(25 days)
Abbott AxSYM® Troponin-I is a Microparticle Enzyme Immunoassay (MEIA) for the quantitative determination of cardiac troponin-I in human serum or plasma on the Abbott AxSYM System. Measurements obtained by this device are used to assist in the diagnosis of acute myocardial infarction (AMI).
AxSYM Troponin-I is a Microparticle Enzyme Immunoassay (MEIA) for the quantitative determination of cardiac troponin-I in human serum or plasma. AxSYM Troponin-I is calibrated with Abbott Troponin-I Calibrators. Abbott Troponin-I Controls are assayed for the verification of the accuracy and precision of the AxSYM System. Both assays are automated, in vitro immunoassays that use antibodies specific for the cardiac isotype of troponin-I. The fluorescent signal measured by both assays is directly proportional to the concentration of cardiac troponin-I in the sample.
Acceptance Criteria and Study for Abbott AxSYM® Troponin-I
This document describes the acceptance criteria and the study conducted to demonstrate the substantial equivalence of the Abbott AxSYM® Troponin-I assay.
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria for the AxSYM Troponin-I assay were implicitly defined by demonstrating substantial equivalence to a predicate device and achieving clinically acceptable sensitivity and specificity for the diagnosis of Acute Myocardial Infarction (AMI). While specific quantitative acceptance criteria for sensitivity and specificity were not explicitly stated as "acceptance criteria" in the provided text, the reported performance was considered sufficient for regulatory approval.
| Metric | Acceptance Criteria (Implicit) | Reported Device Performance (AxSYM Troponin-I) |
|---|---|---|
| Correlation with Predicate | Strong correlation (e.g., Spearman coefficient > 0.8) | Spearman correlation coefficient: 0.851 |
| Clinical Sensitivity | High sensitivity using WHO criteria for AMI | 93.9% |
| Clinical Specificity | High specificity using WHO criteria for AMI | 93.4% |
2. Sample Size Used for the Test Set and Data Provenance
- Test Set Sample Size:
- Clinical Study: 246 patients, representing 689 observations (serial samples).
- Method Comparison: 158 specimens for the Passing-Bablok linear regression analysis.
- Data Provenance: The document does not explicitly state the country of origin. The study was described as a "multi-center clinical study," which generally implies prospective data collection, especially given the serial sampling to rule in/rule out AMI. The method comparison data would also be considered prospective.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
- The ground truth for AMI diagnosis in the clinical study was based on the World Health Organization (WHO) criteria for AMI. The document does not specify the number or qualifications of individual experts who applied these criteria to establish the ground truth for each patient. This suggests that the ground truth was established by clinical teams at the participating centers following established medical guidelines, rather than by a panel of independent, reviewing experts for the purpose of the study.
4. Adjudication Method for the Test Set
- The document does not describe a specific adjudication method (e.g., 2+1, 3+1) for establishing the ground truth regarding AMI diagnosis. As mentioned above, the diagnosis was based on WHO criteria, implying a standard clinical diagnostic process.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No, a multi-reader multi-case (MRMC) comparative effectiveness study was not performed. This device is an in vitro diagnostic (IVD) assay (a laboratory test) that provides a quantitative result. Its effectiveness is assessed by its analytical performance and clinical accuracy in diagnosing a condition, not by human reader interpretation or improved human reader performance with AI assistance.
6. Standalone Performance Study
- Yes, a standalone performance study was done. The clinical sensitivity (93.9%) and specificity (93.4%) were determined for the AxSYM Troponin-I assay alone, using a diagnostic cutoff of 2.0 ng/mL, against the clinical diagnosis of AMI based on WHO criteria. This represents the algorithm's (assay's) performance without human interpretation or intervention in the diagnostic output.
7. Type of Ground Truth Used
- Clinical Diagnosis / Outcomes Data (for sensitivity/specificity): The primary ground truth for the clinical study was the World Health Organization (WHO) criteria for AMI. This is a well-established clinical definition for myocardial infarction.
- Predicate Device Measurement (for correlation): For the method comparison, the Dade® Stratus® Cardiac Troponin-I Fluorometric Enzyme Immunoassay served as the reference for comparison, indicating that its measurements were considered the "ground truth" for evaluating analytical agreement.
8. Sample Size for the Training Set
- The document does not explicitly mention a "training set" in the context of machine learning or AI models. The AxSYM Troponin-I is an immunoassay, which does not typically involve traditional machine learning training sets in the same way an AI algorithm for image analysis would. Development and calibration would involve various internal validation samples, but these are 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, the concept of a training set with established ground truth in the AI/ML sense does not directly apply here. For standard immunoassay development, the "ground truth" for calibrator and control materials is established through rigorous analytical methods, often involving reference methods or gravimetric preparation of known analyte concentrations. The accuracy and precision of these materials are critical for the assay's performance.
