(79 days)
Immunoassay for the in vitro quantitative determination of the MB isoenzyme of creatine kinase in human serum and plasma. Measurements of the MB isoenzyme of creatinine kinase are used as an aid in the diagnosis of myocardial infarction.
The electrochemiluminescence immunoassay "ECLIA" is intended for use on the indicated Elecsys and cobas e immunoassay analyzers.
The CK-MB STAT (one-step incubation) Assay is a sandwich immunoassay with streptavidin microparticles and electrochemiluminescence detection.
Results are determined using a calibration curve that is generated specifically on each instrument by a 2 point calibration and a master curve (5-point-calibration) provided with the reagent bar code.
The CK-MB STAT (one-step incubation) application is identical to the CK-MB STAT (two-step incubation) assay, the only difference being for the CK-MB STAT (one-step incubation) application, the sample, reagent 1, reagent 2 and microparticles are added at one time.
This document describes the acceptance criteria and study results for the Elecsys CK-MB STAT Immunoassay, a device used for the quantitative determination of the MB isoenzyme of creatine kinase in human serum and plasma, as an aid in diagnosing myocardial infarction.
This submission is a Special 510(k), indicating a modification to an existing device, the Elecsys CK-MB STAT (two-step incubation) Assay (K132571). The key difference in the modified device is the change to a one-step incubation protocol and its evaluation on the cobas e 601 Immunoassay Analyzer, compared to the predicate's two-step protocol on the cobas e 411.
1. Table of Acceptance Criteria and Reported Device Performance:
The document primarily focuses on demonstrating substantial equivalence to the predicate device by comparing various performance characteristics. The "Acceptance Criteria" for the modified device are generally considered to be equivalent to or better than the performance of the predicate device, or within acceptable clinical laboratory standards.
| Feature | Predicate Device (Elecsys CK-MB STAT, two-step incubation, K132571 on cobas e 411) Acceptance Criteria / Performance | Modified Device (Elecsys CK-MB STAT, one-step incubation on cobas e 601) Reported Performance |
|---|---|---|
| General Assay Features | ||
| Intended Use/Indications | Quantitative determination of MB isoenzyme of creatine kinase in human serum and plasma for myocardial infarction diagnosis on Elecsys and cobas e immunoassay analyzers. | Same |
| Assay Protocol | Two-step Sandwich assay | One-step Sandwich assay |
| Detection Protocol | Electrochemiluminescent Immunoassay | Same |
| Applications | STAT (9 minute) application | Same |
| Instrument Platform | cobas e 411 | Roche cobas e 601 |
| Sample Volume | 15 µL | Same |
| Sample Type | Human serum and plasma (K2-EDTA, K3-EDTA, lithium heparin, sodium heparin) | Same |
| Plasma Type Comparison | (vs. Serum, normally filled tubes) | |
| Na Heparin Plasma | Slope: 0.9 - 1.1; Intercept: ≤ +/- 0.15; r: > 0.95; Relative dev: +/- 20% | Slope: 0.994; Intercept: 0.0010; r: 0.9997; Max deviation: 14.6% |
| Li Heparin Plasma | Slope: 0.9 - 1.1; Intercept: ≤ +/- 0.15; r: > 0.95; Relative dev: +/- 20% | Slope: 0.996; Intercept: 0.0045; r: 0.9996; Max deviation: 12.0% |
| K2-EDTA Plasma | Slope: 0.9 - 1.1; Intercept: ≤ +/- 0.15; r: > 0.95; Relative dev: +/- 20% | Slope: 1.020; Intercept: 0.0082; r: 0.9999; Max deviation: 10.5% |
| K3-EDTA Plasma | Slope: 0.9 - 1.1; Intercept: ≤ +/- 0.15; r: > 0.95; Relative dev: +/- 20% | Slope: 0.988; Intercept: 0.0115; r: 0.9998; Max deviation: 8.7% |
