. The CK concentration of the spiked aliquots were determined in triplicate and the mean of the triplicate determinations was compared to the CK concentration determined for the reference aliquot (mean of n=3). No interference was found at therapeutic concentrations using common drug panels. Cyanokit (Hydroxocobalamin) at therapeutic concentrations interferes with the test. {13}------------------------------------------------ #### Method Comparison to Predicate 4.7. A total of 132 human serum samples were tested in singlicate with the CK assay on cobas c 501 and the CKL assay on INTEGRA 800. 9 of the 132 samples were spiked with human recombinant CK MB. The data were evaluated using Passing Bablok Regression analysis. y = 1.021x + 5.88 U/L r = 0.999 #### CONCLUSIONS 5. The submitted information in this premarket notification supports a substantial equivalence decision.