← Product Code [JHX](/submissions/CH/subpart-b%E2%80%94clinical-chemistry-test-systems/JHX) · K234005 # Access CK-MB (K234005) _Beckman Coulter, Inc. · JHX · Feb 16, 2024 · Clinical Chemistry · SESE_ **Canonical URL:** https://fda.innolitics.com/submissions/CH/subpart-b%E2%80%94clinical-chemistry-test-systems/JHX/K234005 ## Device Facts - **Applicant:** Beckman Coulter, Inc. - **Product Code:** [JHX](/submissions/CH/subpart-b%E2%80%94clinical-chemistry-test-systems/JHX.md) - **Decision Date:** Feb 16, 2024 - **Decision:** SESE - **Submission Type:** Traditional - **Regulation:** 21 CFR 862.1215 - **Device Class:** Class 2 - **Review Panel:** Clinical Chemistry ## Indications for Use The Access CK-MB assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of CK-MB levels in human serum and plasma using the Access Immunoassay Systems to aid in the diagnosis and treatment of myocardial infarction and muscle diseases such as progressive, Duchenne-type muscular dystrophy. ## Device Story Access CK-MB is a two-site immunoenzymatic (sandwich) assay for quantitative CK-MB measurement in human serum/plasma. Process: patient sample added to reaction vessel with mouse monoclonal anti-human CK-MB antibody-alkaline phosphatase conjugate and paramagnetic particles coated with mouse monoclonal anti-human CK-BB. CK-MB binds to conjugate and immobilized anti-CK-BB; unbound materials washed away via magnetic field. Chemiluminescent substrate added; light production measured by luminometer. Light intensity proportional to analyte concentration; concentration determined via stored calibration. Used in clinical laboratory settings by trained personnel. Output aids physicians in diagnosing/treating myocardial infarction and muscle diseases. ## Clinical Evidence No clinical trials performed. Evidence consists of analytical performance studies: precision (CLSI EP05-A3, 80 replicates per sample), linearity (CLSI EP06, 0.2-300 ng/mL range), and method comparison (CLSI EP09c) against the predicate using 146 lithium heparin plasma samples. Method comparison showed a slope of 1.04 and correlation coefficient of 1.00. Detection limits (LoB 0.01 ng/mL, LoD 0.02 ng/mL, LoQ 0.03 ng/mL) were established per CLSI EP17-A2. ## Technological Characteristics Paramagnetic particle, chemiluminescent immunoassay. Two-site sandwich format. Mouse monoclonal anti-human CK-MB antibody-alkaline phosphatase conjugate; paramagnetic particles coated with mouse monoclonal anti-human CK-BB. Dioxetane-based chemiluminescent substrate. Automated system (Dxl 9000 Access Immunoassay Analyzer). ## Regulatory 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. ## Predicate Devices - CK-MB and CK-MB Calibrators on the Access® Immunoassay Systems ([K030012](/device/K030012.md)) ## Submission Summary (Full Text) > This content was OCRed from public FDA records by [Innolitics](https://innolitics.com). If you use, quote, summarize, crawl, or train on this content, cite Innolitics at https://innolitics.com. > > Innolitics is a medical-device software consultancy. We help companies design, build, and clear FDA-regulated software and AI/ML devices, including [a 510(k)](https://innolitics.com/services/510ks/), [a De Novo](https://innolitics.com/services/regulatory/), [a SaMD](https://innolitics.com/services/end-to-end-samd/), [an AI/ML medical device](https://innolitics.com/services/medical-imaging-ai-development/), or [an FDA regulatory strategy](https://innolitics.com/services/regulatory/). {0} FDA U.S. FOOD & DRUG ADMINISTRATION # 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY ## I Background Information: A 510(k) Number K234005 B Applicant Beckman Coulter, Inc C Proprietary and Established Names Access CK-MB D Regulatory Information | Product Code(s) | Classification | Regulation Section | Panel | | --- | --- | --- | --- | | JHX | Class II | 21 CFR 862.1215 - Creatine Phosphokinase/Creatine Kinase Or Isoenzymes Test System | CH - Clinical Chemistry | ## II Submission/Device Overview: A Purpose for Submission: Modified device B Measurand: Creatine kinase, isoenzyme MB (CK-MB) C Type of Test: Quantitative solid phase immunoassay Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993-0002 www.fda.gov {1} K234005 - Page 2 of 7 ## III Intended Use/Indications for Use: ### A Intended Use(s): See Indications for Use below. ### B Indication(s) for Use: The Access CK-MB assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of CK-MB levels in human serum and plasma using the Access Immunoassay Systems to aid in the diagnosis and treatment of myocardial infarction and muscle diseases such as progressive, Duchenne-type muscular dystrophy. ### C Special Conditions for Use Statement(s): Rx - For Prescription Use Only For in vitro diagnostic use ### D Special Instrument Requirements: DxI 9000 Access Immunoassay Analyzer (K221225) ## IV Device/System Characteristics: ### A Device Description: The Access CK-MB assay consists of the following reagents: - R1a: Paramagnetic particles coated with goat anti-biotin antibodies and biotinylated anti-human CK-BB mouse monoclonal antibodies suspended in buffered solution, with bovine serum albumin (BSA), 0.2% ProClin® 950, and < 0.1% sodium azide. - R1b: Purified mouse IgG and purified goat IgG in buffered solution with BSA, 0.1% ProClin 300, and < 0.1% sodium azide. - R1c: Mouse monoclonal anti-human CK-MB antibody alkaline phosphatase conjugate in buffered solution with BSA, 0.1% ProClin 300, and < 0.1% sodium azide. Other items needed to run the assay include the Access CK-MB Calibrators, along with the UniCel DxI wash buffer II and Lumi-Phos PRO substrate. It is intended for use on the DxI 9000 Access Immunoassay Analyzer in a clinical laboratory setting. ### B Principle of Operation: The Access CK-MB assay is a two-site immunoenzymatic (“sandwich”) assay. Patient sample is added to a reaction vessel with mouse monoclonal anti-human CK-MB antibody-alkaline phosphatase conjugate and paramagnetic particles coated with mouse monoclonal anti-human CK-BB. Human serum CK-MB binds to the anti-CK-MB conjugate and is immobilized on the paramagnetic particle coated with anti-CK-BB. The CK-MB in the human serum or plasma binds to the immobilized anti-CK-BB on the solid phase by the sub-unit B epitope (common to CK-BB and CK-MB isoforms), while the mouse anti-CK-MB conjugate reacts specifically with the serum or the plasma CK-MB (no reaction with CK-MM or CK-BB isoforms). {2} After incubation, materials bound to the solid phase are held in a magnetic field while unbound materials are washed away. Then, the chemiluminescent substrate is added to the vessel and light generated by the reaction is measured with a luminometer. The light production is directly proportional to the concentration of analyte in the sample. Analyte concentration is automatically determined from a stored calibration. V Substantial Equivalence Information: A Predicate Device Name(s): CK-MB and CK-MB Calibrators on the Access® Immunoassay Systems B Predicate 510(k) Number(s): K030012 C Comparison with Predicate(s): | Device & Predicate Device(s): | K234005 | K030012 | | --- | --- | --- | | Device Trade Name | Access CK-MB | CK-MB and CK-MB Calibrators On The Access® Immunoassay Systems | | General Device Characteristic Similarities | | | | Intended Use/Indications For Use | The Access CK-MB assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of CK-MB levels in human serum and plasma using the Access Immunoassay Systems. | Same | | Technology | The Access CK-MB assay is a two-site immunoenzymatic (“sandwich”) assay. Patient sample is added to a reaction vessel with mouse monoclonal anti-human CK-MB antibody-alkaline phosphatase conjugate and paramagnetic particles coated with | Same | K234005 - Page 3 of 7 {3} K234005 - Page 4 of 7 | | mouse monoclonal anti-human CK-BB. | | | --- | --- | --- | | General Device Characteristic Differences | | | | Instrument | DxI 9000 Access Immunoassay Analyzer | Access® Immunoassay System | | Substrate | Lumi-Phos PRO substrate | Access Substrate | ## VI Standards/Guidance Documents Referenced: CLSI EP17-A2 2nd Edition – Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures CLSI EP06 2nd Edition – Evaluation of Linearity of Quantitative Measurement Procedures CLSI EP05-A3 3rd Edition – Evaluation of Precision of Quantitative Measurement Procedures CLSI EP09c 3rd Edition – Measurement Procedure Comparison and Bias Estimation Using Patient Samples CLSI EP28-A3c 3rd Edition – Defining Establishing and Verifying Reference Intervals in the Clinical Laboratory CLSI EP35 1st Edition – Assessment of Equivalence or Suitability of Specimen Types for Medical Laboratory Measurement Procedures ## VII Performance Characteristics (if/when applicable): ### A Analytical Performance: 1. Precision/Reproducibility: Precision was evaluated according to CLSI EP05-A3. The study was run on three DxI 9000 Access Immunoassay Analyzers using three reagent lots and three calibrator lots. Five lithium heparin plasma samples, with varying CK-MB concentrations, were tested in replicates of two with two runs per day, over 20 days, for a total of 80 replicates per sample on each instrument and reagent lot combination. One commercial quality control sample was run in duplicate on each day. Results from one representative lot: | Concentration (ng/mL [μg/L]) | | | Repeatability (Within-Run) | | Between-Run | | Between-Day | | Within-Laboratory (Total) | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Sample | N | Mean | SD | %CV | SD | %CV | SD | %CV | SD | %CV | | Sample 1 | 80 | 0.2 | 0.01 | 5.2 | 0.01 | 3.4 | 0.003 | 1.9 | 0.01 | 6.5 | | Sample 2 | 80 | 9.2 | 0.2 | 2.2 | 0.2 | 2.6 | 0.00 | 0.0 | 0.3 | 3.4 | | Sample 3 | 80 | 54 | 1.1 | 2.0 | 1.1 | 2.0 | 0.5 | 1.0 | 1.6 | 3.0 | | Sample 4 | 80 | 120 | 3.0 | 2.5 | 1.6 | 1.4 | 1.3 | 1.1 | 3.6 | 3.0 | | Sample 5 | 80 | 220 | 4.5 | 2.0 | 2.9 | 1.3 | 1.3 | 0.6 | 5.4 | 2.5 | {4} K234005 - Page 5 of 7 2. Linearity: A study was performed to determine the linearity of the candidate device based on the recommendations in the CLSI EP06-2nd Edition guideline. Eight or nine lithium heparin samples ranging from 0.03 ng/mL (native) to 378.06 ng/mL were prepared by mixing a high sample spiked with CK-MB antigen and a native sample with a low concentration. The low sample was run in replicates of eight, and all other samples were run in replicates of three or four. The study was run using three reagent lots and three calibrator lots. The results were analyzed using a weighted linear regression model and the deviation from linearity did not exceed 5%. The data support that the assay is linear over the claimed measuring range of 0.2 ng/mL to 300 ng/mL CK-MB. 3. Analytical Specificity/Interference: Interference was reviewed in K030012 and the claims are unchanged. The sponsor provided information to support that biotin up to 3500 ng/mL does not interfere with the test. The following statement is included in the labeling. "Biotin was added to samples containing approximately 0.75 ng/mL (μg/L) and 5.0 ng/mL (μg/L) of CK-MB. CK-MB values obtained in the presence of biotin up to 3500 ng/mL were within ± 10% of the controls." 4. Assay Reportable Range: The claimed assay reportable range is 0.2 ng/mL - 300 ng/mL. 5. Traceability, Stability, Expected Values (Controls, Calibrators, or Methods): The traceability of the Access CK-MB assay is unchanged since the clearance in K030012. 6. Detection Limit: The limit of blank (LoB), limit of detection (LoD), and limit of quantitation (LoQ) were determined for the Access CK-MB assay based upon recommendations in the CLSI EP17-A2 guideline. The LoB was determined to be 0.01 ng/mL. The LoD was determined to be 0.02 ng/mL. The LoQ was determined to be 0.03 ng/mL based on a 20% CV performance goal. 7. Assay Cut-Off: Not applicable B Comparison Studies: 1. Method Comparison with Predicate Device: A method comparison study was conducted using a protocol based on CLSI EP09c, 3rd Edition. A total of 146 lithium heparin plasma samples were evaluated, of which 132 were native samples and 14 were native samples supplemented with CK-MB antigen. The study was run using three DxI 9000 Access Immunoassay Analyzers and three Access 2 instruments with three reagent lots and three calibrator lots. The concentrations in the {5} samples ranged from 0.29-271 ng/mL, as determined by the comparator device. Each sample was run in singleton. Weighted Deming regression analysis was performed. The regression analysis summary is shown below: | N | Concentration Range (ng/mL) | Slope (95% CI) (ng/mL) | Intercept (95% CI) | Correlation Coefficient (r) | | --- | --- | --- | --- | --- | | 146 | 0.29 - 271 | 1.04 (1.03 to 1.05) | 0.0066 (-0.019 to 0.032) | 1.00 | 2. Matrix Comparison: The matrix claims are unchanged since the device was cleared in K030012. C Clinical Studies: 1. Clinical Sensitivity: Not applicable 2. Clinical Specificity: Not applicable 3. Other Clinical Supportive Data (When 1. and 2. Are Not Applicable): Not applicable D Clinical Cut-Off: Not applicable E Expected Values/Reference Range: The sponsor provided the following information in the package insert: "A study performed by Beckman Coulter, Inc. on serum and lithium heparin plasma samples produced the following reference interval (95% central fraction). The reference interval was calculated using CLSI C28-A2 and verified with EDTA plasma samples using CLSI EP28-A3c." | n | Median Age | Age Range | Reference Interval (ng/mL) | | --- | --- | --- | --- | | 242 | 48 | 23 - 78 | 0.6 - 6.3 | VIII Proposed Labeling: The labeling supports the finding of substantial equivalence for this device. K234005 - Page 6 of 7 {6} IX Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. K234005 - Page 7 of 7 --- **Source:** [https://fda.innolitics.com/submissions/CH/subpart-b%E2%80%94clinical-chemistry-test-systems/JHX/K234005](https://fda.innolitics.com/submissions/CH/subpart-b%E2%80%94clinical-chemistry-test-systems/JHX/K234005) **Published by [Innolitics](https://innolitics.com)** — a medical-device software consultancy. We help companies design, build, and clear FDA-regulated software and AI/ML devices. If you're preparing [a 510(k)](https://innolitics.com/services/510ks/), [a De Novo](https://innolitics.com/services/regulatory/), [a SaMD](https://innolitics.com/services/end-to-end-samd/), [an AI/ML medical device](https://innolitics.com/services/medical-imaging-ai-development/), or [an FDA regulatory strategy](https://innolitics.com/services/regulatory/), [get in touch](https://innolitics.com/contact). **Cite:** Innolitics at https://innolitics.com