Immunoassay for the in vitro quantitative determination of troponin T in human serum and plasma. Elecsys Troponin T can be used as an aid in the differential diagnosis of acute coronary syndrome to identify necrosis, e.g., acute myocardial infarction. The test is further indicated for the risk stratification of patients presenting with acute coronary syndrome and for cardiac risk in patients with chronic renal failure. The test may also be useful for the selection of more intensive therapy and intervention in patients with elevated levels of cardiac Troponin T. The electrochemiluminescence immunoassay "ECLIA" is intended for use on the Roche Elecsys family of immunoassay analyzers.

Device Description

The Elecsys® Troponin T STAT assay is a two step sandwich immunoassay with streptavidin micro particles and electrochemiluminescence detection, for the measurement of human TnT in serum or plasma.

AI/ML Overview

Here's an analysis of the acceptance criteria and the study details for the Elecsys® Troponin T STAT Assay, based on the provided document:

Acceptance Criteria and Device Performance for Elecsys® Troponin T STAT Assay

The document describes a modified device (4th Generation) and compares its performance to a predicate device (3rd Generation). The acceptance criteria are implicitly established by demonstrating comparable or improved performance to the predicate device, particularly for key analytical parameters.

1. Table of Acceptance Criteria (Implicitly based on Predicate Performance) and Reported Device Performance

Characteristic	Acceptance Criteria (Predicate Device Performance)	Reported Device Performance (Modified Device)
Intended Use	Immunoassay for the in vitro quantitative determination of troponin T in human serum and plasma. Aid in differential diagnosis of acute coronary syndrome, risk stratification, and cardiac risk in chronic renal failure. Useful for selection of intensive therapy in patients with elevated cardiac Troponin T. For use on Roche Elecsys family of immunoassay analyzers.	Same
Indications for Use	Aid in differential diagnosis of acute coronary syndrome, risk stratification, and cardiac risk in chronic renal failure. Useful for selection of intensive therapy in patients with elevated cardiac Troponin T.	Same
Assay Principle	Electrochemiluminescent immunoassay	Same
Traceability/ Standardization	Standardized against the 2nd generation Troponin T test	Standardized against the 3rd generation Elecsys Troponin T test; traceable to the 2nd generation test
Calibration Frequency	Elecsys 2010: After 1 month (same reagent lot), after 7 days (same reagent kit on analyzer). Elecsys 1010: With every reagent kit, after 7 days (20-25 °C), after 3 days (25-32 °C).	Elecsys 2010: After 1 month (same reagent lot), after 7 days (same reagent kit on analyzer). Elecsys 1010: With every reagent kit, after 7 days (20-25 °C). (Note: Predicate had additional 3-day frequency for Elecsys 1010 at higher temp; modified device does not list this, implying it's either removed or covered by the 7-day at 20-25C)
Sample Type	Human serum, K3-EDTA and Na-citrate plasma.	Human serum, K2- and K3-EDTA, Li-heparin, and Na-citrate plasma. (Expanded to include K2-EDTA and Li-heparin plasma)
Reagent Stability	Unopened: Up to stated expiration date at 2-8 °C. After opening: 12 weeks at 2-8 °C, 8 weeks on Elecsys 2010, 8 weeks on Elecsys 1010 (20-25 °C; up to 20 hours opened in total).	Same
Calibrator	Elecsys Troponin T STAT CalSet	Same
Controls	Elecsys PreciControl Troponin T or Elecsys PreciControl Cardiac.	Elecsys PreciControl Troponin T. (Note: Predicate allowed "or Elecsys PreciControl Cardiac"; modified device specifies "PreciControl Troponin T")
Duration of Assay	9 minutes	Same
Measuring Range	0.010-25.00 ng/mL	Same
Precision	Within-run (human serum): 1.1% CV at 0.47 ng/mL, 1.1% CV at 2.63 ng/mL, 1.4% CV at 11.5 ng/mL. Within-run (PreciControl): 4.2% CV at 0.10 ng/mL, 3.0% CV at 5.07 ng/mL. Total (human serum): 5.8% CV at 0.47 ng/mL, 5.4% CV at 2.63 ng/mL, 5.7% CV at 11.5 ng/mL. Total (PreciControl): 9.3% CV at 0.10 ng/mL, 6.0% CV at 5.07 ng/mL.	Within-run (human serum): 4.5% CV at 0.047 ng/mL, 2.0% CV at 0.652 ng/mL, 2.9% CV at 6.08 ng/mL. Within-run (PreciControl): 2.2% CV at 0.137 ng/mL, 2.5% CV at 2.89 ng/mL. Total (human serum): 6.2% CV at 0.047 ng/mL, 4.6% CV at 0.652 ng/mL, 5.6% CV at 6.08 ng/mL. Total (PreciControl): 3.5% CV at 0.137 ng/mL, 4.7% CV at 2.89 ng/mL.
Concentration at 10% CV	0.03 ng/mL	Same
Hook Effect	No hook effect up to 400 ng/mL	Same
Analytical Sensitivity	Lower detection limit: 0.01 ng/mL. Lowest concentration giving 10% CV: 0.03 ng/mL.	Same
Limitations – Interference	No interference from: icterus up to 27 mg/dL bilirubin, hemolysis up to 0.1 g/dL, Lipemia up to 1500 mg/dL Intralipid, Biotin up to 50 ng/mL, Rheumatoid factor up to 2000 U/mL. Falsely depressed results with higher hemoglobin. Plasma with heparin or oxalate/fluoride showed sample-dependent low TnT values vs. serum. Contains additives for monoclonal mouse antibodies, antibodies to streptavidin. Extremely high titers of antibodies to ruthenium can cause interference. Results assessed with patient's medical history.	Same limitations reported for icterus, hemolysis, lipemia, biotin, rheumatoid factor, falsely depressed results with higher hemoglobin, and additives for interference. Modified language for plasma interference: "Plasma samples collected using tubes containing oxalate/fluoride revealed sample-dependent low TnT values when compared to results obtained on serum samples." (Note: original also mentioned heparin, which is now an acceptable sample type).

