The specificity and sensitivity of troponin T measurements aid in both the early and late diagnosis of AMI. Troponin T elevations have also been measured in patients with the clinical diagnosis of unstable angina due to the sensitivity of troponin T for detecting minor myocardial damage.

The determination of cTnT in serum is an important component in the diagnosis of myocardial ischemia, e.g. AMI and myocarditis, as well as in monitoring the course of unstable angina pectoris and assessing the associated risk.

Device Description

The Boehringer Mannheim Elecsys ® Troponin T STAT test is based on a two step sandwich immunoassay with streptavidin microparticles and electrochemiluminescence detection. Results are determined via 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.

AI/ML Overview

This document describes the Boehringer Mannheim Elecsys® Troponin T STAT Test, an immunoassay for the quantitative determination of troponin T in human serum and plasma, used in the diagnosis of myocardial ischemia.

Here's an analysis of the provided text regarding acceptance criteria and the study that proves the device meets them:

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

The provided text does not explicitly state specific acceptance criteria or provide a table summarizing device performance metrics against such criteria. It mentions "Specific data on the performance of the test have been incorporated into the draft labeling in Attachment 5," but this attachment is not included in the provided excerpts.

The document primarily focuses on establishing substantial equivalence to a predicate device, the Boehringer Mannheim Elecsys® Troponin T test (cleared by FDA in K961500), rather than detailing performance specifications and meeting predefined acceptance thresholds for this particular iteration of the device.

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 mentions "Comparative studies on 770 patients confirm the prognostic utility of cTnT." This appears to be the sample size for a clinical study related to the prognostic utility of cTnT, which supports the "Indications for Use." However, it's not explicitly stated if this 'test set' was for the modified device's performance validation against specific acceptance criteria, or if it refers to general clinical evidence for Troponin T as a biomarker.

Sample Size (for prognostic utility): 770 patients.
Data Provenance: Not specified regarding country of origin.
Retrospective or Prospective: Not specified.

It's important to note that this is for the prognostic utility of cTnT, not necessarily the performance characteristics (e.g., accuracy, precision) of the device itself. The actual performance data for the device is referenced as being in "Attachment 5," which is not provided.

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)

This information is not provided in the given text.

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

This information is not provided in the given text.

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 device is an in vitro diagnostic (IVD) immunoassay; it is not an AI-assisted diagnostic imaging device. Therefore, an MRMC comparative effectiveness study involving human readers and AI assistance is not applicable and was not conducted.

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

This device is an in vitro diagnostic immunoassay. Its performance is inherently standalone in the sense that the test produces quantitative results directly. There is no "human-in-the-loop" component in the interpretation of the raw quantitative troponin T value produced by the instrument and reagent, although a clinician interprets the clinical significance of that value.

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

For the "Comparison to the Predicate Device," the ground truth implicitly is the performance of the predicate device. For the "Indications for Use" and the prognostic utility cited ("Comparative studies on 770 patients confirm the prognostic utility of cTnT"), the ground truth would likely be clinical outcomes data related to cardiac events and patient prognosis. However, the exact methodology for establishing specific ground truth for the device's analytical performance (e.g., accuracy, precision) is not described in the provided text, other than through comparison to the predicate.

8. The sample size for the training set

The concept of a "training set" as understood in machine learning (ML) or AI is not applicable to this traditional immunoassay device. Immunoassays do not have training sets in this sense. They are developed based on chemical and biological principles, and their performance is validated through analytical and clinical studies.

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

As noted above, the concept of a "training set" is not applicable to this type of device.

