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. 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). 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.

AI/ML Overview

The provided text describes the 510(k) premarket notification for the Beckman Coulter Access CK-MB assay on the Dxl 9000 Access Immunoassay Analyzer. This document focuses on demonstrating substantial equivalence to a previously cleared predicate device (Access CK-MB assay on the Access 2 Immunoassay System, K030012), rather than proving that an AI-driven device meets specific acceptance criteria.

Therefore, many of the requested details regarding AI/ML device validation (e.g., sample size for test set, data provenance, number of experts for ground truth, adjudication methods, MRMC studies, standalone AI performance, training set details) are not applicable to this submission content.

This submission is for an in vitro diagnostic (IVD) immunoassay, which is a chemical/biological test, not an AI or imaging device. The "device" here refers to the measurement system (the assay and the immunoassay analyzer), not an AI algorithm.

However, I can extract the acceptance criteria and performance data for the analytical performance of this IVD device as presented in the document.

Acceptance Criteria and Reported Device Performance (Access CK-MB Assay on Dxl 9000 Access Immunoassay Analyzer)

The studies presented here are analytical validation studies for an in vitro diagnostic immunoassay, not clinical validation studies for an AI/ML or imaging device. The "acceptance criteria" are based on performance claims typically established for IVD assays to demonstrate substantial equivalence to a predicate device and suitability for their intended use.

1. Table of Acceptance Criteria and Reported Device Performance

Performance Characteristic	Acceptance Criteria / Design Goal	Reported Device Performance (Dxl 9000 Access Immunoassay Analyzer)
Method Comparison	Demonstrated substantial agreement with predicate device (Access 2).	Correlation Coefficient: 1.00 (between Access 2 and Dxl 9000).Slope: 1.04 (95% CI: 1.03 - 1.05)Intercept: 0.0066 (95% CI: -0.019 - 0.032)(Range: 0.29 - 271 ng/mL)
Imprecision	Within-laboratory:- SD ≤ 0.04 ng/mL for values ≤ 0.5 ng/mL- CV ≤ 8.0% for values > 0.5 ng/mL	Sample 1 (Mean 0.2 ng/mL):- Repeatability SD: 0.01, %CV: 5.2- Between-run SD: 0.01, %CV: 3.4- Between-day SD: 0.003, %CV: 1.9- Within-Laboratory (Total) SD: 0.01, %CV: 6.5Sample 2 (Mean 9.2 ng/mL):- Within-Laboratory (Total) %CV: 3.4Sample 3 (Mean 54 ng/mL):- Within-Laboratory (Total) %CV: 3.0Sample 4 (Mean 120 ng/mL):- Within-Laboratory (Total) %CV: 3.0Sample 5 (Mean 220 ng/mL):- Within-Laboratory (Total) %CV: 2.5
Linearity	Demonstrated linearity across the measuring interval.	Result: Assay demonstrated linearity across the measuring interval (0.2 - 300 ng/mL).
Limit of Blank (LoB)	Not explicitly stated as acceptance criterion, but determined.	Result: 0.1 ng/mL
Limit of Detection (LoD)	Not explicitly stated as acceptance criterion, but determined.	Result: 0.1 ng/mL
Limit of Quantitation (LoQ)	LoQ ≤ 20% within-lab CV.	Result: 0.2 ng/mL (at ≤ 20% within-lab CV)
Measuring Range	Comparability to predicate.	0.2 - 300 ng/mL (Predicate: 0.1 - 300 ng/mL)
Reference Interval	Updated/verified for all sample types.	Serum, Lithium heparin and EDTA plasma: 0.6 ng/ml - 6.3 ng/ml (Predicate: EDTA plasma: 0.5-5.0 ng/ml; Serum/Lithium heparin plasma: 0.6-6.3 ng/ml)

2. Sample Size Used for the Test Set and Data Provenance

Method Comparison: N=146 samples (Concentration Range: 0.29 - 271 ng/mL).
Imprecision: 80 replicates per sample level. Assays were run for a minimum of 20 days (2 runs per day, in duplicate).
LoB, LoD, LoQ: "multiple reagent lots and 3 instruments over a minimum of 3 days" (LoB) or "minimum of 5 days" (LoD/LoQ).
Data Provenance: Not explicitly stated (e.g., country of origin, retrospective/prospective), but these are typically controlled laboratory studies conducted under GLP (Good Laboratory Practice) guidelines. Given the manufacturer's location (Chaska, MN, USA), it's highly probable the studies were conducted in the US. The studies are prospective analytical validation studies specific to the device, not retrospective analysis of clinical patient data.