| Reagents | Sandwich principle, 9 minutes; 2-step incubation | Sandwich principle, 9 minutes; 1-step incubation |
| Calibrator | CK-MB STAT CalSet | Same |
| Calibration Interval | Specific intervals and conditions (e.g., once per lot, after 12 weeks, as required) | Same |
| Controls | Elecsys PreciControl Cardiac II | Same |
| Traceability/Standardization | Traceable to Abbott IMx CK-MB assay, linearized using human recombinant CK-MB from Seradyn | Same |
| Reagent Stability | Unopened: 2-8°C - up to expiration date; Opened: 2-8°C - 12 weeks; On Analyzers - 8 weeks | Same |
| Linearity | Series 1: y=0.9421 -0.0579; Series 2: y=0.9348-0.116; Series 3: y=0.942-0.0964 | Series 1: y=0.9571 -0.1267 (range: 0.27 to 563 ng/mL); Series 2: y=0.9499-0.0957 (range: 0.13 to 548 ng/mL); Series 3: y=0.9576-0.1188 (range: 0.16 to 328 ng/mL). Linearity was established at ± 11.3% within the stated measuring range. |
| Labeled Performance Characteristics | ||
| Measuring Range | 1-300 ng/mL | Same |
| Precision (CV%) | ||
| Within-run (Repeatability) | @ 5.46 ng/mL: 1.2%@ 29.5 ng/mL: 1.3%@ 93.5 ng/mL: 1.3%@ 301 ng/mL: 1.5%PC1 @ 4.44 ng/mL: 1.3%PC2 @ 57.9 ng/mL: 1.4% | @ 5.34 ng/mL: 1.1%@ 27.3 ng/mL: 1.1%@ 89.2 ng/mL: 1.1%@ 283 ng/mL: 0.8%PC1 @ 4.27 ng/mL: 1.2%PC2 @ 54.3 ng/mL: 0.9% |
| Total (Intermediate) | @ 5.46 ng/mL: 2.5%@ 29.5 ng/mL: 4.2%@ 93.5 ng/mL: 4.1%@ 301 ng/mL: 3.3%PC1 @ 4.44 ng/mL: 2.6%PC2 @ 57.9 ng/mL: 3.0% | @ 5.34 ng/mL: 1.4%@ 27.3 ng/mL: 3.2%@ 89.2 ng/mL: 2.5%@ 283 ng/mL: 2.2%PC1 @ 4.27 ng/mL: 1.4%PC2 @ 54.3 ng/mL: 1.3% |
| Analytical Sensitivity | LoB: 0.1 ng/mL; LoD: 0.3 ng/mL; LoQ: 1 ng/mL (established per CLSI EP17-A) | Same |
| Analytical Specificity (Reactivity) | CK-MM: None; CK-BB: 0.10% | Same |
| Hook Effect | No high-dose hook effect up to 5000 ng/mL | Same |
| Interferences | No interference (recovery within ± 10% compared to unspiked reference) with various substances including: lipids (2000 mg/dL), biotin (50 ng/mL), bilirubin (40 mg/dL), hemoglobin (1000 mg/dL), RF (1700 IU/mL), albumin (14 g/dL), immunoglobulins (IgG: 7 g/dL, IgM: 1 g/dL, IgA: 1.6 g/dL), and 18 common pharmaceuticals. | Same |
| Special Drugs Interferences | No interference (recovery within ± 10% compared to unspiked reference) with 33 special drugs. | Same |
| Limitations | Rare interference from extremely high titers of antibodies; results to be assessed with patient's medical history, clinical exam, and other findings. | Same |
| Clinical Study/Reference Range | ||
| 99th percentile (All Subjects) | Female (N=523): 5.34 ng/mL; Male (N=568): 10.36 ng/mL | Same (as established by predicate) |
| 99th percentile (No self-reported risk factors) | Female (N=120): 4.30 ng/mL; Male (N=102): 7.70 ng/mL | Same (as established by predicate) |
| Method Comparison (Predicate on e 411 vs. Modified on e 601) | n = 115; Min = 1.47 ng/mL; Max = 269 ng/mL; Slope = 0.976; Intercept = 0.053; Tau = 0.991 |
Study Proving Device Meets Acceptance Criteria:
The study conducted is a method comparison study to demonstrate that the modified Elecsys CK-MB STAT (one-step incubation) Assay on the cobas e 601 Immunoassay Analyzer performs substantially equivalently to the legally marketed predicate device, the Elecsys CK-MB STAT (two-step incubation) Assay on the cobas e 411.
Key Information about the Studies:
-
Sample Size used for the Test Set and Data Provenance:
- Plasma Type Comparison: For each plasma type (Na Heparin, Li Heparin, K2-EDTA, K3-EDTA), "at least 30" or specific numbers rounded to 34 or 35 samples were used (e.g., 30 for Na Heparin, 35 for Li Heparin, 34 for K2-EDTA, 35 for K3-EDTA).
