Immunoassay for the in vitro quantitative determination of the MB isoenzyme of creatine kinase in human serum and plasma. 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.

Device Description

The ELECSYS® CK-MB STAT and Elecsys® CK-MB Assays are a two step sandwich immunoassay with streptavidin microparticles and electrochemiluminescence detection.

Results are determined using a calibration curve that is generated specifically on each instrument by a 2-point calibration and a master curve provided with the reagent bar code.

The Elecsys® CK-MB application is identical to the Elecsys® CK-MB STAT assay, the only difference being the length of incubation (18 minutes vs. 9 minutes).

AI/ML Overview

The provided 510(k) summary (K022654) describes the Elecsys® CK-MB STAT and Elecsys® CK-MB Assays, which are in vitro quantitative immunoassays for the MB isoenzyme of creatine kinase. This document focuses on demonstrating substantial equivalence to a predicate device, not on establishing specific acceptance criteria and proving the device meets them through a formal clinical study with ground truth and expert adjudication.

However, based on the information provided, we can extract details about the performance characteristics of the modified devices and how they compare to the original device (which serves as a benchmark for what might be considered "acceptance" for the predicate).

Here’s a breakdown based on the available information:

1. Table of Acceptance Criteria and Reported Device Performance

The concept of "acceptance criteria" in this 510(k) is implicitly derived from the performance of the legally marketed predicate device (the "original device") and the demonstration that the modified devices ("CK-MB STAT (modified device)" and "CK-MB (modified device)") maintain comparable or improved performance characteristics. Since this is an immunoassay and not a diagnostic imaging AI, many of the typical AI-specific criteria (like specificity, sensitivity, ROC AUC) are not directly discussed in the provided text. Instead, the focus is on analytical characteristics.

Characteristic	Acceptance Criteria (Implied from Original Device)	Reported Device Performance (Modified CK-MB STAT & CK-MB)
Intended Use	For quantitative determination of the MB isoenzyme of creatine kinase in human serum and plasma.	Same
Indications for Use	Diagnosis of myocardial ischemia, e.g. in acute myocardial infarction, myocarditis, etc.	Same
Sample types	Serum, plasma (Li-, Na-heparin, K2-EDTA, Na-citrate)	Serum, plasma (Li-, Na- heparin, K3-EDTA, Na-citrate) - K2-EDTA changed to K3-EDTA
Assay	Two-step sandwich assay using biotinylated and ruthenium labeled antibodies and streptavidin microparticles with electrochemiluminescent detection	Same
Antibodies	Murine monoclonal	Same
Incubation time	9 minutes (for STAT)	9 minutes (Modified STAT); 18 minutes (Modified CK-MB)
Measuring range	0.100 - 500.0 ng/ml	Same
Analytical specificity	0.100 ng/ml	Same
Expected values (Median)	1.2 ng/ml in healthy individuals	Women: 0.97 ng/ml; Men: 1.35 ng/ml (for healthy individuals)
Expected values (97.5th percentile)	Not explicitly stated for original device, but implied to be around 5 ng/ml threshold	Women: 2.88 ng/ml; Men: 4.94 ng/ml
Expected values (99th percentile)	Not explicitly stated for original device, but implied to be around 5 ng/ml threshold	Women: 2.88 ng/ml; Men: 6.73 ng/ml
Standardization	Calibrated against commercially available CK-MB test (microparticle immunoassay)	Calibrated against AACC CK-MB reference material (human recombinant CK-MB) - Improved standardization

Note: The "acceptance criteria" here are inferred from the need to demonstrate substantial equivalence. The modified devices either retain the same characteristics as the predicate or show improvements (e.g., standardization method, more detailed expected values).

