(64 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 Assay and the CK-MB Assay are two-step sandwich immunoassays 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 application is identical to the CK-MB assay, with the only difference being the length of incubation (9 minutes vs. 18 minutes).
This document describes the 510(k) Summary for the Elecsys CK-MB STAT and Elecsys CK-MB Immunoassays (4th Generation reagent). The purpose of the submission is to market a new reagent developed by Roche Diagnostics, claiming substantial equivalence to the previous 3rd Generation CK-MB STAT assay (K022654). The new reagent is intended for the in vitro quantitative determination of the MB isoenzyme of creatine kinase in human serum and plasma, used as an aid in diagnosing myocardial infarction on Elecsys and cobas e immunoassay analyzers.
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are generally implied by the performance characteristics of the predicate device and the goals for the new 4th Generation assay. The study demonstrated the performance of the new device (referred to as "4th Generation CK-MB STAT Assay (modified)" or "4th Generation CK-MB 18-Minute assay (modified)") against these implied benchmarks and established its own performance characteristics.
Here's a table summarizing the performance characteristics for both the predicate (3rd Generation Elecsys CK-MB STAT Assay) and the 4th Generation CK-MB STAT Assay (the primary focus of the comparison):
| Feature / Performance Characteristic | Predicate Device: Elecsys 3rd Generation CK-MB STAT Assay (K022654) | 4th Generation CK-MB STAT Assay (modified) | Acceptance Criteria (implied/demonstrated) |
|---|---|---|---|
| Measuring Range | 0.1-500 ng/mL | 1-300 ng/mL | The new device has a slightly more conservative upper limit for the measuring range, but the overall range aligns for clinical utility. |
| Precision (Within-run / Repeatability) - e.g., @ 5.77 ng/mL or 5.46 ng/mL | Elecsys 2010: e.g., 1.5% CV @ 12.4 ng/mL, 2.1% CV @ 39.7 ng/mL | cobas e 411: e.g., 1.2% CV @ 5.46 ng/mL, 1.3% CV @ 29.5 ng/mL | New device demonstrates comparable or improved precision on the cobas e 411 platform. The CVs are generally low, indicating good repeatability. |
| Precision (Total / Intermediate) - e.g., @ 5.77 ng/mL or 5.46 ng/mL | Elecsys 2010: e.g., 2.3% CV @ 5.77 ng/mL, 2.6% CV @ 12.4 ng/mL | cobas e 411: e.g., 2.5% CV @ 5.46 ng/mL, 4.2% CV @ 29.5 ng/mL | New device demonstrates comparable or improved overall precision. |
| Analytical Sensitivity (Lower Detection Limit / LoD) | <0.100 ng/mL | Limit of Blank (LoB): = 0.1 ng/mL, Limit of Detection (LoD): = 0.3 ng/mL | The new device's LoD is slightly higher than the predicate's lower detection limit, but still within clinically acceptable low range. |
| Analytical Specificity (CK-MM, CK-BB reactivity) | CK-MM: None, CK-BB: 0.10% | Same | Achieved the same high specificity as the predicate. |
| Hook Effect | No high-dose hook effect up to 5000 ng/mL | Same | Maintained the excellent hook effect performance of the predicate. |
| Limitations (Interferences) | Hemoglobin <1.5 g/dL, Bilirubin < 34 mg/dL, Intralipid < 1.500 mg/dL, Biotin < 100 ng/mL, Rheumatoid factors ≤ 1500 IU/mL | Hemoglobin ≤1000 mg/dL, Bilirubin ≤ 34 mg/dL, Intralipid ≤ 1.500 mg/dL, Biotin ≤ 30 ng/mL, Rheumatoid factors ≤ 1500 IU/mL, IgG < 7 g/dL, IgM < 1 g/dL, IgA ≤ 1.6 g/dL, Serum Albumin ≤ 20 g/dL | The new device maintains similar immunity to common interferents, with a more stringent biotin tolerance (≤ 30 ng/mL vs. < 100 ng/mL) and additional robust data for immunoglobulins and serum albumin. |
| Method Comparison (Predicate vs 4th Gen STAT - Serum) | Not applicable (new device compared to predicate) | n = 165 samples, Min = 1.08 ng/mL, Max = 283 ng/mL. Passing/Bablok: Slope = 1.053, Intercept = -0.525, Tau/r = 0.982. Linear Regression: Slope = 1.067, Intercept = -0.740, Tau/r = 0.999. | The new device shows good correlation with the predicate, indicating substantial equivalence in measurement across the clinical range. |
| Method Comparison (4th Gen STAT vs 4th Gen 18-minute - Serum) | Not applicable (comparison between two new devices) | n = 115 samples, Min = 1.44 ng/mL, Max = 283 ng/mL. Passing/Bablok: Slope = 1.003, Intercept = -0.005, Tau/r = 0.985. Linear Regression: Slope = 1.006, Intercept = 0.071, Tau/r = 0.999. | Excellent correlation between the two new assays (STAT and 18-minute versions), supporting consistent performance. |
| Matrix Comparison (Plasma vs. Serum) | Not explicitly stated but assumed compatible. | All data passed criteria for Na-heparin, Li-heparin, K2-EDTA, K3-EDTA: Slope: 0.9-1.1, Pearson r > 0.95, Intercept: ≤± 0.15, Single sample pairs: 100% ± 20%. | Demonstrated compatibility with various plasma anticoagulants, showing minimal interference compared to serum. |
| Reagent Stability (On Analyzers) | 8 weeks | 6 weeks | Slightly reduced on-analyzer stability compared to the predicate, but still robust. |
Study Proving Acceptance Criteria:
The studies presented in the 510(k) summary are direct comparisons demonstrating that the new 4th Generation Elecsys CK-MB STAT and Elecsys CK-MB Immunoassays meet performance criteria for substantial equivalence to the predicate device (Elecsys 3rd Generation CK-MB STAT Assay, K022654) and also illustrate the performance characteristics of the new assays themselves.
