(259 days)
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.
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.
This document is a 510(k) summary for a medical device called "Creatine Kinase-MB" by Roche Diagnostics. It describes the device, its intended use, technological characteristics, and performance evaluation data.
Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided text:
Key Takeaway: This document is about a clinical chemistry assay (an in-vitro diagnostic test), not an AI/ML device. Therefore, many of the typical AI/ML study components (like multi-reader multi-case studies, expert adjudication, or separate training/test sets for AI models) are not applicable to this type of device. The "ground truth" here is the reference measurement method or the expected concentration of the analyte.
1. Table of Acceptance Criteria and Reported Device Performance
Since this is an in-vitro diagnostic test and not an AI/ML device, the acceptance criteria are not typically expressed as sensitivity/specificity in an MRMC study for diagnostic imaging. Instead, the acceptance criteria relate to analytical performance characteristics. The document presents the performance data against established analytical standards (CLSI guidelines) and comparisons to a predicate device.
| Acceptance Criterion Category | Specific Criterion (Implicit/Explicit from CLSI Guidelines/Industry Standards) | Reported Device Performance |
|---|---|---|
| Precision | Repeatability (Within-run precision): Acceptable CV/SD for varying analyte concentrations. | Human Serum 1 (17.9 U/L): SD 0.4 U/L, CV 2.2% |
| Human Serum 2 (29.1 U/L): SD 0.4 U/L, CV 1.2% | ||
| Human Serum 3 (524 U/L): SD 2.5 U/L, CV 0.5% | ||
| Human Serum 4 (1040 U/L): SD 4.9 U/L, CV 0.5% | ||
| Human Serum 5 (1826 U/L): SD 25 U/L, CV 1.3% | ||
| Intermediate Precision (Within-lab precision): Acceptable CV/SD for varying analyte concentrations. | Human Serum 1 (17.8 U/L): SD 0.5 U/L, CV 2.8% | |
| Human Serum 2 (29.0 U/L): SD 0.6 U/L, CV 1.9% | ||
| Human Serum 3 (531 U/L): SD 4.4 U/L, CV 0.8% | ||
| Human Serum 4 (1040 U/L): SD 8.4 U/L, CV 0.8% | ||
| Human Serum 5 (1851 U/L): SD 42 U/L, CV 2.3% | ||
| Analytical Sensitivity | Limit of Blank (LoB): Should be below claimed limit of quantitation. | Result: 0.3 U/L, Claim: 3 U/L |
| Limit of Detection (LoD): Should be below claimed limit of quantitation and above LoB. | Result: 1.0 U/L, Claim: 3 U/L | |
| Limit of Quantitation (LoQ): The lowest concentration at which quantitative results can be reported with acceptable precision and accuracy. | Result: 1.9 U/L, Claim: 10 U/L | |
| Linearity/Assay Reportable Range | Measurements across the claimed measuring range should be linear with a high correlation coefficient (R2). | Plasma: y=0.969x + 0.210, R2=0.9996 Serum: y=0.992x + 0.306, R2=0.9999 |
| Endogenous Interferences | No significant interference from common interferents up to specified levels. | Conjugated Bilirubin: No significant interference up to 60 I Index (approx. 1026 µmol/L or 60 mg/dL). |
| Lipemia: No significant interference up to 500 L Index. | ||
| Hemolysis: Interferes, hemolyzed samples should not be used. | ||
| Exogenous Interferences (Drugs) | No significant interference from common drugs at therapeutic concentrations. | No interference with common drug panels, except Cyanokit (Hydroxocobalamin) and Cefoxitin. |
| Method Comparison to Predicate | Results should be comparable to the legally marketed predicate device (e.g., strong correlation, slope near 1, intercept near 0). | Regression: y = 0.977x + 1.12, r = 0.968 (105 human serum samples plus 4 spiked samples). |
| Matrix Comparison (Anticoagulants) | Different sample matrices (serum vs. various plasma types) should yield comparable 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 |
Study Details:
2. Sample Sizes Used for the Test Set and Data Provenance
- Precision (Repeatability & Intermediate Precision):
- 5 human serum samples and 2 control samples.
- Measurements: Two aliquots per run, two runs per day for ≥ 21 days on the same analyzer using 3 lots of reagent.
- Data Provenance: Not explicitly stated (e.g., country of origin), but implies laboratory-based prospective testing as per CLSI guidelines.
- Analytical Sensitivity (LoB, LoD, LoQ):
- LoB: One analyte-free sample. Measured with three lots, 10-fold determination in 6 runs, over 3 days (60 measurements per lot).
- LoD: Five samples with low analyte concentration. Measured with three lots, twofold determination in 6 runs, over 3 days (60 measurements per lot).
- LoQ: 5 human serum samples diluted to low levels. Tested in 5 replicates per sample on 5 days, one run per day.
- Data Provenance: Implies laboratory-based prospective testing as per CLSI guidelines.
- Linearity:
- One serum pool and one plasma pool, diluted to 16 (serum) and 18 (plasma) concentrations.
- Measurements: Measured in triplicate.
- Data Provenance: Implies laboratory-based prospective testing.
- Endogenous Interferences:
- Pooled human serum samples spiked with varying levels of interferent.