2. Sample size used for the test set and the data provenance

The document does not explicitly state the sample size for any test set or the data provenance (country of origin, retrospective/prospective). The data presented for "Expected values" (median, 97.5th, and 99th percentiles) would have been derived from a study on healthy individuals, but the details of this study are not provided in this summary.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

This 510(k) pertains to an in vitro diagnostic immunoassay, not a device relying on human interpretation (like radiology images) or clinical expert consensus for its "ground truth" establishment in the way an AI diagnostic tool would. Therefore, this information is not applicable and not provided in the summary. The "ground truth" for an immunoassay largely relies on biochemical reference methods or validated standards.

4. Adjudication method for the test set

As above, this information is not applicable and not provided for this type of in vitro diagnostic device. Adjudication methods like 2+1 or 3+1 are used for expert consensus on image interpretations or clinical diagnoses, which is not the nature of this submission.

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, an MRMC comparative effectiveness study was not done. This type of study is relevant for AI-assisted diagnostic imaging or interpretation tools, not for an automated quantitative immunoassay like the Elecsys® CK-MB. There is no human-in-the-loop component for interpretation in the conventional sense that would necessitate such a study.

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

Yes, in a sense, the performance described here is standalone performance of the assay itself. The Elecsys® CK-MB assays are automated quantitative immunoassays performed on specific analyzers (Roche Elecsys® 1010 / 2010 and Modular Analytics E170). The results are generated by the algorithm/system, and there is no subsequent human interpretation step that would modify the numerical output of the assay. The measured concentrations are the direct output.

7. The type of ground truth used

The ground truth implicitly used for the standardization of the modified devices is the AACC CK-MB reference material (human recombinant CK-MB). This indicates reliance on a well-defined and recognized reference standard for calibration, which serves as the "ground truth" for accurate measurement.

8. The sample size for the training set

The document does not provide information on the sample size for any "training set." This is because the device as described is an immunoassay, not a machine learning or AI model in the modern sense that requires a "training set." The assay relies on established biochemical reactions, calibrated against reference materials, and characterized through analytical validation.

9. How the ground truth for the training set was established

Not applicable, as there is no "training set" in the context of an AI/ML model for this immunoassay. The calibration and standardization are established using the AACC CK-MB reference material, which serves as the reference standard for analytical accuracy.

Summary

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510(k) Summary - ELECSYS® CK-MB STAT and ELECSYS® CK-MB Assays K022654

Introduction	According to the requirements of 21 CFR 807.92, the following information provides sufficient detail to understand the basis for a determination of substantial equivalence
Submitter name, address, contact	Roche Diagnostics Corporation9115 Hague RdIndianapolis IN 46250(317) 521-3831Contact person: Sherri L. CoenenDate prepared: August 8, 2002
Device Name	Proprietary name: ELECSYS® CK-MB STATELECSYS® CK-MBCommon name: Electrochemiluminescent immunoassay for the detection of CK-MBClassification name: Creatine Kinase Test
Device description	The ELECSYS® CK-MB STAT and Elecsys® CK-MB Assays are a two step sandwich immunoassay with streptavidin microparticles and electrochemiluminescence detection.Results are determined using a calibration curve that is generated specifically on each instrument by a 2-point calibration and a master curve provided with the reagent bar code.The Elecsys® CK-MB application is identical to the Elecsys® CK-MB STAT assay, the only difference being the length of incubation (18 minutes vs. 9 minutes).
Intended use	Immunoassay for the in vitro quantitative determination of the MB isoenzyme of creatine kinase in human serum and plasma.
Predicate	We claim substantial equivalence to the currently marketed Elecsys® CK-MB
Device	STAT Assay. (K974421).
Reagent	The following table describes the similarities and differences between the
Summary	original Elecsys® CK-MB STAT and restandardized assays.

