(54 days)
For the in vitro quantitative determination of troponin T in human serum and plasma.
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 > 14 days.1,5
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
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 ul 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
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
Here's an analysis of the provided text to extract the requested information about acceptance criteria and the study that proves the device meets them:
1. Table of Acceptance Criteria and Reported Device Performance:
The document focuses on demonstrating substantial equivalence to a predicate device rather than explicitly stating acceptance criteria and then proving the device meets them. Instead, it directly compares the performance characteristics of the new device (Elecsys Troponin T) with the predicate device (Cardiac T Troponin T Enzymun Test). Therefore, the "acceptance criteria" are implied by the performance of the predicate device and the new device's ability to demonstrate comparable or superior performance.
| Feature | Predicate Device (Cardiac T Troponin T Enzymun Test) | New Device (Elecsys Troponin T) | Implied Acceptance Criteria (relative to predicate) |
|---|---|---|---|
| NCCLS (modified) Precision | Comparable or better precision | ||
| Within-run %CV | Sample CC1: 8.6 | Sample CC1: 5.12 | Lower %CV (better precision) |
| Sample CC2: 2.3 | Sample CC2: 2.94 | Comparable %CV | |
| Sample HS1: 1.3 | Sample HS1: 2.93 | Comparable %CV | |
| Total run %CV | Sample CC1: 18.2 | Sample CC1: 7.23 | Lower %CV (better precision) |
| Sample CC2: 6.6 | Sample CC2: 5.77 | Comparable %CV | |
| Sample HS1: 4.4 | Sample HS1: 5.42 | Comparable %CV | |
| Sensitivity (Lower Detection Limit) | 0.02 ng/ml | 0.01 ng/ml | Lower (better) detection limit |
| Assay range | 0.02 - 15.0 ng/ml | 0.01 - 25.0 ng/ml | Wider range (especially higher end) |
| Method Comparison (vs. Cardiac T Troponin T) | y = 1.07x - 0.02, r = 0.89 (N=233) | y = -0.033 + 0.996x, r = 0.969 (N=54) (Least Squares), ORy = 0.0094 + 0.96x, r = 0.969 (N=54) (Passing/Bablok) | Strong correlation (r value close to 1) |
| Interfering Substances (Hemoglobin) | No interference up to 1 g/dl | No interference up to 1.5 g/dl | Higher tolerance to interference |
| Interfering Substances (Lipemia) | No interference up to 1500 mg/dl | No interference up to 1500 mg/dl | Comparable tolerance to interference |
| Interfering Substances (Bilirubin) | No interference up to 61 mg/dl | No interference up to 36 mg/dl | (Slightly) Lower tolerance to interference |
| Interfering Substances (Biotin) | No interference up to 20 ng/ml | No interference up to 100 mg/dl | Much higher tolerance to interference |
| Specificity (% cross-reaction to 2,000 ng/ml) | <0.005 for s troponin T, c troponin I, s tropomyosin, c myosin light chain | s troponin T: 0.001c troponin I: 0.002s tropomyosin: 0.001c myosin light chain: 0.003 | Comparable or better (lower) cross-reactivity |
2. Sample sizes used for the test set and the data provenance:
- Precision: For each of the samples (CC1, CC2, HS1, HS2, HS3), N=60 measurements were taken for the Elecsys Troponin T. For the predicate device, for samples CC1, CC2, HS1, N=60 measurements each were also taken. The document does not specify the provenance (country of origin, retrospective/prospective) of these samples.
- Method Comparison: For the Elecsys Troponin T, N=54 samples were used for comparison against the Cardiac T Troponin T. For the predicate device, N=233 samples were used for comparison against the Cardiac T ELISA Troponin T. The provenance of these samples is not specified.
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 document describes an in vitro diagnostic device for quantitative determination of troponin T, which is a laboratory test. The "ground truth" for such a device is typically established through reference methods, certified standards, and clinical diagnosis criteria (e.g., WHO criteria for AMI). It does not involve human expert interpretation of images or other subjective assessments that would require a panel of experts in the way medical imaging devices sometimes do. Therefore, this information is not applicable in the context of this device and study description.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set:
As this is a quantitative in vitro diagnostic device, the concept of "adjudication method" as typically used for subjective diagnostic assessments (like image interpretation) is not directly applicable. The data presented are objective measurements of chemical concentrations and statistical analyses of those measurements.
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:
No. This is an in vitro diagnostic test for blood analysis, not an imaging device or AI-assisted diagnostic tool that involves human readers interpreting cases. Therefore, an MRMC comparative effectiveness study is not relevant to this device.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
The Elecsys Troponin T is a standalone automated in vitro diagnostic assay. The performance characteristics described (precision, sensitivity, assay range, method comparison, interference, specificity) represent the performance of the algorithm/instrument system itself without direct human-in-the-loop performance affecting the measurement process. Human interpretation would come after the quantitative result is generated by the machine, in the context of clinical diagnosis.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
The "ground truth" for the performance characteristics described relies on:
- Reference materials/serum pools: For precision and sensitivity, the values (e.g., 0.103 ng/ml for CC1) represent the concentration within specific control or human serum samples. These concentrations would have been established using highly accurate reference methods or certified standards.
- Predicate device/Reference assay: For method comparison, the "ground truth" for comparison is the results obtained from the predicate device (Cardiac T Troponin T Enzymun Test) or another established assay (Cardiac T ELISA Troponin T). This assesses the new device's agreement with existing, accepted methods.
- Known concentrations of interfering substances: For interference studies, substances were added at known concentrations to assess their impact.
