The Access AccuTnl assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of cardiac troponin I (cTnl) levels in human serum and plasma using the Access Immunoassay Systems to aid in the diagnosis and treatment of myocardial infarction and cardiac muscle damage.

Cardiac troponin I determination aids in the risk stratification of patients with unstable angina or non-ST segment elevation acute coronary syndromes with respect to relative risk of mortality, myocardial infarction, or increased probability of ischemic events requiring urgent revascularization procedures.

Device Description

The Access AccuTnl reagents, AccuTnl calibrators, and the Access and Access 2 Immunoassay Analyzers comprise the Access Immunoassay Systems for the quantitative determination of cardiac troponin I in human serum and plasma.

AI/ML Overview

The provided document describes the Beckman Coulter AccuTnl™ and AccuTnl Calibrators on the Access® Immunoassay Systems. This device is an in-vitro diagnostic test, not an AI/ML-driven device. Therefore, the questions related to AI/ML specific criteria (like sample size for test set, data provenance, number of experts for ground truth, adjudication method, MRMC studies, standalone performance, and training set information) are not applicable to this submission.

However, I can extract the acceptance criteria related to analytical performance and clinical effectiveness for this diagnostic device.

1. Table of Acceptance Criteria and Reported Device Performance

The document references a previous 510(k) submission (K010429) where the analytical studies were summarized. For the current submission (K021814), the focus is on the clinical performance for risk stratification.

Acceptance Criteria Category	Specific Criteria/Outcome Measured	Reported Device Performance
Analytical Studies	Precision, Analytical Sensitivity, Dilution Recovery (Linearity), Method Comparison, Matched Sample Comparison, Analytical Specificity, Stability, Reference Intervals, Equimolarity	No changes made to assay reagents from K010429. Results from K010429 serve as predicate for analytical performance.
Clinical Performance (Risk Stratification)	Relative Risks (RR) and Odds Ratios (OR) for adverse cardiac events (double and triple composite endpoints).	At the 97.5th percentile of the reference range: - RR and OR for double & triple composite endpoints ranged from 1.68 to 3.61 across 3 follow-up periods. - All were statistically significant. At the 99th percentile of the reference range: - RR and OR for double & triple composite endpoints ranged from 1.58 to 3.18 across 3 follow-up periods. - All were statistically significant. At the median concentration at 10% CV imprecision: - RR and OR for double & triple composite endpoints ranged from 1.62 to 3.60 across 3 follow-up periods. - All were statistically significant.
Intended Use Expansion Justification	Demonstration that the assay can stratify patients for potential adverse cardiac events.	The data demonstrate that the Access AccuTnl assay can be utilized to stratify patients for potential adverse cardiac events (double and triple composite endpoints) using three cutoffs at three follow-up periods.

Study that Proves the Device Meets the Acceptance Criteria:

The current submission (K021814) primarily focuses on demonstrating the clinical utility of the AccuTnl assay for risk stratification by analyzing its performance against various clinical endpoints over different follow-up periods and at different cutoffs. The analytical performance is established by referencing the prior 510(k) (K010429).

2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

The document does not explicitly state the sample size for the clinical performance study (test set) or its provenance (country of origin, retrospective/prospective nature). It only provides the summarized results of the clinical performance.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

Not applicable. This is an in-vitro diagnostic device that measures a biomarker. The "ground truth" here pertains to clinical outcomes (death, myocardial infarction, urgent revascularization) rather than expert interpretation of images or other subjective data. These outcomes are typically objectively recorded in patient medical records.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

Not applicable. As noted above, the "ground truth" refers to objective clinical endpoints.

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 in-vitro diagnostic biomarker test, not an AI-assisted diagnostic imaging device/system.

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

Not applicable. This is not an algorithm-only device. It's an immunoassay that provides a quantitative measurement.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)

The ground truth for the clinical performance study appears to be outcomes data, specifically "double composite endpoint consisting of death or myocardial infarction and triple composite endpoint consisting of death or myocardial infarction or urgent revascularization." These are objective clinical events.

8. The sample size for the training set

Not applicable. This is an immunoassay, not an AI/ML device that requires a training set in the typical sense. The assay itself is developed and validated, but there isn't a "training set" of patient data for an algorithm.

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

Not applicable. See response to #8.