- Linearity: 3 series of serum samples were used, with ranges from 0.13 to 563 ng/mL.
- Precision: Not explicitly stated, but CLSI EP5-A2 guidelines typically involve multiple replicates (e.g., 2 runs per day for 20 days) for multiple samples (e.g., controls and patient samples at different concentrations). The performance values provided (e.g., %CV) are derived from such a study.
- Interference (Common Pharmaceuticals and Special Drugs): Not explicitly stated, but "11 numerical values" were tested for general interferents, and "18 commonly used pharmaceuticals" and "33 special drugs" were tested.
- Clinical/Reference Range: 523 female subjects and 568 male subjects ("apparently heart healthy") were used to establish the 99th percentile for the predicate device.
- Method Comparison: A sample size of n = 115 was used, with CK-MB concentrations ranging from 1.47 ng/mL to 269 ng/mL.
- Data Provenance: The document does not explicitly state the country of origin for the data or whether it was retrospective or prospective. Given that Rochester Diagnostics GmbH (Germany) is the submitter, it is likely that parts of the data originated from Europe, but this is not confirmed. The clinical study for reference ranges specifies "Subjects represented 'apparently heart healthy' population," which implies prospective selection, but the details are scarce.
-
Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications:
- For the analytical performance studies (precision, linearity, interference, analytical sensitivity, specificity), the "ground truth" is typically established by the reference methods/standards used for spiking, dilution, or comparison, rather than expert consensus on individual cases. For example, linearity samples are generated by diluting a high-concentration sample with a low-concentration matrix, and the expected values are the "ground truth."
- For the clinical reference range, the "apparently heart healthy" population was selected based on "exclusion of subjects with known poor cardiac health or known peripheral vascular disease." This implies clinical assessment, but the number and qualifications of experts involved in this selection are not specified.
- For the method comparison, the "ground truth" implicitly relies on the predicate device's established performance. No external experts are mentioned for establishing ground truth for the test set.
-
Adjudication Method for the Test Set:
- Not applicable as this is an in-vitro diagnostic device for quantitative measurement, and the studies described are analytical performance evaluations and method comparisons against a predicate device. There is no mention of subjective interpretation of results requiring adjudication.
-
Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
- No, an MRMC comparative effectiveness study was not done. This type of study typically applies to imaging or diagnostic devices where human reader interpretation is a key component, often comparing AI-assisted reading to unassisted reading. The Elecsys CK-MB STAT Immunoassay is an in-vitro diagnostic test that provides a quantitative numerical result, not an image or complex data requiring human interpretation in the same way.
-
Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study:
- Yes, this is effectively a standalone performance study of the modified assay. The device itself (the immunoassay and the analyzer) is an automated system. The studies evaluate the analytical performance of this automated system directly (e.g., precision, linearity, analytical sensitivity, specificity, interference) and compare its output to the predicate device. There is no human-in-the-loop component in the direct measurement and reporting of CK-MB values by the device itself that would require a separate "human-in-the-loop" study.
-
Type of Ground Truth Used:
- The ground truth for the performance studies is rooted in established laboratory standards, reference materials, and comparative methods.
- Linearity: Gravimetric dilutions of known concentration samples.
- Analytical Sensitivity: Statistical treatment of blank and low-concentration samples (CLSI EP17-A standard).
- Analytical Specificity: Spiking samples with known concentrations of interfering substances (e.g., CK-MM, CK-BB, bilirubin, drugs) and measuring recovery.
- Method Comparison: The established values measured by the predicate device (Elecsys CK-MB STAT two-step on cobas e 411) serve as the comparative standard.
- Clinical Reference Range: Derived from measurements in a population of "apparently heart healthy" individuals, based on clinical exclusion criteria.
- The ground truth for the performance studies is rooted in established laboratory standards, reference materials, and comparative methods.
-
Sample Size for the Training Set:
- This document describes a premarket notification (510(k)) for a modified immunoassay device, not a machine learning or AI algorithm in the traditional sense that requires a "training set." The development of such an assay involves extensive R&D, reagent formulation, and optimization which can be considered "training," but it doesn't involve a distinct "training set" of patient data in the same way an AI algorithm for image recognition would have. The performance studies detailed are for validation/testing of the developed assay.