2. Sample Sizes Used for the Test Set and Data Provenance:
- Method Comparison (4th Gen STAT vs. Predicate): n = 165 serum samples.
- Method Comparison (4th Gen STAT vs. 4th Gen 18-Minute): n = 115 serum samples.
- Precision Testing (4th Gen STAT & 4th Gen 18-Minute): Performed using human serum samples and PreciControl Cardiac II over 21 days, according to CLSI EP5-A2. The number of samples for precision is not explicitly stated as 'n=' for unique patients but rather implied through the CLSI methodology.
- Analytical Sensitivity (LoB, LoD, LoQ): Determined in accordance with CLSI EP17-A requirements, involving n ≥ 60 measurements of analyte-free samples.
- Matrix Comparison (Plasma vs. Serum): 35 tubes collected per anticoagulant (Na-heparin, Li-heparin, K2-EDTA, K3-EDTA).
- Clinical Study/Reference Range Study: N = 760 women, 628 men for 3rd Gen (predicate). For 4th Gen, N=523 female, 568 male for all subjects, and N=120 female, 102 male for subjects with no self-reported risk factors. Subjects were "apparently heart healthy" with exclusion of known poor cardiac health.
- Data Provenance: The document does not explicitly state the country of origin for the patient samples. The studies were conducted internally by Roche Diagnostics. The nature of the studies (method comparisons, precision, analytical sensitivity, matrix comparisons) suggests these were primarily prospective laboratory studies designed to characterize the device's performance, rather than retrospective analysis of existing clinical data. The Clinical Study/Reference Range Study would typically involve prospective collection and analysis of de-identified healthy donor samples.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications:
This submission concerns an in vitro diagnostic (IVD) immunoassay, not an imaging device or AI algorithm that requires human experts for ground truth establishment in the same way. The "ground truth" for this device is established through:
- Reference Methods: Comparison against a legally marketed predicate device (Elecsys 3rd Generation CK-MB STAT Assay) and comparison between the two new assays (STAT and 18-minute versions). The predicate device itself was cleared based on its own performance relative to established methods.
- Industry Standards: Adherence to CLSI (Clinical and Laboratory Standards Institute) guidelines (EP5-A2 for precision, EP17-A for analytical sensitivity, EP6-A for linearity). These guidelines define rigorous statistical and experimental approaches for evaluating assay performance.
Therefore, the "ground truth" is not established by a panel of human experts reviewing individual cases but by the analytical characteristics of the device when measured against well-defined reference standards and methods in laboratory settings, overseen by qualified laboratory scientists and statisticians.
4. Adjudication Method for the Test Set:
Not applicable in the context of an IVD immunoassay. Adjudication methods like 2+1 or 3+1 are typically used in clinical imaging studies where multiple human readers interpret results, and a consensus or tie-breaking mechanism is needed to establish ground truth for a dataset. For this immunoassay, performance is evaluated against quantitative measurements from other assays or statistical targets derived from CLSI guidelines.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
No, an MRMC comparative effectiveness study was not done. This type of study is relevant for evaluating the impact of an AI system on human reader performance, particularly in diagnostic imaging. The Elecsys CK-MB STAT and Elecsys CK-MB Immunoassays are standalone laboratory diagnostic devices that provide quantitative measurements, not AI tools designed to assist human readers.
6. Standalone Performance Study (Algorithm Only):
Yes, the studies presented are essentially standalone performance studies of the reagent (the "algorithm" in a broad sense for an IVD). The various performance characteristics (measuring range, precision, analytical sensitivity, analytical specificity, hook effect, interference, and method comparisons) directly represent the performance of the immunoassay system (reagent + instrument) without human-in-the-loop assistance in interpreting the final quantitative result. The device provides a numerical value (ng/mL) directly.
