(15 days)
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. Measurement of creatine kinase is used in the diagnosis and treatment of myocardial infarction.
The Access CK-MB reagents, calibrators, and the Access Immunoassay Analyzers (Access, Access 2, and Synchron LXi 725) comprise the Access Immunoassay Systems for the quantitative determination of CK-MB in human serum and plasma.
This document describes the analytical studies performed for the Beckman Coulter Access CK-MB assay. The studies focus on demonstrating the performance of the device rather than comparing it to human readers or establishing ground truth from expert consensus or pathology, as typically seen in AI-based diagnostic device submissions.
Here's a breakdown of the requested information based on the provided text:
1. Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria with specific numerical thresholds for each metric. Instead, it presents the results of analytical studies to demonstrate the device's performance characteristics. This is common for in-vitro diagnostic devices where the "acceptance" is often implied by meeting established scientific and regulatory standards for assay performance.
| Performance Metric | Reported Device Performance |
|---|---|
| Within-run Imprecision | 1.15%CV to 2.32%CV |
| Between-run Imprecision | 1.47%CV to 2.89%CV |
| Total Imprecision | 2.66%CV to 3.54%CV |
| Analytical Sensitivity (LoD) | <0.1 ng/mL |
| Dilution Recovery (Linearity) | 102% average recovery (range 95% to 109%) |
| Method Comparison (Correlation to predicate) | y = 0.879x + 0.907, r = 0.997 |
| Analytical Specificity | No significant interference / cross-reactivity |
| Reagent Stability (open) | 56 days |
| Calibrator Stability (open) | 60 days |
| Calibration Curve Stability | 56 days |
| Reference Intervals (Li-Heparin plasma/serum) | 0.6 - 6.3 ng/mL |
| Reference Intervals (EDTA plasma) | 0.5 - 5.0 ng/mL |
2. Sample Size for Test Set and Data Provenance
- Test Set Sample Size:
- Method Comparison: 120 samples.
- Imprecision: Not explicitly stated as a single number for a "test set." Imprecision studies usually involve multiple replicates across different runs/days. The levels tested ranged from 4.5 to 172.3 ng/mL.
- Dilution Recovery: Not explicitly stated as a single number, but involved "lithium heparin plasma samples."
- Analytical Specificity: Not explicitly stated.
- Reference Intervals: Not explicitly stated.
- Data Provenance: Not specified (e.g., country of origin). The studies appear to be retrospective for the method comparison (comparing existing samples) and prospective for the analytical performance studies (performed by the manufacturer).
3. Number of Experts and Qualifications for Ground Truth
- Not Applicable. This is an in-vitro diagnostic assay for quantitative measurement of a biomarker. The "ground truth" is typically established by meticulously prepared analytical samples (dilutions, spiked samples, known concentrations) or by comparing the device's measurements to a recognized gold standard method (the predicate device in this case). It does not involve human expert interpretation of images or clinical cases to establish a diagnostic ground truth.
4. Adjudication Method for Test Set
- Not Applicable. As this is an assay for quantitative measurement, there is no adjudication process involving human review of results in the traditional sense, as would be expected for a diagnostic imaging or clinical decision-support AI.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No. This is an in-vitro diagnostic (IVD) device, specifically an immunoassay for measuring a biomarker. MRMC studies are typically conducted for diagnostic imaging devices or AI systems that assist human readers in interpreting complex data. The performance of this device is assessed by its analytical characteristics (precision, accuracy, linearity, etc.) rather than its impact on human reader performance.
6. Standalone (Algorithm Only) Performance
- Yes. The described studies are all of the standalone performance of the assay system (reagents and analyzer) without human-in-the-loop performance being a primary metric. The analytical results (imprecision, sensitivity, linearity, method comparison) directly represent the algorithm's (assay's) performance.
7. Type of Ground Truth Used
- Analytical Standards and Predicate Device Comparison:
- For metrics like imprecision, analytical sensitivity, and dilution recovery, the ground truth is based on known concentrations in controls, calibrators, or prepared samples.
- For method comparison, the "ground truth" is the results obtained from the legally marketed predicate device (Access® CK-MB Assay for Use on the Access® Immunoassay Analyzer, K000716). The comparison aims to show substantial equivalence.
8. Sample Size for Training Set
- Not Stated/Not Applicable in the traditional sense. This is not a machine learning or AI device that undergoes a discrete "training" phase with a dataset, as typically understood in the context of deep learning. Instead, the device's "training" and optimization would involve extensive R&D, formulation development, and internal testing during its development phase, which is not typically detailed in 510(k) summaries as a "training set" with specific sample numbers.
9. How Ground Truth for Training Set Was Established
- Not Applicable. See point 8. The "ground truth" during the development of such an assay would be established through a rigorous process of chemical and biological validation using highly characterized reference materials and established analytical methods to ensure the assay correctly measures CK-MB.
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JAN 1 7 2003
510(k) SUMMARY
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.
