This in vitro diagnostic procedure is a solid- phase enzyme immunoassay intended for the quantitative determination of Troponin I in human serum and plasma on the Bayer Immuno 1 system. When used in combination with other clinical data such as presenting symptoms and diagnostic procedures, measurement of Troponin I aids in the diagnosis of acute myocardial infarction.

Device Description

The Baver Immuno 1 Troponin I™ assay is an enzyme label sandwich assay using a monoclonal and a polvclonal antibody. A Troponin I specific monoclonal antibody is labeled with fluorescein and a Troponin I specific goat affinity purified antibody is labeled with alkaline phosphatase (ALP). The solid phase consists of a suspension of magnetizable particles coated with antibody to fluorescein (mIMP reagent). Sample or cailbrator, R1 reagent containing fluorescein - antibody conjugate. R2 reagent containing ALP-antibody conjugate and mIMP reagent are mixed and incubated at 37°C. In the presence of Troponin I a (fluorescein-conjugate: Troponin I:ALPconjugate) complex is formed and captured by the anti fluorescein antibodies on the magnetic particles. The particles are washed and para-nitrophenvl phosphate solution is added. The ALP in the antibody conjugate reacts with the substrate to form para-nitrophenoxide and phosphate. Increasing absorbance due to the formation of para-nitrophenoxide is monitored at 405 nm and 450 nm. The dose response curve is directly proportional to the concentration of Troponin I in the sample. A linear point fit is used to construct the dose response curve. The Baver Immuno 1 Troponin ITM assay has a range of 0 to 200 ng/ml and liquid calibrators are provided with values of 0, 5, 10, 20, 60 and 200 ng/ml Troponin I. Bayer Immuno 1 Troponin I TEST point controls are provided with values of 3, 7, 50 ng/mL Troponin I.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the Bayer Immuno 1™ System Troponin I method, based on the provided text:

Acceptance Criteria and Device Performance

The submission relies on demonstrating substantial equivalence to a predicate device, the Dade Stratus® Troponin I kit. Therefore, the "acceptance criteria" are implicitly defined by the performance characteristics of the predicate device and the new device's ability to demonstrate comparable performance. The key performance indicators evaluated are imprecision (precision), linearity (recovery), correlation with the predicate device, and minimum detectable concentration (detection limit).

Performance Characteristic	Acceptance Criteria (Implicitly based on predicate/industry standards)	Reported Device Performance (Bayer Immuno 1™ Troponin I Method)
Imprecision (Total)	Not explicitly stated as a numerical criterion, but expected to be within acceptable limits for a quantitative assay.	Ranges from 4.3% (at 2.9 ng/mL Troponin I) to 2.1% (at 47.8 ng/mL Troponin I).
Linearity (Recovery)	Not explicitly stated as a numerical criterion, but expected to demonstrate accurate recovery across a range of concentrations.	Recoveries range from 88% to 110% when diluting human AMI patient pools with troponin I-free normal human serum. Recoveries average 97.9% (range 85% to 116%) with Immuno 1 Sample diluent B.
Correlation	Strong correlation (e.g., r > 0.95) with the predicate device.	r = 0.98 with the Dade Stratus® Troponin I method.
Minimum Detectable Concentration	Expected to be sufficiently low for clinical utility.	0.1 ng/mL.
Cross Reactivity	Minimal or undetectable cross-reactivity with related substances.	Minimal or undetectable with human cardiac Troponin T, human cardiac Troponin C, human skeletal Troponin I, human skeletal Troponin T, bovine actin, and bovine tropomyosin.
Expected Values (Normal Population)	Results in healthy individuals should be below the detection limit.	197 healthy Red Cross blood donors all showed results below 0.1 ng/mL.
Expected Values (Angina Patients)	Majority of angina patients should have results below detection limit or slightly elevated.	60 out of 64 angina patients had results below 0.1 ng/mL; 4 had results between 0.2 and 0.6 ng/mL.
Expected Values (AMI Patients)	AMI patients should show elevated Troponin I levels.	41 hospitalized AMI patients all had results greater than or equal to 0.9 ng/mL.