Summary of Acceptance: The modified device demonstrates comparable performance across most parameters and shows improvements in sample types accepted (K2-EDTA and Li-heparin plasma) and potentially tighter precision at some concentrations compared to its predicate. The calibration frequency has a slight difference for Elecsys 1010 at higher temperatures, and the specific controls used are now narrower. The modifications in precision values suggest that new studies were done to establish these figures, and they are presented as the device's performance. The "acceptance criteria" for these would have been to meet or demonstrate improved analytical performance metrics compared to the predicate, which appears to be the case (e.g., lower CVs at comparable or different concentration points).

2. Sample Size Used for the Test Set and Data Provenance

The document does not explicitly state a single dedicated "test set" sample size or its provenance in the way one would for a clinical validation or a standalone AI study. Instead, it describes analytical performance characteristics that would have been derived from various studies using different samples:

Precision (Within-run and Total): The precision data is reported for "human serum" and "PreciControl" (a control material). It lists specific CVs at different concentration points. While the exact number of samples or runs to generate these CVs is not provided, this would typically involve multiple replicates of samples at different concentrations across multiple runs and days.
Interference Studies: These require testing samples spiked with various interferents (icterus, hemolysis, lipemia, biotin, rheumatoid factor) and comparing them to unspiked samples.
Sample Type Evaluation: Plasma samples (K3-EDTA, Na-citrate, K2-EDTA, Li-heparin) are compared to serum samples, implying a set of patient samples collected in different tube types.
Data Provenance: The document does not specify the country of origin of the data or whether it was retrospective or prospective. Given it's an in-vitro diagnostic device submission, the analytical studies are typically conducted by the manufacturer, likely in a controlled laboratory setting.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications

This is an analytical device (immunoassay) for quantitative measurement of a biomarker. Therefore, traditional "ground truth" as established by expert consensus (e.g., radiologists interpreting images) or pathology is not applicable in the same way as for diagnostic imaging or pathology devices.

