(259 days)
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No
The device description and performance studies focus on standard in-vitro diagnostic assay principles and analytical performance metrics, with no mention of AI or ML.
No.
The device is an in-vitro diagnostic test used to measure CK-MB levels, which aid in diagnosis; it does not provide therapy or treatment.
Yes
Explanation: The "Intended Use / Indications for Use" section explicitly states that "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." This directly indicates the device's role in diagnosis.
No
The device is an in-vitro diagnostic assay, which is a reagent-based test performed on automated clinical chemistry analyzers. It involves chemical reactions and photometric measurements, indicating it is a physical product and not solely software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use/Indications for Use: The description explicitly states it is an "in-vitro test for the quantitative determination of the catalytic activity of creatine kinase MB subunit (CK-MB) in human serum and plasma". This clearly indicates it is used to test samples taken from the human body outside of the body.
- Device Description: The description details a "two reagent assay for the quantitative determination of creatine kinase-MB (CK-MB) in human serum and plasma". This further confirms it is a test performed on biological samples.
- Input Imaging Modality: It is listed as "Not Applicable (In-vitro diagnostic test)", which is consistent with an IVD.
- Anatomical Site: It is listed as "Not Applicable (In-vitro diagnostic test using serum and plasma)", again consistent with an IVD.
- Description of the training set, sample size, data source, and annotation protocol: Listed as "Not Applicable (In-vitro diagnostic test)".
- Description of the test set, sample size, data source, and annotation protocol: Listed as "Not Applicable (In-vitro diagnostic test)".
- Summary of Performance Studies: The studies described (Precision, Detection Limit, Linearity, Interferences, Method Comparison, Matrix Comparison) are typical analytical performance studies conducted for IVD devices.
- Predicate Device(s): The listed predicate device is "Roche CK-MB", which is also an IVD.
All of these points strongly indicate that this device is an In Vitro Diagnostic.
N/A
Intended Use / Indications for Use
The Creatine Kinase-MB assay is an in-vitro test for the quantitative determination of the catalytic activity of creatine kinase MB subunit (CK-MB) in human serum and plasma on Roche/Hitachi cobas c systems.
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.
Prescription Use (Part 21 CFR 801 Subpart D)
Product codes (comma separated list FDA assigned to the subject device)
JHW
Device Description
The Creatine Kinase-MB assay is a two reagent assay for the quantitative determination of creatine kinase-MB (CK-MB) in human serum and plasma on automated clinical chemistry analyzers. The rate of the NADPH formation is directly proportional to the catalytic CK-MB activity. It is determined by measuring the increase in absorbance photometrically.
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)
Precision according to CLSI EP5-A3:
- Repeatability and Intermediate Precision: 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. Samples were randomized in each run separately.
- Repeatability Summary (CV %): Human Serum 1 (2.2), Human Serum 2 (1.2), Human Serum 3 (0.5), Human Serum 4 (0.5), Human Serum 5 (1.3), PreciControl ClinChem Multi 1 (0.8), PreciControl ClinChem Multi 2 (0.5).
- Intermediate Precision Summary (CV %): Human Serum 1 (2.8), Human Serum 2 (1.9), Human Serum 3 (0.8), Human Serum 4 (0.8), Human Serum 5 (2.3), PreciControl ClinChem Multi 1 (1.7), PreciControl ClinChem Multi 2 (1.5).
Detection Limit: LoB, LoD and LoQ according to CLSI EP17-A2:
- Limit of Blank (LoB): One analyte free sample measured with three lots in 10-fold determination in 6 runs, distributed over 3 days, on one cobas c 501 analyzer. Total 60 measurements per lot. Result: 0.3 U/L (Claim: 3 U/L).
- Limit of Detection (LoD): Five samples with low-analyte concentration measured with three lots in twofold determination in 6 runs, distributed over 3 days, on one cobas c 501 analyzer. Total 60 measurements per lot. Result: 1.0 U/L (Claim: 3 U/L).
- Limit of Quantitation (LoQ): Low Level Sample Set (5 human serum samples diluted with 0.9% NaCl) tested in 5 replicates per sample on 5 days, one run per day on one cobas c 501 analyzer. Result: 1.9 U/L (Claim: 10 U/L).
