(37 days)
ELITech Clinical Systems CK NAC SL is intended for the quantitative in vitro determination of creatine kinase (CK) in human serum and plasma on ELITech Clinical Systems Selectra analyzers. It is not intended for use in Point of Care settings. Creatine phosphokinase and its isoenzymes measurements are used in the diagnosis and treatment of myocardial infarction and muscle diseases such as progressive, Duchenne-type muscular dystrophy.
ELITech Clinical Systems ELICAL 2 is a multi-parametric calibrator for in vitro diagnostic use in the calibration of quantitative ELITech Clinical Systems methods on ELITech Clinical Systems Selectra analyzers.
ELITech Clinical Systems ELITROL I and ELITROL II are multi-parametric control sera for in vitro diagnostic use in accuracy control of quantitative ELITech Clinical Systems methods on ELITech Clinical Systems Selectra analyzers.
CK NAC SL is available as kit only. It consists of 2 reagents R1 & reagent R2: Reagent R1 contains: Imidazole buffer (pH 6.10), D-Glucose, N-Acetyl-L-Cysteine, Magnesium acetate, NADP, EDTA, Hexokinase (microorganisms), sodium azide. Reagent R2 contains: Creatine phosphate, ADP, AMP, Diadenosine pentaphosphate, Glucose-6-phosphate Dehydrogenase (G-6-PDH) (micro-organisms), sodium azide.
ELITech Clinical Systems ELICAL2 is a lyophilized calibrator based on human serum containing constituents to ensure optimal calibration. ELICAL 2 is prepared exclusively from the blood of donors tested individually and found to be negative for HbsAg and to the antibodies to HCV and HIV according to FDA-approved methods.
ELITROL I and ELITROL II are two level quality control products consisting of a lyophilized human serum containing constituents at desired levels. ELITROL I and ELITROL II are prepared exclusively from the blood of donors tested individually and found to be negative for HbsAg and to antibodies to HCV and HIV according to FDA-approved methods.
Here's an analysis of the provided text regarding the ELITech Clinical Systems CK NAC SL device, focusing on acceptance criteria and supporting studies:
Preface: This document primarily details the analytical performance of the ELITech Clinical Systems CK NAC SL reagent, calibrator (ELICAL 2), and controls (ELITROL I and ELITROL II). It is a 510(k) summary, which focuses on demonstrating substantial equivalence to a predicate device, rather than defining novel clinical acceptance criteria. The "acceptance criteria" in this context refer to the performance metrics that the device achieved and that were deemed acceptable for substantial equivalence. There are no explicit "acceptance criteria" presented as threshold values that needed to be met; rather, the successful demonstration of performance comparable to the predicate device and established guidelines served as the de facto acceptance.
1. Table of Acceptance Criteria and Reported Device Performance
As mentioned above, explicit numerical acceptance criteria were not predefined in the document. Instead, the reported performance metrics were presented and implicitly accepted if they demonstrated substantial equivalence and adherence to CLSI guidelines. The table below summarizes the key performance characteristics reported for the ELITech Clinical Systems CK NAC SL, its calibrator, and controls.
