ELECSYS TROPONIN I AND TROPONIN I STAT TEST SYSTEMS
Device Facts
| Record ID | K082699 |
|---|---|
| Device Name | ELECSYS TROPONIN I AND TROPONIN I STAT TEST SYSTEMS |
| Applicant | Roche Diagnostics |
| Product Code | MMI · Clinical Chemistry |
| Decision Date | Aug 19, 2009 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 862.1215 |
| Device Class | Class 2 |
Indications for Use
Elecsys Troponin I Immunoassay: Immunoassay for the in vitro quantitative determination of cardiac troponin I in human serum and plasma. The Elecsys Troponin I assay is intended to aid in the diagnosis of myocardial infarction. The electrochemiluminescence immunoassay "ECLIA" is intended for use on the Elecsys and MODULAR Analytics E170 immunoassay analyzers. Elecsys Troponin I STAT Immunoassay: Immunoassay for the in vitro quantitative determination of cardiac troponin I in human serum and plasma. The Elecsys Troponin I STAT assay is intended to aid in the diagnosis of myocardial infarction. The electrochemiluminescence immunoassay "ECLIA" is intended for use on the Elecsys analyzers. Elecsys PreciControl Troponin: The Elecsys PreciControl Troponin I used for quality control of the Elecsys Troponin I and Elecsys Troponin I STAT immunoassays on the Elecsys and MODULAR Analytics E170 Analyzers. Elecsys Troponin I CalSet: The Elecsys Troponin I CalSet is used for calibrating the quantitative Elecsys Troponin I assay on the MODULAR ANALYTICS E170 analyzers. Elecsys Troponin I STAT CalSet: The Elecsys Troponin I STAT CalSet is used for calibrating the quantitative Elecsys Troponin I STAT assay on the Elecsys analyzers.
Device Story
The Elecsys Troponin I and Troponin I STAT immunoassays are two-step sandwich immunoassays utilizing streptavidin-coated microparticles and electrochemiluminescence (ECLIA) detection. The device processes human serum or plasma samples on Elecsys or MODULAR Analytics E170 analyzers. Calibration is performed using a 2-point calibration curve and a master curve provided via reagent barcode. The system produces quantitative Troponin I concentration results (ng/mL). These results are used by clinicians in conjunction with patient medical history and clinical examinations to aid in the diagnosis of myocardial infarction. The device is intended for use in clinical laboratory settings by trained laboratory personnel.
Clinical Evidence
Prospective study of 402 patients (chest pain, 24h duration) across 5 sites. AMI diagnosis based on ESC/AHA/ACC criteria. Overall sensitivity 90.11% (95% CI: 82.26-94.71%) and specificity 97.75% (95% CI: 95.43-98.91%). Cut-off study (n=358) used ROC analysis to establish 0.3 ng/mL threshold (AUC 0.9565). Reference range study (n=1,137 healthy individuals) confirmed levels < 0.3 ng/mL.
Technological Characteristics
Two-step sandwich immunoassay; streptavidin-coated microparticles; electrochemiluminescence (ECLIA) detection. Reagents, calibrators, and controls are lyophilized human serum-based products. Analyzers: Elecsys and MODULAR Analytics E170. Connectivity: Automated analyzer-based. Calibration: 2-point calibration with master curve via barcode.
Indications for Use
Indicated for in vitro quantitative determination of cardiac troponin I in human serum and plasma to aid in the diagnosis of myocardial infarction. For use by clinicians in prescription settings.
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
- Beckman Coulter Access AccuTnI Immunoassay (K021814)
- Elecsys PreciControl Cardiac II (K072437)
- Elecsys proBNP II CalSet (K072437)
Submission Summary (Full Text)
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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE
A. 510(k) Number:
k082699
B. Purpose for Submission:
New device
C. Measurand:
Troponin I
D. Type of Test:
Quantitative immunoassay
E. Applicant:
Roche Diagnostics, Inc.
F. Proprietary and Established Names:
Elecsys Troponin I Immunoassay
Elecsys Troponin I STAT Immunoassay
Elecsys PreciControl Troponin
Elecsys Troponin I CalSet
Elecsys Troponin I STAT CalSet
G. Regulatory Information:
1. Regulation section:
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| Device | Regulation | Classification | Product Code |
| --- | --- | --- | --- |
| Elecsys Troponin I | 21 CFR § 862.1215 | II | MMI |
| Elecsys Troponin I STAT | 21 CFR § 862.1215 | II | MMI |
| Elecsys PreciControl Troponin | 21 CFR § 862.1660 | I, reserved | JJY |
| Elecsys Troponin I CalSet | 21 CFR § 862.1150 | II | JIT |
| Elecsys Troponin I STAT CalSet | 21 CFR § 862.1150 | II | JIT |
4. Panel:
Chemistry (75)
H. Intended Use:
1. Intended use(s):
See Indications for use below.