Linearity according to CLSI EP6-A:
- Dilution series prepared using human sample pools (one serum, one plasma) with CKMB concentrations above measuring range. Dilutions made using 0.9% NaCl. Serum (16 concentrations), Plasma (18 dilution steps). Samples measured in triplicate.
- Linear Regression Results:
- Plasma: y=0.969 + 0.210, correlation coefficient (R2)=0.9996
- Serum: y=0.992x + 0.306, correlation coefficient (R2)=0.9999
- Linear Regression Results:
Endogenous Interferences - H, L and I Indices:
- Effect of hemoglobin, lipemia (Intralipid), Bilirubin determined on cobas c 501 analyzer using pooled human serum samples spiked with varying levels of interferent.
- Conjugated Bilirubin: No significant interference up to an I index of 60 for conjugated (approximate 1026 µmol/L or 60 mg/dL).
- Unconjugated Bilirubin: No significant interference up to an I index of 20 for unconjugated (approximate 342 µmol/L or 20 mg/dL).
- Lipemia: No significant interference up to an L index of 500.
- Hemolysis interferes with the assay.
Exogenous Interferences - Drugs:
- Two sample pools (low and high CKMB concentration) were spiked with drugs. CKMB concentration determined in triplicate and compared to unspiked reference.
- No interference at therapeutic concentrations using common drug panels with the exceptions of Cyanokit (Hydroxocobalamin) and Cefoxitin which interfere with the test.
Method Comparison to Predicate:
- Sample size: 105 human serum samples (4 spiked with CK MB rec human).
- Tested in singlicate with the CK-MB assay on cobas c 501 and on the predicate device.
- Results calculated using Passing/Bablok regression: y = 0.977x + 1.12, t = 0.968.
Matrix Comparison - Anticoagulants:
- Effect of anticoagulants determined by method comparison using samples drawn into serum and different plasma collection tubes (K2 EDTA, K3 EDTA, Li Heparin, and Gel Separation).
- Sample sizes: Li Heparin (31 tubes), K2 EDTA (30 tubes), K3 EDTA (31 tubes), Gel Separation (31 tubes).
- Serum data used as reference.
- Regression results:
- Serum vs. Serum Gel Separation: y = 0.996x + 0.804, r = 1.00
- Serum vs. Li-heparin: y = 1.00x - 0.616, r = 0.999
- Serum vs. K2-EDTA: y = 1.00x - 0.717, r = 0.999
- Serum vs. K3-EDTA: y = 0.995x - 0.062, r = 1.00
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.
Roche CK-MB, K003158
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.
Not Found
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 shows the logo for the Department of Health & Human Services - USA. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is a stylized image of three human profiles facing to the right. The profiles are stacked on top of each other, with the top profile being the most prominent.
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
May 26, 2017
ROCHE DIAGNOSTICS NOEL MENCIAS REGULATORY AFFAIRS CONSULTANT 9115 HAGUE ROAD INDIANAPOLIS IN 46250
Re: K162526
Trade/Device Name: Creatine Kinase-MB Regulation Number: 21 CFR 862.1215 Regulation Name: Creatine phosphokinase/creatine kinase or isoenzymes test system Regulatory Class: II Product Code: JHW Dated: March 3, 2017 Received: March 6, 2017
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,
Kellie B. Kelm -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) K162526
Device Name Creatine Kinase-MB
Indications for Use (Describe)
The Creatine Kinase-MB assay is an in-vitro test for the quantitative determination of the catalytic activity of creatine kinase MB subunit (CK-MB) in human serum and plasma on Roche/Hitachi cobas c systems.
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.
| 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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3
510(k) Summary K162526
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of 21 CFR 807.92.