- Known concentrations of related proteins: For specificity, known concentrations of related troponins or other cardiac proteins were tested to determine cross-reactivity.
8. The sample size for the training set:
The document does not specify a separate "training set" in the context of machine learning, as this is an immunoassay system. It describes the analytical performance of the device. The "calibration" refers to the instrument's calibration using specific calibrator solutions (2-point calibration and master curve via reagent bar code), which is part of setting up the analytical process, not a "training set" for an AI algorithm.
9. How the ground truth for the training set was established:
As noted in point 8, the concept of a "training set" in the AI sense is not applicable. The "ground truth" for the instrument's calibration is established through:
- Calibrator solutions: These are solutions with known, pre-defined concentrations of troponin T supplied by the manufacturer (Boehringer Mannheim).
- Master curve: This curve, provided via the reagent bar code, establishes the relationship between the signal detected by the instrument and the concentration of troponin T. This master curve would have been developed by the manufacturer using a comprehensive set of reference materials and validated methods.
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| JUN 11 1996510(k) Summary | ||
|---|---|---|
| Introduction | According to the requirements of 21 CFR 807.92, the following informationprovides sufficient detail to understand the basis for a determination ofsubstantial equivalence. | |
| 1) Submittername, address,contact | Boehringer Mannheim Corporation9115 Hague Rd.Indianapolis, IN 46250(317) 845-2000 | |
| Contact Person: LeeAnn Chambers | ||
| Date Prepared: April 12, 1996 | ||
| 2) Device name | Proprietary name: Elecsys Troponin T | |
| Common name: troponin test | ||
| 3) Predicatedevice | We claim substantial equivalence to the CARDIAC T® Troponin T EnzymunTest assay. | |
| 4) DeviceDescription | The Elecsys ® Troponin T test principle is based on a two step sandwich withstreptavidin microparticles and electrochemiluminescence detection. | |
| Total duration of assay: 9 minutes.1st incubation: 15 ul 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 complex2nd incubation: after the addition of streptavidin-coated microparticles, the complex becomes bound to the solid phase via interaction of biotin and streptavidinThe 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 | ||
| Continued on next page |
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510(k) Summary, Continued
ा में बना दें कि दे दिया था।
संस्थान
संस्थान
संस्थान
संस्थान
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| 4) DeviceDescription,cont. | • Results are determined via a calibration curve which is instrument-specifically generated by 2-point calibration and a master curve providedvia the reagent bar code | |
|---|---|---|
| 5) Intended use | For the in vitro quantitative determination of troponin T in human serum andplasma. | |
| 5) Indicationsfor use | Diagnosis of acute myocardial infarction (AMI) is generally based on thepresence of at least two of three classic findings: clinical symptoms,diagnostic ECG, and serological findings of abnormal levels of total CK, LDor their isoenzymes. Often, due to the presence of clinical symptoms andchanges in the ECG, the CK, CK-MB, LD and LD1 serve primarily toconfirm and monitor the course of the infarction. At other times, when chestpain is atypical, or ECG changes are non-diagnostic or absent, these markersprovide important diagnostic information. Limitations to these serummarkers include a relatively narrow diagnostic window, difficulty ininterpreting small increases and a lack of cardiac specificity. Troponin T canbe an effective serum marker whose cardiac specificity and wide diagnosticwindow makes it a valuable tool in the diagnosis of AMI.2,4Troponin T has been shown to be elevated in all patients with AMI who arediagnosed by World Health Organization (WHO) criteria.1 Troponin Tfrequently appears in serum as early as one to three hours after the onset ofpain.2,5 The sensitivity of troponin T reaches 100% within hours and remainsat a high sensitivity level until day five. After 48 hours the CK-MB assay isfrequently of little diagnostic value.1 Troponin T also remains elevated longerthan total LD.3 Its levels can be measured for up to 14 days.5 Thus, thediagnostic window is broader due to the length of time troponin T is elevatedin serum. The time interval of elevation in serum ranges from three hours to> 14 days.1,5 |
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510(k) Summary. Continued
5) Indications The specificity and sensitivity of troponin T measurements aid in both the for use, (cont.) 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 The Boehringer Mannheim Elecsys Troponin T is substantially equivalent to to predicate other products in commercial distribution intended for similar use. Most device notably it is substantially equivalent to the currently marketed Cardiac T Troponin T Enzymun-Test.
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510(k) Summary, Continued
- 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 TEnzymun Test |
|---|---|---|
| Reaction testprinciple | streptavidin microparticles andelectrochemiluminescencetechnology | streptavidin-coated tubes andenzyme immunoassaytechnology |
| Sample type | human serum and plasma | human serum |
| Samplevolume | 15µl | 140µl |
| Instrumentrequired | Elecsys 2010 | ES 300 |
| Calibration | a two point calibration renewalis recommended every 7 daysor 1 month if the same reagentlot is used and the reagent packis consumed within 7 days | a full calibration curve run isrecommended every 2 weeks |
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510(k) Summary, Continued
F. Substantial
Performance Characteristics:
equivalence,
(cont.)
க்கத்துகள்
இங்கிலாந்துக்கு
இக்கிய
| 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 higheststandard) | 0.01 - 25.0 ng/ml | 0.02 - 15.0 ng/ml |
| MethodComparison | vs. Cardiac T Troponin T (Least Squares)N = 54y = -0.033 + 0.996xr = 0.969(Passing/Bablok)N = 54y = 0.0094 + 0.96xr = 0.969 | vs. Cardiac T ELISA Troponin T:(Passing/Bablok)N = 233y = 1.07x - 0.02r = 0.89 |
| Interferingsubstances | 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 |
§ 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.