2. Indication(s) for use:
Elecsys Troponin I Immunoassay: Immunoassay for the in vitro quantitative determination of cardiac troponin I in human serum and plasma. The Elecsys Troponin I assay is intended to aid in the diagnosis of myocardial infarction. The electrochemiluminescence immunoassay "ECLIA" is intended for use on the Elecsys and MODULAR Analytics E170 immunoassay analyzers.
Elecsys Troponin I STAT Immunoassay: Immunoassay for the in vitro quantitative determination of cardiac troponin I in human serum and plasma. The Elecsys Troponin I STAT assay is intended to aid in the diagnosis of myocardial infarction. The electrochemiluminescence immunoassay "ECLIA" is intended for use on the Elecsys analyzers.
Elecsys PreciControl Troponin: The Elecsys PreciControl Troponin I used for quality control of the Elecsys Troponin I and Elecsys Troponin I STAT immunoassays on the Elecsys and MODULAR Analytics E170 Analyzers.
Elecsys Troponin I CalSet: The Elecsys Troponin I CalSet is used for calibrating the quantitative Elecsys Troponin I assay on the MODULAR ANALYTICS E170 analyzers.
Elecsys Troponin I STAT CalSet: The Elecsys Troponin I STAT CalSet is used for calibrating the quantitative Elecsys Troponin I STAT assay on the Elecsys analyzers.
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3. Special conditions for use statement(s):
Prescription use
4. Special instrument requirements:
Roche Elecsys 2010 and Roche Modular Analytics E170
I. Device Description:
All reagents, controls and calibrators are sold separately.
a. Elecsys Troponin I Immunoassay and Elecsys Troponin I STAT Immunoassays: The Elecsys Troponin I and Troponin I STAT immunoassays are two step sandwich immunoassays with streptavidin microparticles and electrochemiluminescence detection. Results are determined using 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. The Elecsys Troponin I STAT immunoassay is completed in half time when compared to the Elecsys Troponin I immunoassay, however the composition of the reagents is identical.
b. Elecsys PreciControl Troponin: The Elecsys PreciControl Troponin is a lyophilized product consisting of human serum containing Troponin I in two concentration ranges and Troponin T. Although the control contains both Troponin subunits, only the Troponin I has assayed values. This material is not for use with Troponin T assays. All products derived from human blood are prepared exclusively from the blood of donors tested individually and shown to be free from HBsAg and antibodies to HCV and HIV. The testing methods applied were FDA-approved or cleared in compliance with the European Directive 98/79/EC, Annex II, List A.
c. Elecsys Troponin I CalSet and Elecsys Troponin I STAT CalSet: The Elecsys Troponin I CalSet and Elecsys Troponin I STAT CalSet are lyophilized products consisting of human serum with added Troponin I in two concentration ranges. During manufacture the analyte is spiked into the matrix at the desired concentration levels. All products derived from human blood are prepared exclusively from the blood of donors tested individually and shown to be free from HBsAg and antibodies to HCV and HIV. The testing methods applied were FDA-approved or cleared in compliance with the European Directive 98/79/EC, Annex II, List A.
J. Substantial Equivalence Information:
1. Predicate device name(s) and 2. Predicate k number(s):
| Device | Predicate k number | Predicate device name |
| --- | --- | --- |
| Elecsys Troponin I | k021814 | Beckman Coulter Access AccuTnI |
| Elecsys Troponin I STAT | k021814 | Beckman Coulter Access AccuTnI |
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3. Comparison with predicate:
| Similarities – Elecsys Troponin I | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Assay Protocol | Sandwich Principle | Same |
| Sample Type | Human serum and plasma | Same |
| Differences - Elecsys Troponin I | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Intended Use / Indication for Use | Immunoassay for the in vitro quantitative determination of cardiac troponin I in human serum and plasma. The Elecsys Troponin I assay is intended to aid in the diagnosis of myocardial infarction. The electrochemiluminescence immunoassay “ECLIA” is intended for use on the Elecsys and MODULAR Analytics E170 immunoassay analyzers. | The Access AccuTnI assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of cardiac troponin I (cTnI) levels in human serum and plasma using the Access Immunoassay Systems to aid in the diagnosis and treatment of myocardial infarction and cardiac muscle damage. Cardiac troponin I determination aids in the risk stratification of patients with unstable angina or 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. |
| Detection Protocol | Electrochemiluminescence | Chemiluminescence |
