I-STAT CARDIAC TROPONIN (CTNI) TEST

K031739 · I-Stat Corporation · MMI · Sep 2, 2003 · Clinical Chemistry

Device Facts

• Record ID: K031739
• Device Name: I-STAT CARDIAC TROPONIN (CTNI) TEST
• Applicant: I-Stat Corporation
• Product Code: MMI · Clinical Chemistry
• Decision Date: Sep 2, 2003
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1215
• Device Class: Class 2

Intended Use

The i-STAT® cTnI Test is an in vitro diagnostic test for the quantitative measurement of cardiac troponin I in heparinized whole blood or plasma samples. Cardiac troponin I measurements can be used as an aid in the diagnosis and treatment of myocardial infarction and in the risk stratification of patients with acute coronary syndromes with respect to their relative risk of mortality. The cartridge is to be used with the i-STAT 1 Analyzer, but not the i-STAT Portable Clinical Analyzer or the Philips Medical Systems (formerly Agilent Technologies) Blood Analysis Module (BAM). As part of the i-STAT System, the cTnI test is to be used by trained health care professionals in accordance with a facility’s policies and procedures.

Device Story

i-STAT cTnI is a single-use cartridge-based diagnostic test for point-of-care use. User applies ~16 microliters of fresh whole blood to cartridge; inserts into thermally controlled i-STAT 1 Analyzer. Device performs automated two-site ELISA: sample incubated with enzyme-linked antibody conjugate; analyte captured by monoclonal anti-cTnI antibody; sandwich complex treated with substrate; alkaline phosphatase cleavage produces amperometric signal. Analyzer measures signal; displays/stores results; transmits via infrared to printer or database. Used by trained healthcare professionals in clinical settings. Provides rapid quantitative cTnI levels to assist clinicians in diagnosing myocardial infarction and assessing mortality risk in acute coronary syndrome patients.

Clinical Evidence

Clinical performance was evaluated at three external sites comparing i-STAT cTnl (whole blood/plasma) to the Stratus CS (plasma) in patients with acute, severe, and prolonged chest pain (N=189). Deming regression analysis showed a correlation coefficient of 0.975 for i-STAT whole blood vs. Stratus CS plasma. Bench testing confirmed the lower limit of detection (0.02 ng/mL), insensitivity to hematocrit (0-65% PCV), and consistent detection of various cTnl isoforms (83-122% relative response). Imprecision studies (Level 1-3 controls) showed CVs ranging from 7.6% to 8.5%.

Technological Characteristics

Two-site ELISA; electrochemical detection. Cartridge contains plastic conduits, sensor chips, heating elements. Analyte captured by monoclonal anti-cTnI antibody; detection via alkaline phosphatase-labeled polyclonal antibody. Amperometric signal measurement. Connectivity: infrared data transfer. Conforms to EN61326 EMC. Requires i-STAT 1 Analyzer.

Indications for Use

Indicated for quantitative measurement of cardiac troponin I in heparinized whole blood or plasma to aid in diagnosis and treatment of myocardial infarction and risk stratification of patients with acute coronary syndromes.

Regulatory Classification

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.

Predicate Devices

• Dade Behring Stratus® CS Cardiac Troponin I TestPak (K981098)

Submission Summary (Full Text)

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K031739

# 510(k) Summary

This summary of the 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1900 and CFR 807.92.

The assigned 510(k) number is:

Summary prepared on: June 3, 2003

#### Submitted by:

i-STAT Corporation 104 Windsor Center Drive E. Windsor, NJ 08520 Phone: [phone] FAX: [phone]

#### Contact:

Gregory W. Shipp, MD Vice-President, Medical Affairs i-STAT Corporation 104 Windsor Center Drive East Windsor, NJ 08520 Phone: [phone] Fax: [phone]

#### Establishment Registration Number: 2245578

#### Identification of Device:

Device Name: Cardiac Troponin 1 (cTnl) Test Proprietary/Trade Name: i-STAT® cTnl Test Common Name: cardiac troponin I, cTnl Device Classification: II Regulation Number: CFR§ 862.1215 Panel: Immunoassay Method, Troponin Subunit Product Code: MMI

## Identification of the Predicate Device:

Device Name: Dade Behring Stratus CS Cardiac Troponin I TestPak

## Intended Use of the Device:

The i-STAT cTnl test is an in vitro diagnostic test for the quantitative measurement of cardiac troponin I in heparinized whole blood or plasma samples. Cardiac troponin I measurements can be used as an aid in the diagnosis and treatment of myocardial infarction and in the risk stratification of patients with acute coronary syndromes with respect to their relative risk of mortality.

The cartridge is to be used with the i-STAT 1 Analyzer, but not with the i-STAT Portable Clinical Analyzer or the Philips Medical Systems (formerly Agilent Technologies) Blood Analysis Module (BAM). As part of the i-STAT System, the cTnl test is to be used by trained health care professionals in accordance with a facility's policies and procedures.