7. Type of Ground Truth Used:
The ground truth for evaluating this immunoassay is primarily based on:
- Reference Measurement (Predicate Device): The performance of the new 4th Generation assay is compared against the established performance of the legally marketed 3rd Generation predicate device.
- Analytical Standards: Performance metrics like precision, analytical sensitivity (LoB, LoD, LoQ), and linearity are established using statistical methods defined by CLSI guidelines (e.g., EP5-A2, EP17-A, EP6-A). This involves using control materials and samples with known or precisely characterized analyte concentrations.
- Biological Samples: Human serum and plasma samples are used to assess performance characteristics, including method comparisons and matrix effects. The "true" value for these clinical samples is often assigned by the reference method or by a highly characterized comparative method.
- Traceability: The CK-MB STAT assay is traceable to the Abbott IMx CK-MB assay and linearized using human recombinant CK-MB from Seradyn, indicating an effort to link its measurements to recognized standards.
8. Sample Size for the Training Set:
The document does not specify a distinct "training set" sample size in the context of machine learning or AI. For IVD reagents, the development process involves extensive internal testing and optimization (which can be considered analogous to "training" and "validation" phases in AI development, but with biochemical and analytical methodology), but these details are typically not provided as specific "training set sizes" in 510(k) summaries. The data presented are performance validation data.
9. How the Ground Truth for the Training Set Was Established:
As above, the concept of a "training set" and its "ground truth" doesn't directly apply in the machine learning sense here. For reagent development and optimization, the "ground truth" during development would be established through a combination of:
- Known concentration standards and calibrators: Used to ensure the assay accurately measures CK-MB levels.
- Reference methods: Comparing experimental formulations against existing, well-characterized CK-MB assays.
- Clinical samples: Testing various formulations with a wide range of human serum and plasma samples, with consensus values likely derived from established methods or expert laboratories.
- Biochemical principles: Ensuring the immunoassay's capture and detection mechanisms accurately target the MB isoenzyme of creatine kinase.
The summary details the methods for determining analytical performance characteristics, indicating a rigorous scientific approach to developing and validating the device.
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K B257/
510(k) Summary for Elecsys CK-MB STAT and Elecsys CK-MB Immunoassays
| Date prepared: | October 17, 2013 |
|---|---|
| Purpose of submission | Roche Diagnostics hereby submits this 510(k) to provide FDA with notification of intent to market a new device named Elecsys CK-MB Gen.4 reagent. All data in this submission was generated using the CK-MB STAT assay on the cobas e 411 analyzer as indicated. Method comparison data is included for the CK-MB STAT and CK-MB (18-minute) assay, as well as CK-MB STAT and Predicate device. |
This candidate device is a new reagent that was developed by Roche Diagnostics. The previous generation of reagent, CK-MB STAT, was cleared in 510(k) K022654 and serves as the predicate device. The candidate and predicate devices use the same calibrator and controls. Only the reagents differ. This submission presents data to support clearance of this new reagent.
| Measurand | CK-MB |
|---|---|
| Type of test | Quantitative colorimetric method; Cpk or Isoenzymes |
| Applicant | Kelli TurnerRoche Diagnostics9115 Hague RoadIndianapolis, IN 46250Telephone: (317) 521-4515Fax: (317) 521-2324Email: Kelli.Turner@Roche.com |
OCT 1 8 2013
| Candidate device names | Proprietary name:(1) Elecsys CK-MB STAT Immunoassay(2) Elecsys CK-MB ImmunoassayCommon name:(1) CK-MB STAT Immunoassay(2) CK-MB Immunoassay |
|---|---|
| ------------------------ | ----------------------------------------------------------------------------------------------------------------------------------------------------------------- |
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510(k) Summary for Elecsys CK-MB STAT and Elecsys CK-MB Immunoassays, Continued
.
Regulatory information
| Product Code | Classification | Regulation | Panel |
|---|---|---|---|
| JHY | Class II | 21 CFR 862.1215(Creatinephosphokinase/creatinekinase or isoenzymes testsystem) | ClinicalChemistry |
Continued on next page
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510(k) Summary for Elecsys CK-MB STAT and Elecsys CK-MB Immunoassays, Continued ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
| Intended use | CK-MB STAT Reagent and CK-MB Reagent have the same intended uses: |
|---|---|
| Immunoassay for the in vitro quantitative determination of the MB isoenzymeof creatine kinase in human serum and plasma. Measurements of the MBisoenzyme of creatinine kinase are used as an aid in the diagnosis ofmyocardial infarction. | |
| The electrochemiluminescence immunoassay "ECLIA" is intended for use onthe indicated Elecsys and cobas e immunoassay analyzers. | |
| Indications foruse | Immunoassay for the in vitro quantitative determination of the MB isoenzymeof creatine kinase in human serum and plasma. Measurements of the MBisoenzyme of creatinine kinase are used as an aid in the diagnosis ofmyocardial infarction. |
| The electrochemiluminescence immunoassay "ECLIA" is intended for use onthe indicated Elecsys and cobas e immunoassay analyzers. | |
| Specialconditions foruse | For prescription use only |
| Specialinstrumentrequirements | The electrochemiluminescence immunoassay "ECLIA" is intended for use onthe indicated Elecsys and cobas e immunoassay analyzers. |
| Candidatedevicedescription | The CK-MB STAT Assay and the CK-MB Assay are two-step sandwichimmunoassays with streptavidin microparticles andelectrochemiluminescence detection. Results are determined using acalibration curve that is generated specifically on each instrument by a 2-point calibration and a master curve (5-point-calibration) provided with thereagent bar code. |
| The CK-MB STAT application is identical to the CK-MB assay, with theonly difference being the length of incubation (9 minutes vs. 18 minutes). | |
| Continued on next page |
:
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510(k) Summary for Elecsys CK-MB STAT and Elecsys CK-MB Immunoassays, Continued
and the control control control control control controllers and consideration of the consideration of the consideration of the consideration of the consideration of the consi
Predicate Roche Diagnostics claims substantial equivalence to CK-MB, 3rd generation, device immunoassay, cleared in K022654.
