(56 days)
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.
The Elecsys Troponin T STAT is a two step sandwich immunoassay with streptavidin micro particles and electrochemiluminescence detection, for the measurement of human TnT in serum or plasma.
The provided document is a 510(k) summary for the Elecsys Troponin T STAT test, comparing it to an older version of the same device (K984105). The purpose of this submission is to demonstrate substantial equivalence, primarily due to expanding the intended use of the device.
Therefore, the document does not contain a new study that establishes acceptance criteria and proves the device meets them from scratch. Instead, it asserts that the new version of the device is substantially equivalent to the predicate device (an older, already cleared version) and thus meets the established performance characteristics of the predicate. The "acceptance criteria" for the new device are essentially that its performance characteristics are "Same" as the predicate.
Here's an analysis of the provided information based on your request, highlighting what is present and what is not:
1. A table of acceptance criteria and the reported device performance
The document presents a comparison between the "Elecsys® Troponin T STAT (modified intended use)" and the "Predicate device Elecsys® Troponin T STAT (K984105)". For most performance characteristics, the new device's performance is simply stated as "Same" as the predicate. This implies that the predicate device's performance characteristics serve as the de facto acceptance criteria.
| Characteristic | Acceptance Criteria (Predicate Device Performance) | Reported Device Performance (New Device) |
|---|---|---|
| Intended Use | Immunoassay for the in vitro quantitative determination of troponin T in human serum and plasma. The electrochemiluminescence immunoassay "ECLIA" is intended for use on the Roche Elecsys family of immunoassay analyzers. | Expanded intended use to include: aid in differential diagnosis of acute coronary syndrome to identify necrosis (e.g., AMI), risk stratification in acute coronary syndrome and chronic renal failure, and selection of more intensive therapy/intervention in patients with elevated cTnT. |
| Assay principle | Electrochemiluminescent immunoassay | Same |
| Traceability/standardization | Standardized against the 2nd generation Elecsys Troponin T test | Same |
| Calibration interval | Elecsys 2010: After 1 month (same lot), After 7 days (same kit on analyzer); Elecsys 1010: With every reagent kit, After 7 days (20-25 °C), After 3 days (25-32 °C) | Same |
| Sample type | Human serum, EDTA and citrate plasma. | Same |
| Reagent stability | Unopened: Up to 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. | Same |
| 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 | 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 concentrations. Plasma samples with heparin or oxalate/fluoride showed sample-dependent low TnT values compared to serum. Contains additives to minimize effects of interference due to monoclonal mouse antibodies and antibodies to streptavidin. Extremely high titers of antibodies to ruthenium can cause interference. Results should be assessed with patient's medical history, clinical examination, and other findings. | Same |
2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)
The document primarily focuses on demonstrating substantial equivalence by stating that the new device's analytical performance characteristics are "Same" as the predicate device (K984105).
- Test Set (for performance characteristics listed as "Same"): The document does not provide details of a new test set or clinical study conducted specifically for this 510(k) submission to validate these "Same" characteristics. It relies on the previously established performance of the predicate device.
- For the expanded Indications for Use related to acute coronary syndrome, risk stratification, and renal failure: The document mentions "Comparative studies on 770 patients confirm the prognostic utility of cTnT." This suggests that the clinical utility for these expanded indications has been demonstrated, likely through existing literature or previous studies supporting the general use of cTnT, rather than a new study specific to this submission's device to prove new performance characteristics.
- Data Provenance: Not specified (country, retrospective/prospective for the 770 patients).
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)
Not applicable. This is an in-vitro diagnostic device measuring a biomarker (Troponin T). The "ground truth" for the test set comes from the known analytical characteristics of the specified samples and controls (e.g., concentration levels in control materials, samples with known interferents). The clinical utility for the expanded indications would be based on clinical outcomes relevant to myocardial damage, risk stratification, etc., not expert consensus on image interpretation.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
Not applicable. Adjudication methods are typically relevant for subjective assessments, like medical imaging interpretation, where multiple experts might disagree on findings. This device measures a quantitative biomarker, so "adjudication" in that sense is not relevant. The accuracy of the measurement is assessed against reference methods or known concentrations.
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
Not applicable. This is an in-vitro diagnostic device for biomarker measurement, not an AI-assisted diagnostic tool that involves human readers interpreting cases.
6. If a standalone (i.e. algorithm only without human-in-the loop performance) was done
This refers to the performance of the immunoassay device itself. The characteristics listed (precision, sensitivity, measuring range, hook effect, interference) are all measures of the device's standalone performance. The document asserts this performance is "Same" as the predicate device.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)
For the analytical performance characteristics (precision, sensitivity, measuring range, etc.), the ground truth would be based on:
- Reference materials with known concentrations: Calibrators and controls (e.g., Elecsys Troponin T STAT CalSet, Elecsys PreciControl Troponin T or Elecsys PreciControl Cardiac).
