ELECSYS TROPONIN T

K961500 · Boehringer Mannheim Corp. · MMI · Jun 11, 1996 · Clinical Chemistry

Device Facts

• Record ID: K961500
• Device Name: ELECSYS TROPONIN T
• Applicant: Boehringer Mannheim Corp.
• Product Code: MMI · Clinical Chemistry
• Decision Date: Jun 11, 1996
• 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

Elecsys Troponin T is an in vitro diagnostic immunoassay for quantitative troponin T measurement in human serum and plasma. It utilizes a two-step sandwich immunoassay principle: 15 μl sample incubation with biotinylated and ruthenium-labeled monoclonal anti-troponin T antibodies; subsequent binding to streptavidin-coated microparticles. Microparticles are magnetically captured on an electrode surface; application of voltage induces chemiluminescent emission measured by a photomultiplier. The device operates on the Elecsys 2010 instrument. Results are calculated via a master curve (provided by reagent bar code) and 2-point calibration. The test aids clinicians in diagnosing AMI and assessing myocardial damage, particularly when ECG or other markers are non-diagnostic. It provides a broad diagnostic window (up to 14 days) and high cardiac specificity, assisting in clinical decision-making for patients with chest pain or suspected myocardial injury.

Clinical Evidence

Bench testing only. Precision studies (N=60 per sample) showed within-run CVs of 2.35-5.12% and total CVs of 4.15-7.23%. Sensitivity (lower detection limit) is 0.01 ng/ml. Method comparison against the predicate (N=54) yielded a correlation coefficient of r=0.969. Specificity testing showed minimal cross-reactivity (<0.003%) with skeletal troponin T, cardiac troponin I, tropomyosin, and myosin light chain. Interference testing performed for hemoglobin, lipemia, bilirubin, and biotin.

Technological Characteristics

Two-step sandwich immunoassay; streptavidin-coated microparticles; electrochemiluminescence detection; ruthenium complex label; biotinylated monoclonal antibodies. Requires Elecsys 2010 instrument. Sample volume: 15 μl. Assay duration: 9 minutes. Calibration: 2-point, master curve via bar code.

Indications for Use

Indicated for the diagnosis of acute myocardial infarction (AMI) and detection of minor myocardial damage in patients with unstable angina. Used as an adjunct to clinical symptoms, ECG, and other serological markers.

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

• CARDIAAC T® Troponin T Enzymun Test (K961500)

Submission Summary (Full Text)

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K961500
510(k) Summary
JUN 11 1996

## 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.

## 1) Submitter name, address, contact

Boehringer Mannheim Corporation
9115 Hague Rd.
Indianapolis, IN 46250
[phone]

Contact Person: LeeAnn Chambers
Date Prepared: April 12, 1996

## 2) Device name

Proprietary name: Elecsys Troponin T
Common name: troponin test

## 3) Predicate device

We claim substantial equivalence to the CARDIAAC T® Troponin T Enzymun Test assay.

## 4) Device Description

The Elecsys ® Troponin T test principle is based on a two step sandwich with streptavidin microparticles and electrochemiluminescence detection.

Total duration of assay: 9 minutes.

- 1st incubation: 15 μl of sample, a biotinylated monoclonal troponin T-specific antibody and a monoclonal troponin T-specific antibody labeled with a ruthenium complex react to form a sandwich complex
- 2nd incubation: after the addition of streptavidin-coated microparticles, the complex becomes bound to the solid phase via interaction of biotin and streptavidin
- The reaction mixture is aspirated into the measuring cell where the microparticles are magnetically captured onto the surface of the electrode. Unbound substances are then removed with ProCell. Application of a voltage to the electrode then induces chemiluminescent emission which is measured by a photomultiplier

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4) Device Description, cont.
- Results are determined via a calibration curve which is instrument-specifically generated by 2-point calibration and a master curve provided via the reagent bar code

5) Intended use
For the in vitro quantitative determination of troponin T in human serum and plasma.

5) Indications for use
Diagnosis of acute myocardial infarction (AMI) is generally based on the presence of at least two of three classic findings: clinical symptoms, diagnostic ECG, and serological findings of abnormal levels of total CK, LD or their isoenzymes. Often, due to the presence of clinical symptoms and changes in the ECG, the CK, CK-MB, LD and LD1 serve primarily to confirm and monitor the course of the infarction. At other times, when chest pain is atypical, or ECG changes are non-diagnostic or absent, these markers provide important diagnostic information. Limitations to these serum markers include a relatively narrow diagnostic window, difficulty in interpreting small increases and a lack of cardiac specificity. Troponin T can be an effective serum marker whose cardiac specificity and wide diagnostic window makes it a valuable tool in the diagnosis of AMI.²,⁴

Troponin T has been shown to be elevated in all patients with AMI who are diagnosed by World Health Organization (WHO) criteria.¹ Troponin T frequently appears in serum as early as one to three hours after the onset of pain.²,⁵ The sensitivity of troponin T reaches 100% within hours and remains at a high sensitivity level until day five. After 48 hours the CK-MB assay is frequently of little diagnostic value.¹ Troponin T also remains elevated longer than total LD.³ Its levels can be measured for up to 14 days.⁵ Thus, the diagnostic window is broader due to the length of time troponin T is elevated in serum. The time interval of elevation in serum ranges from three hours to &gt;14 days.¹,⁵

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5) Indications for use, (cont.)

