(71 days)
The CKI method is an in vitro diagnostic test for the quantitative measurement of creatine kinase in human serum and plasma on the Dimension® clinical chemistry system. Measurements of creatine phosphokinase and its isoenzymes are used in the diagnosis and treatment of myocardial infarction and muscle diseases such as progressive, Duchenne-type muscular dystrophy.
The creatine kinase MB (MBI) method is an in vitro diagnostic test for the quantitative measurement of creatine kinase MB isoenzyme activity in human serum and plasma on the Dimension® clinical chemistry system. Measurements of creatine phosphokinase and its isoenzymes are used in the diagnosis and treatment of myocardial infarction and muscle diseases such as progressive, Duchenne-type muscular dystrophy.
The CKI/MBI CAL is an in vitro diagnostic product for the calibration of the Creatine Kinase (CKI) and Creatine Kinase MB (MBI) methods on the Dimension® clinical chemistry system.
Dimension® (CKI) Flex® Reagent Cartridge (DF38): In a coupled enzyme reaction, the creatine kinase in patient samples catalyzes the transphosphorylation of phosphate from creatine phosphate to adenosine diphosphate (ADP) producing adenosine-triphosphate (ATP). Hexokinase (HK) phosphorylates glucose from the ATP to phosphorylate glucose. The resulting qlucose-6-phosphate is oxidized by qlucose-6-phosphate dehydrogenase (G-6-PDH) with the simultaneous reduction of nicotinamide adenine dinucleotide phosphate (NADP). The rate of formation of NADPH is directly proportional to the CK activity in the sample and is measured bichromatically at 340 and 540 nm.
Dimension® (MBI) Flex® Reagent Cartridge (DF32): The activity of the CK-MM isoenzyme is inhibited by an antibody specific for the CK-M subunit. The activity of the B subunit of creatine kinase MB isoenzyme is not inhibited, and it is on this basis that CK-MB can be measured. In an enzyme coupled reaction, creatine kinase in patient samples catalyzes the transphosphorylation of creatine phosphate to adenosine-diphosphate (ADP), producing adenosine-triphosphate (ATP). Hexokinase (HK) uses the ATP to phosphorylate glucose_The resulting glucose-6-phosphate is oxidized by glucose-6phosphate dehydrogenase (G-6-PDH) with the simultaneous reduction of nicotinamide adenine dinucleotide phosphate (NADP) to NADPH. The rate of formation of NADPH is measured bichromatically at 340, 540 nm and is directly proportional to CK-B activity in the sample.
CKI/MBI Calibrator (DC32): CKI/MBI CAL is a liquid, multi-analyte, human serum albumin based product containing creatine kinase (human source) and creatine kinase MB (porcine source). The kit consists of four vials per level (2 and3) with 2.0 mL per vial. Level 1 calibrator for CKI/MBI is not included in the CKI/MBI CAL carton. Purified Water Diluent or reagent grade water is required for use as Calibrator Level 1. Description of the manufacturing, value assignment and stability testing process are provided in this submission report.
Here's an analysis of the provided text regarding the acceptance criteria and study for the Dimension® Creatine Kinase MB Flex® Reagent Cartridge (DF32) and CKI/MBI Calibrator (DC32):
1. Table of Acceptance Criteria and Reported Device Performance
The submission does not explicitly list "acceptance criteria" with numerical targets for performance metrics. Instead, it relies on demonstrating substantial equivalence to predicate devices. The performance is implied by the comparison tables, showing that the new devices perform comparably to the predicates in terms of intended use, technology, measuring range, and analytical sensitivity.