。
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510(k) Summary for Elecsys CK-MB STAT and Elecsys CK-MB Immunoassays, Continued
| Substantialequivalence - | There are two tables in this summary: |
|---|---|
| similarities | The first table compares the CK-MB STAT generation 4 immunoassay(Master Assay) with the predicate device. |
| The second table exhibits the comparison between CK-MB STAT generation4 immunoassay to the CK-MB 18-minute generation 4 immunoassay. | |
| Continued on next page |
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Comparison of Assays, Similarities and Differences
Table 1 CK-MB STAT 3td Generation vs. CK-MB STAT 4th Generation
| Assay Comparison | ||
|---|---|---|
| Feature | Predicate Device: Elecsys 3rdGeneration CK-MB STAT Assay(K022654) | 4th Generation CK-MB STAT Assay(modified) |
| General Assay Features | ||
| IntendedUse/Indicationsfor Use | Immunoassay for the in vitroquantitative determination of MBisoenzyme of creatine kinase in humanserum and plasma. Measurements ofthe MB isoenzyme of creatine kinaseare used as an aid in the diagnosis ofmyocardial infarction. | Same |
| AssayProtocol | Two-step Sandwich assay usingbiotinylated and ruthenium labeledantibodies and streptavidinmicroparticles | Same |
| DetectionProtocol | ElectrochemiluminescentImmunoassay | Same |
| Applications | STAT application (noted as CK-MBSTAT in the labeling) and 18-minuteapplication (noted as CK-MB in thelabeling). | STAT application (noted as CK-MBSTAT in the labeling) |
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Comparison of Assays-Similarities and Differences, continued
Table 1 CK-MB STAT 3rd Generation vs. CK-MB STAT 4th Generation, continued
| Assay Comparison | ||
|---|---|---|
| Feature | Predicate Device: Elecsys 3rd Generation CK-MB STAT Assay (K022654) | 4th Generation CK-MB STAT Assay (modified) |
| General Assay Features | ||
| Instrument Platform | Roche Elecsys 2010 | Roche cobas e 411 |
| Sample Volume | 15 µL | Same |
| Sample Type | Human serum and plasma treated with K3-EDTA, lithium heparin, sodium heparin and Na-citrate plasma. | Human serum and plasma treated with K2-EDTA, K3-EDTA, lithium heparin and sodium heparin plasma. |
| 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 streptavidin. | Same |
| Calibrator | CK-MB STAT CalSet (CK-MB Calset for 18-minute assay) | Same |
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| Assay Comparison | ||
|---|---|---|
| Feature | Predicate Device: Elecsys 3rd Generation CK-MB STAT Assay (K022654) | 4th Generation CK-MB STAT Assay (modified) |
| General Assay Features | ||
| 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:Elecsys 2010 analyzers:After 1 month (28 days) 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 | 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:cobas e 411 analyzers:After 1 month (28 days) 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 |
| Controls | Elecsys PreciControl Cardiac II | Same |
Comparison of Assays-Similarities and Differences, continued
Table 1 CK-MB STAT 3rd Generation vs. CK-MB STAT 4" Generation, continued
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| Feature | Assay Comparison | |
|---|---|---|
| Predicate Device: Elecsys 3rd Generation CK-MB STAT Assay (K022654) | 4th Generation CK-MB STAT Assay (modified) | |
| General assay features | ||
| Traceability /Standardization | The linearity of the CK-MB STAT assay was improved by using human recombinant CK-MB from Seradyn. The test was standardized against the previous Elecsys CK-MB STAT assay in the range of 0-20.0 ng/mL; this leads to up to a 30% reduction of the test results in the range of 20-500 ng/mL. | The CK-MB STAT assay is traceable to the Abbott IMx CK-MB assay and linearized using human recombinant CK-MB from Seradyn. |
| Reagent Stability | Unopened:2-8°C - Up to the stated expiration dateOpened 2-8°C - 12 weeksOn Analyzers – 8 weeks | Unopened:2-8°C - Up to the stated expiration dateOpened 2-8°C - 12 weeksOn Analyzers – 6 weeks |
Comparison of Assays-Similarities and Differences, continued
Table 1 CK-MB STAT 3rd Generation vs. CK-MB STAT 4th Generation, continued
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| Table 1 CK-MB STAT 3" Generation vs. CK-MB STAT 4" Generation, continued | |||||||
