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.

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.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information based on the provided document:

Creatine Kinase Device Performance Study Summary

1. Acceptance Criteria and Reported Device Performance

Feature / Metric	Acceptance Criteria (Claim in Document)	Reported Device Performance
Limit of Blank (LoB)	Claim: 7 U/L	0.3 U/L
Limit of Detection (LoD)	Claim: 7 U/L	1.0 U/L
Limit of Quantitation (LoQ)	Claim: 7 U/L	3.3 U/L
Precision (Repeatability)	Achieved with Human Serum samples and PreciControl ClinChem Multi controls. Specific acceptance limits for CV/SD are not explicitly stated as "acceptance criteria" but implied by the presentation of successful results. For example: Human Serum 1 (18.7 U/L) CV <= 3.0%, Human Serum 3 (477 U/L) CV <= 0.6%, PreciControl ClinChem Multi 2 (301 U/L) CV <= 0.4%.	Human Serum 1: Mean 18.7 U/L, SD 0.6 U/L, CV 3.0%Human Serum 2: Mean 137 U/L, SD 0.8 U/L, CV 0.6%Human Serum 3: Mean 477 U/L, SD 3.0 U/L, CV 0.6%Human Serum 4: Mean 946 U/L, SD 5.3 U/L, CV 0.6%Human Serum 5: Mean 1816 U/L, SD 9.4 U/L, CV 0.5%PreciControl ClinChem Multi 1: Mean 154 U/L, SD 0.9 U/L, CV 0.6%PreciControl ClinChem Multi 2: Mean 301 U/L, SD 1.3 U/L, CV 0.4%
Precision (Intermediate)	Similar to repeatability, specific acceptance limits for CV/SD are not explicitly stated, but implied by successful results. For example: Human Serum 1 (18.7 U/L) CV <= 3.2%, Human Serum 3 (477 U/L) CV <= 0.6%, PreciControl ClinChem Multi 2 (301 U/L) CV <= 0.9%.	Human Serum 1: Mean 18.7 U/L, SD 0.6 U/L, CV 3.2%Human Serum 2: Mean 137 U/L, SD 1.1 U/L, CV 0.8%Human Serum 3: Mean 477 U/L, SD 3.1 U/L, CV 0.6%Human Serum 4: Mean 946 U/L, SD 5.8 U/L, CV 0.6%Human Serum 5: Mean 1816 U/L, SD 10 U/L, CV 0.6%PreciControl ClinChem Multi 1: Mean 154 U/L, SD 1.7 U/L, CV 1.1%PreciControl ClinChem Multi 2: Mean 301 U/L, SD 2.6 U/L, CV 0.9%
Linearity (Serum)	Pearson correlation coefficient (R) of 0.9999	y=1.001x-0.646, Pearson correlation coefficient (R)=0.9999
Linearity (Plasma)	Pearson correlation coefficient (R) of 0.9999	y=1.002x-1.205, Pearson correlation coefficient (R)=0.9999
Matrix Comparison (Anticoags)	Good correlation (r >= 0.998) and slope close to 1, intercept close to 0 implied for substantial equivalence.	Serum vs. Serum Gel Separation: y = 0.998x + 0.010, r = 0.999Serum vs. Li-heparin: y = 1.00x - 1.994, r = 0.998Serum vs. K2-EDTA: y = 0.993x - 2.016, r = 0.998Serum vs. K3-EDTA: y = 0.981x - 2.671, r = 0.999
Interference (Hemolysis)	No significant interference up to an H index of 100 (approx. 62.1 µmol/L or 100 mg/dL).	No interference up to Level 1: 103 H Index, Level 2: 130 H Index.
Interference (Lipemia)	No significant interference up to an L index of 1000.	No interference up to Level 1: 1356 L Index, Level 2: 1143 L Index.
Interference (Unconjugated Bilirubin)	No significant interference up to an I index of 60 for conjugated and unconjugated bilirubin (approx. 1026 µmol/L or 60 mg/dL).	No interference up to Level 1: 67 I Index, Level 2: 67 I Index.
Interference (Conjugated Bilirubin)	No significant interference up to an I index of 60 for conjugated and unconjugated bilirubin (approx. 1026 µmol/L or 60 mg/dL).	No interference up to Level 1: 68 I Index, Level 2: 76 I Index.
Interference (Drugs)	No interference at therapeutic concentrations using common drug panels. (Exception noted for Cyanokit).	No interference found at therapeutic concentrations using common drug panels. (Cyanokit (Hydroxocobalamin) at therapeutic concentrations interferes with the test).
Method Comparison (Predicate)	The objective is for results to demonstrate substantial equivalence to the predicate device (COBAS INTEGRA Creatine Kinase, K951595) via Passing Bablok Regression where the slope is close to 1 and the intercept close to 0, and a high correlation coefficient (r).	y = 1.021x + 5.88 U/L, r = 0.999