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| Submitter Name | Roche Diagnostics | |
|---|---|---|
| Address | 9115 Hague Road | |
| P.O. Box 50416 | ||
| Indianapolis, IN 46250-0457 | ||
| Contact | Noel B. Mencias | |
| Phone: (317) 521-3172 | ||
| FAX: (317) 521-2324 | ||
| Email: noel.mencias@roche.com | ||
| Date Prepared | May 23, 2017 | |
| Proprietary Name | Creatine Kinase-MB | |
| Common Name | Creatine Kinase-MB | |
| Classification Name | Creatine phosphokinase/creatine kinase or isoenzymes test system. | |
| Product Codes, | ||
| Regulation Numbers | JHW, 21 CFR § 862.1215 | |
| Predicate Devices | Roche CK-MB, K003158 | |
| Establishment Registration | For the Creatine Kinase-MB assay, the establishment registration number for | |
| Roche Diagnostics GmbH in Mannheim, Germany is 9610126. The | ||
| establishment registration number for Roche Diagnostics in the United States is |
- | |
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1. DEVICE DESCRIPTION
The Creatine Kinase-MB assay is a two reagent assay for the quantitative determination of creatine kinase-MB (CK-MB) in human serum and plasma on automated clinical chemistry analyzers. The rate of the NADPH formation is directly proportional to the catalytic CK-MB activity. It is determined by measuring the increase in absorbance photometrically.
INDICATIONS FOR USE 2.
The Creatine Kinase-MB assay is an in-vitro test for the quantitative determination of the catalytic activity of creatine kinase MB subunit (CK-MB) in human serum and plasma on Roche/Hitachi cobas c systems.
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.
3. TECHNOLOGICAL CHARACTERISTICS
Human CK-MB is composed of two subunits, CK-M and CK-B which both have an active site. With the aid of specific antibodies to CK-M, the catalytic activity of CK-M subunits in the sample is inhibited to 99.6 % without affecting the CK-B subunits. The remaining CK-B activity, corresponding to half the CK-MB activity, is determined by the total CK method. As the CK-BB isoenzyme only rarely appears in serum and the catalytic activity of the CK-M and CK-B subunits hardly differ, the catalytic activity of the CK-MB isoenzyme can be calculated from the measured CK B activity by multiplying the result by 2.
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Figure 1: CK MB: UV test
| Creatine phosphate + ADP | CK
→ | creatine + ATP |
|--------------------------|------------|-----------------------------------|
| ATP + D-glucose | HK
→ | ADP + G6P |
| G6P + NADP+ | G6PDH
→ | D-6-phosphogluconate + NADPH + H+ |
The rate of the NADPH formation is directly proportional to the catalytic CK-MB activity. It is determined by measuring the increase in absorbance photometrically.
The following table compares the Candidate Creatine Kinase-MB with its predicate device, Roche CK-MB (K003158).
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| Feature | Predicate Device
Creatine Kinase-MB (K003158) | Candidate Device
Creatine Kinase-MB |
|----------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------|
| Intended Use | For the quantitative in vitro
determination of the MB isoenzyme
of creatine kinase in human serum
and plasma. | Same |
| Test Principle | Human CK-MB is composed of two
subunits, CK-M and CK-B which both
have an active site.
With the aid of specific antibodies to
CK-M, the catalytic activity of CK-M
subunits in the sample is inhibited to
99.6 % without affecting the CK-B
subunits. The remaining CK-B
activity, corresponding to half the CK-
MB activity, is determined by the total
CK method. As the CK-BB isoenzyme
only rarely appears in serum and the
catalytic activity of the CK-M and
CK-B subunits hardly differ, the
catalytic activity of the CK-MB
isoenzyme can be calculated from the
measured CK B activity by
multiplying the result by 2.
The rate of the NADPH formation is
directly proportional to the catalytic
CK-MB activity. It is determined by
measuring the increase in absorbance
photometrically. | Same |
Table 1: Assay Comparison
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| Feature | Predicate Device
Creatine Kinase-MB (K003158) | Candidate Device
Creatine Kinase-MB |
|------------------------------|----------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------|
| Sample Type/Matrix | Serum and plasma, free from
hemolysis. Acceptable anticoagulants
are heparin and EDTA. | Serum: Non-hemolyzed serum.
Plasma: Li-Heparin, K2-, K3-EDTA.
