(54 days)
Immunoassay for the in vitro quantitative determination of the MB isoenzyme of creatine kinase (CK-MB) in human serum and plasma.
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 kinase and its isoenzymes are used in the diagnosis and treatment of myocardial infarction and muscle diseases such as progressive, Duchenne-type muscular dystrophy
The Elecsys® CK-MB test principle is based on a two-step sandwich with Streptavidin microparticles and electrochemiluminescence detection.
Total duration of the assay: 9 minutes
1st incubation: 15 µl of sample, a biotinylated monoclonal CK-MB-specific antibody and a monoclonal CK-MB-specific antibody labeled with a ruthenium complex react to form a sandwich complex
2nd incubation: after the addition of streptavidin-coated microparticles, the complex becomes bound to the solid phase via interaction of biotin and streptavidin.
• The reaction mixture is aspirated into the measuring cell where the microparticles are magnetically captured onto the surface of the electrode. Unbound substances are then removed with ProCell. Application of a voltage to the electrode then induces chemiluminescent emission which is measured by a photomultiplier.
• Results are determined via a calibration curve which is instrument-specifically generated by 2-point calibration and a master curve provided via the reagent bar code.
The provided document is a 510(k) summary for the "Elecsys® CK-MB" device, a creatine kinase MB isoenzyme immunoassay. It compares this new device to a predicate device, the "Abbott IMx CK-MB".
This document does not describe acceptance criteria for a study or a study proving the device meets acceptance criteria in the typical format of a clinical trial for an AI/algorithm-based diagnostic device. Instead, it presents performance characteristics of the Elecsys® CK-MB device as part of establishing substantial equivalence to a predicate device for regulatory approval.
Therefore, many of the requested fields are not applicable or cannot be extracted directly from this type of regulatory submission. The information provided is primarily about the analytical performance of the immunoassay.
Here's an attempt to answer the questions based on the available information:
1. A table of acceptance criteria and the reported device performance
The document does not explicitly state "acceptance criteria" in the sense of predefined thresholds for performance that the device must meet to be deemed acceptable. Instead, it presents various performance characteristics and then compares them to the predicate device or a reference method. The goal of this 510(k) summary is to demonstrate that the new device is "substantially equivalent" to the predicate, implying that its performance is comparable and safe/effective.
However, we can infer some implicit performance "targets" or comparisons from the data presented, especially regarding precision and analytical range. The "reported device performance" is directly stated in the table.
| Performance Characteristic | Implicit "Acceptance Criteria" (Inferred from comparison/regulatory context) | Reported Device Performance (Elecsys® CK-MB) |
|---|---|---|
| Precision (Within Run %CV) | Comparable to predicate device (Abbott IMx CK-MB) | 3.0 - 3.9% (various concentrations) |
| Precision (Total Run %CV) | Comparable to predicate device (Abbott IMx CK-MB) | 4.1 - 5.1% (various concentrations) |
| Lower Detection Limit | Clinically relevant and comparable or better than predicate device | 0.150 ng CK-MB / ml |
| Assay Range | Clinically relevant and comparable or better than predicate device | 0.100 - 500.0 ng/ml |
| Method Comparison (vs. Abbott IMx CK-MB) | High correlation (r-value) with predicate device; slope and intercept close to 1 and 0 respectively. | y = 0.9735 + 1.0224x (Least Squares), r = 0.996 |
| y = 0.2095 + 0.9465x (Passing/Bablok), r = 0.996 | ||
| Interfering Substances (Hemoglobin) | No interference up to certain physiological/pathological levels. | No interference at 1.0 g/dl |
| Interfering Substances (Lipemia) | No interference up to certain physiological/pathological levels. | No interference at 1,500 mg/dl |
| Interfering Substances (Bilirubin) | No interference up to certain physiological/pathological levels. | No interference at 28 mg/dl |
| Specificity (CK-BB Cross-reactivity) | Low cross-reactivity | 0.0000 - 0.1600% (various concentrations) |
| Specificity (CK-MM Cross-reactivity) | Low cross-reactivity | 0.0000 - 0.0500% (various concentrations) |
2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)
- Precision:
- For Elecsys® CK-MB: N = 60 for each of 5 sample types (HS1, HS2, HS3, CCI, CCII).
- For Abbott IMx CK-MB (predicate): N = 48 for each of 3 sample types (1, 2, 3).
- Method Comparison: N = 95 for comparison against Abbott IMx CK-MB.
- Data Provenance: Not specified (e.g., country of origin, retrospective/prospective). This is common for analytical performance studies in 510(k) summaries unless there are specific clinical studies involved.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)
Not applicable. This device is an immunoassay for quantitative determination of a biomarker. The "ground truth" for its performance is established by reference methods or comparison to a predicate device, not by human expert consensus or adjudication in the way an imaging diagnostic device might. The "truth" is the actual concentration of CK-MB as measured by a gold standard or accepted method.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
Not applicable, for the same reasons as in point 3.
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 is an in-vitro diagnostic (IVD) immunoassay, not an AI-assisted diagnostic tool that involves human readers interpreting results.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
This is a standalone analytical device. Its performance characteristics (precision, sensitivity, assay range, method comparison, interfering substances, specificity) are inherently "standalone" in this context. It performs the measurement and outputs a quantitative result without human-in-the-loop performance assessment in the way an AI algorithm might be evaluated.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)
The "ground truth" in these analytical studies is typically:
- Reference measurements: For method comparison, the predicate device (Abbott IMx CK-MB) or other established methods (e.g., Hybritech Tandem®-E CK-MB) serve as the reference.
- Known concentrations: For studies like precision, sensitivity, and specificity, samples with known concentrations of the analyte (CK-MB) or interfering substances are used.
8. The sample size for the training set
Not applicable. This is not an AI/machine learning device that requires a "training set" in the conventional sense. The device's calibration curve is generated via a 2-point calibration and a master curve provided via the reagent bar code, which is an intrinsic part of the manufacturing and operational setup, not a data-driven training process.
9. How the ground truth for the training set was established
Not applicable, as there is no "training set" in the machine learning context. For the instrument's internal calibration, the "ground truth" is established by carefully prepared standards with known concentrations, following established analytical chemistry and manufacturing protocols.
§ 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.