- Measurements: Tested in triplicate.
- Data Provenance: Implies laboratory-based prospective testing.
- Exogenous Interferences (Drugs):
- Two sample pools (low and high CKMB concentration).
- Measurements: Aliquots spiked with drugs, determined in triplicate.
- Data Provenance: Implies laboratory-based prospective testing.
- Method Comparison to Predicate:
- 105 human serum samples (plus 4 spiked with CK MB rec human).
- Data Provenance: Not explicitly stated origins of human serum samples, but implies prospective collection for this comparison.
- Matrix Comparison (Anticoagulants):
- 31 Li Heparin tubes, 30 K2 EDTA tubes, 31 K3 EDTA tubes, and 31 Gel Separation tubes.
- Data Provenance: Implies prospective collection of samples drawn into different tubes.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and the Qualifications of Those Experts
Not applicable. This is an analytical performance study for an in-vitro diagnostic assay. Ground truth is established by reference methods, known concentrations, or comparison to a predicate device, not by expert medical image interpretation.
4. Adjudication Method for the Test Set
Not applicable. There is no human interpretation or adjudication component in the analytical performance testing described for this device. Measurements are objective quantitative values.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, If So, What Was the Effect Size of How Much Human Readers Improve with AI vs Without AI Assistance
Not applicable. This device is an in-vitro diagnostic test, not an AI-assisted diagnostic imaging tool or a device requiring human readers/interpreters in its primary use.
6. If a Standalone (i.e. algorithm only without human-in-the loop performance) Was Done
This is fundamentally a "standalone" device in the sense that its performance is measured analytically on its own, producing a quantitative result. There is no "human-in-the-loop" performance as would be relevant for an AI-powered diagnostic imaging tool. The device provides a direct measurement.
7. The Type of Ground Truth Used
The "ground truth" for this device's performance studies is based on:
- Reference Methods/Known Concentrations: For precision, linearity, and analytical sensitivity, samples with known or expected concentrations (e.g., controls, highly purified analytes, or diluted samples) are used.
- Comparison to a Legally Marketed Predicate Device: For method comparison, the results from the new device are compared to those obtained from the established predicate device, which serves as a de facto "truth" or reference standard for equivalence.
- CLSI Guidelines: The studies follow CLSI (Clinical and Laboratory Standards Institute) guidelines (e.g., EP5-A3, EP17-A2, EP6-A), which define how analytical performance characteristics should be determined using standard laboratory practices.
8. The Sample Size for the Training Set
Not applicable. This is not an AI/ML device, so there is no "training set" in the context of model development. The laboratory studies described are for system validation, not algorithm training.
9. How the Ground Truth for the Training Set Was Established
Not applicable. As there is no "training set" for an AI/ML model, there is no ground truth established for such a set.
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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.
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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,
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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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 RoadP.O. Box 50416Indianapolis, IN 46250-0457 | |
| Contact | Noel B. MenciasPhone: (317) 521-3172FAX: (317) 521-2324Email: 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 forRoche Diagnostics GmbH in Mannheim, Germany is 9610126. Theestablishment registration number for Roche Diagnostics in the United States is1823260. |
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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 DeviceCreatine Kinase-MB (K003158) | Candidate DeviceCreatine Kinase-MB |
|---|---|---|
| Intended Use | For the quantitative in vitrodetermination of the MB isoenzymeof creatine kinase in human serumand plasma. | Same |
| Test Principle | Human CK-MB is composed of twosubunits, CK-M and CK-B which bothhave an active site.With the aid of specific antibodies toCK-M, the catalytic activity of CK-Msubunits in the sample is inhibited to99.6 % without affecting the CK-Bsubunits. The remaining CK-Bactivity, corresponding to half the CK-MB activity, is determined by the totalCK method. As the CK-BB isoenzymeonly rarely appears in serum and thecatalytic activity of the CK-M andCK-B subunits hardly differ, thecatalytic activity of the CK-MBisoenzyme can be calculated from themeasured CK B activity bymultiplying the result by 2.The rate of the NADPH formation isdirectly proportional to the catalyticCK-MB activity. It is determined bymeasuring the increase in absorbancephotometrically. | Same |
Table 1: Assay Comparison
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| Feature | Predicate DeviceCreatine Kinase-MB (K003158) | Candidate DeviceCreatine Kinase-MB |
|---|---|---|
| Sample Type/Matrix | Serum and plasma, free fromhemolysis. Acceptable anticoagulantsare 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 asrequired following quality controlprocedures | After reagent lot change and as requiredfollowing quality control procedures |
| Traceability/Standardization | Traceable to IFCC | This method has been standardizedagainst the IFCC Method for CreatineKinase with addition of antibodies. |
| Reagent Stability | 2-8 °C until expiration date | Same |
| Reagent On-Board Stability | 28 days opened and refrigerated on theanalyzer | On-board in use and refrigerated on theanalyzer: 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 (0.17µkat/L) |
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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 + 0.210correlation coefficient (R2)=0.9996 |
| Serum | y=0.992x + 0.306correlation 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 IndexLevel 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 IndexLevel 2: 67 I Index | |
| Lipemia | Level 1: 753 L IndexLevel 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.
§ 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.