| Traceability/Standardization | Standardized against a commercially available Troponin I assay | Not stated. |
| Calibration Interval | Calibration must be | An active calibration curve is |
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| Differences - Elecsys Troponin I | | |
| --- | --- | --- |
| Item | Device | Predicate |
| | performed once per reagent lot using fresh reagent. Renewed calibration: • After 1 month (28 days) when using the same reagent lot • After 7 days (when using the same reagent kit on the analyzer) | required for all tests. For the Access AccuTnI assay, calibration is required every 56 days. |
| Reagent Stability | Unopened • Up to stated expiration date stored at 2-8°C After Opening • 4 weeks at 2-8°C • 4 weeks on the analyzers | Unopened • Up to stated expiration date stored at 2-8°C After Opening • Stable at 2 - 10°C for 56 days after initial use |
| Calibrator | Elecsys Troponin I STAT CalSet | Access AccuTnI Calibrators |
| Controls | Elecsys PreciControl Troponin | Commercial control material |
| Instrument | Modular Analytics E170 | Access Immunoassay Systems |
| Expected values | Age 20 - 79, expected value < 0.3 ng/mL: Values less than 0.3 ng/mL will be reported as “< 0.3 ng/mL”. | Age 19 - 88: 97.5th percentile: 0.03 ng/mL 99th percentile: 0.04 ng/mL |
| Measuring Range | 0.3-25.00 ng/mL | 0.01 - 100 mcg/L (ng/mL) |
| Cut-off | 0.3 ng/mL | 0.5 ng/mL |
| No Hook Effect up to | 1000 ng/mL | 1,920 ng/mL |
| Limit of Blank | Studies performed and LoB is less than LoQ (0.3 ng/mL) | Not given |
| Limit of Detection | Studies performed and LoB is less than LoQ (0.3 ng/mL) | 0.01 ng/mL (LDL) |
| Limit of Quantitation | 0.3 ng/mL at 10% CV | 0.03 ng/mL at 20% CV 0.06 ng/mL at 10% CV |
Similarities - Elecsys Troponin I STAT
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| Item | Device | Predicate |
| --- | --- | --- |
| Assay Protocol | Sandwich Principle | Same |
| Detection Protocol | Electrochemiluminescence | Same |
| Sample Type | Human serum and plasma | Same |
| Differences - Elecsys Troponin I STAT | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Intended Use / Indication for Use | Immunoassay for the in vitro quantitative determination of cardiac troponin I in human serum and plasma. The Elecsys Troponin I STAT assay is intended to aid in the diagnosis of myocardial infarction. The electrochemiluminescence immunoassay “ECLIA” is intended for use on the Elecsys analyzers. | The Access AccuTnI assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of cardiac troponin I (cTnI) levels in human serum and plasma using the Access Immunoassay Systems to aid in the diagnosis and treatment of myocardial infarction and cardiac muscle damage.Cardiac troponin I determination aids in the risk stratification of patients with unstable angina or 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. |
| Calibration Interval | Calibration must be performed once per reagent lot using fresh reagent. Renewed calibration: • After 1 month (28 days) when using the same reagent lot • After 7 days (when using the same reagent kit on the analyzer) | An active calibration curve is required for all tests. For the Access AccuTnI assay, calibration is required every 56 days. |
| Reagent Stability | Unopened • Up to stated expiration date stored at 2-8°C After Opening • 4 weeks at 2-8°C • 4 weeks on the | Unopened • Up to stated expiration date stored at 2-8°C After Opening • Stable at 2 - 10°C for 56 days after initial use |
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| Differences - Elecsys Troponin I STAT | | |
| --- | --- | --- |
| Item | Device | Predicate |
| | analyzers | |
| Calibrator | Elecsys Troponin I STAT CalSet | Access AccuTnI Calibrators |
| Controls | Elecsys PreciControl Troponin | Commercial control material |
| Instrument | Elecsys 2010 | Access Immunoassay Systems |
| Expected values | Age 20 – 79, expected value < 0.3 ng/mL: Values less than 0.3 ng/mL will be reported as “< 0.3 ng/mL”. | Age 19 – 88: 97.5th percentile: 0.03 ng/mL 99th percentile: 0.04 ng/mL |
| Measuring Range | 0.3-25.00 mcg/L (ng/mL) | 0.01 – 100 mcg/L (ng/mL) |
| Cut-off | 0.3 ng/mL | 0.5 ng/mL |
| No Hook Effect up to | 1,000 ng/mL | 1,920 ng/mL |
| Limit of Blank | Studies performed and LoB is less than LoQ (0.3 ng/mL) | Not given |
| Limit of Detection | Studies performed and LoB is less than LoQ (0.3 ng/mL) | 0.01 ng/mL (LDL) |
| Limit of Quantitation Functional Sensitivity | 0.3 ng/mL at 10% CV | 0.03 ng/mL at 20% CV 0.06 ng/mL at 10% CV |
Similarities - Elecsys PreciControl Troponin
| Item | Device | Predicate |
| --- | --- | --- |
| Levels | Two | Same |
| Format | Lyophilized, based on human serum | Same |
| Freeze-thaw stability | After thawing- use only once | Same |
| Reconstituted volume | 2 mL | Same |