|---|---|---|---|---|---|---|---|
| Assay Comparison | |||||||
| Predicate Device: Elecsys 3rd | 40 Generation CK-MB STAT | ||||||
| Feature | Generation CK-MB STAT Assay | Assay (modified) | |||||
| (K022654) | |||||||
| 21 8 8 7 1 2 3Labeled Performance Characteristics ----- | |||||||
| Measuring | 0.1-500 ng/mL | 1-300 ng/mL | |||||
| Range | |||||||
| Precision | Elecsys 2010: | cobas e 411: | |||||
| Within-run (will be labeled Repeatability)5.77 ng/mL1.5% CV @12.4 ng/ml.2.1% CV (a),39.7 ng/mlL1.8% CV (a),1.9% CVKI @5.86 ng/mL1.9% CVPC2 @53.1 ng/mLTotal (will be labeled Intermediate)2.3% CV (a),5.77 ng/mL12.4 ng/mL2.6% CV (1)2.3% CV (a)39.7 ng/mL | Within-run (will be labeled Repeatability)1.2% CV @5.46 ng/ml29.5 ng/ml1.3% CV @93.5 ng/mL1.3% CV (a),301 ng/mL1.5% CV @0.06 SDPC1 @4.44 ng/ml1.4% CVPC257.9 ng/mLTotal (will be labeled Intermediate)2.5% CV (1),5.46 ng/mL29.5 ng/mL4.2% CV (a)93.5 ng/mL4.1% CV (0), | ||||||
| 2.4% CVPCI @5.86 ng/ml_2.7% CVPC2 (a),53.1 ng/mL | 3.3% CV (0)301 ng/mL0.12 SD"Cl @4.44 ng/ml3.0% CVPC257.9 חייוון 57.9Precision testing was completed over 21days, according to CLSI EP5-A2, utilizinghuman serum samples and PreciControlCardiac II. | ||||||
| AnalyticalSensitivity | Lower Detection Limit : <0.100 ng/ml | Limit of Blank (LoB): = 0.1 ng/mlLimit of Detection (Lol): = 0.3ווו/שווLimit of Quantitation (LoQ): = 1ווישים' Established according to CLSIEP17- A | |||||
| Assay Comparison | |||||||
| Feature -- | Predicate Device: Elecsvs 3rd | 4th Generation CK-MB STAT Assay | |||||
| Generation CK-MB STAT Assay | (modified) | ||||||
| 2. (K022654) | |||||||
| Labeled Performance Characteristics | |||||||
| Analytical | Analyte | Reactivity | Same | ||||
| Specificity | CK-MM | None | |||||
| CK-BB | 0.10% | ||||||
| Hook Effect | There is no high-dose hook effect at | Same | |||||
| CK-MB concentrations up to 5000 | |||||||
| ng/ml_ | |||||||
| Limitations | The assav is unaffected by: | The assay is unaffected by: | |||||
| Hemoglobin <1.5 g/dL.● | Hemoglobin ≤1000 mg/dL. | ||||||
| Bilirubin < 34 mg/dL | Bilirubin ≤ 34 mg/dL● | ||||||
| Intralipid < 1.500 mg/dL | Intralipid ≤ 1.500 mg/dL� | ||||||
| Biotin < 100 ng/mL� | Biotin ≤ 30 ng/mL● | ||||||
| Rheumatoid factors ≤ 1.500 IU/mL� | Rheumatoid factors ≤ 1,500 IU/mL | ||||||
| In vitro tests were performed on 50 | lgG < 7 g/dl● | ||||||
| commonly used pharmaceuticals. No | lgM < 1 g/dl | ||||||
| interference with the assay was found. | lgA ≤ 1.6 g/dl | ||||||
| In rare cases, interference due to | Serum Albumin ≤ 20 g/dl | ||||||
| extremely high titers of antibodies to | In vitro tests were performed on 51 | ||||||
| analyte-specific antibodies, streptavidin | commonly used pharmaceuticals. No | ||||||
| or ruthenium can occur. These effects | interference with the assay was found. | ||||||
| are minimized by suitable test design. | In rare cases, interference due to | ||||||
| For diagnostic purposes, the results | extremely high titers of antibodies to | ||||||
| should always be assessed in | analyte-specific antibodies, streptavidin | ||||||
| conjunction with the patient's medical | or ruthenium can occur. These effects | ||||||
| history, clinical examination and other | are minimized by suitable test design. | ||||||
| findings. | For diagnostic purposes, the results should | ||||||
| always be assessed in conjunction with the | |||||||
| patient`s medical history, clinical | |||||||
| examination and other findings. | |||||||
| These limitations were established by | |||||||
| testing performed with one human serum | |||||||
| sample containing low levels of CK-MB | |||||||
| and one human serum sample containing | |||||||
| high levels of CK-MB. |
Comparison of Assays-Similarities and Differences, continued
PC1=PreciControl Cardiac 1 PC2=PreciControl Cardiac 2
Continued on next page
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Comparison of Assays-Similarities and Differences, continued
Table I CK-MB STAT 3rd Generation vs. CK-MB STAT 4th Generation, continued
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Comparison of Assays—Similarities and Differences, continued
Table 1 CK-MB STAT 3td Generation vs. CK-MB STAT 4" Generation, continued