Non-hemolyzed plasma. |
| Calibrator | Calibrator f.a.s. CK-MB | Calibrator f.a.s. CK-MB (K101456) |
| Calibration Interval | After reagent lot change and as
required following quality control
procedures | After reagent lot change and as required
following quality control procedures |
| Traceability/Standardization | Traceable to IFCC | This method has been standardized
against the IFCC Method for Creatine
Kinase with addition of antibodies. |
| Reagent Stability | 2-8 °C until expiration date | Same |
| Reagent On-Board Stability | 28 days opened and refrigerated on the
analyzer | On-board in use and refrigerated on the
analyzer: 8 weeks |
| Measuring Range | 5 - 2300 U/L (0.08 - 38.4 µkat/L) | 10 - 2000 U/L (0.17-33.4 µkat/L) |
| Lower Limits of Measurement | LDL=5 U/L | Limit of Blank = 3 U/L (0.05 µkat/L)
Limit of Detection = 3 U/L (0.05 µkat/L)
Limit of Quantitation = 10 U/L (0.17
µkat/L) |
9
NON-CLINICAL PERFORMANCE EVALUATION 4.
The following performance data were provided in support of the substantial equivalence determination:
Precision according to CLSI EP5-A3
Detection Limit: LoB, LoD and LoQ according to CLSI EP17-A2
Linearity according to CLSI EP6-A
Endogenous Interferences - H, L and I Indices
Endogenous Interferences - Triglycerides
Exogenous Interferences - Drugs
Method Comparison to Predicate
Matrix Comparison - Anticoagulants
4.1. Precision
Repeatability and Intermediate Precision 4.1.1.
Precision experiments are performed in Accordance with CLSI Guideline EP5-A3. Two aliquots per run, two runs per day for $\ge$ 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.
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Reproducibility 4.1.2.
| Table 2: | Repeatability Summary |
|---|---|
| ---------- | ----------------------- |
| Specimen | Mean (U/L) | SD (U/L) | CV (%) |
|---|---|---|---|
| Human Serum 1 | 17.9 | 0.4 | 2.2 |
| Human Serum 2 | 29.1 | 0.4 | 1.2 |
| Human Serum 3 | 524 | 2.5 | 0.5 |
| Human Serum 4 | 1040 | 4.9 | 0.5 |
| Human Serum 5 | 1826 | 25 | 1.3 |
| PreciControl ClinChem Multi 1 | 41.0 | 0.3 | 0.8 |
| PreciControl ClinChem Multi 2 | 99.2 | 0.5 | 0.5 |
Table 3: Intermediate Precision Summary
| Specimen | Mean (U/L) | SD (U/L) | CV (%) |
|---|---|---|---|
| Human Serum 1 | 17.8 | 0.5 | 2.8 |
| Human Serum 2 | 29.0 | 0.6 | 1.9 |
| Human Serum 3 | 531 | 4.4 | 0.8 |
| Human Serum 4 | 1040 | 8.4 | 0.8 |
| Human Serum 5 | 1851 | 42 | 2.3 |
| PreciControl ClinChem Multi 1 | 40.2 | 0.7 | 1.7 |
| PreciControl ClinChem Multi 2 | 98.7 | 1.5 | 1.5 |
Analytical Sensitivity 4.2.
4.2.1. Limit of Blank (LoB)
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 cobas 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.
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Limit of Detection (LoD) 4.2.2.
For determination of LoD five samples with low-analyte concentration (approximately up to 4 times the LoB) were measured with three lots in twofold determination in 6 runs, distributed over 3 days, on one cobas c 501 analyzer. In total 60 measurements will be obtained per lot.
4.2.3. Limit of Quantitation (LoQ)
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, LoD, and Low Results Table 4:
| Result (U/L) | Claim (U/L) | |
|---|---|---|
| Limit of Blank (LoB) | 0.3 | 3 |
| Limit of Detection (LoD) | 1.0 | 3 |
| Limit of Quantitation (LoQ) | 1.9 | 10 |
Linearity/Assay Reportable Range 4.3.
Regression Analysis 4.3.1.
The linearity study was conducted to demonstrate that measurements across the claimed measuring range for each parameter are linear. The study was performed according to CLSI guideline EP6-A.
Dilution series were prepared using the human sample pools (one serum pool and one plasma pool) with CKMB concentrations above the upper end of the measuring range. Dilutions were made using 0.9% NaCl. The dilution series contain 16 concentrations for serum and 18 dilution steps for plasma. Samples were measured in triplicate and data analysis was done separately for each sample.