-
How the Ground Truth for the Training Set was Established:
- As noted above, the concept of a "training set" and associated "ground truth establishment" is not directly applicable in the context of this traditional immunoassay device's submission. The "training" for such a device is the iterative process of optimizing reagent concentrations, incubation times, antibody pairs, and detection methods during its analytical development, often guided by known chemical principles and calibrated against reference standards. The studies presented here are to validate the final optimized product.
{0}------------------------------------------------
Special 510(k) Summary
| Introduction | According to the requirements of 21 CFR 807.92, the following information provides sufficient detail to understand the basis for a determination of substantial equivalence. | |
|---|---|---|
| Submitter Name, Address, Contact | Roche Diagnostics9115 Hague Road, PO. Box 0416Indianapolis, IN 46250-50416Contact Person: Kelli TurnerPhone: (317) 521-4515 FAX: (317) 521-2324 Email: kelli.turner@roche.com Date Prepared: April 28, 2014 | |
| Device Name | Proprietary name: | Elecsys CK-MB STAT Immunoassay |
| Common name: | CK-MB STAT Assay | |
| Classification name: | Colorimetric method; Cpk or Isoenzymes | |
| Product Code: | JHY | |
| Predicate Device: | CK-MB STAT Immunoassay, Roche |
Continued on next page
Roche Diagnostics
{1}------------------------------------------------
Establishment For the CK-MB STAT Assay, the establishment registration number for Registration Roche Diagnostics GmbH in Mannheim, Germany, is 9610126 and for Penzberg, Germany, is 9610529. The establishment registration number for Roche Diagnostics United States is 1823260
Classification . The FDA has classified the CK-MB STAT as a Class II device.
| Panel | ProductCode | Classification Name | Regulation Citation |
|---|---|---|---|
| Clinical Chemistry | JHY | Colorimetric Method, CpkOr Isoenzymes | 21 CFR 862.1215 |
Performance To date, no performance standards that affect this device have been Standards finalized under Section 514 of the Act.
Proposed draft labeling sufficient to describe the device, the intended use, Proposed Labeling and the directions for use on the cobas e 601 immunoassay analyzer is attached. We believe the draft version of the device labeling presented in Section V contains all of the technical information required per 21 CFR 809.10 for the CK-MB STAT (one-step incubation) Assays.
{2}------------------------------------------------
| AnalyzerPlatform | Precision of the CK-MB STAT (one-step incubation) assay wasevaluated on one cobas e 601 Immunoassay Analyzers according toCLSI EP5-A2 guidelines. A method comparison between the ElecsysCK-MB STAT (two-step incubation) and CK-MB STAT (one-stepincubation) was performed and summarized in Section III, 510(k)summary, Method Comparison. |
|---|---|
| DeviceDescription | The CK-MB STAT (one-step incubation) Assay is a sandwich immunoassaywith streptavidin microparticles and electrochemiluminescence detection. |
| Results are determined using a calibration curve that is generated specificallyon each instrument by a 2 point calibration and a master curve (5-point-calibration) provided with the reagent bar code. | |
| The CK-MB STAT (one-step incubation) application is identical to the CK-MB STAT (two-step incubation) assay, the only difference being for the CK-MB STAT (one-step incubation) application, the sample, reagent 1, reagent 2and microparticles are added at one time. | |
| Note: Calibrators and controls are packaged and sold separately. |
Intended Use
Immunoassay for the in vitro quantitative determination of the MB isoenzyme of creatine kinase in human serum and plasma The electrochemiluminescence immunoassay "ECLIA" is intended for use on the indicated and cobas e immunoassay analyzers.
{3}------------------------------------------------
| Indications for use | Immunoassay for the in vitro quantitative determination of the MB isoenzyme of creatine kinase in human serum and plasma. Measurements of the MB isoenzyme of creatinine kinase are used as an aid in the diagnosis of myocardial infarction.The electrochemiluminescence immunoassay "ECLIA" is intended for use on the indicated Elecsys and cobas e immunoassay analyzers. |
|---|---|
| Special conditions for use | For prescription use only |
| Special instrument requirements | The electrochemiluminescence immunoassay "ECLIA" is intended for use on the indicated Elecsys and cobas e immunoassay analyzers. |
| Substantial Equivalence | The CK-MB STAT Immunoassay is substantially equivalent to other devices legally marketed in the United States.CK-MB STAT (one-step incubation) Immunoassays, is equivalent to CK-MB STAT (two-step) Immunoassay, Roche Diagnostics (K132571). |
| Substantial Equivalence Comparison | The following table compares the CK-MB STAT Immunoassay (one- step incubation) with the predicate device. |
Continued on next page
· .