2. Sample Sizes Used for the Test Set and Data Provenance

Detection Limits (LoB, LoD):
- LoB: One analyte-free sample, measured with three lots, 10-fold determination in 6 runs (total 60 measurements per lot).
- LoD: Five low-analyte concentration samples, measured with three lots, two-fold determination in 6 runs (total 60 measurements per lot).
Limit of Quantitation (LoQ):
- Five human serum samples, tested in 5 replicates per sample on 5 days.
Precision (Repeatability & Intermediate):
- Not explicitly stated as a single number, but experiments conducted with multiple human serum samples (5) and control materials (2), with two aliquots per run, two runs per day for ≥ 21 days on the same analyzer using 3 lots of reagent.
Linearity (Serum & Plasma):
- Two separate dilution series (serum and plasma), each with 14 concentrations, measured in triplicate.
Matrix Comparison - Anticoagulants:
- For each of the four tube types (Serum Gel Separation, Li-heparin, K2-EDTA, K3-EDTA), 30 tubes were filled completely. This implies 30 samples for each comparison.
Interferences - H, L, I Indices:
- Pooled human serum samples spiked with varying levels of interferent. The resulting sample series (10 dilution steps per sample) were tested in triplicate.
Interferences - Drugs:
- Two sample pools (low and high CK concentrations), divided into aliquots. Each spiked aliquot measured in triplicate.
Method Comparison to Predicate:
- 132 human serum samples (9 of which were spiked with human recombinant CK MB). Samples tested in singlicate.

Data Provenance: The document explicitly mentions "human serum samples" and "pooled human serum samples." The manufacturer is Roche Diagnostics Operations, located in Indianapolis, IN, USA. Based on the context of FDA submission for a device to be marketed in the USA, it is highly probable the data is retrospective and likely collected in a clinical laboratory setting (possibly in the USA or aligned with international standards like CLSI), but the specific country of origin for the patient samples is not stated.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications

N/A. This is a submission for an in vitro diagnostic device that quantitatively measures a biomarker (Creatine Kinase). The "ground truth" for the test set is established by the reference measurement procedure or the known concentration of the analyte in calibrators/controls, not by expert interpretation of images or clinical data. Therefore, human experts for ground truth adjudication are not applicable in this context.

4. Adjudication Method for the Test Set

N/A. See explanation above. The measurements are quantitative chemical analyses against instrument-derived values and established reference methods/materials, not subjective interpretations.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No. This is an in vitro diagnostic device for quantitative measurement of a biomarker in biological samples. MRMC studies are typically performed for imaging devices or other diagnostic tools where human interpretation plays a significant role, to evaluate how AI assistance impacts human reader performance. This is not applicable here.

6. Standalone (Algorithm Only) Performance Study

Yes, the entire submission is a standalone performance study of the Creatine Kinase assay on the Roche/Hitachi cobas c systems. The device itself is an "algorithm only" in the sense that it is an automated analytical system (reagent + instrument) that produces quantitative results without human intervention in the measurement process itself, beyond sample loading and system maintenance. The studies described (Detection Limits, Precision, Linearity, Interference, Method Comparison) directly assess the performance of this standalone analytical system.

7. Type of Ground Truth Used

The ground truth for the performance studies relies on:

Reference Materials/Methods: For calibration and verification of accuracy, the method is stated to be traceable to IFCC (International Federation of Clinical Chemistry and Laboratory Medicine) Method for Creatine Kinase.
Known Concentrations: For studies like LoB, LoD, LoQ, linearity, and interference, samples are either analyte-free, spiked with known concentrations of analyte or interferents, or diluted from samples with established reference values. This essentially uses calibrated reference standards and materials as the ground truth.
Predicate Device Measurements: For method comparison, the predicate device's results (COBAS INTEGRA Creatine Kinase cleared in K951595 on the COBAS INTEGRA analyzer) serve as a comparative ground truth to establish substantial equivalence.

8. Sample Size for the Training Set

N/A. This is not a machine learning or AI-based diagnostic device in the modern sense that requires a "training set" of data to learn from. It is a traditional in vitro diagnostic assay based on a defined enzymatic chemical reaction and photometric measurement. The development of such assays involves extensive research and development to optimize reagents and instrument parameters, but not in the framework of a "training set" as understood in AI/ML.

9. How the Ground Truth for the Training Set Was Established

N/A. As explained above, there is no "training set" in the context of an AI/ML device for this product. The development of the assay involves chemical and enzymatic principles, optimized through laboratory experimentation and knowledge of biochemistry, rather than learning from a dataset via a specified ground truth.

Summary

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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.