- Method comparison against established reference methods (implied for original predicate clearance).
- Defined levels of interferents (e.g., specific concentrations of bilirubin, hemoglobin, intralipid) to test interference.
For the expanded clinical indications (aid in differential diagnosis of acute coronary syndrome, risk stratification, cardiac risk in chronic renal failure, selection of therapy), the ground truth for clinical utility would be based on:
- Patient outcomes data: Diagnosis of AMI, major adverse cardiac events, mortality, response to specific treatments, etc. This is supported by the statement "Comparative studies on 770 patients confirm the prognostic utility of cTnT."
8. The sample size for the training set
The document does not describe a training set for the new device, as it is claiming substantial equivalence to an existing predicate device based on its inherent analytical characteristics being the "Same." Immunoassays typically do not have a "training set" in the machine learning sense. The development of an immunoassay involves optimizing reagents, antibodies, and protocols, which is an iterative process often using many samples, but not typically referred to as a "training set" in this context.
9. How the ground truth for the training set was established
Not applicable for the reasons stated above (no "training set" in the ML sense). The ground truth for developing and validating an immunoassay would be established via highly characterized reference materials and patient samples with clinically confirmed diagnoses or outcomes.
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| MAY 17 2004 | 510(k) Summary |
|---|---|
| Introduction | According to the requirements of 21 CFR 807.92, the following information provides sufficient detail to understand the basis for a determination of substantial equivalence. |
| Submittername, address,contact | Roche Diagnostics9115 Hague RoadIndianapolis, IN 46250317-521-3723 |
| Contact Person: Theresa M. AmbroseDate Prepared: May 11, 2004 | |
| Device Name | Proprietary name: Elecsys Troponin T ® STAT test |
| Common name: Troponin T test | |
| Classification name: Immunoassay method, troponin subunit | |
| Predicatedevice | The Elecsys Troponin T STAT is substantially equivalent to the currently marketed Elecsys ® Troponin T STAT (K984105). |
| DeviceDescription | The Elecsys Troponin T STAT 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. |
| Comparison topredicatedevice | The Elecsys Troponin T STAT is substantially equivalent to the currentlymarketed currently marketed Elecsys ® Troponin T STAT (K984105). Thebelow tables compare Elecsys® Troponin T STAT with the predicate device,Elecsys® Troponin T STAT (K984105) |
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| Character-istic | Elecsys® Troponin T STAT(modified intended use) | Predicate device Elecsys®Troponin T STAT(K984105) |
|---|---|---|
| IntendedUse | Immunoassay for the in vitro quantitativedetermination of troponin T in human serum andplasma. Elecsys Troponin T can be used as an aidin the differential diagnosis of acute coronarysyndrome to identify necrosis, e.g., acutemyocardial infarction. The test is furtherindicated for the risk stratification of patientspresenting with acute coronary syndrome and forcardiac risk in patients with chronic renal failure.The test may also be useful for the selection ofmore intensive therapy and intervention inpatients with elevated levels of cardiac TroponinT. The electrochemiluminescence immunoassay"ECLIA" is intended for use on the RocheElecsys family of immunoassay analyzers. | Immunoassay for the invitro quantitativedetermination of troponin Tin human serum and plasma.Theelectrochemiluminescenceimmunoassay "ECLIA" isintended for use on theRoche Elecsys family ofimmunoassay analyzers. |
| Character-istic | Elecsys® Troponin T STAT(modified intended use) | Predicate device Elecsys®Troponin T STAT(K984105) |
| Indicationsfor Use | Troponin T (TnT) is a component of thecontractile apparatus of the striated musculature.Although the function of TnT is the same as in allstriated muscles, TnT originating exclusivelyfrom the myocardium (cardiac TnT, molecularweight 39.7 kD) clearly differs from skeletalmuscle TnT. As a result of its high tissuesensitivity, cardiac troponin T (cTnT) is acardiospecific, highly sensitive marker formyocardial damage. In cases of acute myocardialinfarction, troponin T levels rise about 3-4 hoursafter the occurrence of cardiac symptoms and canremain elevated for up to 14 days.The determination of cTnT in serum is animportant component in the diagnosis ofmyocardial ischemia, e.g. AMI and myocarditis,as well as in monitoring the course of unstableangina pectoris and assessing the associated risk.Comparative studies on 770 patients confirm theprognostic utility of cTnT. It has also beenshown that cTnT-positive patients benefitparticularly from antithrombotic therapystrategies (e.g. low molecular weight heparin,GPIIb/IIIa antagonists).Elevated serum cTnT values are detectable inabout 30% of patients suffering from renal failure(e.g. chronic hemodialysis patients). The cTnTdetected in these patients is of cardiac origin. Ithas been demonstrated e.g. with RT-PCR, thatcTnT is not expressed in regenerated skeletalmusculature of patients with renal failure.Clinical data increasingly demonstrate that suchpatients have a high risk of subsequentlysuffering cardiovascular complications. | Same |
| Characteristic | Elecsys® Troponin T STAT(modified intended use) | Predicate device Elecsys®Troponin T STAT (K984105) |