Summary

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SEP 2 7 2002

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:

K021814/

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: May 31, 2002

Device Names

Proprietary Name:	AccuTnl™ and AccuTnl Calibrators on the Access®
	Immunoassay Systems
Common Name:	Troponin I Enzyme Immunoassay
Classification Name:	Immunoassay, Troponin Subunits

Predicate Device

AccuTnl™ and AccuTnI Calibrators on the Access® Immunoassay System Beckman Coulter, Inc. Chaska, MN 55318

510(k) Number: K010429

Device Description

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Intended Use

The Access AccuTnl assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of cardiac troponin | (cTnl) levels in human serum and plasma using the Access Immunoassay Systems to aid in the diagnosis and treatment of myocardial infarction and cardiac muscle damage.

Cardiac troponin I determination aids in the risk stratification of patients with unstable angina or non-ST seqment elevation acute coronary syndromes with respect to relative risk of mortality, myocardial infarction, or increased probability of ischemic events requiring urgent revascularization procedures.

Summary of Analytical Studies

No changes have been made to the assay reagents submitted under K010429. The 510(k) Summary for K010429 summarizes analytical studies including precision, analytical sensitivity, dilution recovery (linearity), method comparison, matched sample comparison, analytical specificity, stability, reference intervals, and equimolarity.

Summary of Clinical Performance

Relative Risks (RR), Odds Ratios (OR), and clinical sensitivity and specificity were calculated relative to three Access AccuTnl cutoffs (97.5TH and 99TH percentiles of the reference range, and the median concentration at 10% CV imprecision), three follow-up periods (30 days, 42 days, and 10 months), and two endpoints (double composite endpoint consisting of death or myocardial infarction and triple composite endpoint consisting of death or myocardial infarction or urgent revascularization).

At the 97.5 Th percentile of the reference range, relative risks and odds ratios for the double and triple composite endpoints ranged from 1.68 to 3.61 for all three follow-up periods. All relative risks and odds ratios were statistically significant for both composite endpoints and the three follow-up periods.

At the 9911 percentile of the reference range, relative risks and odds ratios for the double and triple composite endpoints ranged from 1.58 to 3.18 for all three follow-up periods. All relative risks and odds ratios were statistically significant for both composite endpoints and the three follow-up periods.

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Image /page/2/Picture/0 description: The image shows the logo for Beckman Coulter. The logo consists of a stylized oval shape on the left, with two curved lines inside. To the right of the oval is the text "BECKMAN" in a bold, sans-serif font, stacked above the text "COULTER" in the same font.

At the median concentration at 10% CV imprecision, relative risks and odds ratios for the double and triple composite endpoints ranged from 1.62 to 3.60 for all three follow-up periods. All relative risks and odds ratios were statistically significant for both composite endpoints and the three follow-up periods.

The data demonstrate that the Access AccuTnl assay can be utilized to stratify patients for potential adverse cardiac events (double and triple composite endpoints) using three cutoffs at three follow-up periods.

Conclusion

Access AccuTnl and AccuTnl calibrators on the Access Immunoassay Systems, with the addition of a risk stratification for use to the intended use, is substantially equivalent to Access AccuTnl and AccuTnl calibrators on the Access Immunoassay System with indications as an aid in the diagnosis and treatment of myocardial infarction and cardiac muscle damage (K010429).

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DEPARTMENT OF HEALTH & HUMAN SERVICES

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Food and Drug Administration 2098 Gaither Road Rockville MD 20850

SEP 2 7 2002

Mr. Brent Taber Senior Regulatory Specialist Beckman Coulter Inc. 1000 Lake Hazeltine Drive Chaska, MN 55318-1084

Re: K021814

Trade/Device Name: AccuTnI™ and AccuTnI Calibrators on the Access® Immunoassay Systems Regulation Number: 21 CFR 862.1215 Regulation Name: Creatine phosphokinase/creatine kinase ot isoenzymes test system Regulatory Class: Class II Product Code: MMI Dated: August 15, 2002 Received: August 16, 2002

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 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 complics 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 (QS) 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/cdrh/dsma/dsmamain.html".

Sincerely yours,

Steven Sutman

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

Page of

510(k) Number (if known): JJ (x) 8/

Device Name: AccuTnl™ and AccuTnl Calibrators on the Access® Immunoassay Systems

Indications For Use:

Sean Cooper

(Division Sign-Off)

Division of Clinical Laboratory Devices

510(k) Number K021814

(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)

Over-The Counter Use ____________

(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.