Without explicit acceptance criteria, we can infer the reported device performance from the comparison to the predicate devices.
| Feature | Predicate Device (Roche CK-MB Reagent K003158) Acceptance Criteria (Implied by Predicate) | Dimension® (MBI) Flex® Reagent Cartridge (DF32) Reported Performance |
|---|---|---|
| Intended Use | Immunoinhibition assay for quantitative in vitro determination of CK-MB in human serum and plasma on Roche automated clinical chemistry analyzers. | Quantitative measurement of creatine kinase MB isoenzyme activity in human serum and plasma on the Dimension® clinical chemistry system. |
| Device Technology | Immunological UV Assay | Bichromatic rate |
| Measuring Range | 3 - 2300 U/L | 3 - 125 U/L |
| Analytical Sensitivity | 3 U/L | 3 U/L |
For CKI (DF38):
| Feature | Predicate Device (Roche CK-NAC Reagent K834502) Acceptance Criteria (Implied by Predicate) | Dimension® (CKI) Flex® Reagent Cartridge (DF38) Reported Performance |
|---|---|---|
| Intended Use | In vitro assay for quantitative determination of creatine kinase (CK) in human serum and plasma on Roche automated clinical chemistry analyzers. | Quantitative measurement of creatine kinase in human serum and plasma on the Dimension® Clinical Chemistry System. |
| Device Technology | UV Test | Bichromatic rate |
| Measuring Range | 3-2300 U/L | 7 - 1000 U/L |
| Analytical Sensitivity | 3 U/L | 7 U/L |
For CKI/MBI Calibrator (DC32):
| Feature | Predicate Devices (K990460, K003158) Acceptance Criteria (Implied by Predicate) | CKI/MBI Calibrator (DC32) Reported Performance |
|---|---|---|
| Intended Use | Calibration of quantitative Roche methods. | Calibration of CKI and MBI methods on the Dimension® clinical chemistry system. |
| Analyte | Creatine kinase (rabbit muscle) / Creatine kinase-MM (human) and CK-BB (porcine brain) | Creatine kinase (human source) and creatine kinase-MB (porcine source) |
| Matrix | Human serum | Human serum albumin |
| Form | Lyophilized | Liquid |
| Levels | Two levels | CKI - Three levels |
| MBI - Five levels |
2. Sample Size Used for the Test Set and Data Provenance
The summary states: "Comparative testing described in the protocol included in this submission demonstrates substantial equivalent performance."
- Sample Size: The document does not specify the sample size used for the comparative testing (test set patients or samples).
- Data Provenance: The document does not specify the data provenance (e.g., country of origin, retrospective or prospective nature of the samples). It only mentions "human serum and plasma" as sample types.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This information is not applicable as the devices are in vitro diagnostic reagents and calibrators designed for quantitative laboratory measurement, not for interpretation by human experts. The "ground truth" in this context would be the measured values from the predicate devices or reference methods. The performance is assessed by analytical comparison, not expert consensus on diagnoses.
4. Adjudication Method for the Test Set
This is not applicable to this type of in vitro diagnostic device. Adjudication methods like 2+1 or 3+1 are typically used in clinical studies where human readers interpret medical images or conduct clinical assessments, and disagreements need resolution. For laboratory assays, performance is assessed through statistical methods comparing results to a reference.
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
This is not applicable. This submission concerns in vitro diagnostic reagents and calibrators, not an AI-assisted diagnostic tool that would involve human readers interpreting results. Therefore, an MRMC study and AI-assisted performance improvement are not relevant to this submission.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done
This is not applicable. The device is an in vitro diagnostic reagent system that functions on a clinical chemistry analyzer. It is an algorithm-driven system in the sense that the analyzer's software processes the photometric measurements, but it's not a standalone "algorithm" in the context of AI or image interpretation. Its performance is its standalone performance on the Dimension® system, generating quantitative results. The comparison is made against existing predicate assays.
7. The Type of Ground Truth Used
The "ground truth" for proving substantial equivalence in this context is the results obtained from the legally marketed predicate devices (Roche CK-NAC Reagent, Roche CK-MB Reagent, and their respective calibrators). The comparative testing would involve analyzing samples with both the new device and the predicate to show similar results.
8. The Sample Size for the Training Set
This information is not applicable in the context of this submission. "Training set" typically refers to data used to train a machine learning model. These are chemical reagents and calibrators, whose performance is based on established biochemical reactions, not on data-driven machine learning models. Performance is validated through analytical studies, not an AI training process.
9. How the Ground Truth for the Training Set Was Established
This information is not applicable for the same reasons as point 8.
§ 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.