| Differences – Elecsys PreciControl Troponin | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Intended Use | Used for quality control of the Elecsys Troponin I and Elecsys Troponin I STAT immunoassays on the Elecsys and MODULAR Analytics E170 Analyzers. | Used for quality control of specified immunoassays on the elecsys and cobas e immunoassay analyzers |
| Analyte Constituents | Troponin T and Troponin I | CK-MB, Digitoxin, Myoglobin, NT-proBNP |
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| Differences - Elecsys PreciControl Troponin | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Reconstituted Stability | 5 hrs at 20-25°C | 3 hrs at 20-25°C |
| | 4 days at 2-8°C | 3 days at 2-8°C |
| | 3 months at -20°C (freeze only once) | 3 months at -20°C (freeze only once) |
| Similarities - Elecsys Troponin I CalSet | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Levels | Two | Same |
| Freeze-thaw stability | After thawing- use only once | Same |
| Reconstituted volume | 1 mL | Same |
| Differences - Elecsys Troponin I CalSet | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Intended Use | Used for calibrating the quantitative Elecsys Troponin I assay on the Elecsys and MODULAR ANALYTICS E170 analyzers. | Used for calibrating the quantitative elecsys proBNP II assay on elecsys and cobas e immunoassay analyzers. |
| Format | Lyophilized, based on human serum | Lyophilized, based on equine serum |
| Analyte Constituents | Troponin I | CK-MB, Digitoxin, Myoglobin, NT-proBNP |
| Similarities - Elecsys Troponin I CalSet STAT | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Levels | Two | Same |
| Freeze-thaw stability | After thawing- use only once | Same |
| Reconstituted volume | 1 mL | Same |
| Differences - Elecsys Troponin I CalSet STAT | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Intended Use | Used for calibrating the quantitative Elecsys Troponin I STAT assay on the Elecsys analyzers. | Used for calibrating the quantitative elecsys proBNP II assay on elecsys and cobas e immunoassay analyzers. |
| Format | Lyophilized, based on human serum | Lyophilized, based on equine serum |
| Analyte Constituents | Troponin I | CK-MB, Digitoxin, |
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| Differences - Elecsys Troponin I CalSet STAT | | |
| --- | --- | --- |
| Item | Device | Predicate |
| | | Myoglobin, NT-proBNP |
K. Standard/Guidance Document Referenced (if applicable):
CLSI EP5-A2: Evaluation of Precision Performance of Clinical Chemistry Devices; Approved Guideline, 2nd ed
CLSI EP9-A2: Method Comparison and Bias Estimation Using Patient Samples
CLSI EP17-A: Protocols for Determination of Limits of Detection and Limits of Quantitation; Approved Guideline
L. Test Principle:
The Elecsys Troponin I Immunoassay and Elecsys Troponin I STAT Immunoassays use a sandwich principle for measurement of troponin I in serum or plasma. Two biotinylated monoclonal cardiac troponin I-specific antibodies labeled with a ruthenium complex react to form a sandwich complex during the first incubation period. Then, streptavidin-coated microparticles are added resulting in the binding of the complex to the solid phase via interaction of biotin and streptavidin. This occurs during a second incubation phase. Once this incubation is completed, 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 a wash. 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 (5-point calibration) provided via the reagent barcode. The differences between the Elecsys Troponin I Immunoassay and Elecsys Troponin I STAT Immunoassays are that the STAT assay is completed in half the time as the other assay and is limited to use on specific analyzers.
The PreciControl Troponin contains two concentrations of troponin I and is used for monitoring the accuracy and precision of the Elecsys Troponin I and Elecsys Troponin I STAT immunoassays.
The Elecsys Troponin I CalSet and STAT CalSet are calibrators containing two concentrations of troponin I. All calibration information is included on a barcoded card which is loaded into the respective instrument systems.
M. Performance Characteristics (if/when applicable):
1. Analytical performance:
a. Precision/Reproducibility:
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Elecsys Troponin I immunoassay and Elecsys Troponin I STAT:
Precision was evaluated using multiple serum or plasma pools. Samples were analyzed at a total of six laboratories within the US and outside of the US. Some laboratories had duplicate instrumentation and precision was performed on both analyzers. Samples were assayed in duplicate with a minimum of two runs per day using one reagent lot. Several sites did separate runs of serum and/or human plasma (HP) or had duplicate instrumentation indicated by #. The low control was also evaluated on both analyzers. The sponsor is using 0.3 ng/mL as the low limit of the measuring range based on precision of ≤ 10% CV at that value.