{4}------------------------------------------------
Comparison of Assays, Similarities and Differences
Table 1 CK-MB STAT (two-step incubation) vs. CK-MB STAT (one-step incubation)
| Assay Comparison | ||
|---|---|---|
| Feature | Predicate Device: Elecsys CK-MB STAT (two-step incubation) Assay (K132571) | CK-MB STAT (one-step incubation) Assay (modified) |
| General Assay Features | ||
| Intended Use/ Indications for Use | Immunoassay for the in vitro quantitative determination of MB isoenzyme of creatine kinase in human serum and plasma.The electrochemiluminescence immunoassay “ECLIA” is intended for use on Elecsys and cobas e immunoassay analyzers. | Same |
| Assay Protocol | Two step Sandwich assay using biotinylated and ruthenium labeled antibodies and streptavidin microparticles | Sandwich assay using biotinylated and ruthenium labeled antibodies and streptavidin microparticles |
| Detection Protocol | Electrochemiluminescent Immunoassay | Same |
| Applications | STAT (9 minute) application | Same |
{5}------------------------------------------------
Comparison of Assays—Similarities and Differences, continued
·
Table 1 continued
| Assay Comparison | |||||||
|---|---|---|---|---|---|---|---|
| Feature | Predicate Device: Elecsys CK-MB STAT (two-step incubation) Assay (K132571) | CK-MB STAT (one-step incubation) Assay (modified) | |||||
| General Assay Features | |||||||
| Instrument Platform | cobas e 411 | Roche cobas e 601 | |||||
| Sample Volume | 15 µL | Same | |||||
| Sample Type | Human serum and plasma treated with K2-EDTA, K3-EDTA, and lithium heparin and sodium heparin plasma. | Same | |||||
| Specification | Na Hepar in Plasma | Li Hepar in Plasma | K2-EDTA Plasma | K3-EDTA Plasma | |||
| Sample size normally filled tubes | at least 30 | 35 | 34 | 35 | 35 | ||
| Slope (BaPa) | 0.9 - 1.1 | 0.994 | 0.996 | 1.020 | 0.988 | ||
| Intercept (BaPa) | ≤ +/- 0.15 | 0.0010 | 0.0045 | 0.0082 | 0.0115 | ||
| Correlation on r | > 0.95 | 0.9997 | 0.9996 | 0.9999 | 0.9998 | ||
| Relative deviation for single sample pairs | +/- 20% | max deviation on 14.6 % | max deviation on 12.0 % | max deviation on 10.5 % | max deviation on 8.7 % | ||
| Reagents | Sandwich principle. Total duration of assay: 9 minutes.• 1st incubation: 15 µL of sample, a biotinylated monoclonal anti-CK-MB antibody, and a monoclonal CK-MB-specific antibody labeled with a ruthenium complex react to form a sandwich complex.• 2nd incubation: After addition of streptavidin-coated microparticles, the complex becomes bound to the solid phase via interaction of biotin and | Sandwich principle. Total duration of assay: 9 minutes• Antigen in the sample (15 µL), a biotinylated monoclonal anti-CK-MB antibody, a monoclonal CK-MB-specific antibody labeled with a ruthenium complex and streptavidin-coated microparticles react to form a sandwich complex, which is bound to a solid phase |
{6}------------------------------------------------
Comparison of Assays—Similarities and Differences, continued
Table 1 continued
| Assay Comparison | ||
|---|---|---|
| Feature | Predicate Device: Elecsys CK-MB STAT (two-step incubation) Assay (K132571) | CK-MB STAT (one-step incubation) Assay (modified) |
| General Assay Features | ||
| Calibrator | CK-MB STAT CalSet | Same |
| Calibration Interval | Calibration must be performed once per reagent lot using fresh reagent (i.e. not more than 24 hours since the reagent kit was registered on the analyzer). Renewed calibration is recommended as follows:• After 12 weeks when using the same reagent lot.• After 7 days (when using the same reagent kit on the analyzer).• As required: e.g. quality control findings outside the specified limits | Same |
| Controls | Elecsys PreciControl Cardiac II | Same |
{7}------------------------------------------------
Comparison of Assays—Similarities and Differences, continued
.