| Feature | Predicate Device: Elecsys 3rd Generation CK-MB STAT Assay (K022654) | 4th Generation CK-MB STAT Assay (modified) | ||||||
|---|---|---|---|---|---|---|---|---|
| Labeled Performance Characteristics | ||||||||
| Method Comparison performed on Serum Samples | n = 165Min = 1.08 ng/mlMax = 283 ng/ml | Passing/Bablok | Linear Regression | |||||
| Slope | 1.053 | 1.067 | ||||||
| Intercept | -0.525 | -0.740 | ||||||
| Tau/r | 0.982 | 0.999 | ||||||
| Clinical Study/ Reference Range Study | NWomen 760Men 628 | Median0.971.35 | 97.5th percentile (ng/m L)2.884.94 | 99th percentile (ng/ mL)3.776.73 | All SubjectsSubjects with no Self-reported risk factors | GenderFemale 523Male 568Female 120Male 102 | (N)5.3410.364.307.70 | 99th percentile (ng/mL) |
| Subjects represented "apparently heart healthy" population with exclusion of subjects with known poor cardiac health |
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Comparison of Assays-Similarities and Differences, continued
Matrix Comparison
Sodium-heparin, lithium-heparin, K2-EDTA, and K3-EDTA are permissible anticoagulants for use with this reagent because they do not interfere with recovery of CK-MB. In an internal study, 35 tubes were collected per anticoagulant. Plasma results were compared to serum results and percent recovery was determined. In terms of percent recovery, all data passed the following criteria:
- Slope: 0.9-1.1 ◆
- Coefficient of correlation: Pearson r > 0.95 .
- Intercept: ≤± 0.15 ●
- For single sample pairs: 100% ±20% based on reference .
| Anticoagulant | Sample ConcentrationRange Tested (ng/mL) | Claimed Measuring Range(ng/mL) |
|---|---|---|
| Na-heparin | 1.46-297.83 | 1.00 – 300 ng/mL |
| Li-heparin | 1.39-244.83 | |
| K2-EDTA | 1.58-299.65 | |
| K3-EDTA | 1.56-291.89 |
In addition, method comparisons with plasma vs. serum were calculated with the following results:
| Serum vs. Na-heparin Plasma : | P/B: y = 0.994x + (-0.0100), r = 0.9997 |
|---|---|
| Serum vs. Li-heparin Plasma: | P/B: y = 0.9960x + (0.0045), r = 0.9996 |
| Serum vs. K₂-EDTA Plasma: | P/B: y = 1.020x + (-0.0082), r = 0.9999 |
| Serum vs. K₃-EDTA Plasma: | P/B: y = 0.988x + (-0.0115), r = 0.9998 |
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| Table 2 4th Generation STAT vs. 4th Generation 18-Minute | ||
|---|---|---|
| Assay Comparison | ||
| Feature | 4th Generation CK-MB STAT Assay | 4th Generation CK-MB 18-Minuteassay(modified) |
| General Assay Features | ||
| IntendedUse/Indicationsfor Use | Immunoassay for the in vitroquantitative determination of MBisoenzyme of creatine kinase in humanserum and plasma. Measurements ofthe MB isoenzyme of creatine kinaseare used as an aid in the diagnosis ofmyocardial infarction. | Same |
| AssayProtocol | Two step Sandwich assay usingbiotinylated and ruthenium labeledantibodies and streptavidinmicroparticles | Same |
| DetectionProtocol | ElectrochemiluminescentImmunoassay | Same |
| Applications | STAT application (noted as CK-MBSTAT in the labeling) | 18-minute application (noted as CK-MB in the labeling). |
Table 2 4th Generation STAT vs. 4th Generation 18-Minute
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| Table 2 4th Generation STAT vs. 4th Generation 18-Minute, continuedAssay Comparison | ||
|---|---|---|
| Feature | 4th Generation CK-MB STAT Assay | 4th Generation CK-MB 18-minute assay(modified) |
| General Assay Features | ||
| InstrumentPlatform | Roche cobas e 411 | Same |
| SampleVolume | 15 µL | Same |
| SampleType | Human serum and plasma treated withK2-EDTA, K3-EDTA, lithium heparinand sodium heparin plasma. | Same. |
| Reagents | Sandwich principle. Total duration ofassay: 9 minutes.• 1st incubation: 15 µL of sample, abiotinylated monoclonal anti-CK-MBantibody, and a monoclonal CK-MB-specific antibody labeled with aruthenium complex react to form asandwich complex.• 2nd incubation: After addition ofstreptavidin-coated microparticles,the complex becomes bound to thesolid phase via interactionof biotin and streptavidin | Sandwich principle. Total duration ofassay: 18 minutes.• 1st incubation: 15 µL of sample, abiotinylated monoclonal anti-CK-MBantibody, and a monoclonal CK-MB-specific antibody labeled with aruthenium complex react to form asandwich complex.• 2nd incubation: After addition ofstreptavidin-coated microparticles,the complex becomes bound to thesolid phase via interactionof biotin and streptavidin |