| Troponin I STAT on e2010 | n | Concentration (ng/mL) | CV % |
| --- | --- | --- | --- |
| Site | | | |
| 1 | 63 | 0.323 | 8.8 |
| 2 #2 | 84 | 0.329 | 5.6 |
| 3 #2 | 63 | 0.347 | 7.9 |
| | | | |
| Troponin 18 Minute on E170 | n | Concentration (ng/mL) | CV % |
| Site | | | |
| 5 #2 | 63 | 0.319 | 6.8 |
| | | | |
| Troponin Control 1 on 2010 and E170 | n | Concentration (ng/mL) | CV % |
| Site/Instrument/Assay | | | |
| 2 2010,STAT | 84 | 0.376 | 5.3 |
| 3 2010, STAT | 63 | 0.395 | 4.7 |
| 4 2010, STAT | 63 | 0.384 | 6.7 |
| 6 E170, 18 Min | 63 | 0.322 | 5.6 |
| 5 E170, 18 Min | 63 | 0.324 | 6.2 |
Additional precision studies were conducted for samples up to 18.0 ng/mL for both the Troponin I STAT and Troponin I immunoassays at US and non-US sites. Results are summarized are below:
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| Elecsys Troponin I STAT Assay | Elecsys Troponin I STAT Assay | Elecsys Troponin I Assay |
| --- | --- | --- |
| US Site 1
Repeatability
4.8% CV @ 0.323 ng/mL
3.3% CV @ 0.496 ng/mL
2.2% CV @ 0.627 ng/mL
1.7% CV @ 21.400 ng/mL
4.2% CV @ 0.439 ng/mL
2.9% CV @ 17.800 ng/mL
Within-lab
8.9% CV @ 0.323 ng/mL
5.9% CV @ 0.496 ng/mL
5.3% CV @ 0.627 ng/mL
3.2% CV @ 21.400 ng/mL
6.7% CV @ 0.439 ng/mL
3.6% CV @ 17.800 ng/mL
US Site 2
Repeatability
3.0% CV @ 0.483 ng/mL
3.9% CV @ 0.329 ng/mL
1.8% CV @ 2.180 ng/mL
2.1% CV @ 0.691 ng/mL
4.0% CV @ 0.376 ng/mL
2.3% CV @ 17.300 ng/mL
Within-lab
4.0% CV @ 0.483 ng/mL
5.7% CV @ 0.329 ng/mL
2.4% CV @ 2.180 ng/mL
2.9% CV @ 0.691 ng/mL
5.3% CV @ 0.376 ng/mL
2.6% CV @ 17.300 ng/mL | EU Site 1
Repeatability
2.5% CV @ 0.447 ng/mL
4.1% CV @ 0.347 ng/mL
0.7% CV @ 7.600 ng/mL
3.1% CV @ 0.498 ng/mL
2.6% CV @ 0.395 ng/mL
0.6% CV @ 17.600 ng/mL
Within-lab
6.1% CV @ 0.447 ng/mL
16.1% CV @ 0.190 ng/mL
8.0% CV @ 0.347 ng/mL
4.3% CV @ 7.600 ng/mL
5.4% CV @ 0.498 ng/mL
4.8% CV @ 0.395 ng/mL
1.9% CV @ 17.600 ng/mL | Repeatability
5.3% CV @ 0.322 ng/mL
5.2% CV @ 0.425 ng/mL
2.7% CV @ 17.6 ng/mL
7.0% CV @ 0.340 ng/mL
2.6% CV @ 18.0 ng/mL
Within-lab
8.7% CV @ 0.322 ng/mL
7.3% CV @ 0.425 ng/mL
4.7% CV @ 17.6 ng/mL
8.0% CV @ 0.340 ng/mL
4.4% CV @ 18.0 ng/mL |
b. Linearity/assay reportable range:
Elecsys Troponin I immunoassay: Linearity was evaluated on the Roche
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MODULAR Analytics E170. Three separate dilution series were prepared from three separate serum pools. Each high pool was assayed multiple times to determine the mean value prior to dilution. The samples were analyzed in three separate runs. Only native samples were used for this study. Diluent was used for a troponin free sample. Each serum pool was serially diluted to make 10 different concentrations. Each dilution was tested in triplicate and the median value was compared to the expected value. Linearity and recoveries were calculated against the expected values after dilution using Passing-Bablock, linear, and Deming regressions. Troponin I concentrations covered the measuring range of the assay.
| | Slope (95% CI) | Intercept (95% CI) | Correlation |
| --- | --- | --- | --- |
| Passing-Bablock | 0.9798 (0.9682, 0.9884) | -0.0089 (-0.0271, 0.0205) | Tau = 0.9939 |
| Linear Regression | 0.9834 (0.9758, 0.9910) | -0.06843 (-0.1333, -0.0035) | r = 0.9994 |
| Deming Regression | 0.9838 (0.9762, 0.9914) | -0.0718 (-0.1367, -0.0069) | r = 0.9996 |
## Elecsys Troponin I STAT immunoassay:
Linearity was evaluated on the Roche Elecsys 2010. Three separate serum pools were prepared and dilutions and analysis used the same process as for the Elecsys Troponin I reagent. Each high pool was assayed multiple times to determine the mean value prior to dilution. Only native samples were used for this study. Diluent was used for a troponin free sample. Troponin I concentrations covered the measuring range of the assay.