Table 1 continued
:
| Assay Comparison | ||
|---|---|---|
| Feature | Predicate Device: Elecsys CK-MB STAT (two-step incubation) Assay (K132571) | CK-MB STAT (one-step incubation) Assay (modified) |
| General assay features | ||
| Traceability /Standardization | The CK-MB STAT assay is traceable to the Abbott IMx CK-MB assay andlinearized using human recombinantCK-MB from Seradyn | Same |
| Reagent Stability | Unopened:2-8°C - Up to the stated expiration dateOpened 2-8°C - 12 weeksOn Analyzers - 8 weeks | Same |
| Linearitydetermined withserum samples. | Series 1: y=0.9421 -0.0579Series 2: y=0.9348-0.116Series 3: y=0.942-0.0964 | Series 1: y=0.9571 -0.1267(range: 0.27 to 563 ng/mL)Series 2: y=0.9499-0.0957(range: 0.13 to 548 ng/mL)Series 3: y=0.9576-0.1188(range: 0.16 to 328 ng/mL)Note: linearity was established at ±11.3% within the stated measuringrange. |
{8}------------------------------------------------
Comparison of Assays—Similarities and Differences, continued
Table 1 continued
| Assay Comparison | ||
|---|---|---|
| Feature | Predicate Device: Elecsys CK-MB STAT (two-step incubation) Assay (K132571) | CK-MB STAT (one-step incubation) Assay (modified) |
| Labeled Performance Characteristics | ||
| Measuring Range | 1-300 ng/mL | Same |
| Precision | cobas e 411:Within-run (will be labeled Repeatability)1.2% CV @ 5.46 ng/mL1.3% CV @ 29.5 ng/mL1.3% CV @ 93.5 ng/mL1.5% CV @ 301 ng/mL1.3% CVPC1 @ 4.44 ng/mL1.4% CVPC2 @ 57.9 ng/mLTotal (will be labeled Intermediate)2.5% CV @ 5.46 ng/mL4.2% CV @ 29.5 ng/mL4.1% CV @ 93.5 ng/mL3.3% CV @ 301 ng/mL2.6% CVPC1 @ 4.44 ng/mL3.0% CVPC2 @ 57.9 ng/mL | cobas e 601:Within-run (will be labeled Repeatability)1.1% CV @ 5.34 ng/mL1.1% CV @ 27.3 ng/mL1.1% CV @ 89.2 ng/mL0.8% CV @ 283 ng/mL1.2% CVPC1 @ 4.27 ng/mL0.9% CVPC2 @ 54.3 ng/mLTotal (will be labeled Intermediate)1.4% CV @ 5.34 ng/mL3.2% CV @ 27.3 ng/mL2.5% CV @ 89.2 ng/mL2.2% CV @ 283 ng/mL1.4% CVPC1 @ 4.27 ng/mL1.3% CVPC2 @ 54.3 ng/mL |
| Analytical Sensitivity | Limit of Blank (LoB): = 0.1 ng/mlLimit of Detection (LoD): = 0.3 ng/mlLimit of Quantitation (LoQ): = 1 ng/mlEstablished according to CLSI EP17- A | Same |
| Feature | Predicate Device: Elecsys CK-MB STAT (two-step incubation) Assay (K132571) | CK-MB STAT (one-step incubation) Assay (modified) |
| Labeled Performance Characteristics | ||
| Analytical Specificity | AnalyteReactivity | Same |
| CK-MMNone | ||
| CK-BB0.10% | ||
| Hook Effect | There is no high-dose hook effect at CK-MB concentrations up to 5000 ng/mL | Same |
| Limitations | Each interferent was evaluated at 11 numerical values. All samples were tested in duplicate. The results reported represent recovery of ± 10 % compared to the unspiked reference sample.The results of the interferences are presented below: | Same |
| Interferent testedNo interference up to | ||
| Intralipid® (Lipemia)2000 mg/dL | ||
| Biotin50 ng/mL | ||
| Bilirubin40 mg/dL | ||
| Hemoglobin1000 mg/dL | ||
| Rheumatoid Factor1700 IU/mL | ||
| Human Serum albumin14 g/dL | ||
| Human IgG7 g/dL | ||
| Human IgM1 g/dL | ||
| Human IgA1.6 g/dL | ||
| Assay Comparison | ||
| Feature | Predicate Device: Elecsys CK-MB STAT (two-step incubation) Assay (K132571) | CK-MB STAT (one-step incubation) Assay (modified) |
| Labeled Performance Characteristics | ||