3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications of Experts

Not applicable. This is an IVD assay measuring an analyte (CK-MB concentration). The "ground truth" for these analytical studies is the quantitative measurement of the CK-MB concentration by a reference method or the predicate device, not expert consensus interpretation of images or clinical outcomes.

4. Adjudication Method for the Test Set

Not applicable. See point 3.

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

Not applicable. This is an IVD assay, not an AI/ML or imaging device. There are no "human readers" interpreting results in the way an MRMC study would apply.

6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done

Not applicable. This is an IVD assay, not an AI algorithm. The performance described is the standalone analytical performance of the instrument/assay system.

7. The Type of Ground Truth Used

For Method Comparison, the "ground truth" or reference was the predicate device (Access 2 Immunoassay System) which measured CK-MB concentrations in patient samples.
For Imprecision, Linearity, LoB/LoD/LoQ, the "ground truth" is the true analytical concentration of the analyte in control materials or spiked samples, assessed through various statistical methods (e.g., CLSI guidelines). It's essentially the actual concentration values.

8. The Sample Size for the Training Set

Not applicable. This device is an immunoassay, not an AI/ML algorithm that requires a "training set" in the computational learning sense. The "training" in manufacturing would relate to calibrating the instrument and assay reagents.

9. How the Ground Truth for the Training Set Was Established

Not applicable. See point 8. The "ground truth" for assay calibration (analogous to training) would be established by reference materials traceable to international standards, if available, or highly characterized in-house control materials with assigned values. The document mentions "Liquid calibrators prepared from buffered bovine serum albumin matrix with recombinant CK-MB at specified levels." These calibrators define the "ground truth" for the device's internal calibration.

Summary

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February 16, 2024

Beckman Coulter, Inc Neha Desai Staff Quality and Regulatory Affairs 1000 Lake Hazeltine Drive Chaska, Minnesota 55318

Re: K234005

Trade/Device Name: Access CK-MB Regulation Number: 21 CFR 862.1215 Regulation Name: Creatine Phosphokinase/Creatine Kinase Or Isoenzymes Test System Regulatory Class: Class II Product Code: JHX Dated: December 18, 2023 Received: December 19, 2023

Dear Neha Desai:

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 (the 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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database available at https://www.accessdata.fda.gov/scripts/cdrb/cfdocs/cfpmn/pmn.cfm identifies.combination product submissions. 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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).

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Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

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 Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safetyreporting-combination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Paula V. Caposino -S

Paula Caposino, Ph.D. Acting Deputy Division Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health

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Indications for Use

510(k) Number (if known) K234005

Device Name Access CK-MB

Indications for Use (Describe)

Type of Use (Select one or both, as applicable)
Prescription Use (Part 21 CFR 801 Subpart D)	Over-The-Counter Use (21 CFR 801 Subpart C)

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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.

510(k) Number K234005

Submitted Bv:

Beckman Coulter, Inc. 1000 Lake Hazeltine Drive Chaska, MN 55318

Primarv Contact:

Neha Desai Staff Quality and Regulatory Affairs Phone: (612) 244-9788 Email: nhdesai@beckman.com

Alternate Contact:

Kuljeet Kaur Senior Manager, Regulatory Affairs Phone: (952) 465-1914 Email: kkaur@beckman.com

Common Name: CK-MB Enzyme Immunoassay Trade Name: Access CK-MB Classification Code: JHX Classification Requlation: 21 CFR 862.1215

Predicate Device Device Name: Access CK-MB 510(k) Numbers: K030012

Device Description

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mouse anti-CK-MB conjugate reacts specifically with the serum or the plasma CK-MB (no reaction with CK-MM or CK-BB isoforms).

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.