| | Slope (95% CI) | Intercept (95% CI) | Correlation |
| --- | --- | --- | --- |
| Passing-Bablock | 0.9848 (0.9759, 0.9954) | -0.0017 (-0.0533, 0.0238) | Tau= 0.9787 |
| Linear Regression | 0.9838 (0.9767, 0.9908) | -0.0131 (-0.0431, 0.0693) | r =0.9977 |
| Deming Regression | 0.9841 (0.9770, 0.9911) | -0.0109 (-0.0453, 0.0671) | r = 0.9997 |
The sponsor is claiming a measuring range for both assays of 0.30 – 25.0 ng/mL (mcg/L). Values above the measuring range are reported as > 25.0 ng/mL (mcg/L). Values < 0.3 ng/mL are reported as < 0.3 ng/mL.
High dose hook effect was evaluated by testing normal human sera spiked with troponin I at 1,070 ng/mL and 1,300 ng/mL. There was no hook effect observed up to 1,300 ng/mL, however the sponsor sets the hook effect claim at 1,000 ng/mL in the labeling.
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c. Traceability, Stability, Expected values (controls, calibrators, or methods):
## Calibrators
Elecsys Troponin I CalSet and Elecsys Troponin I STAT CalSet are traceable master calibrators which are standardized against another commercially available troponin I assay. Master calibrator value assignment occurs after 2 independent series are analyzed on 4 reference instruments. New lots of Troponin I CalSet and Troponin I STAT CalSet are analyzed multiple times against the master calibrators on the appropriate platform. The target value for the calibrators is then calculated as the median of the determined values.
## Controls
Elecsys PreciControl Troponin is traceable to analysis against the master calibrators on the aforementioned platforms using specific reagent lots and multiple runs per instrument. The target values for the controls are then calculated as the median of the determined values.
## Stability
The calibrators and controls are lyophilized. After reconstitution, they are stable for on-board the instruments for 5 hours, four days after opening at 2-8° C and 3 months at -20°C. Controls and calibrators should only be thawed once.
On-board calibration stability was verified on the Elecsys 2010 and the MODULAR Analytics E170 by measuring troponin I recovery in controls and human serum samples. Calibration is recommended every 7 days if the kit is not consumed and every 4 weeks with the same reagent lot and the reagent pack is consumed within 7 days.
The stability protocols and acceptance criteria were reviewed and found to be acceptable.
## d. Detection limit:
Limits of Blank (LoB) and Limits of Detection (LoD) for Elecsys Troponin I and Elecsys Troponin I STAT were evaluated using CLSI EP17-A guideline. Limits of Quantitation (LoQ) for the two devices were established by determining the concentration with corresponds to an inter-assay CV of 10%. Studies were performed on analytical platforms appropriate to the devices.
## Elecsys Troponin I:
LoB was determined by analyzing 5 troponin I free human serum samples on
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one MODULAR Analytics E170 in singlicate in 6 runs over four days. LoB is < 0.3 ng/mL however, the sponsor is using the LoQ, 0.3 ng/mL, as the lowest limit of the measuring range.
LoD was determined by analyzing 5 human sera containing low amounts of troponin I on one MODULAR Analytics E170 in singlicate in 6 runs over three days. LoD < 0.3 ng/mL however the sponsor is using the LoQ, 0.3 ng/mL, as the lowest limit of the measuring range.
LoQ was determined by analyzing 6 serum samples and two controls with concentrations ranging from 0.0251 ng/mL to 17.1026 ng/mL were tested in singlicate on one MODULAR Analytics E170 for 10 days. The concentration with an inter-assay ≤ 10% CV was 0.3 ng/mL. The sponsor is using the LoQ as the lowest limit of the measuring range.
## Elecsys Troponin I STAT:
LoB was determined by analyzing 5 troponin I free human serum samples on two Elecsys 2010s in 6 runs over four days. LoB < 0.3 ng/mL. The sponsor is using the LoQ, 0.3 ng/mL, as the lowest limit of the measuring range.
LoD was determined by analyzing 5 human sera containing low amounts of troponin I on two Elecsys 2010s in 6 runs over three days. LoD < 0.3 ng/mL. The sponsor is using the LoQ, 0.3 ng/mL, as the lowest limit of the measuring range.