Study Details

Sample sizes used for the test set and the data provenance:
- Imprecision: Human serum samples were analyzed. The number of samples is not explicitly stated, but the analysis involved duplicate measurements on two instruments over 18 days. This suggests a total of 18 days * X samples/day (where X is at least 1) * 2 duplicates * 2 instruments = at least 72 measurements (if only one sample type was used per run).
- Linearity: Human AMI patient pools. The number of pools or individual samples is not specified.
- Correlation: 279 patient samples.
- Expected Values:
  - Healthy Red Cross blood donors: 197 specimens.
  - Angina patients: 64 specimens.
  - AMI patients: 41 specimens.
- Data Provenance: Not explicitly stated, but likely retrospective as it involves analyzing "patient samples" and "specimens." The mention of "clinical trial sites" for the correlation study suggests multi-site data collection, but specific countries are not mentioned.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- For expected values in different patient populations (healthy, angina, AMI), the "clinical diagnosis of angina" and "clinical diagnosis of AMI" serve as the ground truth. The number and qualifications of clinicians making these diagnoses are not specified.
- For the correlation study, the "Dade Stratus® Troponin I method" is used as a reference for the Troponin I values in the patient samples, rather than an expert panel.
Adjudication method for the test set:
- No adjudication method (e.g., 2+1, 3+1) is mentioned, as the study primarily relies on quantitative measurements and comparison to a predicate device or predefined clinical diagnoses.
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:
- No MRMC study was done. This submission is for an in-vitro diagnostic (IVD) assay which provides a quantitative measurement, not an AI-assisted diagnostic imaging or interpretation device that would involve human "readers."
If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- This is an in-vitro diagnostic assay, which by nature operates as a standalone system to measure analyte concentration. The performance characteristics described are "algorithm only" in the sense that they represent the performance of the assay itself in generating a quantitative result. There is no human "in-the-loop" once the sample is processed by the Immuno 1 system.
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- For correlation: The predicate device's measurements (Dade Stratus® Troponin I method) served as the comparative "ground truth" for the new device's measurements.
- For expected values: Clinical diagnoses (e.g., "clinical diagnosis of angina," "clinical diagnosis of AMI") were used to categorize patients for expected value determination.
- For linearity and imprecision: Ground truth is established by the known concentrations in engineered samples (calibrators, controls, diluted pools) or by statistical analysis of repeat measurements.
The sample size for the training set:
- This submission describes performance characteristics and validation studies. No specific "training set" for an algorithm is mentioned, as the device is a chemical immunoassay, not a machine learning model.
How the ground truth for the training set was established:
- As there is no distinct "training set" for an algorithm in this context, this question is not applicable. The assay itself involved development and optimization, but standard laboratory practices and known concentrations in controls and calibrators would have guided this, rather than a formal "ground truth for a training set" as understood in AI/ML contexts.

Summary

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K973616

DEC - 5 1997

510K SUMMARY OF SAFETY AND EFFECTIVENESS

BAYER IMMUNO 1™ SYSTEM TROPONIN I METHOD, SETPOINT CALIBRATORS AND TESTPOINT CONTROLS FOR THE IMMUNO 1 SYSTEM. Bayer Corporation, 511Benedict Avenue, Tarrytown, New York 10591

Listed below is a comparison of the performance between the Immuno 1 Troponin I method ( T01-3887-51) and a similar device that was granted FDA determination of substantial equivalence: the Dade Stratus® Troponin I kit. The information used in this summary of Safety and Effectiveness was extracted from the Troponin I Method Sheet and from data on file at Bayer Corp.

INTENDED USE

ASSAY DESCRIPTION

The Dade Stratus® Troponin I assay utilizes the binding of two Troponin I monoclonal antibodies in a two site "sandwich" immunoassay. Both the Dade Stratus® and Bayer Immuno 17M Troponin Tassays utilize an alkaline phospatase enzyme conjugated antibody. The Bayer Immuno 17M Troponin I assay uses a para-nitrophen; I phosphate substrate and measures

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increasing absorbance due to the formation of para-nitrophenoxide at 405 nm and 450 nm, while the Dade Stratus® Troponin I assay uses 4-Methylumberlliferyl Phosphate as the substrate and measures front surface fluorescence. The Bayer Immuno 11M Troponin I test uses liquid calibrators prepared with a buffered bovine serum albumin and cardiac Troponin I at specific levels while the Dade Stratus® Troponin I uses frozen liquid calibrators prepared from buffered bovine matrix and human cardiac troponin I at specified levels.