Linear regression analysis was done according to EP6-A.
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.
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Table 5: Linearity Results
| Sample Type | Linear Regression |
|---|---|
| Plasma | y=0.969 + 0.210 |
| correlation coefficient (R2)=0.9996 | |
| Serum | y=0.992x + 0.306 |
| correlation coefficient (R2)=0.9999 |
Endogenous Interferences 4.4.
4.4.1. I, H, and L Indices
The effects of interference by hemoglobin, lipemia (Intralipid), Bilirubin on the CK-MB test system is determined on the cobas c 501 analyzer using pooled human serum samples spiked with varying levels of interferent. The resulting sample series were tested in triplicate and the mean values used to calculate % recovery, by comparing the measured concentration to the expected concentration (which is the CK-MB concentration when no interferent was added).
Interference – I, H, and L Indices Table 6:
| Interferent | No Interference up to | Claim |
|---|---|---|
| Conjugated Bilirubin | Level 1: 76 I Index | |
| Level 2: 76 I Index | No significant interference up to an I index of 60 for conjugated and 20 for unconjugated bilirubin (approximate conjugated bilirubin concentration: 1026 µmol/L or 60 mg/dL and approximate unconjugated bilirubin concentration: 342 µmol/L or 20 mg/dL). | |
| Unconjugated Bilirubin | Level 1: 28 I Index | |
| Level 2: 67 I Index | ||
| Lipemia | Level 1: 753 L Index | |
| Level 2: 632 L Index | No significant interference up to an L index of 500. There is poor correlation between the L index (corresponds to turbidity) and triglycerides concentration. |
Hemolysis interferes with the assay. Hemolyzed samples should not be used.
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Exogenous Interferences – Drugs 4.5.
Two sample pools, containing a low and high concentration of CKMB were used. These sample pools were divided into an appropriate number of aliquots. One aliquot was not spiked with the drugs and was used as the reference sample for CKMB concentration. The CKMB 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 CKMB concentrations, were spiked with the respective amount of drug. The CKMB concentration of the spiked aliquots were determined in triplicate and the mean of the triplicate determinations was compared to the CKMB concentration determined for the reference aliquot (mean of n=3).
No interference was found at therapeutic concentrations using common drug panels with the exceptions of Cyanokit (Hydroxocobalamin) and Cefoxitin which interfere with the test.
Method Comparison to Predicate 4.6.
A total of 105 human serum samples were tested in singlicate with the CK-MB assay on cobas c 501 and on the predicate device. 4 samples were spiked with CK MB rec human. The results
were calculated using Passing/Bablok regression.
$$\mathbf{y} = 0.977\mathbf{x} + 1.12$$
t = 0.968
Matrix Comparison - Anticoagulants 4.7.
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 Li Heparin 31 tubes, for K2 EDTA 30 tubes, for K3 EDTA 31 tubes and 31 gel Separation tubes were collected and filled completely.
Method comparison was executed by using the serum data as the reference. Slope, Intercept and Correlation were calculated.
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| Anticoagulant | Regression |
|---|---|
| Serum vs. Serum Gel Separation | $y = 0.996x + 0.804, r = 1.00$ |
| Serum vs. Li-heparin | $y = 1.00x - 0.616, r = 0.999$ |
| Serum vs. K2-EDTA | $y = 1.00x - 0.717, r = 0.999$ |
| Serum vs. K3-EDTA | $y = 0.995x - 0.062, r = 1.00$ |
Table 7: Matrix Comparison Results
5. CLINICAL PERFORMANCE EVALUATION
Not applicable.
6. ADDITIONAL INFORMATION
Other Devices Marketed With This Assay 6.1.
The Creatine Kinase-MB assay continues to use:
- Calibrator f.a.s. CK-MB •
- PreciControl ClinChem Multi 1 and 2 •
- Diluent NaCl 9% .
There have been no changes to these items marketed with the new Creatine Kinase-MB assay.
CONCLUSIONS 7.
The submitted information in this premarket notification supports a substantial equivalence decision.