ELECSYS TROPONIN T STAT TEST

K984105 · Boehringer Mannheim Corp. · MMI · Dec 8, 1998 · Clinical Chemistry

Device Facts

• Record ID: K984105
• Device Name: ELECSYS TROPONIN T STAT TEST
• Applicant: Boehringer Mannheim Corp.
• Product Code: MMI · Clinical Chemistry
• Decision Date: Dec 8, 1998
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1215
• Device Class: Class 2

Intended Use

For the in vitro quantitative determination of troponin T in human serum and plasma

Device Story

The Elecsys Troponin T STAT test is an in vitro diagnostic assay for quantitative measurement of cardiac troponin T (cTnT) in human serum or plasma. It utilizes a two-step sandwich immunoassay principle with streptavidin-coated microparticles and biotinylated antibodies. Detection is achieved via electrochemiluminescence. The device is intended for use in clinical laboratory settings by trained personnel. The assay requires a 2-point calibration and a master curve provided via reagent bar code. Results are used by clinicians to diagnose myocardial infarction, monitor unstable angina, and assess cardiovascular risk in patients, including those with renal failure. The test provides rapid, sensitive detection of myocardial damage, aiding in clinical decision-making regarding antithrombotic therapy and patient management.

Clinical Evidence

Clinical evidence includes comparative studies on 770 patients confirming the prognostic utility of cTnT. Literature cited supports the use of cTnT for AMI diagnosis, risk stratification in unstable angina, and identification of cardiovascular risk in renal failure patients. No specific bench testing metrics (e.g., sensitivity/specificity percentages) are provided in the summary text.

Technological Characteristics

Two-step sandwich immunoassay; streptavidin microparticle and biotinylated antibody capture system; electrochemiluminescence detection; mouse monoclonal antibodies; human recombinant troponin T calibrator; 9-minute assay duration; in vitro diagnostic reagent system.

Indications for Use

Indicated for the diagnosis of myocardial ischemia (e.g., AMI, myocarditis) and monitoring of unstable angina pectoris in patients. Used to assess associated risk and detect minor myocardial damage. Applicable to patients with renal failure to identify high risk of cardiovascular complications.

Regulatory Classification

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.

Predicate Devices

• Boehringer Mannheim Elecsys Troponin T test (K961500)

Submission Summary (Full Text)

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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 Corporation<br>9115 Hague Rd<br>Indianapolis, IN 46250<br>[phone] |
| | 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. |
| | <i>Continued on next page</i> |

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# 510(k) Summary, Continued

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| Intended use | For the in vitro quantitative determination of troponin T in human serum and<br>plasma |
|------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Indications for<br>use | The specificity and sensitivity of troponin T measurements aid in both the<br>early and late diagnosis of AMI. Troponin T elevations have also been<br>measured in patients with the clinical diagnosis of unstable angina due to the<br>sensitivity of troponin T for detecting minor myocardial damage. |
| Comparison to<br>the predicate<br>device | The modified Boehringer Mannheim Elecsys Troponin T test is substantially<br>equivalent to other products in commercial distribution intended for similar<br>use. Most notably, it is substantially equivalent to the Boehringer Mannheim<br>Elecsys 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 quantitative<br>determination of troponin T in<br>human serum and plasma | For the in vitro quantitative<br>determination of troponin T in<br>human serum and plasma |
| Indications<br>for use | An important component in the<br>diagnosis of myocardial<br>ischemia, eg. AMI and<br>myocarditis, as well as in<br>monitoring the course of<br>unstable angina pectoris and<br>assessing the associated risk. | An aid in both the early and late<br>diagnosis of AMI. Troponin T<br>elevations have also been<br>measured in patients with the<br>clinical diagnosis of unstable<br>angina due to the sensitivity of<br>troponin T for detecting minor<br>myocardial damage. |
| Sample type | Human serum, plasma | Human serum, plasma |
| Assay<br>reaction<br>principle | Two step sandwich<br>immunoassay using streptavidin<br>particle and biotinylated<br>antibody capture system | Two step sandwich immunoassay<br>using streptavidin particle and<br>biotinylated antibody capture<br>system |
| Antibody | Mouse monoclonal (no change<br>in antibody) | Mouse monoclonal |
| Measure-<br>ment<br>approach | Electrochemiluminescence | Electrochemiluminescence |
| Duration of<br>assay | 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.
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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 [phone]. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at [phone]. 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 [phone] or [phone], 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.

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. 1-6

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.
- 9. 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.
- 10. 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.
- 11. 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.
- 12. 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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- 13. 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.
- 14. 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.
- 15. 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)

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510(k) Number *IC984105*