Summary

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DEC 8 1998

K984105

510(k) Summary

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	Boehringer Mannheim Corporation9115 Hague RdIndianapolis, IN 46250(317) 845-3723
	Contact person: Priscilla A. Hamill
	Date prepared: November 13, 1998
Device name	Proprietary name: Elecsys ® Troponin T STAT Test
	Common name: Troponin T Test
	Classification name: Immunoassay method, troponin subunit
Predicate device	We claim substantial equivalence to the currently marketed Boehringer Mannheim Elecsys ® Troponin T test.
Device description	The Boehringer Mannheim Elecsys ® Troponin T STAT test is based on a two step sandwich immunoassay with streptavidin microparticles and electrochemiluminescence detection.
	Results are determined via 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.
	Continued on next page

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510(k) Summary, Continued

Intended use	For the in vitro quantitative determination of troponin T in human serum andplasma
Indications foruse	The specificity and sensitivity of troponin T measurements aid in both theearly and late diagnosis of AMI. Troponin T elevations have also beenmeasured in patients with the clinical diagnosis of unstable angina due to thesensitivity of troponin T for detecting minor myocardial damage.
Comparison tothe predicatedevice	The modified Boehringer Mannheim Elecsys Troponin T test is substantiallyequivalent to other products in commercial distribution intended for similaruse. Most notably, it is substantially equivalent to the Boehringer MannheimElecsys Troponin T test cleared by FDA in K961500.
	Continued on next page

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510(k) Summary, Continued

Similarities

The following table compares the modified Boehringer Mannheim Elecsys Troponin T test with the predicate device. Specific data on the performance of the test have been incorporated into the draft labeling in Attachment 5. Labeling for the predicate device is provided in Attachment 6.

Similarities

Feature	Modified device	Predicate device
Intended use	For the in vitro quantitativedetermination of troponin T inhuman serum and plasma	For the in vitro quantitativedetermination of troponin T inhuman serum and plasma
Indicationsfor use	An important component in thediagnosis of myocardialischemia, eg. AMI andmyocarditis, as well as inmonitoring the course ofunstable angina pectoris andassessing the associated risk.	An aid in both the early and latediagnosis of AMI. Troponin Televations have also beenmeasured in patients with theclinical diagnosis of unstableangina due to the sensitivity oftroponin T for detecting minormyocardial damage.
Sample type	Human serum, plasma	Human serum, plasma
Assayreactionprinciple	Two step sandwichimmunoassay using streptavidinparticle and biotinylatedantibody capture system	Two step sandwich immunoassayusing streptavidin particle andbiotinylated antibody capturesystem
Antibody	Mouse monoclonal (no changein antibody)	Mouse monoclonal
Measure-mentapproach	Electrochemiluminescence	Electrochemiluminescence
Duration ofassay	9 minutes	9 minutes

Continued on next page

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510(k) Summary, Continued

Differences: The following differences between the modified Boehringer Differences Mannheim Elecsys Troponin T test and the predicate device are not significant for purposes of determining substantial equivalence.

Component concentrations have been modified .
Modified device calibrator contains human recombinant troponin T rather . than bovine heart troponin T, used in the predicate device calibrator.
の 2007年07月17日 10時間 2007 0000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000

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Image /page/4/Picture/2 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized depiction of an eagle with three curved lines representing its wings or feathers. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" is arranged in a circular fashion around the eagle symbol.

DEC 8 1998

Priscilla A. Hamill Regulatory Affairs Consultant Boehringer Mannheim Corporation 9115 Haque Road Indianapolis, IN 46250

Re: K984105

Trade Name: Elecsys® Troponin T Stat Test Regulatory Class: II Product Code: MMI Dated: November 13, 1998 November 17, 1998 Received:

Dear Ms. Hamill:

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 Requlations, 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. this response to your premarket notification Please note: 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.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

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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" (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 Gutman

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

510(k) Number (if known):

Device Name: Boehringer Mannheim ® Elecsys Troponin T STAT

Indications for Use:

Troponin T (TnT) is a component of the contractile apparatus of the striated musculature. Although the function of TnT is the same in all striated muscles, TnT originating exclusively from the myocardium (cardiac TnT, molecular weight 39.7 kD) clearly differs from skeletal muscle TnT. As a result of its high tissue-specificity, cardiac troponin T (cTnT) is a cardiospecific, highly sensitive marker for myocardial damage. In cases of acute myocardial infarction, troponin T levels in serum rise about 3-4 hours after the occurrence of cardiac symptoms and can remain elevated for up to 14 days.