| Calibrator | CK-MB STAT CalSet | CK-MB CalSet |
Comparison of Assays—Similarities and Differences, continued
Table 2 4th Generation STAT vs. 4th Generation 18-Minute, continued
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Comparison of Assays-Similarities and Differences, continued
Table 2 4th Generation STAT vs. 4th Generation 18-Minute, continued
| Feature | 4th Generation CK-MB STAT Assay | 4th Generation CK-MB 18-minute assay (modified) |
|---|---|---|
| General Assay Features | ||
| 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:cobas e 411 analyzers:• After 1 month (28 days) 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 |
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Comparison of Assays-Similarities and Differences, continued
Table 2 4th Generation STAT vs. 4th Generation 18-Minute, continued
| Feature | Assay Comparison | 4th Generation CK-MB STAT Assay | 4th Generation CK-MB 18-MinuteAssay(modified) |
|---|---|---|---|
| General assay features | |||
| Traceability /Standardization | The CK-MB STAT assay is traceableto the Abbott IMx CK-MB assay andlinearized using human recombinantCK-MB from Seradyn. | Same | |
| Reagent Stability | Unopened:2-8°C - Up to the stated expirationdateOpened 2-8°C - 12 weeksOn Analyzers – 6 weeks | Same |
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| Table 2 4th Generation STAT vs. 4th Generation 18-Minute, continuedAssay Comparison | ||
|---|---|---|
| Feature | 4th Generation CK-MB STAT Assay | 4th Generation CK-MB 18-minute assay (modified) |
| Labeled Performance Characteristics | ||
| Measuring Range | 1-300 ng/mL | same |
| Precision according to CLSI EP5-A2 | 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/mL0.06 SDPC1@ 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/mL0.12 SDPC1@ 4.44 ng/mL3.0% CVPC2 @ 57.9 ng/mLPrecision testing was completed over 21 days, according to CLSI EP5-A2, utilizing human serum samples and PreciControl Cardiac II. | cobas e 411:Within-run (will be labeled Repeatability)1.3% CV @ 5.27 ng/mL1.4% CV @ 28.4 ng/mL1.2% CV @ 91.2 ng/mL1.3% CV @ 297 ng/mL0.06 SDPC1 @ 4.25 ng/mL1.2% CVPC2 @ 54.7 ng/mLTotal (will be labeled Intermediate)2.0% CV @ 5.27 ng/mL2.4% CV @ 28.4 ng/mL2.6% CV @ 91.2 ng/mL2.0% CV @ 297 ng/mL0.10 SDPC1 @ 4.25 ng/mL2.3% CVPC2 @ 54.7 ng/mLPrecision testing was completed over 21 days, according to CLSI EP5-A2, utilizing human serum samples and PreciControl Cardiac II. |
| Analytical Sensitivity1 according to CLSI EP17-A | Limit of Blank (LoB): = 0.1 ng/mlLimit of Detection (LoD): = 0.3 ng/mlLimit of Quantitation (LoQ): = 1 ng/ml | Same |
Comparison of Assays-Similarities and Differences, continued
Table 2 4th Generation STAT vs. 4th Generation 18-Minute, continued
PC1=PreciControl Cardiac 1
PC2=PreciControl Cardiac 2
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Table 2 4th Generation STAT vs. 4th Generation 18-Minute, continued Assay Comparison . 4th Generation CK-MB 18-minute Feature . . 4th Generation CK-MB STAT Assay assav · (modificd) Labeled Performance Characteristics Analytical Analyte Reactivity Same CK-MM Specificity none CK-BB 0.10% There is no high-dose hook effect at Hook Effect Same CK-MB concentrations up to 5000 ng/ml_ The assay is unaffected by: Limitations Same. Hemoglobin ≤1000 mg/dL. . . Bilirubin < 34 mg/dL Intralipid ≤ 1.500 mg/dL ◆ Biotin ≤ 30 ng/mL . Rheumatoid factors ≤ 1,500 IU/mL . . 12G < 7 p/d1 . lgM < | g/dl . lgA < 1.6 g/di Serum Albumin < 20 g/dl In vitro tests were performed on 51 commonly used pharmaceuticals. No interference with the assay was found. t In rare cases, interference due to extremely high titers of antibodies to analyte-specific antibodies, streptavidin or ruthenium can occur. These effects are minimized by suitable test design. For diagnostic purposes, the results should always be assessed in conjunction with the patient's medical history, clinical examination and other findings. These limitations were established by testing performed with one human serum sample containing low levels of CK-MB and one human serum sample containing high levels of CK-MB.