| Limitations, continued | In vitro tests were performed on 18 commonly used pharmaceuticals. No interference with the assay was found. Criterion: Recovery within ± 10% compared to the unspiked reference sample. | Same |
| These included samples with the following: | ||
| Drug | Concentration | |
| Acetylcysteine | 150 mg/L | |
| Ampicillin-Na | 1000 mg/L | |
| Ascorbic acid | 300 mg/L | |
| Ca- Dobesilate | 200 mg/L | |
| Cyclosporine | 5 mg/L | |
| Cefoxitin | 2500 mg/L | |
| Heparin | 5000 U | |
| Intralipid | 10000 mg/L | |
| Levodopa | 20 mg/L | |
| Methyldopa + 1.5H2O | 20 mg/L | |
| Metronidazole | 200 mg/L | |
| Phenylbutazone | 400 mg/L | |
| Doxycycline | 50 mg/L | |
| Acetylsalicylic Acid | 1000 mg/L | |
| Rifampicin | 60 mg/L | |
| Acetaminophen | 200 mg/L | |
| Ibuprofen | 500 mg/L | |
| Theophylline | 100 mg/L | |
| Assay Comparison | ||
| Feature | Predicate Device: Elecsys CK-MBSTAT (two-step incubation) Assay(K132571) | CK-MB STAT (one-step incubation)Assay (modified) |
| Limitations,continued | Labeled Performance Characteristics | |
| Testing was performed on 33 special drugswith concentrations shown in the tablebelow. No interference with the assay wasfound. Criterion: Recovery within ± 10%compared to the unspiked referencesample. | Same | |
| Special Drug | Concentration | |
| Carvedilol | 50 mg/L | |
| Propanolol | 160 mg/L | |
| Marcumar | 9 mg/L | |
| Reteplase | 20 U/L | |
| Suprarenin(Adrenalin) | 3 mg/L | |
| Methylprednislon | 40 mg/L | |
| Verapamil | 480 mg/L | |
| Lidocain | 500 mg/L | |
| Enalapril | 40 mg/L | |
| Captopril | 150 mg/L | |
| Lisinopril | 40 mg/L | |
| Aldactone(Spironolacton) | 400 mg/L | |
| Torasemid | 5 mg/L | |
| Insulin | 150 I.U. | |
| Tolbutamid | 10.5 mg/L | |
| Gentamycin | 420 mg/L | |
| Lovostatin | 80 mg/L | |
| Pravastatin | 8 mg/L | |
| Simvastin | 80 mg/L | |
| Bisprolol | 20 mg/L | |
| Nitrolingual(Glyceroltrinitrat) | 1.6 mg/L | |
| Heparin | 7500 I.U. | |
| Metropolol | 200 mg/L | |
| Molsidomin | 16 mg/L | |
| Nicardipin | 160 mg/L | |
| Nifedipin | 60 mg/L | |
| Propafenon | 900 mg/L | |
| Solatol | 480 mg/L | |
| Streptokkinase | 10 000 000 I.U. | |
| Urokinase | 4200000 mg/L | |
| Digoregen (Digoxin) | 0.5 mg/L | |
| Digimerck minor(Digitoxin) | 0.21 mg/L | |
| Clopidrogel | 300 mg/L | |
| Assay Comparison | ||
| Feature | Predicate Device: Elecsys CK-MBSTAT (two-step incubation) Assay(K132571) | CK-MB STAT (one-step incubation)Assay (modified) |
| Labeled Performance Characteristics | ||
| Limitations,continued | In rare cases, interference due toextremely high titers of antibodies toanalyte-specific antibodies, streptavidinor ruthenium can occur. These effectsare minimized by suitable test design.For diagnostic purposes, the results shouldalways be assessed in conjunction with thepatient's medical history, clinicalexamination and other findingsThese limitations were established bytesting performed with one human scrumsample containing low levels of CK-MBand one human serum sample containinghigh levels of CK-MB. | Same |
PC1=PreciControl Cardiac 1
PC2=PreciControl Cardiac 2
Continued on next page
.
{9}------------------------------------------------
Comparison of Assays-Similarities and Differences, continued
Table 1 continued
{10}------------------------------------------------
{11}------------------------------------------------
{12}------------------------------------------------
Continued on next page
.