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510(k) Summary - ELECSYS® CK-MB STAT and ELECSYS®

• のお気になる。

CK-MB, continued

Characteristic	CK-MB STAT(original device)	CK-MB STAT(modified Device)	CK-MB(modified Device)
Intended Use	For quantitativedetermination of the MBisoenzyme of creatinekinase in human serumand plasma.	Same	Same
Indications forUse	Diagnosis of myocardialischemia, e.g. in acutemyocardial infarction,myocarditis, etc.	Same	Same
Sample types	Serum, plasma (Li-, Na-heparin, K2-EDTA, Na-citrate)	Serum, plasma (Li-,Na- heparin, K3-EDTA, Na-citrate)	Same
Assay	Two-step sandwich assayusing biotinylated andruthenium labeledantibodies andstreptavidinmicroparticles withelectrochemiluminescentdetection	Same	Same
Antibodies	Murine monoclonal	Same	Same
Incubationtime	9 minutes	9 minutes	18 minutes
Measuringrange	0.100 - 500.0 ng/ml	Same	Same
Analyticalspecificity	0.100 ng/ml	Same	Same

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510(k) Summary - ELECSYS® CK-MB STAT and ELECSYS® CK-MB, continued

Characteristic	CK-MB STAT(original device)	CK-MB STAT(modified Device)	CK-MB(modifiedDevice)
Expectedvalues	• Median in healthyindividuals 1.2 ng/ml• Recommendedthreshold 5 ng/ml	• Median:women 0.97 ng/mlmen 1.35 ng/ml• 97.5th percentile:women 2.88 ng/mlmen 4.94 ng/ml• 99th percentile:women 2.88 ng/mlmen 6.73 ng/ml	Same
Standardization	Calibrated againstcommercially availableCK-MB test(microparticleimmunoassay)	Calibrated againstAACC CK-MBreference material(human recombinantCK-MB)	Same

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/3/Picture/1 description: The image is a black and white seal for the Department of Health & Human Services USA. The seal is circular with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" around the perimeter. In the center of the seal is an abstract image of an eagle.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

AUG 2 9 2002

Ms. Sherri L. Coenen Regulatory Affairs Consultant Regulatory Submissions, Centralized Diagnostics Roche Diagnostics Corporation 9115 Hague Road P.O. Box 50457 Indianapolis, IN 46250-0457

Re: K022654

Trade/Device Name: Elecsys® CK-MB STAT and Elecsys® CK-MB Regulation Number: 21 CFR 862.1215 Regulation Name: Creatine phosphokinase/creatine kinase or isoenzymes test system Regulatory Class: Class II Product Code: JHY Dated: August 8, 2002 Received: August 9, 2002

Dear Ms. Coenen:

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 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.

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); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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Page 2 -

This letter will allow you to begin marketing your device as described in your 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 advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 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/cdrb/dsmaldsmamain.html".

Sincerely yours,

Steven Butman

Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory-Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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INDICATIONS FOR USE STATEMENT

510(k) Number (if known): N/A

Device Name: ELECSYS® CK-MB

Indications For Use:

022654

The electrochemiluminescence immunoassay "ECLIA" is intended for use on the Roche Elecsys® 1010 / 2010 and Modular Analytics E170 (Elecsys module) Immunoassay Analyzers.

Alain Cooger

(Division Sign-Off) (Division of Clinical Laboratory Devices 510(k) Number

(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE) Prescription Use V Over-The-Counter Use OR (Per 21 CFR 801.109)

(Optional Format 1-2-96)

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INDICATIONS FOR USE STATEMENT

Page 2 of 2

510(k) Number (if known): N/A K 022265 4

Device Name: ELECSYS® CK-MB STAT

Indications For Use:

The electrochemiluminescence immunoassay "ECLIA" is intended for use on the Roche Elecsys 1010 / 2010 and Modular Analytics E170 (Elecsys module) Immunoassay Analyzers.

Tom Cooper

(Division Sign-Off)

Division of Clinical Laboratory Devices 1022405 510(k) Number _

(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrenee of CDRH, Office of Device Evaluation (ODE) Prescription Use Over-The-Counter Use OR (Per 21 CFR 801.109)

(Optional Format 1-2-96)

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.