Comparative studies on 770 patients confirm the prognostic utility of cTnT. It has also been shown that cTnT-positive patients benefit particularly from antithrombotic therapy strategies (e.g. low molecular weight heparin, BPIIb/IIIa antagonists). 8.9

Elevated serum cTnT values are detectable in about 30% of patients suffering from renal failure (e.g. chronic hemodialysis patients). The cTnT detected in these patients is of cardiac origin. It has been demonstrated e.g. with RT-PCR, that cTnT is not expressed in regenerated skeletal musculature of patients with renal failure. '611' Clinical data increasingly demonstrate that such patients have a high risk of subsequently suffering cardiovascular complications. 12-15

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References

Katus HA. Remppis A. Looser S. et al. Enzyme-linked immunoassay of dardiac troponin T 1. for the detection of acute myocardial infarction in patients. Mol Cell Cardiol 1989:21(7):1349-1353.
Katus HA, et al. Non-invasive assessment of perioperative myocardial cell damage by 2. circulating cardiac troponin T. Br Heart J 1991;65:259-64.
Ravkilde J. et al. Diagnostic performance and prognostic value of serum troponin T in 3. suspected acute myocardial infarction. Scandinavian J Clin Lab Invest 1993;53:677-685.
Katus HA, Scheffold T, Remppis A, Zehelein J. Proteins of the troponin complex. র Laboratory Medicine 1992;23(5):311-317.
Hamm CW, Ravkilde .. Gerhardt W, Jorgensen P, Peheim E, Ljungdahl L, et al. The న్ prognostic value of serum troponin T in unstable angina. N Engl J Med 1992;327(3):146-50.
Ohmann EM, et al. Risk stratification with admission cardiac troponin T levels in acute 6. myocardial ischemia. N Engl J Med 1996; 335:1333-4.
Christenson RH, Duh SH, Newby LK, Ohmann EM, Califf RM, Granger CB, et al. Cardiac 7. troponin T and cardiac troponin I; relative values in short term risk stratification of patients with acute coronary syndromes. Clin Chem 1998;44(3):494-501.
Lindahl B, Venge P, Wallentin L. Troponin Tidentifies patients with unstable coronary 8. artery disease who benefit from long-term antithrombotic protection. J Am Coll Cardiol 1997;29(1):43-8.
1. Hamm CW, Heeschen C, Goldmann BU, Barnathan E, Simoons MLI. Value of troponins in predicting therapeutic efficacy of Abcixmab in patients with unstable angina. J Am Coll Cardiol 1998;31(2)Suppl A 185A 837-6.
1. Haller C. Zehelein J. Remppis A. Muller-Bardorff M. Katus HA. Cardiac troponin T in patients with end-stage renal disease; absence of expression in truncal skeletal muscle. Clin Chem 1998:44(5):930-938.
1. Ricchiuti V, Voss, EM, Ney A, Odland M, Anderson PAW, Apple FS. Troponin T isoforms expressed in renal diseased skeletal muscle will not cause false positive results by the second generation c TnT assay by Boehringer Mannheim. ClinChem, 1998; in press.
1. Ishigami M, Yamaguchi S. Usefulness of serum troponin T in prediction of cardiac death in hemodialysis patients. J Am Soc Neph 1994;5.N3 P455.

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1. Kirvan K, Ryan L, Holleman C, Williamson E, Sedot F. Troponin I and troponin T in dialysis treated chronic renal failure – a one year follow-up. Clin Chem 1998;44(6):Suppl.A133, 579.
1. Muller-Bardorff M Schweikhart B, Giannitsis F, Schsarz B, Agrawal B, Katus HA, Troponin T in patients with renal failure. Clin Chem 1998:44(6):Suppl.A117,508.
1. Porter GA, Norton TL, Bennett WM. Troponin T (TnT), A predictor of death in chronic hemodialysis patients (CHDP). Am J Kidn Diseases 1998;31(3)A27.

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Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use
(Per 21 CFR 801.109)
✓

Over-the-Counter Use ------------------------------------

(Optional format 1-2-96)

(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number IC984105

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.