The specificity and sensitivity of troponin T measurements aid in both the early and late diagnosis of AMI. 6 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. In cases of AMI with minimal cardiac damage, low elevations of CK and CK-MB are difficult to interpret due to the presence of normal levels of these enzymes in the blood, and their lack of cardiac specificity. The specificity of troponin T to cardiac tissue is of value in these difficult patients. 4,6

References

1. Katus HA, Scheffold T, Remppis A, And Zehlein J. Proteins of the troponin complex. Laboratory Medicine. 1992;23(No. 5):311-317.
2. Katus HA, Remppis A, Neumann FJ, et al. Diagnostic efficiency of troponin T measurements in acute myocardial infarction. Circulation. 1991;83(No. 3):902-912.
3. Katus HA, et al. Enzyme linked immuno assay of cardiac troponin T for the detection of acute myocardial infarction in patients. J Mol Cell Cardiol 1989;21:1349-1353.
4. Remppis A, Katus HA, Scheffold T, et al. Diagnostic efficiency of troponin T measurements in acute myocardial infarction. Eur Heart J 11. 1990;(suppl):351.
5. Mair J, Artner-Dworzak E, Puschendorf B, and Dienstl F. Plasma troponin T in acute myocardial infarction. Eur Heart J 11. 1990;(suppl):351.
Mair J, Artner-Dworzak E, Lechleitner P, et al. Cardiac troponin T in diagnosis of acute myocardial infarction. Clin Chem. 1991;37(No. 6):845-854.

6) Comparison to predicate device

The Boehringer Mannheim Elecsys Troponin T is substantially equivalent to other products in commercial distribution intended for similar use. Most notably it is substantially equivalent to the currently marketed Cardiac T Troponin T Enzymun-Test.

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6) Comparison to predicate device (cont.)

The following table compares the Elecsys Troponin T with the predicate device, Cardiac T Troponin T Enzymun Test. Specific data on the performance of the test have been incorporated into the draft labeling in attachment 5. Labeling for the predicate device in provided in attachment 6.

Similarities:

- Intended use: immunoassay for the in vitro quantitative determination of troponin T
- The same antibodies are used for both assays - monoclonal anti-troponin T antibodies (mouse)
- Capture principle: streptavidin / biotin
- Two-step sandwich immunoassay
- for use as an adjunct to other diagnostic procedures and test currently used (i.e., WHO criteria or current clinical pathway for the diagnosis of myocardial injury

Differences:

| Feature | Elecsys Troponin T | Cardiac T Troponin T Enzymun Test |
| --- | --- | --- |
| Reaction test principle | streptavidin microparticles and electrochemiluminescence technology | streptavidin-coated tubes and enzyme immunoassay technology |
| Sample type | human serum and plasma | human serum |
| Sample volume | 15μl | 140μl |
| Instrument required | Elecsys 2010 | ES 300 |
| Calibration | a two point calibration renewal is recommended every 7 days or 1 month if the same reagent lot is used and the reagent pack is consumed within 7 days | a full calibration curve run is recommended every 2 weeks |

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## F. Substantial equivalence, (cont.)

## Performance Characteristics:

| Feature | Elecsys Troponin T | | | | | Cardiac T Troponin T Enzymun Test | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| NCCLS (modified.) | | | | | | | | |
| Precision | | | | | | | | |
| Sample | CC1 | CC2 | HS1 | HS2 | HS3 | | | |
| N | 60 | 60 | 60 | 60 | 60 | 60 | 60 | 60 |
| Mean | 0.103 | 2.506 | 5.992 | 1.298 | 0.439 | 0.062 | 0.326 | 2.144 |
| wi/in run %CV | 5.12 | 2.94 | 2.93 | 2.35 | 2.90 | 8.6 | 2.3 | 1.3 |
| total run %CV | 7.23 | 5.77 | 5.42 | 4.15 | 4.56 | 18.2 | 6.6 | 4.4 |
| Sensitivity | Lower Detection Limit: 0.01 ng/ml | | | | | Lower Detection Limit: 0.02 ng/ml | | |
| Assay range (LDL to highest standard) | 0.01 - 25.0 ng/ml | | | | | 0.02 - 15.0 ng/ml | | |
| Method Comparison | vs. Cardiac T Troponin T (Least Squares)
N = 54
y = -0.033 + 0.996x
r = 0.969
(Passing/Bablok)
N = 54
y = 0.0094 + 0.96x
r = 0.969 | | | | | vs. Cardiac T ELISA Troponin T:
(Passing/Bablok)
N = 233
y = 1.07x - 0.02
r = 0.89 | | |
| Interfering substances | No interference up to: | | | | | No interference up to: | | |
| Hemoglobin | 1.5 g/dl | | | | | 1 g/dl | | |
| Lipemia | 1500 mg/dl | | | | | 1500 mg/dl | | |
| Bilirubin | 36 mg/dl | | | | | 61 mg/dl | | |
| Biotin | 100 mg/dl | | | | | 20 ng/ml | | |
| Specificity | % cross reaction (to 2,000 ng/ml) | | | | | % cross reaction (to 2,000 ng/ml) | | |
| s troponinT | 0.001 | | | | | <0.005 | | |
| c troponin I | 0.002 | | | | | <0.005 | | |
| s tropomyosin | 0.001 | | | | | <0.005 | | |
| c myosin light chain | 0.003 | | | | | <0.005 | | |