The assigned 510(k) number is:
Submitter's Name and Address
Beckman Coulter, Inc. 1000 Lake Hazeltine Drive Chaska, MN 55318 Telephone: (952)368-1323 Fax: (952)368-7610 Contact: Brent Taber
Date Prepared: December 31, 2002
Device Names
| Proprietary Name: | CK-MB and CK-MB Calibrators on the Access®Immunoassay Systems |
|---|---|
| ------------------- | ------------------------------------------------------------------- |
- Common Name: CK-MB Enzyme Immunoassay
Classification Name: Fluorometric Method, CPK or Isoenzymes
Predicate Device
Access® CK-MB Assay for Use on the Access® Immunoassay Analyzer Beckman Coulter, Inc. Chaska, MN 55318
510(k) Number: K000716
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Device Description
The Access CK-MB reagents, calibrators, and the Access Immunoassay Analyzers (Access, Access 2, and Synchron LXi 725) comprise the Access Immunoassay Systems for the quantitative determination of CK-MB in human serum and plasma.
Intended 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.
| Attribute | Current Access CK-MB | Modified Access CK-MB |
|---|---|---|
| IntendedUse | For the measurement ofCK-MB in human serum andplasma | For the measurement ofCK-MB in human serum andplasma |
| AssayPrinciples | Utilizes the binding ofCK-MB to specific monoclonalantibodies in a two site"sandwich" immunoassay;Utilizes alkaline phosphataseenzyme conjugated tomonoclonal antibody | Utilizes the binding ofCK-MB to specific monoclonalantibodies in a two site"sandwich" immunoassay;Utilizes alkaline phosphataseenzyme conjugated tomonoclonal antibody |
| SolidSupport | Paramagnetic particles | Paramagnetic particles |
| DetectionSystem | Utilizes dioxetane-basedchemiluminescent substrate;Measures light production froma chemiluminescent reaction | Utilizes dioxetane-basedchemiluminescent substrate;Measures light production froma chemiluminescent reaction |
| Calibrators | Liquid calibrators preparedfrom buffered bovine serumalbumin matrix withrecombinant CK-MB atspecified levels | Liquid calibrators preparedfrom buffered bovine serumalbumin matrix withrecombinant CK-MB atspecified levels |
Comparison of Technological Characteristics
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Summary of Analytical Studies
Within run imprecision ranged from 1.15%CV to 2.32%CV, Precision: between-run imprecision ranged from 1.47%CV to 2.89%CV and total imprecision ranged from 2.66%CV to 3.54%CV at levels ranging between 4.5 and 172.3 ng/mL.
Analytical Sensitivity: The lowest detectable level of CK-MB distinguishable from zero (Access CK-MB calibrator S0) with 95% confidence is <0.1 ng/mL.
Dilution Recovery (Linearity): Linearity studies performed by diluting lithium heparin plasma samples with Access Sample Diluent A provided an average recovery of the samples of 102%, with individual sample average recoveries ranging from 95% to 109%.
Method Comparison: A comparison of CK-MB values from 120 samples, ranging from 0.6 to 208.7 ng/mL (modified CK-MB), run with both the modified Access CK-MB assay and the current CK-MB assay demonstrated good agreement with the following statistical data: y = 0.879x + 0.907, r = 0.997.
Analytical Specificity: There was no significant interference from therapeutic drugs, biological substances, or heterophile samples. There was no significant cross-reactivity with other creatine kinase isoenzymes (CK-BB or CK-MM).
Stability: CK-MB reagents are stable for 56 days after opening and calibrators are stable for 60 days after opening. The calibration curve is stable for 56 days.
Reference Intervals: Separate reference intervals were calculated for lithium heparin plasma and serum, and EDTA plasma. The lithium heparin plasma and serum reference interval (95% central fraction) is 0.6 - 6.3 ng/mL. The EDTA plasma reference interval (95% central fraction) is 0.5 - 5.0 ng/mL.
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Conclusion
CK-MB and CK-MB Calibrators on the Access Immunoassay Systems is substantially equivalent to Access® CK-MB Assay for Use on the Access® Immunoassay Analyzer for the measurement of CK-MB in human serum and plasma.
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Food and Drug Administration 2098 Gaither Road Rockville MD 20850
JAN 1 7 2003
Mr. Brent Taber Senior Regulatory Specialist Beckman Coulter, Inc. 1000 Lake Hazeltine Chaska, MN 55318-1084
K030012 Re:
Trade/Device Name: CK-MB and CK-MB Calibrators on the Access Immunoassay Systems Regulation Number: 21 CFR 862.1215 Regulation Name: Creatine phosphokinase/creatine kinase or isoenzymes test system. Regulatory Class: Class II Product Code: JHX, JIS Dated: December 31, 2002 Received: January 2, 2003
Dear Mr. Taber:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA), You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820).
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This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 594-3084. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.
Sincerely yours,
Steven Putman
Steven I. Gutman, M.D., M.B.A. Director Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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INDICATIONS FOR USE STATEMENT
Page / of /
510(k) Number (if known): K030012
Device Name: CK-MB and CK-MB Calibrators on the Access® Immunoassay Systems
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. Measurement of creatine kinase is used in the diagnosis and treatment of myocardial infarction.
Han Coogen
(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number. K030012
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
Prescription Use
(Per 21 CFR 801.109) X
OR
Over-The Counter Use
(Optional Format 1-2-96)
§ 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.