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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

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Indications for Use

510(k) Number (if known) K160570

Device Name Creatine Kinase

Indications for Use (Describe)

Type of Use (Select one or both, as applicable)

Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 801 Subpart C)

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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

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1. DEVICE DESCRIPTION

2. INDICATIONS FOR USE

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

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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 reagentsystem intended for use on COBASINTEGRA for the quantitative determinationof 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 quantitativedetermination of creatine kinase (CK) inhuman serum and plasma onRoche/Hitachi cobas c systems.
Sample Types	Serum and plasma, free from hemolysis.Acceptable anticoagulants are heparin andEDTA.	Serum: Non hemolyzed serum is thespecimen of choice and alsorecommended by IFCC.Plasma: Li-Heparin, K2-, K3-EDTA.
Test Principle	The CK is activated by N-acetylcysteine(NAC). In a primary reaction the activatedCK catalyzes the dephosphorylation ofcreatine phosphate. In a coupled reactioncatalyzed by hexokinase (HK) glucose isphoshorylated by the ATP formed in theprimary reaction to form D-glucose-6-phosphate (G6P). Finally D-glucose-6-phosphate dehydrogenase (G6PDH)catalyzes the oxidation of G6P by NADP toform D-6-phosphogluconate and NADPH.The rate of NADPH formation is directlyproportional to catalytic CK activity. It isdetermined by measuring the increase inabsorbance at 340nm.	The CK is activated by N-acetylcysteine(NAC). In a primary reaction the activatedCK catalyzes the dephosphorylation ofcreatine phosphate. In a coupled reactioncatalyzed by hexokinase (HK) glucose isphoshorylated by the ATP formed in theprimary reaction to form D-glucose-6-phosphate (G6P). Finally D-glucose-6-phosphate dehydrogenase (G6PDH)catalyzes the oxidation of G6P by NADPto form D-6-phosphogluconate andNADPH. The rate of NADPH formation isdirectly proportional to catalytic CKactivity. It is determined by measuring theincrease in absorbance at 340nm (main)and 546nm (sub).
Reagent Shelf LifeStability	+ 2 to +8 ℃ until expiration date	2-8 ℃ until expiration date
Reagent On-BoardStability	On-board in use at +8ºC: 4 weeks	On-board in use and refrigerated on theanalyzer: 8 weeks

Table 1:	Substantial Equivalence – Assay Similarities
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Assay Comparison Similarities
Feature	Predicate Device:COBAS INTEGRA Creatine Kinase(K951595)	Candidate Device:Creatine Kinase
Sample Stability	CK activity in serum remains stable for 24hat +22 °C or 10 days at +4 °C and -20 °C.	Stability in serum:2 days at 20-25 °C7 days at 4-8 °C4 weeks at -20 °CStability in EDTA/heparin plasma:2 days at 15-25 °C7 days at 2-8 °C4 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 standardizedagainst the IFCC Method for CreatineKinase
Calibrator	Calibrator (human)	Calibrator for automated systems (C.f.a.s.)(K101456)
Calibration frequency	Each lot	After reagent lot change and as requiredfollowing 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 ofMeasurement	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 ReagentsR1 liquid, and R2 and SR granulatesR1: Buffer in vial A (15.8 mL).R2: Enzyme granulate in vial B (0.5 g for12.3 mL).R3 = SR: Creatine phosphate granulate invial C (0.7 g for 5 mL).	2 ReagentsR1 Imidazole buffer: 123 mmol/L, pH 6.5(37 °C); EDTA: 2.46 mmol/L; Mg2+: 12.3mmol/L; ADP: 2.46 mmol/L; AMP: 6.14mmol/L; diadenosine pentaphosphate: 19µmol/L; NADP+ (yeast): 2.46 mmol/L; N-acetylcysteine: 24.6 mmol/L; HK (yeast):≥ 36.7 µkat/L; G6PDH (E. coli): ≥ 23.4µkat/L; preservative; stabilizers; additives.R2 CAPSO* buffer: 20 mmol/L, pH 8.8 (37°C); glucose: 120 mmol/L; EDTA: 2.46mmol/L; creatine phosphate: 184 mmol/L;preservative; stabilizers.*CAPSO:3(-cyclohexylamine)-2-hydroxy-1-propanesulfonic acid

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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.

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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

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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
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Sample type	Linear Regression
Serum	y=1.001x-0.646Pearson correlation coefficient (R)=0.9999
Plasma	y=1.002x-1.205Pearson 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.

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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
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Interferent	No interference up to	Claim
Hemolysis	Level 1: 103 H IndexLevel 2: 130 H Index	No significant interference up to an Hindex of 100 (approximatehemoglobin concentration: 62.1umol/L or 100 mg/dL). The level ofinterference may be variabledepending on the exact content oferythrocytes.
Lipemia	Level 1: 1356 L IndexLevel 2: 1143 L Index	No significant interference up to an Lindex of 1000. There is poorcorrelation between the L index(corresponds to turbidity) andtriglycerides concentration. Highlylipemic specimens (L index > 1000)may cause high absorbance flagging.Choose diluted sample treatment forautomatic rerun.

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Interferent	No interference up to	Claim
Unconjugated Bilirubin	Level 1: 67 I IndexLevel 2: 67 I Index	No significant interference up to an Iindex of 60 for conjugated andunconjugated bilirubin (approximateconjugated and unconjugatedbilirubin concentration: 1026 µmol/Lor 60 mg/dL)
Conjugated Bilirubin	Level 1: 68 IndexLevel 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.

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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.

Regulation Number and Section

§ 862.1215 Creatine phosphokinase/creatine kinase or isoenzymes test system.

(a)
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.(b)
Classification. Class II.