| Assay principle | Electrochemiluminescentimmunoassay | Same |
| Traceability/standardization | Standardized against the 2ndgeneration Elecsys Troponin Ttest | Same |
| Calibration interval | Elecsys 2010• After 1 month when usingthe same reagent lot• After 7 days when using thesame reagent kit on theanalyzerElecsys 1010• With every reagent kit• After 7 days (20-25 °C)• After 3 days (25-32 °C) | Same |
| Sample type | Human serum, EDTA andcitrate plasma. | Same |
| Reagent stability | Unopened• Up to the stated expirationdate 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 hoursopened in total) | Same |
| Calibrator | Elecsys Troponin T STATCalSet | Same |
| Controls | Elecsys PreciControl TroponinT or Elecsys PreciControlCardiac. | Same |
| Duration of assay | 9 minutes | same |
| Characteristic | Elecsys® Troponin T STAT(modified intended use) | Predicate device Elecsys®Troponin T STAT(K984105) |
| 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/mLWithin-run (PreciControl)• 9.3% CV at 0.10 ng/mL• 6.0% CV at 5.07 ng/mL | Same |
| Hook effect | No hook effect up to 400 ng/mL | Same |
| Analytical sensitivity | Lower detection limit: 0.01 ng/mLLowest concentration giving10 % CV: 0.03 ng/mL | Same |
Continued on next page
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Predicate device (continued)
Continued on next page
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Predicate device (continued)
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The performance characteristics of the Elecsys® Troponin T STAT test and Substantial the predicate device are compared in the table below. equivalence: performance characteristics
Continued on next page
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| Characteristic | Elecsys® Troponin T STAT(modified intended use) | Predicate device Elecsys®Troponin T STAT(K984105) |
|---|---|---|
| Limitations –interference | No interference from | Same |
| • icterus up to 27 mg/dLbilirubin | ||
| • hemolysis up to 0.1 g/dL, | ||
| • Lipemia up to 1500 mg/dLIntralipid | ||
| • Biotin up to 50 ng/mL | ||
| • Rheumatoid factor up to2000 U/mL | ||
| Falsely depressed results areobtained when using sampleswith higher hemoglobinconcentrations. | ||
| Plasma samples collectedwith heparin oroxalate/fluoride revealedsample-dependent low TnTvalues compared to resultsobtained on serum samples. | ||
| Contains additives tominimize the effects ofinterference due to• Monoclonal mouseantibodies• Antibodies to streptavidin | ||
| Extremely high titers ofantibodies to ruthenium cancause interference. | ||
| Results should be assessed inconjunction with thepatient's medical history,clinical examination, andother findings |
Substantial equivalence: performance characteristics (continued)
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/7/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is an abstract image of an eagle or bird-like figure, represented by three stylized lines forming the body and head, and two lines forming the legs and feet.
MAY 1 7 2004
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Theresa M. Ambrose, PhD, DABCC, FACB, RAC Regulatory Principial Roche Diagnostics Corp. 9115 Hague Road Indianapolis, IN 46250
Re: K040733 Trade/Device Name: Elecsys Troponin T STAT Regulation Number: 21 CFR 862.1215 Regulation Name: Creatine phosphokinase/creatine kinasc or isoenzymes test system Regulatory Class: Class II Product Code: MMI Dated: March 19, 2004 Reccived: March 22, 2004
Dear Dr. Ambrosc:
We have reviewed your Scction 510(k) premarket notification of intent to market the device we nave roved your be determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate for ass stated in the encreased of 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, de neces that have been that do not require approval of a premarket approval application (PMA). and Oosmetee Prove, market the device, subject to the general controls provisions of the Act. The r ou may, arovisions 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 r that FDA has made a determination that your device complies with other requirements of the Act that I DI Hab Intace a s and regulations administered by other Federal agencies. You must on any I caerar statutes and st including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practice SFR Part 867, 140 million 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) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific 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 (301) 594-3084. 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/dsma/dsmamain.html.
Sincerely yours,
Jean M. Cooper, MS, DVM.
Yean M. Cooper, MS, D.V.M. 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):___K040733
Device Name: Elecsys Troponin T STAT
Indications For Use:
Immunoassay for the in vitro quantitative determination of troponin T in human serum and plasma. The minutioussey for the in 'niv quanassay "ECLIA" is intended for use on the Roche Elecsys family of immunoassay analyzers.
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 lucinity neerosis, brg, assno coronary syndrome and for cardiac risk in patients with chronic renal or patients presenting that be useful for the selection of more intensive therapy and intervention in patients with elevated levels of cardiac Troponin T.
Prescription Use X = (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)
Hanlonge
Division Sign-Off
Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K040733
§ 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.