(86 days)
No
The summary describes a standard in vitro diagnostic assay for measuring creatine kinase activity using photometric detection. There is no mention of AI or ML in the device description, intended use, or performance studies.
No.
This device is an in vitro diagnostic test for the quantitative determination of creatine kinase, used to aid in the diagnosis and monitoring of certain conditions, not to treat them.
Yes
Explanation: The intended use explicitly states that the determination of CK and CK isoenzyme activities by this device is "utilized in the diagnosis and monitoring of myocardial infarction and myopathies."
No
The device is an in vitro diagnostic test that utilizes reagents and automated clinical chemistry analyzers to measure creatine kinase in serum and plasma. This involves physical components and chemical reactions, not solely software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The "Intended Use / Indications for Use" section explicitly states that the device is an "in vitro test for the quantitative determination of creatine kinase (CK) in human serum and plasma". This is the defining characteristic of an in vitro diagnostic device – it's used to examine samples taken from the human body outside of the body itself.
- Device Description: The description further clarifies that it's an "assay for the quantitative determination of creatine kinase (CK) in human serum and plasma". This reinforces its use with biological samples.
- Anatomical Site: The "Anatomical Site" is listed as "Not Applicable (In vitro diagnostic test using serum and plasma)", which again confirms its use with samples outside the body.
- Performance Studies: The performance studies described are typical for an IVD, focusing on analytical performance characteristics like detection limits, precision, linearity, and interference.
- Predicate Device: The mention of a "Predicate Device(s)" with a K number (K951595) indicates that this device is being compared to a previously cleared IVD.
All of these points strongly indicate that this device is an In Vitro Diagnostic.
N/A
Intended Use / 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.
Product codes (comma separated list FDA assigned to the subject device)
JHS, 21 CFR § 862.1215
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.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Not Found
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Detection Limits according to CLSI EP17-A2:
LoB, LoD, and LoQ studies were performed based upon CLSI EP17-A2.
LoB: 0.3 U/L (Claim: 7 U/L)
LoD: 1.0 U/L (Claim: 7 U/L)
LoQ: 3.3 U/L (Claim: 7 U/L)
Precision according to CLSI EP5-A2:
Precision experiments were 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.
- Repeatability Summary (CV%): ranges from 0.4% to 3.0% for Human Serum samples and PreciControl ClinChem Multi controls.
- Intermediate Precision Summary (CV%): ranges from 0.6% to 3.2% for Human Serum samples and PreciControl ClinChem Multi controls.
Linearity according to CLSI EP6-A:
Linearity was assessed 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.
- 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:
The effect of the presence of anticoagulants on analyte recovery was determined by method comparison, using serum data as reference.
- 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
Interferences - H, L and I Indices:
Effects of hemoglobin, lipemia (Intralipid), and Bilirubin were determined.
- Hemolysis: No significant interference up to an H index of 100 (approximate hemoglobin concentration: 62.1 umol/L or 100 mg/dL).
- Lipemia: No significant interference up to an L index of 1000. Highly lipemic specimens (L index > 1000) may cause high absorbance flagging.
- Unconjugated Bilirubin & Conjugated Bilirubin: 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).
Interferences – Drugs:
No interference was found at therapeutic concentrations using common drug panels. Cyanokit (Hydroxocobalamin) at therapeutic concentrations interferes with the test.
Method Comparison to Predicate:
Sample size: 132 human serum samples (9 spiked with human recombinant CK MB).
Comparison of CK assay on cobas c 501 and CKL assay on INTEGRA 800.
Results from Passing Bablok Regression analysis: y = 1.021x + 5.88 U/L, r = 0.999.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Not Found
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Creatine Kinase, K951595
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
K101456, K042389, K062972, K102016
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 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.
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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
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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)
| 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
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 | |||
|---|---|---|---|---|
| ---------- | ---------------------------------------------- | -- | -- | -- |
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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 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.
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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 | |
|---|---|---|
| ---------- | ------------------- | -- |
| 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.
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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 |
|---|---|
| ---------- | -------------------------------- |
| 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. |
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| 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.
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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.