(25 days)
The TROP method is used on the Dimension® RxL clinical chemistry system with the heterogeneous immunoassay module to quantitatively measure cardiac troponin-1 in human serum and plasma. Measurements of TROP 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.
The TROP method is a one-step enzyme immunoassay. Sample is incubated with chromium dioxide particles (CrOz) coated with a monoclonal antibody specific for cardiac troponin-1 and conjugate reagent [alkaline phosphatase (ALP) labeled monoclonal antibody specific for cardiac troponin-I] to form a particle/cardiac troponin-I/conjugate sandwich. Unbound conjugate and analyte are removed by magnetic separation and washing. The sandwich bound ALP initiates an amplification cascade. ALP dephosphorylates synthetic flavin adenine dinucleotide phosphate (FADP) to give FAD. FAD binds to APO D-amino acid oxidase and converts it to active holo D-amino acid oxidase. Each molecule of holo D-amino acid oxidase then produces multiple molecules of hydrogen peroxide (H2O2), which in the presence of horseradish peroxidase (HRP), converts 3,5-dichloro-2-hydroxybenzenesulfonic acid (DCHBS) and 4-aminoantipvrine (4-AAP) to a colored product that absorbs at 510nm. The color measured is directly proportional to the concentration of cardiac troponin-I present in the patient sample.
Here's a breakdown of the acceptance criteria and the study proving the device meets them, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
| Acceptance Criteria | Reported Device Performance |
|---|---|
| Substantial Equivalence to Predicate Device: The primary acceptance criterion for this 510(k) submission is to demonstrate substantial equivalence to the legally marketed predicate device, the Stratus® Cardiac Troponin-I Fluorometric Enzyme Immunoassay. This is based on comparable technology, monoclonal antibodies, detection method, solid support, specimen type, sample size, intended use, and indications for use. | Achieved: The TROP method for the Dimension® RxL system is deemed "substantially equivalent in principle and performance" to the Stratus® Cardiac Troponin-I assay. |
| Correlation Coefficient: A strong positive correlation between results from the new device and the predicate device, indicating consistent measurement across a range of troponin-I concentrations. | Achieved: A correlation coefficient of 0.9918 was reported. This indicates a very strong positive linear relationship between the two assays. |
| Slope (Regression Analysis): A slope close to 1, demonstrating that the measurements from both devices change at a similar rate. | Achieved: A slope of 1.10 was reported. While not exactly 1, it is close, suggesting a generally comparable rate of change, perhaps with a slight proportional difference. |
| Intercept (Regression Analysis): An intercept close to 0, indicating minimal constant bias between the two devices. | Achieved: An intercept of -0.075 ng/mL was reported. This value is close to zero, suggesting a very small negative bias, which is acceptable for demonstrating substantial equivalence. |
| Measurement Range: The device should be able to measure cardiac troponin-I within a clinically relevant range. | Achieved: The study included samples ranging from 0.00 to 47.87 ng/mL, which covers a significant portion of the clinically relevant range for cardiac troponin-I in diagnosing myocardial infarction. |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size: 111 clinical patient samples.
- Data Provenance: The document does not explicitly state the country of origin. It refers to "clinical patient samples," implying they were obtained from a clinical setting, likely in the US given the FDA submission. The study is retrospective in the sense that these were pre-existing patient samples used for comparison.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document does not describe the use of experts to establish a "ground truth" for the test set in the traditional sense of diagnostic imaging or clinical interpretation.
For this type of in vitro diagnostic (IVD) device, the "ground truth" for the comparison study is the measurement result from the predicate device (Stratus® Cardiac Troponin-I assay). The performance of the new device is being compared against the established performance of the predicate. Therefore, the "experts" in this context would be the developers and regulatory approvers of the predicate device, although their specific qualifications are not detailed in this document.
4. Adjudication Method for the Test Set
No adjudication method is described. As mentioned above, the comparison is against the predicate device's results, not an independent assessment by experts requiring adjudication.
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
This is an in vitro diagnostic (IVD) device designed for quantitative measurement of a biomarker in serum/plasma. It is not an imaging or AI-assisted diagnostic device that involves human readers or interpretation of complex medical cases. Therefore, an MRMC study is not applicable and was not performed.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
This refers to the performance of the device itself (the TROP method on the Dimension® RxL system) without human interpretation affecting the measurement of troponin-I. The comparison study is a standalone performance assessment of the new IVD device against an existing one. The results of the new device are directly compared to the results of the predicate device.
7. The Type of Ground Truth Used
For this comparison study, the ground truth is the quantitative measurement of cardiac troponin-I provided by the predicate device (Stratus® Cardiac Troponin-I Fluorometric Enzyme Immunoassay). The objective was to show that the new device produces results that are highly correlated and comparable to the predicate.
8. The Sample Size for the Training Set
The provided summary does not detail a "training set" in the context of machine learning or AI models. This is a traditional IVD device comparison. The method itself was likely developed and calibrated using internal data, but that is not referred to as a "training set" in this document.
9. How the Ground Truth for the Training Set Was Established
Since there is no "training set" described in the context of the 510(k) submission for an AI/ML device, this question is not directly applicable. For the development of an IVD, the initial calibration and development of the assay would typically rely on:
- Reference standards: Materials with known concentrations of cardiac troponin-I.
- Spiked samples: Healthy samples to which known amounts of troponin-I are added.
- Clinical samples: Samples from patients with known clinical diagnoses (e.g., confirmed MI) to evaluate clinical performance and establish reference ranges.
However, the specific details of this initial development and calibration are not part of the 510(k) substantial equivalence comparison provided.
