TROPONIN I ASSAY FOR THE BAYER IMMUNO 1 SYSTEM ( IN VITRO DIAGNOSTIC SYSTEM) by BAYER CORP.

This in vitro diagnostic method intended to quantitatively measure the concentration of cardiac Troponin 1 (Tn1) in human serum and plasma (lithium heparin) using the Bayer Immuno 1 system. When used in conjunction with other clinical data, such as presenting symptoms and diagnostic procedures, measurements of cardiac Tnl aids in the diagnosis of acute myocardial infarction (AMI) and in the risk stratification of patients with non-ST segment-elevation, acute coronary syndromes with respect to relative risk of mortality, myocardial infarction, or increased probability of ischemic events requiring urgent revalcularization procedures.

This diagnostic method is not intended for use on any other system.

Device Description

The proposed Bayer Immuno 1™ Troponin I assay is an enzyme label sandwich assay using a monoclonal and polyclonal antibody. A Troponin I specific monoclonal antibody is labeled with fluorescein and a Troponin I specific goat affinity purified antibody is labeled with alkaline phosphatase (ALP). The solid phase consists of a suspension of magnetizable particles coated with antibody to fluorescein (mIMP reagent). Sample or calibrator, R1 reagent containing fluoresceinantibody conjugate, R2 reagent containing ALP-antibody conjugate and mIMP reagent are mixed and incubated at 37° C. In the presence of Troponin I a (fluorescein-conjugate: Troponin I:ALPconjugate) complex is formed and captured by the anti-fluorescein antibodies on the magnetic particles. The particles are washed and para-nitrophenyl phosphate solution is added. The ALP in the antibody conjugate reacts with the substrate to form para-nitrophenoxide and phosphate. Increasing absorbance due to the formation of para-nitrophenoxide is monitored at 405 nm and 450 nm. The dose response curve is directly proportional to the concentration of Troponin I in the sample. A linear point to point fit is used to construct the dose response curve. The Bayer Immuno 1 Troponin I assay has a range of 0 to 200 ng/mL and liguid calibrators are provided with values of 0,5,10,20,60, and 200 ng/mL Troponin I.

AI/ML Overview

The provided document is a 510(k) summary for the Bayer Immuno 1™ System Troponin I Method, submitted to the FDA in 1999. It describes the device and its intended use, particularly focusing on an additional indication for risk stratification.

Based on the information provided in the document, here's a breakdown of the acceptance criteria and the study details:

1. A table of acceptance criteria and the reported device performance

The document does not explicitly state "acceptance criteria" or present a study comparing the device performance against specific targets for analytical or clinical performance (e.g., sensitivity, specificity, accuracy). Instead, it states that the proposed device is "substantially equivalent in technical performance and intended use to the FDA cleared device" (Bayer Immuno 1™ Troponin I Assay cleared under Document Control No. K973616). The changes are "limited to modifications in the indications for use."

Therefore, the "acceptance criteria" in this context would likely be that the updated device maintains the performance characteristics of the predicate device and that the new indication for use is supported without compromising safety or effectiveness. The document highlights the new indication for use: "...in the risk stratification of patients with 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."

Therefore, the "reported device performance" is essentially that it performs equivalently to the predicate device for its original indications and its added indication for risk stratification is supported. However, no specific performance metrics (like sensitivity, specificity, or agreement rates) related to this new indication are present in this summary.

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 provide any details on the sample size used for a test set, the country of origin of the data, or whether it was retrospective or prospective. The summary focuses on the device description and regulatory aspects rather than detailed clinical study results.

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)

The document does not provide any information about experts used to establish ground truth or their qualifications. Given that this is an in vitro diagnostic device for measuring Troponin I, the "ground truth" would typically refer to validated clinical outcomes (e.g., confirmed myocardial infarction, mortality) rather than expert consensus on image interpretation.

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

The document does not mention any adjudication method for a test set.

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

This document describes an immunoassay method for measuring Troponin I, not an AI-assisted diagnostic tool or imaging system that would involve "human readers" or an MRMC study. Therefore, no MRMC comparative effectiveness study was done in the context of improving human reader performance with AI assistance.

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

This is an immunoassay device that provides a quantitative measurement. The device itself is "standalone" in that it performs the measurement without human-in-the-loop performance influencing the test result. However, the interpretation of the Troponin I concentration and its use in diagnosis and risk stratification requires clinical input (e.g., "When used in conjunction with other clinical data, such as presenting symptoms and diagnostic procedures..."). The summary does not present any data on the standalone performance in terms of diagnostic accuracy or risk stratification without clinical context.

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

The document does not explicitly state the type of ground truth used for any studies that might have supported the new indication. For the risk stratification indication, it is highly probable that the ground truth would have been based on outcomes data such as mortality, confirmed myocardial infarction, or the need for revascularization procedures. However, this is inferred, not stated. For the underlying quantitative measurement, the ground truth would be the true concentration of Troponin I in the sample.

8. The sample size for the training set

The document does not provide any information about the sample size for a training set. This is a traditional immunoassay device, not a machine learning or AI-based system that typically uses training sets in the same manner.

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

As described above, this is an immunoassay device, so the concept of a "training set" for ground truth establishment in the context of machine learning is not applicable here.

Summary

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DEC - 6 1999

K993353

510(k) Summary of Safety and Effectiveness Information

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This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of the SMDA 1990 and 21 CFR 807.92

Sponsor:	Gabriel Muraca, Manager RABayer CorporationBusiness Group Diagnostics511 Benedict AvenueTarrytown, N.Y. 10591-5097Phone: 914-524-3494Fax: 914-524-2500
Device Name:	Bayer Immuno 1™ System Troponin I Method
Classification Name:	Immunoassay Method
Predicate Device:	Bayer Immuno 1™ System Troponin I Method

Device Description:

The Bayer Immuno 1 Troponin I Assay was previously cleared under Document Control No. K973616. The proposed Bayer Immuno 1 Troponin I Assay is substantially equivalent in technical performance and intended use to the FDA cleared device. Changes are limited to modifications in the indications for use. The additional indication for use is:

...in the risk stratification of patients with 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.

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Image /page/1/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle with three stripes forming its body and wings. The eagle is enclosed in a circle with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

DEC - 6 1998

Mr. Gabriel J. Muraca, Jr. Manager Regulatory Affairs Bayer Corporation Business Group Diagnostics 511 Benedict Avenue Tarrytown, New York 10591-5097

Re: K993353

Trade Name: Troponin I Assay for the Bayer Immuno 1™ System Regulatory Class: II Product Code: MMI Dated: September 30, 1999 Received: October 5, 1999

Dear Mr. Muraca:

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we 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). 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 (Premarket Approval), 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 895. A substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic QS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations.

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Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770) 488-7655.

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"(21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers 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 Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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510(k) Number (if known):

Device Name: Troponin I

Indications For Use:

This diagnostic method is not intended for use on any other system.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use	✓	OR	Over-The-Counter Use
(Per 21 CFR 801.109)

signature
Optional Formal 1-2-96

(Division Sign-Off)

Division of Clinical Laboratory Devices

510(k) Number	K993353
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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.