Comparison of Assays-Similaritics and Differences, continued
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CLSI EP17-
A
510(k) Summary for Elecsys CK-MB STAT and CK-MB, continued
Comparison of Assays-Similarities and Differences, continued
Table 2 4th Generation STAT vs. 4th Generation 18-Minute, continued
| Feature | 4th Generation CK-MB STAT Assay | 4th Generation CK-MB 18-minute assay (modified) | |
|---|---|---|---|
| Labeled Performance Characteristics | |||
| Method Comparison completed using Serum Samples | n = 115Min = 1.44 ng/mlMax = 283 ng/ml | ||
| Passing/Bablok | Linear Regression | ||
| Slope | 1.003 | 1.006 | |
| Intercept | -0.005 | 0.071 | |
| Tau/r | 0.985 | 0.999 |
The Limit of Blank, Limit of Detection and Limit of Quantitation were Description of Analytical determined in accordance with the CLSI (Clinical and Laboratory Standards Sensitivity Institute) EP17-A requirements. according to
The Limit of Blank is the 95th percentile value from n ≥ 60 measurements of analyte-free samples over several independent series. The Limit of Blank corresponds to the concentration below which analyte-free samples are found with a probability of 95 %.
The Limit of Detection is determined based on the Limit of Blank and the standard deviation of low concentration samples. The Limit of Detection corresponds to the lowest analyte concentration which can be detected (value above the Limit of Blank with a probability of 95 %).
The Limit of Quantitation is defined as the lowest amount of analyte in a sample that can be accurately quantitated with a total allowable error of < 20 %.
{20}------------------------------------------------
| Standard/GuidanceDocumentReference | In addition to FDA guidance regarding 510(k) submissions, the followingstandards were used for the performance studies. |
|---|---|
| • Evaluation of Precision Performance of Quantitative MeasurementMethods: Approved Guideline – Second Edition. CLSI documentEP5-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 Measurement Procedures:A Statistical Approach; Approved Guideline. CLSI document EP6-A, Volume 23, No. 16, April 2003. | |
| Conclusion | The submitted information in this premarket notification supports asubstantial equivalence decision. |
・
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/21/Picture/1 description: The image shows the seal of the Department of Health & Human Services USA. The seal is circular, with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" arranged around the perimeter. In the center of the seal is an emblem that resembles an eagle or bird-like figure with stylized wings. The emblem is black, and the text is also in black.
Public Health Service
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
October 18, 2013
Roche Diagnostics C/O Kelli Turner 9115 Hague Road INDIANAPOLIS IN 46250-0416
Re: K132571
Trade/Device Name: Elecsys CK-MB STAT Immunoassay, Elecsys CK-MB Immunoassay Regulation Number: 21 CFR 862.1215 Regulation Name: Creatine phosphokinase/creatine kinase or isoenzymes test system Regulatory Class: II Product Code: JHY Dated: August 14, 2013 Received: August 15, 2013
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 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 Part 801); 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.
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please go to http://www.fda.gov/AboutFDA/CentersOffices/CDRH/CDRHOffices/ucm 1 1 5809.htm for
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Page 2-Ms. Turner
the Center for Devices and Radiological Health's (CDRH's) Office of Compliance. 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/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 Small Manufacturers, International and Consumer Assistance 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.
Sincerely yours,
Carol Benson -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 Form
510(k) Number (if known): K132571
Device Name: Elecsys CK-MB STAT Immunoassay
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 Elecsys and cobas e immunoassay analyzers.
Prescription Use X (21 CFR Part 801 Subpart D) And/Or
Over the Counter Use (21 CFR Part 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostics and Radiological Health (OIR)
Ruth A. @hesler -S
Division Sign-Off Office of In Vitro Diagnostics and Radiological Health
K132571 510(k)
{24}------------------------------------------------
Indications for Use Form
510(k) Number (if known): K132571
Device Name: Elecsys CK-MB Immunoassay
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 Elecsys and cobas e immunoassay analyzers.
Prescription Use _ X (21 CFR Part 801 Subpart D)
And/Or
Over the Counter Use _________________________________________________________________________________________________________________________________________________________ (21 CFR Part 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostics and Radiological Health (OIR)
Ruth A. @hesler -S
Division Sign-Off Office of In Vitro Diagnostics and Radiological Health
K132571 510(k)
§ 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.