Intended Use

Parameter	Access CK-MB Assay on Access®Immunoassay System (Predicate)	Access CK-MB Assay onDxl 9000 Access®Immunoassay Analyzer
Intended use	The Access CK-MB assay is aparamagnetic particle, chemiluminescentimmunoassay for the quantitativedetermination of CK-MB levels in humanserum and plasma using the AccessImmunoassay Systems to aid in thediagnosis and treatment of myocardialinfarction and muscle diseases such asprogressive, Duchenne-type musculardystrophy.	Same
Technology	The Access CK-MB assay is a two-siteimmunoenzymatic (“sandwich”) assay.Patient sample is added to a reaction vesselwith mouse monoclonal anti-human CK-MBantibody-alkaline phosphatase conjugateand paramagnetic particles coated withmouse monoclonal anti-human CK-BB.	Same
Solid Support	Paramagnetic Particles	Same
Detection System	Utilizes dioxetane-based chemiluminescentsubstrate; Measures light production from achemiluminescent reaction.	Same
Calibration	Liquid calibrators prepared from bufferedbovine serum albumin matrix withrecombinant CK-MB at specified levels.	Same

Comparison of Technological Characteristics to the Predicate (Assay)

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Parameter	Access CK-MB Assay on Access®Immunoassay System (Predicate)	Access CK-MB Assay onDxl 9000 Access®Immunoassay Analyzer
Sample Type	Serum and plasma	Same
Reference Interval	EDTA plasma: 0.5 ng/ml - 5.0 ng/mlSerum and Lithium heparin plasma:0.6 ng/ml - 6.3 ng/ml	Serum, Lithium heparinand EDTA plasma:0.6 ng/ml - 6.3 ng/ml
Measuring Range	0.1 - 300 ng/mL	0.2 - 300 ng/mL
Instrument	Access® Immunoassay system	Dxl 9000 Access®Immunoassay Analyzer
Substrate	Access Substrate	Lumi-Phos Pro Substrate

Standard/Guidance Document Referenced (if applicable):

CLSI EP05-A3: Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline - Third Edition

CLSI EP06-2nd Edition : Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline

CLSI EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline - Second Edition

CLSI EP09c 3rd Edition: Measurement Procedure Comparison and Bias Estimation Using Patient Samples; Third Edition

CLSI EP28-A3c Defining, Establishing, and Verifying Reference Intervals in the Clinical Laboratory - Third Edition

CLSI EP35 Assessment of Equivalence of Suitability of Specimen Types for Medical Laboratory Measurement Procedures - First Edition

Summary of Studies

Method Comparison:

A study based on CLSI EP09c 3rd Edition, Measurement Procedure Comparison and Bias Estimation Using Patient Samples; Approved Guidelines, 3rd Edition compared the Access 2 Immunoassay System and the Dxl 9000 Access Immunoassay Analyzer.

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N	ConcentrationRange*ng/mL	Slope	Slope95% CI	Intercept	Intercept95% CI	CorrelationCoefficientR
146	[0.29 - 271]	1.04	1.03 - 1.05	0.0066	-0.019-0.032	1.00

*Range is Access 2 values

Imprecision:

The assay was designed to have within-laboratory imprecision as listed below:

SD ≤ 0.04 ng/mL for values ≤ 0.5 ng/mL

CV ≤ 8.0% for values > 0.5 ng/mL

A study based on CLSI EP05-A3 performed on the Dxl 9000 Access Immunoassay Analyzer tested multiple samples in duplicate in 2 runs per day for a minimum of 20 days.

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

Linearity: A study based on CLSI EP06-Ed2 performed on the Dxl 9000 Access Immunoassay Analyzer determined the assay demonstrated linearity across the measuring interval.

Limit of Blank (LoB), Limit of Detection (LoD) and Limit of Quantitation (LoQ): Limit of Blank (LoB), Limit of Detection (LoD), and Limit of Quantitation (LoQ) studies were conducted on the Dxl 9000 Access Immunoassay Analyzer following CLSI quideline EP17-A2. The LoB study included multiple reagent lots and 3 instruments over a minimum of 3 days. The LoD and LoQ studies included multiple reagent lots and 3 instruments over a minimum of 5 days.

	ng/mL (µg/L)
Limit of Blank (LoB)	0.1
Limit of Detection (LoD)	0.1
Limit of Quantitation (LoQ)≤ 20% within-lab CV	0.2

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Substantial Equivalence Comparison Conclusion

Beckman Coulter's Access CK-MB Assay on the Dxl 9000 Access Immunoassay Analyzer is substantially equivalent to the Access CK-MB Assay on the Access 2 Immunoassay System (K030012) as demonstrated through the information and data provided in this submission. The performance testing presented in this submission provides evidence that the device is safe and effective in its intended use.

Regulation Number and Section

§ 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.