PERFORMANCE CHARACTERISTICS

Total imprecision of Bayer Immuno 1™ Troponin I method ranges from 4.3% with a low human control having a mean troponin I value of 2.9 ng/mL to 2.1% for a high control having a mean troponin I value of 47.8 ng/mL. These estimates of imprecision were made by analyzing human serum samples in duplicate on two Immuno 1 instruments on each of 18 days. The results are calculated from a calibration curve generated on each instrument on the first day.

Linearity recoveries range from 88% to 110% determined by diluting human AMI patient pools with troponin I free normal human serum. Recoveries determined by diluting AMI patient pools with Immuno 1 Sample diluent B range from 85% to 116% with an average recovery of 97.9%. A Correlation study at two clinical trial sites between the Bayer Immuno 1™ Troponin I method and the Dade Stratus® Troponin I method using a total of 279 patient samples yielded regression statistics of r = 0.98, Immuno 1 = 0.96 x Stratus - 0.2. Troponin I in the 279 patient samples ranged from 0 to 77.1 ng/mL.

Minimum Detectable Concentration of the Bayer Immuno 17M Troponin I method is 0.1 ng/mL. This is a multisystem estimate of two (2) times the with-in run standard deviation of the zero calibrator.

Cross Reactivity to human cardiac Troponin T, human cardiac Troponin C, human skeletal Troponin I, human skeletal Troponin T, bovine actin and bovine tropomyosin is minimal or undetectable.

EXPECTED VALUES

Specimens from 197 healthy Red Cross blood donors were all found to give results below the minimum detectable concentration of 0.1 ng/mL. Specimens from 64 patients hospitalized with a clinical diagnosis of angina gave results less than the minimum detectable concentration for 60 patients and in the range 0.2 to 0.6 ng/mL for the other 4. Specimens from 41 hospitalized patients with a clinical diagnosis of AMI had results greater than or equal to 0.9 ng/mL.

The Bayer Immuno 17ª Troponin I method is substantially equivalent to the Dade Stratus® Troponin I method currently approved for clinical use in the United States.

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Image /page/2/Picture/2 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle or bird-like figure with three curved lines forming its body and wings. The logo is surrounded by the text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" in a circular arrangement.

DEC - 5 1997

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Gabriel Muraca, Jr. . Manager Regulatory Affairs Bayer Corporation 511 Benedict Avenue Tarrytown,, New York 10591-5097

Re: K973616 Troponin I Assay for Immuno 1™ System Requlatory Class: II Product Code: MMI November 18, 1997 Dated: November 19, 1997 Received:

Dear Mr. Muraca:

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 Requlations, Title 21, Parts 800 to 895. ਮੁ 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 requlation 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 requlations.

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Page 2

Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity (shirtor) in 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 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 Litman

Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radioloqical Health

Enclosure

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Page 1 of 1

510(k) Number (if known): K973616

Device Name: Bayer Immuno 1TM System Troponin I (TnI)

Indications For Use:

This in vitro diagnostic method is intended to quantitatively measure the
reasure the manage in TV (D.) indexemen servim and plasma (II) This in vitro diagnostic method is intention is numan serum and plasma (lithium
concentration of cardiac Troponin 17% and we alling wed in conjunction with concentration of cardiac Tropolitir (111) in nation in conjunction with
heparin) using the Bayer Immuno 11M system. When used in conjunction with heparin) using the Bayer Inimalio I - System - and diagnostic procedures,
other clinical data such as presenting symptoms and diagnosis of acute myocardia other clinical data such as presenting symptoms and any
measurement of cardiac Troponin I aids in the diagnosis of acute myocardial infarction (AMI).

This diagnostic method is not intended for use on any other system.

(Division Sign-Off)
Division of Clir Laboratory zvices
510(k) Number. K973616

(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_

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.