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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.

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:

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

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