| Performance Metric Category | Specific Test/Parameter | Reported Device Performance (ELITech Clinical Systems CK NAC SL) | Notes / Implicit Acceptance Criteria Context |
|---|---|---|---|
| Precision | Within-run CV% (Level 1) | 0.7% (Mean 147 U/L) | Results demonstrate good precision, aligning with typical IVD requirements for reproducibility. |
| Within-run CV% (Level 2) | 1.1% (Mean 406 U/L) | ||
| Within-run CV% (Level 3) | 1.1% (Mean 1154 U/L) | ||
| Total CV% (Level 1) | 1.7% (Mean 147 U/L) | ||
| Total CV% (Level 2) | 2.4% (Mean 406 U/L) | ||
| Total CV% (Level 3) | 3.9% (Mean 1154 U/L) | ||
| Linearity/Assay Range | Measuring Range | 10 to 1714 U/L | Assessed per CLSI EP6-A. Considered acceptable for the intended use. |
| Upper Linearity (with dilution) | 17140 U/L | ||
| Detection Limit | Limit of Detection (LoD) | 1 U/L | Determined per CLSI EP17-A. Represents the lowest detectable concentration. |
| Limit of Quantification (LoQ) | 5 U/L | Determined per CLSI EP17-A. Represents the lowest quantifiable concentration. | |
| Interference | Unconjugated Bilirubin | No significant interference up to 30.0 mg/dL | "No significant interference" defined as within ± 10% recovery. |
| Conjugated Bilirubin | No significant interference up to 29.5 mg/dL | ||
| Triglycerides | No significant interference up to 3133 mg/dL | ||
| Acetaminophen | No significant interference up to 30 mg/dL | ||
| Ascorbic Acid | No significant interference up to 20.0 mg/dL | ||
| Acetylsalicylic Acid | No significant interference up to 200 mg/dL | ||
| Method Comparison | Correlation (y = 1.012x + 2) | r = 0.998, r² = 0.995, Sy.x = 29 U/L | Compared against Roche Diagnostics CKL on cobas c111. High correlation coefficient (r) and r² indicate strong agreement, supporting substantial equivalence. |
| Matrix Comparison | Serum vs. Plasma (y = 0.939x + 9) | r = 1.000, r² = 1.000, Sy.x = 9 U/L | Compares serum and lithium heparin plasma samples. Extremely high correlation indicates suitability for both sample types. |
| Stability (CK NAC SL) | On-board stability | 28 days | Established through real-time studies. |
| Shelf-life | 14 months (followed on 3 batches) | Established through real-time studies. | |
| Stability (ELITROL I/II) | Shelf-life (unreconst.) | 30 months at 2-8°C | Based on a commercial vendor (K041227). |
| Reconstituted stability | 12h (15-25°C), 5 days (2-8°C), 4 weeks (frozen once) (-25 to -15°C) | Based on a commercial vendor (K041227). | |
| Stability (ELICAL 2) | Shelf-life (unreconst.) | Until expiration date printed on label (2-8°C) | Based on a commercial vendor (K033501). |
| Reconstituted stability | 8 hours (15-25°C), 2 days (2-8°C), 4 weeks (frozen once) (-25 to -15°C) | Based on a commercial vendor (K033501). |
2. Sample Size Used for the Test Set and Data Provenance
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Precision Study:
- Sample Size: For each of the 3 levels of samples, 'n' = 80 measurements were performed (presumably 2 runs/day x 2 measures/run x 20 days).
- Data Provenance: Not explicitly stated, but typically these studies use commercially available control materials or pooled patient samples. Given the context of IVD submissions, these would be laboratory-generated data, likely in a controlled environment. The country of origin is not specified, but the submitter is ELITech Clinical Systems SEPPIM S.A.S in France, so the studies were likely conducted within their facilities or partner labs. Retrospective or prospective is not specified, but it would be prospective data collection for the study.
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Linearity/Assay Reportable Range:
- Sample Size: Not explicitly stated how many samples were used, but it involved multiple dilutions across the claimed range.
- Data Provenance: Not specified, but laboratory-generated.
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Detection Limit:
- Sample Size: 15 measurements of 4 samples (total 60 measurements) with low analyte concentrations.
- Data Provenance: Not specified, but laboratory-generated.
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Interference Study:
- Sample Size: Not explicitly stated how many samples were initially spiked with interferents, but the results describe "concentrations up to..." of various interferents.
- Data Provenance: Not specified, but laboratory-generated using spiked samples.
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Method Comparison Study:
- Sample Size: 100 patient serum samples.
- Data Provenance: "100 serum patient samples." The country of origin is not specified. This is prospective data collected for the study.
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Matrix Comparison Study:
- Sample Size: 40 paired serum and lithium heparin plasma samples.
- Data Provenance: Patient samples. Country of origin not specified. This is prospective data collected for the study.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
For this type of in vitro diagnostic device (IVD) for quantitative measurement of creatine kinase (CK), the "ground truth" for the test set is established by:
- Reference Methods: The values of calibrators and control materials are traceable to the IFCC method (Schumann, 2002), which is a widely accepted international reference method for enzymes. This method itself (and its development) would involve expert consensus and established protocols.
