(455 days)
For the quantitative determination of creatine kinase activity in serum and plasma. Rx only.
Measurements of Creatine Kinase are used in the diagnosis and treatment of myocardial infaction and muscle disease, such as progressive Duchenne-type muscular dystrophy.
The Pointe Scientific Creatine Kinase (CK) Reagent Set consists of ready-to-use liguid reagents:
- . CK R1 (buffer) contains: Imidazole buffer (pH 6.7) 100.0 mmol/L; NADP 2.0 mmol/L: HK (Baker's yeast) 2.5 KU/L: Glucose 20.0 mmol/L: Magnesium Acetate 10.0 mmol/L; EDTA 2.0 mmol/L and N-acetylcysteine (NAC) 20.0 mmol/L.
- . CK R2 (enzyme reagent) contains: Imidazole buffer (pH 6.7) 100.0 mmol/L: ADP 2.0 mmol/L: AMP 5.0 mmol/L: Diadensosine pentaphosphate 10.0 mmol/L: Creatine phosphate 30.0 mmol/L; G6PDH (Baker's yeast) 1.5 KU/L and EDTA 2.0 mmol/L.
The kinetic procedure presented is a modification of Szasz of the Rosalki technique, which optimizes the reaction by reactivation of CK activity with N-actyl-L-cysteine (NAC).
Creatine Kinase specifically catalyzes the transphosphorylation of ADP to ATP. Through a series of coupled enzymatic reactions, NADPH is produced at a rate directly proportional to the CK activity. The method determines the NADPH absorbance increase per min at 340 nm.
The provided document describes the analytical performance studies for the Pointe Scientific Creatine Kinase (CK) Reagent Set, which supports its substantial equivalence to a predicate device.
Here's an analysis of the acceptance criteria and study details:
1. A table of acceptance criteria and the reported device performance:
The document doesn't explicitly state "acceptance criteria" in a separate table for each test. Instead, it presents the study results and implies that these results were considered acceptable for demonstrating substantial equivalence. For some tests, like Linearity, an acceptable deviation is stated.
However, based on the provided performance data, we can infer the acceptance criteria that the manufacturer likely aimed for to support their claims.
| Performance Study | Implied Acceptance Criteria (Inferred from results/general practice) | Reported Device Performance (Pointe Scientific Creatine Kinase (CK) Reagent Set) |
|---|---|---|
| Method Comparison (Serum vs. Predicate) | High correlation (e.g., R > 0.975), acceptable bias | Correlation Coefficient: 0.9991, Regression: y = 1.041x - 5.2 |
| Method Comparison (Plasma vs. Predicate) | High correlation (e.g., R > 0.975), acceptable bias | Correlation Coefficient: 0.9946, Regression: y = 1.032x - 0.4 |
| Precision (Controls & Patient Samples - Serum/Plasma) | Low CV% for repeatability and total precision (typically 10% from control) up to clinically relevant concentrations | Bilirubin, Ascorbic Acid, Hemoglobin, Intralipid showed no significant interference at high concentrations (e.g., Bilirubin 60 mg/dL, Hemoglobin 500 mg/dL) |
2. Sample size used for the test set and the data provenance:
- Method Comparison (Serum):
- Sample Size: 120 de-identified remnant serum samples. 4 samples were altered by mixing.
- Data Provenance: Obtained from a commercial repository. Retrospective. Country of origin not specified, but likely within the US given the FDA submission.
- Method Comparison (Plasma):
- Sample Size: 123 de-identified remnant plasma samples. 2 samples were altered by mixing.
- Data Provenance: Obtained from a commercial repository. Retrospective. Country of origin not specified.
- Precision Studies:
- Sample Size: 2 commercial quality controls, 3 serum pools, and 3 plasma pools. Each pool/control was tested in duplicate twice per day for 20 days (n=80 per sample type).
- Data Provenance: Not explicitly stated, but common practice is for manufacturers to prepare pools or use commercially available controls.
- Linearity/Assay Range Study:
- Sample Size: A set of 12 serum samples and 12 plasma samples (prepared by admixture of high-level and low-level pools).
- Data Provenance: Not explicitly stated, likely prepared in-house or from common available resources.
- Detection Capability (LoB, LoD, LoQ):
- LoB: Saline (1 sample * 20 repetitions * 3 days).
- LoD: 20 low-level depleted serum samples and 20 depleted plasma samples.
- LoQ: 5 low activity samples (each run in 8 duplicates over 5 days).
- Data Provenance: Not explicitly stated, likely prepared in-house or from common available resources.
- Dilution Recovery Studies:
- Sample Size: Three contrived high-level samples for both serum and plasma.
- Data Provenance: Not explicitly stated, likely prepared in-house.
- Analytical Specificity (Endogenous Substances):
- Sample Size: Not explicitly stated, but interference testing was conducted using "randomly selected serum and plasma samples ranging from 43 U/L to 268 U/L."
- Data Provenance: Not explicitly stated.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
This is a diagnostic reagent for quantitative determination of an analyte (Creatine Kinase), not an imaging or qualitative diagnostic device requiring expert interpretation of results to establish ground truth.
- Ground Truth for Method Comparison: The predicate device's results (Beckman Coulter Creatine Kinase (CK-Nac) on the Beckman Coulter Olympus AU400 Clinical Chemistry Analyzer) serve as the "reference" or "ground truth" for comparison. This is a common method for demonstrating substantial equivalence for in vitro diagnostic (IVD) devices. No human experts are used to establish ground truth in this context; rather, the established method of the predicate device is the reference.
- Ground Truth for other studies (Precision, Linearity, Detection, Dilution Recovery, Specificity): The "ground truth" is typically established by the analytical method itself, or by preparing samples with known concentrations/characteristics, without the need for human expert consensus.
4. Adjudication method (e.g., 2+1, 3+1, none) for the test set:
No adjudication method is relevant or mentioned as this device measures an objective biochemical marker. The 'ground truth' is the quantitative measurement itself or the reference method's result.
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:
No. This is not applicable. The device is a diagnostic reagent for quantitative measurement of creatine kinase, not an AI-powered diagnostic system for image interpretation or a device requiring human readers/scorers. Therefore, MRMC studies are not relevant.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
The device is a reagent set used on an automated chemistry analyzer (Shenzhen Mindray BA-800M Chemistry Analyzer). The performance studies presented are for the "algorithm only" in the sense that they demonstrate the analytical performance of the reagent on the analyzer without human interpretation of the raw data to generate the numerical result. The "human-in-the-loop" would be a lab technician performing the test and reviewing the results, but the analytical performance itself is standalone.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc):
- Method Comparison: The results obtained from the legally marketed predicate device (Beckman Coulter Creatine Kinase (CK-Nac) on the Beckman Coulter Olympus AU400 Clinical Chemistry Analyzer) served as the reference for comparison.
- Precision, Linearity, Detection, Dilution Recovery, Analytical Specificity: Ground truth is based on the inherent analytical properties of the method/reagent including samples with known concentrations (e.g., prepared standards, spiked samples, qualified controls, or established reference material). Linearity was assessed against expected values based on known admixtures. Detection limits were determined using statistical methods on low-level and blank samples.
8. The sample size for the training set:
There is no "training set" in the context of this 510(k) submission for a diagnostic reagent. This device is not an AI/machine learning algorithm that requires training data. The studies performed are analytical validation studies.
9. How the ground truth for the training set was established:
Not applicable, as there is no training set for this type of medical device.
§ 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.