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NOV 2 5 1997
Section II
510(k) Summary
AxS YM Troponin-I 510(k)
October 1997
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Section II
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510(k) Summary Abbott AxSYM® Troponin-I
Summary of Safety and Effectiveness Information Supporting a Substantially Equivalent Determination
The following information as presented in the Premarket Notification [510(k)] for Abbott AxSYM® Troponin-I constitutes data supporting a substantially equivalent determination.
AxSYM Troponin-I is a Microparticle Enzyme Immunoassay (MEIA) for the quantitative determination of cardiac troponin-I in human serum or plasma. AxSYM Troponin-I is calibrated with Abbott Troponin-I Calibrators. Abbott Troponin-I Controls are assayed for the verification of the accuracy and precision of the AxSYM System.
Substantial equivalence has been demonstrated between the AxSYM Troponin-I assay and the Dade® Stratus® Cardiac Troponin-I Fluorometric Enzyme Immunoassay.
The intended use of the AxSYM Troponin-I assay is for the quantitative determination of cardiac troponin-I in serum or plasma. Troponin-I values are used to assist in the diagnosis of acute myocardial infarction (AMI).
The intended use of the Stratus Cardiac Troponin-I assay is for the quantitative determination of cardiac troponin-I levels in serum and plasma. Cardiac troponin-I determinations aid in the diagnosis of myocardial infarction and in the risk stratification of patients with acute coronary syndromes with respect to their relative risk of mortality.
Both assays are automated, in vitro immunoassays that use antibodies specific for the cardiac isotype of troponin-I. The fluorescent signal measured by both assays is directly proportional to the concentration of cardiac troponin-I in the sample. A Passing-Bablok linear regression analysis between these two assays, using 158 specimens, yielded a Spearman correlation coefficient of 0.851, a slope of 3.42 ng/mL, and Y-axis intercept of -1.09 ng/mL.
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In a multi-center clinical study, a total of 246 patients, representing 689 observations, were followed with serial sampling to rule-in or rule-out for AMI. Clinical diagnosis was based upon the World Health Organization (WHO) criteria for AMI. There were 49 patients who ruled-in for AMI. Using 2.0 ng/mL as a diagnostic cutoff, the AxSYM Troponin-I assay demonstrated a clinical sensitivity of 93.9% and a clinical specificity of 93.4%.
In conclusion, these data demonstrate that the AxSYM Troponin-I assay is as safe and effective as, and is substantially equivalent to the Dade Stratus Cardiac Troponin-I Fluorometric Enzyme Immunoassay.
Prepared and Submitted October 30, 1997 by: Laura Granitz Senior Regulatory Specialist ADD Regulatory Affairs 1-847-938-0092 Abbott Laboratories 200 Abbott Park Road Abbott Park, IL 60064-3537
AxSYM Troponin-I 510(k) October 1997 atmi510k.lwp
Section II Page 2
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Image /page/3/Picture/2 description: The image is a black and white logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle with three curved lines extending from its head, resembling wings or feathers. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the eagle, with the eagle positioned in the center of the text.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
NOV 25 1997
Granitz Laura · Senior Regulatory Specialist Abbott Laboratories 200 Abbott Park Road 60064-3537 Abbott Park, Illinois
Re : K974103 Abbott AxSYM® Troponin-I Requlatory Class: II Product Code: MMI October 30, 1997 Dated: Received: October 31, 1997
Dear Ms. Granitz:
We have reviewed your Section 510(k) notification of intent to market the device referenced above and we have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to 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). You may, therefore, market the device, subject to the general controls provisions The general controls provisions of the Act 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 (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic QS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory In addition, FDA may publish further announcements action. concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations.
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Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770) 488-7655.
This letter will allow you to begin marketing your device as described in your 510 (k) premarket notification. The FDA deboing 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 advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to
premarket notification" (21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsmamain.html".
Sincerely yours,
Steven Sutman
Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health
Enclosure
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510(k) Number (if known): K 974103
Abbott AxSYM® Troponin-I Device Name: _________________________________________________________________________________________________________________________________________________________________
Indications For Use:
Abbott AxSYM® Troponin-I is a Microparticle Enzyme Immunoassay (META) for_ the quantitative determination of cardiac troponin-I in human serum or plasma on the Abbott AxSYM System. Measurements obtained by this device are used to assist in the diagnosis of acute myocardial infarction (AMI).
(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
| Prescription Use | ✓ |
|---|---|
| (Per 21 CFR 801.109) |
OR
| Over-The-Counter Use | ________________ |
|---|---|
| ---------------------- | ------------------ |
(Optional Format 1-2-96)
| (Division Sign-Off) | |
|---|---|
| Division of Clinical Laboratory Devices | |
| 510(k) Number | k94103 |
§ 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.