- Predicate Device Measurements: In the method comparison study, the predicate device (Roche Diagnostics CKL on a cobas c111 analyzer) essentially serves as the "ground truth" or reference for comparison, reflecting its established accuracy and validation.
- Internal Validation: The value assignment for Elitrol I and II and Elical 2 involves testing against predetermined values on multiple instruments and calculation of median/mean values. This process is overseen by qualified laboratory personnel, but not typically "experts" in the sense of clinicians establishing a diagnosis.
Number of Experts: Not applicable in the traditional sense of medical experts reviewing individual cases. The ground truth relies on established analytical methods and comparisons to a legally marketed predicate device.
Qualifications of Experts: Not applicable for establishing ground truth of individual cases. The reference methods (e.g., IFCC) are developed and maintained by international bodies comprising experts in clinical chemistry and enzymology.
4. Adjudication Method for the Test Set
Adjudication methods (like 2+1, 3+1) are typically used in studies where a human expert consensus is required for complex qualitative or semi-quantitative assessments (e.g., image interpretation, pathology review).
For this quantitative diagnostic device performing biochemical measurements, such adjudication methods are not applicable. The "adjudication" is inherent in the analytical methods themselves:
- Agreement with Reference Method: Traceability to the IFCC method provides the "gold standard."
- Agreement with Predicate Device: The method comparison study assesses device performance against a legally marketed, previously cleared device.
- Statistical Analysis: Performance is assessed using statistical methods (e.g., regression analysis, CV%) rather than expert consensus on individual data points.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and the Effect Size of Human Improvement
No, an MRMC comparative effectiveness study was not done.
MRMC studies are typically performed for devices that involve human interpretation, such as diagnostic imaging systems where multiple readers evaluate cases with and without AI assistance to measure improvements in diagnostic accuracy, efficiency, or confidence.
This submission is for a fully automated in vitro diagnostic reagent and associated calibrators/controls, where the analysis is performed by an instrument (ELITech Clinical Systems Selectra analyzers). There is no "human reader" component in the analytical process that the device assists, therefore, an MRMC study and related effect sizes are not relevant here.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done
The entire performance evaluation described for the ELITech Clinical Systems CK NAC SL device (precision, linearity, detection limits, interference, method comparison, matrix comparison) represents standalone performance.
The device is an "algorithm only" (or rather, a reagent-based chemistry system) that provides quantitative results. There is no human intervention in the generation of the CK concentration value itself beyond the initial sample loading and instrument setup. The performance studies detailed in the submission are precisely evaluating this standalone analytical performance.
7. The Type of Ground Truth Used
The ground truth used for the performance studies is multi-faceted:
- Reference Method Traceability: For calibrators and controls, the values are traceable to the IFCC method (Schumann, 2002), which is an international reference method for creatine kinase. This is a highly robust and standardized form of ground truth based on rigorously defined analytical procedures.
- Predicate Device Values: For the method comparison study, the measurements obtained from the legally marketed Roche Diagnostics CKL reagent on a cobas c111 analyzer served as the comparative ground truth. This is a common approach in 510(k) submissions to demonstrate substantial equivalence.
- Spiked Samples/Known Concentrations: For studies like linearity, detection limits, and interference, samples prepared with known concentrations of the analyte or interferents are used.
8. The Sample Size for the Training Set
The document describes performance studies, which are analogous to validation or test sets. It does not provide information on a "training set".
This type of device (a chemical reagent kit for measuring biomarkers) typically does not involve machine learning algorithms that require a distinct training set in the way AI/ML software devices do. Its analytical characteristics are determined by the chemical principles of the assay and optimization through traditional laboratory methods, not by training on a large dataset of results.
9. How the Ground Truth for the Training Set Was Established
As noted in section 8, there is no explicit "training set" reported for this device in the context of an AI/ML algorithm. Therefore, the question of how ground truth for a training set was established is not applicable.
Any internal development and optimization of the reagent formulation or instrument parameters would be based on established chemical principles, analytical testing, and potentially iterative refinement to meet desired performance benchmarks, rather than training on a separate labeled dataset.
§ 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.