Ground Truth (Analytical): For an immunoassay, the "ground truth" or reference values are established through highly controlled laboratory methods, calibrated against international standards if available, and verified through other reference methods or highly accurate assays. The device itself is designed to measure the concentration of Troponin T, and its accuracy is assessed against the expected concentration in reference materials or patient samples already characterized.
Experts: The development and validation of such an assay would involve analytical chemists, biochemists, clinical chemists, and other scientific experts who design, perform, and interpret these analytical studies, rather than clinical experts establishing a "diagnosis" as ground truth.

4. Adjudication Method for the Test Set

Adjudication methods like 2+1 or 3+1 are typically used in clinical studies where human interpretation of data (e.g., images, clinical symptoms) is being evaluated and discrepancies resolved. This is not directly applicable to the analytical performance studies of an immunoassay device. The performance metrics (precision, sensitivity, specificity, interference) are determined by quantitative laboratory measurements and statistical analysis.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. MRMC studies are relevant for devices where human readers interpret output (e.g., medical images) and the AI's impact on their performance is being evaluated. This document is for an automated immunoassay where the device provides a quantitative result directly. The device's "effectiveness" is in its analytical accuracy and precision in measuring Troponin T.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study

Yes, the studies presented indirectly represent a standalone performance evaluation. The Elecsys® Troponin T STAT Assay is an automated immunoassay designed to provide a quantitative measurement. The precision, measuring range, analytical sensitivity, hook effect, and interference studies describe the performance of the algorithm/device itself (the immunoassay system) independent of human interpretation of the primary data (other than loading samples and reading the final numerical result). This is inherently a "standalone" evaluation for such a device.

7. Type of Ground Truth Used

For this immunoassay, the "ground truth" is established through:

Reference Materials/Standards: Calibrators and control materials with known or assigned Troponin T concentrations are used to calibrate the device and verify its accuracy. The document states its traceability to the 2nd and 3rd generation Troponin T tests.
Spiked Samples: For interference studies, samples are "spiked" with known concentrations of interferents, and the ground truth is the expected Troponin T concentration in the absence of interference.
Comparative Methods: Although not explicitly detailed in this summary, often new assays are compared to established reference methods or highly accurate laboratory methods to establish accuracy.

8. Sample Size for the Training Set

The document describes a 510(k) for a device modification, focusing on analytical performance rather than a machine learning algorithm that requires a "training set" in the computational sense. Therefore, there is no explicit mention of a "training set" as it would apply to AI/ML models.

The device is an immunoassay, meaning its "learning" or optimization during development would involve:

Reagent Formulation and Optimization: Iterative testing and adjustment of antibodies, buffers, and detection systems.
Calibration Curve Development: Generating data points to establish the relationship between signal and concentration.

These development activities would involve numerous experiments and a large number of samples, but not usually referred to as a "training set" in this context.

9. How the Ground Truth for the Training Set Was Established

As noted above, a "training set" in the computational sense is not directly applicable here. The "ground truth" during device development (analogous to training) would be established by:

Careful preparation of standard solutions with known concentrations of Troponin T.
Characterization of patient samples or quality control materials using established reference methods or highly accurate laboratory assays to determine their true Troponin T levels.
These known concentrations are then used to develop and validate the device's ability to accurately measure Troponin T, forming the basis for its calibration and performance specifications.