{13}------------------------------------------------
Comparison of Assays-Similarities and Differences, continued
| Feature | Predicate Device: Elecsys CK-MBSTAT (two-step incubation) Assay(K132571) | CK-MB STAT (one-stepincubation) Assay (modified) | ||
|---|---|---|---|---|
| Labeled Performance Characteristics | ||||
| ClinicalStudy/referencerange | Gender (N) | 99thpercentile(ng/mL) | Same | |
| AllSubjects | Female | 523 | 5.34 | |
| Subjects | Male | 568 | 10.36 | |
| Subjectswith noSelf-reportedriskfactors | Female | 120 | 4.30 | |
| Male | 102 | 7.70 | ||
| Subjects represented "apparently hearthealthy" population with exclusion ofsubjects with known poor cardiac healthor known peripheral vascular diseaseonly. | ||||
| Additional Performance Characteristics | ||||
| MethodComparisonElecsys CK-MBSTAT on cobase 411(two-stepincubation) vs.Elecsys CK-MBSTAT on cobase 601 (one-stepincubation) | n = 115 | Passing/Bablok | ||
| Min = 1.47 ng/ml | ||||
| Max = 269 ng/ml | ||||
| Slope | 0.976 | |||
| Intercept | 0.053 | |||
| Tau | 0.991 |
Continued on next page
- 100
{14}------------------------------------------------
| Standard/GuidanceDocumentReference | In addition to FDA guidance regarding 510(k) submissions, the followingstandards were used for the performance studies. |
|---|---|
| • Evaluation of Precision Performance of QuantitativeMeasurement Methods; Approved Guideline – Second Edition.CLSI document EP5-A2, Volume 24, No. 25, August 2004. | |
| • Protocols for Determination of Limits of Detection and Limits ofQuantitation; Approved Guideline. CLSI document EP 17-A,Volume 24, No. 34, October 2004. | |
| • Evaluation of the Linearity of Quantitative MeasurementProcedures: A Statistical Approach; Approved Guideline. CLSIdocument EP6-A, Volume 23, No. 16, April 2003. | |
| Data for CK-MB STAT (one-step incubation) is on file at RocheDiagnostics. | |
| Conclusion | The submitted information in this premarket notification supports asubstantial equivalence decision. The differences between predicate andcandidate do not impact the indications for use or technologicalcharacteristics. |
{15}------------------------------------------------
Image /page/15/Picture/0 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle or bird-like figure with three curved lines representing its body and wings. The logo is surrounded by text that reads "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" in a circular arrangement.
DEPARTMENT OF HEALTH & HUMAN SERVICES
Public Health Service
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
May 8, 2014
ROCHE DIAGNOSTICS KELLI TURNER REGULATORY AFFAIRS PRINCIPLE 9115 HAGUE ROAD INDIANAPOLIS IN 46250
Re: K140404
:
Trade/Device Name: Elecsys CK-MB STAT Immunoassay Regulation Number: 21 CFR 862.1215 Regulation Name: Creatine phosphokinasc/creatine kinase or isoenzymes test system Regulatory Class: II Product Code: JHY Dated: April 07, 2014 Received: April 08, 2014
Dear Ms. Turner:
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 Eederal 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 (2) CFR Parts 801 and 809): medical device 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.
{16}------------------------------------------------
Page 2-Ms. Turner
If you desire specific advice for your device on our labeling regulations (2) 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/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 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/ReportalProblem/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.
Courtney H. Lias -S
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
{17}------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration
Indications for Use
510(k) Number (if known)
Device Name
Elecsys CK-MB STAT Immunoassay
Indications for Use (Describe)
Immunoassay for the in vitro quantitation of the MB iscenzyme of creatine kinasc in human secum and plasma. Measurements of the MB isoenzyme of creatine kinase are used as an aid in the diagnosis of myocardial infanction.
The electrochemiluminescence immunoassay "ECLIA" is intended for use on Elecsys and cobas e immunoassay analyzers.
Type of Use (Select one or both, as applicable)
2 Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 801 Subpart C)
Form Approved: OMB No. 0910-0120
Expiration Date: January 31, 2017
See PRA Statement on last page.
PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON A SEPARATE PAGE IF NEEDED.
FOR FDA USE ONLY
Concurrence of Center for Devices and Radiological Health (CDRH) (Signature)
Ruth A. Chesler -S
§ 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.