LoQ was determined by analyzing 10 serum samples and two controls with concentrations ranging from 0.0251 ng/mL to 17.1026 ng/mL were tested in singlicate on one Elecsys 2010 for 10 days. The concentration with an inter-assay ≤ 10% CV was 0.3 ng/mL. The sponsor is using the LoQ, 0.3 ng/mL, as the lowest limit of the measuring range.
## e. Analytical specificity:
Cross-reactivity and endogenous interference studies:
Analytical specificity was evaluated on the Elecsys 2010 with the Elecsys Troponin I STAT reagent for possible cross reactants of skeletal muscle TnI, recombinant cardiac troponin T (TnT), purified troponin C (TnC) and skeletal muscle TnT, as well as endogenous interferents of hemolysis, biotin, lipemia, bilirubin and rheumatoid factors.
Two samples of different Troponin I concentrations were analyzed in duplicate for each cross reactant and interferent. One sample had Troponin I values within the clinical decision range of 0.3-0.5 ng/mL. The second sample had Troponin I values ranging from approximately 2.5-2.8 ng/mL.
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Samples were split and spiked with the appropriate compounds at various concentrations and compared to an unaltered aliquot of the sample.
Concentrations up to 2000 ng/mL of skeletal TnI, recombinant cardiac TnT, purified troponin C (TnC), and skeletal muscle TnT did not cross-react with the assay.
Hemoglobin up to 0.4 g/dL, biotin up to 30 ng/mL, lipemia (Intralipid) up to 1,500 mg/dL, bilirubin up to 25 mg/dL and rheumatoid factors up to 1,500 IU/mL did not interfere with the assay. Labeling states that grossly hemolyzed samples should not be used.
52 potentially interfering common compounds and prescription drugs were tested in 100 times higher than expected dose level in plasma. A list of these compounds can be found in the package insert.
f. Assay cut-off:
The sponsor determined the AMI cut-off to be 0.3 ng/mL. See clinical sensitivity 3a below.
2. Comparison studies:
a. Method comparison with predicate device:
A method comparison was conducted between the predicate and the Elecsys 2010 using the Troponin I STAT reagent. 114 samples with troponin I values covering the measuring range were analyzed in singlicate. Regression was calculated using Passing-Bablock, Standardized Linearity and Deming equations. The results are summarized below.
Troponin I STAT/Elecsys 2010 vs Predicate
| | Slope (95% CI) | Intercept (95% CI) | Correlation |
| --- | --- | --- | --- |
| Passing-Bablock | 0.7954 (0.7586, 0.8553) | 0.2187 (0.1565, 0.2787) | Tau = .8058 |
| Linear Regression | 0.7878 (0.7403,0.8353) | 0.3204 (0.1668, 0.4740) | r = 0.9465 |
| Deming Regression | 0.8198 (0.7726, 0.8673) | 0.2168 (0.632, 0.3704) | r = 0.9519 |
Based on the method comparison, clinical data was used to determine substantial equivalency. See section M.3.a. To demonstrate equivalence between the two reagent systems, comparisons were performed between the Troponin I immunoassay reagent on the MODULAR Analytics E170 and the Troponin I STAT immunoassay reagent on the Elecsys 2010. 115 samples were analyzed on the E170 and the Elecsys 2010. All samples were run in
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singlicate and covered the measuring range. Regression was calculated using Passing-Bablock, Standardized Linearity and Deming equations. The results are summarized below.
Troponin I/E170 vs Troponin I Stat/Elecsys 2010
| | Slope (95% CI) | Intercept (95% CI) | Correlation |
| --- | --- | --- | --- |
| Passing-Bablock | 0.9743 (0.9637, 0.9896) | -0.0172 (-0.0713, 0.0174) | Tau =0.9616 |
| Linear Regression | 0.9934 (0.9720, 1.0148) | -0.0623 (-0.2099, 0.0854) | r = 0.9971 |
| Deming Regression | 1.0000 (0.9786, 1.0214) | -0.1080 (-0.2556, 0.0397) | r = 0.9934 |
# b. Matrix comparison:
In order to demonstrate equivalence of TnI results among serum, lithium heparin, K2-EDTA and K3-EDTA plasmas, sample pairs were evaluated across the measuring range (0.33-24.83 ng/mL). Both native and spiked samples were included in the studies. Results of the plasmas versus serum were analyzed by Passing-Bablock, Linear Regression and Deming Regression. Results are summarized below:
| Serum vs. K2-EDTA | | Passing/Bablok | LinReg | Deming | Method | Correlation |
| --- | --- | --- | --- | --- | --- | --- |
| Slope | N=39 | 0.9696 | 0.9425 | 0.9489 | Kendall's tau | 0.9487 |
| | LCL 95% | 0.9530 | 0.9048 | 0.9112 | Spearman's rho | 0.9903 |
| | UCL 95% | 0.9870 | 0.9802 | 0.9866 | Pearson's r | 0.9929 |
| Intercept | | 0.0171 | 0.1771 | 0.1095 | | |
| | LCL 95% | -0.0795 | -0.2206 | -0.2883 | | |
| | UCL 95% | 0.1716 | 0.5749 | 0.5072 | | |
| Serum vs. K3-EDTA | | Passing/Bablok | LinReg | Deming | Method | Correlation |
| --- | --- | --- | --- | --- | --- | --- |
| Slope | N=21 | 0.9660 | 0.9407 | 0.9468 | Kendall's tau | 0.9143 |
| | LCL 95% | 0.9362 | 0.8876 | 0.8937 | Spearman's rho | 0.974 |
| | UCL 95% | 0.9939 | 0.9938 | 0.9999 | Pearson's r | 0.9932 |
| Intercept | | -0.0166 | 0.2492 | 0.1757 | | |
| | LCL 95% | -0.2011 | -0.3883 | -0.4618 | | |
| | UCL 95% | 0.3917 | 0.8867 | 0.8132 | | |
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| Serum vs. Lithium Heparin | | Passing/Bablok | LinReg | Deming | Method | Correlation |
| --- | --- | --- | --- | --- | --- | --- |
| Slope | N= 49 | 1.0000 | 0.9423 | 0.9702 | Kendall's tau | 0.8844 |
| | LCL 95% | 0.9191 | 0.8734 | 0.9013 | Spearman's rho | 0.975 |
| | UCL 95% | 1.0372 | 1.0112 | 1.0391 | Pearson's r | 0.9703 |
| Intercept | | -0.0765 | 0.1271 | -0.1025 | | |
| | LCL 95% | -0.1257 | -0.4391 | -0.6687 | | |
| | UCL 95% | 0.1097 | 0.6933 | 0.4637 | | |
# 3. Clinical studies:
# a. Clinical Sensitivity:
A prospective study was conducted with 402 patients at 5 sites (2 US, 3 non-US). Inclusion criteria were chest pain for 24 hours and clinicians' diagnoses using the ESC/AHA/ACC criteria on the Elecsys 2010 and Modular Analytics E170. A breakdown of AMI and non-AMI frequency by site is below.
| | Site 1 | Site 2 | Site 3 | Site 4 | Site 5 | Total |
| --- | --- | --- | --- | --- | --- | --- |
| Non-AMI | 123 | 99 | 11 | 4 | 74 | 311 (77%) |
| AMI | 25 | 48 | 1 | 5 | 12 | 91 (23%) |
| Total | 148 | 147 | 12 | 9 | 86 | 402 |
Sensitivity and specificity of the Acute Myocardial Infarction (AMI) cutoff as defined by ESC/ACC/AHA criteria for the candidate device were evaluated at various time intervals against the predicate. Blood samples were taken at 0-6 hrs, 6-12 hrs, and $>12$ hrs. post admission. The summarized sensitivities and specificities are below:
| Time | Sensitivity % (n/N) | LCL Sens % | UCL Sens % |
| --- | --- | --- | --- |
| All | 90.11(82/91) | 82.26 | 94.71 |
| 0-6h | 80.90(71/97) | 72.19 | 88.35 |
| 6-12h | 84.62(44/52) | 72.19 | 88.35 |
| >12h | 90.70(39/43) | 78.40 | 96.32 |
| Time | Specificity % (n/N) | LCL Spec % | UCL Spec % |
| --- | --- | --- | --- |
| All | 97.75(304/311) | 95.43 | 98.91 |
| 0-6h | 98.06(304/310) | 95.84 | 99.11 |
| 6-12h | 99.00(199/201) | 95.84 | 99.11 |
| >12h | 95.52(65/68) | 87.81 | 98.49 |
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b. Clinical specificity:
See 3.a. clinical sensitivity above.
c. Other clinical supportive data (when a. and b. are not applicable):
4. Clinical cut-off:
A separate cutoff study was performed prior to the clinical studies performed in M.3.a above. 652 subjects from one US site and one non-US site were evaluated for chest pain. Using the clinician's diagnosis, based on the ESC/AHA/ACC criteria, 358 subjects (102 females, 256 males) were included in the determination of the AMI cut-off study. Multiple blood samples were drawn and analyzed using the Troponin I assay and plotted using ROC analysis. A summary is below showing the standard deviation, and lower and upper confidence limits.
The cut-off was determined to be 0.3 ng/mL with a CV ≤ 10%.
| AUC | Std | LCL | UCL |
| --- | --- | --- | --- |
| 0.9565 | 0.0158 | 0.91263 | 0.97885 |
5. Expected values/Reference range:
In a study of 1,137 apparently healthy individuals from 4 US sites and 2 European sites, the troponin I levels were determined to be < 0.3 ng/mL
N. Proposed Labeling:
The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.
O. Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.