Summary

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JUL 1 1 2005

K051752

510(k) Summary – Elecsys® Troponin T STAT Assay

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	Roche Diagnostics 9115 Hague Rd Indianapolis IN 46250 (317) 521-3723
	Contact person: Theresa M. Ambrose
	Date prepared: June 28, 2005
Device Name	Proprietary name: Elecsys® Troponin T STAT Assay
	Common name: Troponin T Test
	Classification name: Immunoassay method, troponin subunit
Device Description	The Elecsys® Troponin T STAT assay is a two step sandwich immunoassay with streptavidin micro particles and electrochemiluminescence detection, for the measurement of human TnT in serum or plasma .
Intended use	Immunoassay for the in vitro quantitative determination of troponin T in human serum and plasma. Elecsys Troponin T can be used as an aid in the differential diagnosis of acute coronary syndrome to identify necrosis, e.g., acute myocardial infarction. The test is further indicated for the risk stratification of patients presenting with acute coronary syndrome and for cardiac risk in patients with chronic renal failure. The test may also be useful for the selection of more intensive therapy and intervention in patients with elevated levels of cardiac Troponin T. The electrochemiluminescence immunoassay "ECLIA" is intended for use on the Roche Elecsys family of immunoassay analyzers.
Predicate Device	We claim substantial equivalence to the Elecsys ® Troponin T STAT reagent currently marketed on the Elecsys 2010 and MODULAR ANALYTICS E170. (K040733).
	Continued on next page

Confidential

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510(k) Summary – Elecsys® Troponin T STAT Assay, Continued

The table below indicates the similarities and differences between the Substantial modified Elecsys® Elecsys Troponin T STAT and its predicate device equivalency -(current Troponin T STAT, K040733). device comparison

Characteristic	Current Elecsys® Troponin T STAT(3rd Gen.) (K040733)	Modified device Elecsys®Troponin T STAT (4th Gen.)
Intended Use	Immunoassay for the in vitroquantitative determination of troponinT in human serum and plasma.Elecsys Troponin T can be used as anaid in the differential diagnosis ofacute coronary syndrome to identifynecrosis, e.g., acute myocardialinfarction. The test is furtherindicated for the risk stratification ofpatients presenting with acutecoronary syndrome and for cardiacrisk in patients with chronic renalfailure. The test may also be usefulfor the selection of more intensivetherapy and intervention in patientswith elevated levels of cardiacTroponin T. Theelectrochemiluminescenceimmunoassay "ECLIA" is intendedfor use on the Roche Elecsys familyof immunoassay analyzers.	Same
Indications for Use	Elecsys Troponin T can be used as anaid in the differential diagnosis ofacute coronary syndrome to identifynecrosis, e.g., acute myocardialinfarction. The test is furtherindicated for the risk stratification ofpatients presenting with acutecoronary syndrome and for cardiacrisk in patients with chronic renalfailure. The test may also be usefulfor the selection of more intensivetherapy and intervention in patientswith elevated levels of cardiacTroponin T.	Same

Assay principle	Electrochemiluminescentimmunoassay	Same
Traceability/standardization	Standardized against the 2nd generation Troponin T test	Standardized against the 3rd generation Elecsys Troponin T test; traceable to the 2nd generation test
Calibration frequency	Elecsys 2010• After 1 month when using the samereagent lot• After 7 days when using the samereagent kit on the analyzerElecsys 1010• With every reagent kit• After 7 days (20-25 °C)• After 3 days (25-32 °C)	Elecsys 2010• After 1 month when using thesame reagent lot• After 7 days when using the samereagent kit on the analyzerElecsys 1010• With every reagent kit• After 7 days (20-25 °C)
Sample type	Human serum, K3-EDTA and Na-citrate plasma.	Human serum, K2- and K3-EDTA,Li-heparin, and Na-citrate plasma
Reagent stability	Unopened• Up to the stated expiration date at 2-8 °CAfter opening• 12 weeks at 2-8 °C• 8 weeks on Elecsys 2010• 8 weeks on Elecsys 1010 (20-25 °C;up to 20 hours opened in total)	Same
Calibrator	Elecsys Troponin T STAT CalSet	Same
Controls	Elecsys PreciControl Troponin T orElecsys PreciControl Cardiac.	Elecsys PreciControl Troponin T
Duration of assay	9 minutes	Same

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Special 510(k): Device Modification – Elecsys® Troponin T