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Image /page/0/Picture/0 description: The image shows the word "DADE" in a bold, sans-serif font. The letters are large and black, contrasting with the white background. The font appears slightly distressed, giving it a textured look.
OCT 2 0 1997
Image /page/0/Picture/2 description: The image shows the text "K973650" at the top. Below that is a black rectangle with the words "DADE INTERNATIONAL" in white letters. The text is in all caps and is centered within the rectangle. The image appears to be a scan or photocopy of a document.
Chemistry Systems 20 Box 6101 1010. 00 3114
Summary of Safety and Effectiveness Information
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.
| Submitter's Name: | Rebecca S. AyashDade International Inc.Building 500, Mailbox 514P.O. Box 6101Newark, DE 19714-6101Phone: (302) 451-0276FAX: (302) 451-0299 |
|---|---|
| Date of Preparation:Device Name: | 9/24/97Cardiac Troponin-I (TROP) Method |
| Classification Name: | Immunoassay Method, Troponin Subunit |
| Predicate Device: | Stratus® Cardiac Troponin-I Fluorometric EnzymeImmunoassay |
Device Description: The TROP method is a one-step enzyme immunoassay. Sample is incubated with chromium dioxide particles (CrOz) coated with a monoclonal antibody specific for cardiac troponin-1 and conjugate reagent [alkaline phosphatase (ALP) labeled monoclonal antibody specific for cardiac troponin-I] to form a particle/cardiac troponin-I/conjugate sandwich. Unbound conjugate and analyte are removed by magnetic separation and washing. The sandwich bound ALP initiates an amplification cascade. ALP dephosphorylates synthetic flavin adenine dinucleotide phosphate (FADP) to give FAD. FAD binds to APO D-amino acid oxidase and converts it to active holo D-amino acid oxidase. Each molecule of holo D-amino acid oxidase then produces multiple molecules of hydrogen peroxide (H2O2), which in the presence of horseradish peroxidase (HRP), converts 3,5-dichloro-2-hydroxybenzenesulfonic acid (DCHBS) and 4-aminoantipvrine (4-AAP) to a colored product that absorbs at 510nm. The color measured is directly proportional to the concentration of cardiac troponin-I present in the patient sample.
Intended Use: The TROP method is used on the Dimension® RxL clinical chemistry system with the heterogeneous immunoassay module to quantitatively
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Intended Use: The TROP method is used on the Dimension® RxL clinical chemistry system with the heterogeneous immunoassay module to quantitatively measure cardiac troponin-1 in human serum and plasma. Measurements of TROP 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.
| Item | Dimension® RxL TROP | Stratus® Cardiac Troponin-I |
|---|---|---|
| Technology | Sandwich formatmonoclonal antibodyimmunoassay | Sandwich formatmonoclonal antibodyimmunoassay |
| Monoclonal Antibodies• Tag• Capture | • 2B1.9• 2F6.6 | • 2B1.9• 2F6.6 |
| Detection | Colorimetric ratemeasurement at 510nmand 700nm | Front surface fluorometrymeasurement at 577nmand 600nm |
| Solid Support | Chrome | Glass fiber paper |
| Specimen type | serum or plasma | serum or plasma |
| Sample Size | 60μL | 100μL |
| Intended Use | For the quantitativedetermination of cardiactroponin-I levels in serumand plasma | For the quantitativedetermination of cardiactroponin-I levels in serumand plasma |
| Indications for Use | To aid in diagnosis ofmyocardial infarction andto aid in the riskstratification of patientswith acute coronarysyndromes with respectto their relative risk ofmortality | To aid in diagnosis ofmyocardial infarction andto aid in the riskstratification of patientswith acute coronarysyndromes with respectto their relative risk ofmortality |
Comparison to Predicate Device:
Comments on Substantial Equivalence: Split sample comparison between the TROP method on the Dimension® RxL clinical chemistry system and the Stratus® cardiac Troponin-I assay gave a correlation coefficient of 0.9918, slope of 1.10 and an intercept of -0.075 ng/mL when tested with 111 clinical patient samples ranging from 0.00 to 47.87 ng/mL.
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Conclusion: The TROP method for the Dimension® RxL system with the heterogeneous immunoassay module is substantially equivalent in principle and performance to the Stratus® Cardiac Troponin-I assay based on the split sample comparison summarized on the previous page.
Rebecca S. Ayash
Rebecca S. Ayash Regulatory Affairs and Compliance Manager Date: 9/24/97
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Image /page/3/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular arrangement of the words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA". Inside the circle is an abstract symbol that resembles an eagle or a stylized human figure. The logo is black and white.
OCT 20 1997
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Rebecca S. Ayash Regulatory Affairs and Compliance Manger Dade International, Inc. Building 500, Mailbox 514 P.O. Box 6101 19714-6101 Newark, Delaware
K973650 Re : Cardiac Troponin-I (TROP) Method Regulatory Class: II Product Code: MMI Dated: September 24, 1997 September 25, 1997 Received:
Dear Ms. Ayash:
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 qeneral 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 requlations 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 OS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Reqister. 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 requlations.
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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 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 advice for your device on our labeling requlation (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 Litman
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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Indications Statement
Device Name: Cardiac Troponin-l (TROP) Method
Indications for Use: The TROP method for the Dimension® RxL with the heterogeneous immunoassay module is a device used to measure cardiac troponin-1 in serum and plasma to 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.
Rebecca S. Ayash
Rebecca S. Ayash Regulatory Affairs and Compliance Manager Date: 9/24/97
(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
73650
510(k) Number
Division Sign Off
Division Sign-Off/ Office of Device Evaluation
\ prescription use
§ 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.