STAT ,Continued

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Special 510(k): Device Modification – Elecsys® Troponin T STAT ,Continued

Measuring range	0.010-25.00 ng/mL	Same
Precision	Within-run (human serum)• 1.1% CV at 0.47 ng/mL• 1.1% CV at 2.63 ng/mL• 1.4% CV at 11.5 ng/mLWithin-run (PreciControl)• 4.2% CV at 0.10 ng/mL• 3.0% CV at 5.07 ng/mLTotal (human serum)• 5.8% CV at 0.47 ng/mL• 5.4% CV at 2.63 ng/mL• 5.7% CV at 11.5 ng/mLTotal (PreciControl)• 9.3% CV at 0.10 ng/mL• 6.0% CV at 5.07 ng/mL	Within-run (human serum)• 4.5% CV at 0.047 ng/mL• 2.0% CV at 0.652 ng/mL• 2.9% CV at 6.08 ng/mLWithin-run (PreciControl)• 2.2% CV at 0.137 ng/mL• 2.5% CV at 2.89 ng/mLTotal (human serum)• 6.2% CV at 0.047 ng/mL• 4.6% CV at 0.652 ng/mL• 5.6% CV at 6.08 ng/mLWithin-run (PreciControl)• 3.5% CV at 0.137 ng/mL• 4.7% CV at 2.89 ng/mL
Concentration at 10%CV:	0.03 ng/mL	Same
Hook effect	No hook effect up to 400 ng/mL	Same
Analytical sensitivity	Lower detection limit: 0.01 ng/mLLowest concentration giving 10 %CV: 0.03 ng/mL	Same

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Special 510(k): Device Modification – Elecsys® Troponin T

STAT ,Continued

Limitations –interference	No interference from• icterus up to 27 mg/dL bilirubin• hemolysis up to 0.1 g/dL,• Lipemia up to 1500 mg/dLIntralipid• Biotin up to 50 ng/mL• Rheumatoid factor up to 2000U/mL	Same
	Falsely depressed results are obtainedwhen using samples with higherhemoglobin concentrations.	Same
	Plasma samples collected withheparin or oxalate/fluoride revealedsample-dependent low TnT valuescompared to results obtained onserum samples.	Plasma samples collected usingtubes containing oxalate/fluoriderevealed sample-dependent lowTnT values when compared toresults obtained on serum samples.
	Contains additives to minimize theeffects of interference due to• Monoclonal mouse antibodies• Antibodies to streptavidin	Same
	Extremely high titers of antibodies toruthenium can cause interference.	Same
	Results should be assessed inconjunction with the patient's medicalhistory, clinical examination, andother findings	Same

. I

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/5/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized depiction of an eagle or bird-like figure with three curved lines forming its body and wings. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged in a circular fashion around the emblem.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

JUL 1 1 2005

Theresa M. Ambrose, Ph.D., RAC Regulatory Principal Roche Diagnostics 9115 Hague Road Indianapolis, IN 46250

Re: K051752

Trade/Device Name: Roche Elecsys® Troponin T STAT Regulation Number: 21 CFR 862.1215 Regulation Name: Creatine phosphokinase/creatine kinase or isoenzymes test system Regulatory Class: Class II Product Code: MMI Dated: June 28, 2005 Received: June 29, 2005

Dear Dr. Ambrose:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and 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) that do not require approval of a premarket approval application (PMA). 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 (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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Page 2 -

This letter will allow you to begin marketing your device as described in your Section 510(k) rms letter will and in your is of your 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 information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240) 276-0484. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Carol C. Benson

Carol C. Benson, M.A. Acting Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known): K051752-

Device Name: Roche Elecsys ® Troponin T STAT

Indications For Use:

Prescription Use XXX (Part 21 CFR 801 Subpart D) AND/OR

Over-The-Counter Use (21 CFR 807 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

	Division Sign-Off Office of In Vitro Diagnostic Device Page 1 of 1 Evaluation and Safety
Confidential	510(k) K051752

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.