## Description of the Device:

The i-STAT cTnl test is contained in a single test cartridge. In use, the user scans a barcode and then places approximately 16 microliters of fresh whole blood in the cartridge is inserted into the thermally controlled i-STAT 1 Analyzer, and all analytical steps are performed automatically. Patient and user information may be entered into the analyzer via a keypad during the automated analysis cycle.

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As the analyzer performs several quality checks and controls the temperature of the sensors via resistive heating to the underside of the sensor chips, the substrate/wash fluid is released into a conduit within the cartridge and a metered volume of the sample over the sensor chips. The enzyme-linked antibody conjugate dissolves into the sample and the sample incubates for a controlled time. The sample is then pushed into a waste chamber and the substrate/wash solution is brought over the sensors. The alkaline phosphatase captured on the cTnl sensor cleaves the substrate present in the substrate/wash fluid, giving rise to an amperometric signal which is measured.

The cTnl test cartridge is assembled from plastic components that provide the conduits for fluid handling and house the sensor chips. The test is identified to the user through the name and color code on the cartridge label and by the analyzer through features integral to the cartridge.

# Comparison to Technological Features of the Predicate Device:

The following is a comparison of technological features of the i-STAT and Stratus CS Cardiac Troponin I methods:

| Characteristic | Stratus CS | i-STAT System |
|-----------------------|--------------------------|----------------------------|
| Assay methodology | Two site ELISA | Two site ELISA |
| Capture site | Heterogeneous | Heterogeneous |
| Capture antibodies | Monoclonal | Monoclonal |
| Enzyme label antibody | Monoclonal | Polyclonal |
| Enzyme label | Alkaline phosphatase | Alkaline phosphatase |
| Analysis sequence | Sequential capture/label | Simultaneous capture/label |
| Analysis time | 14 minutes | 10 minutes |
| Sample type | Plasma | Whole blood or plasma |
| Enzyme detection | Fluorescent | Electrochemical |

## Summary of Non-Clinical Performance in Support of Substantial Equivalence:

- Studies established that the i-STAT cTnl test is insensitive to hematocrit levels from 0 to 65 . %PCV.
- . Studies established that isoforms of cTnl were detected to similar extents by the i-STAT and Stratus CS methods. When free cTnl. IC complex, ITC complex, dephosphorated, and phosphorated isoforms were tested, the relative responses for the two methods ranged from 83% to 122%.
- . Studies established that the interference effects from common medications, particularly those commonly prescribed to patients with cardiovascular conditions, were similar to the effects for those drugs on the Stratus CS cardiac troponin I test.
- . Studies established that the lower limit of detection (LLD) for the i-STAT method is a comparable 0.02 ng/mL versus 0.03ng/mL for the Stratus CS method.
- . The imprecision of the i-STAT cTnl test using plasma controls was established using inhouse and user studies. The Level 1 Control %CV was 7.8% at 0.53 ng/mL. the Level 2 Control %CV was 8.5% at 2.17 ng/mL, and the Level 3 Control %CV was 7.6% at 31.82 ng/mL. This includes within-lot, lot-to-lot, vial-to-vial, analyzer-to-analyzer, and operator-tooperator components of the imprecision.

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Summary of Clinical Test Performance is Support of Substantial Equivalence Claims: Studies conducted at three external clinical sites compared the results of the i-STAT cTnl test to those of the Dade Behring Stratus CS STAT Fluorometric Analyzer using the Stratus CS Cardiac Troponin I TestPak for samples from patients who presented to the hospital with acute, severe, and prolonged chest pain. Heparinized whole blood and plasma samples were analyzed on the i-STAT System while plasma samples were analyzed on the Stratus CS. The methods were compared using Deming regression analysis. The results are summarized in the table below:

| | | i-STAT whole blood vs<br>Stratus CS plasma | | i-STAT plasma vs<br>i-STAT whole blood | |
|-------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------|-------------------------------------------|----------------------------------------|-------------------------------------------|
| Statistic | Definition | all<br>samples | samples<br>where<br>[cTnl] < 3.0<br>ng/mL | all<br>samples | samples<br>where<br>[cTnl] < 3.0<br>ng/mL |
| N | The number of patient<br>samples included in the data<br>set | 189 | 112 | 188 | 118 |
| Mean | The average of the<br>comparative method result<br>over the sample population | 4.79 | 0.738 | 4.27 | 0.712 |
| Range | The range of comparative<br>method results obtained over<br>the sample population | 0 - 46.27 | 0 to 2.90 | 0 to 37.9 | 0 to 2.95 |
| Sxx | The pooled estimate of the<br>within-sample standard<br>deviation of the comparative<br>method over the sample<br>population | 0.28 | 0.029 | 0.31 | 0.048 |
| Syy | The pooled estimate of the<br>within-sample standard<br>deviation of the test method<br>over the sample population | 0.31 | 0.046 | 0.36 | 0.065 |
| Slope | The Deming slope of the<br>correlation | 0.883 | 0.880 | 0.948 | 1.002 |
| Intercept | The Deming intercept of the<br>correlation | 0.029 | -0.036 | 0.052 | -0.010 |
| Correlation | The correlation coefficient<br>determined from regression | 0.975 | 0.975 | 0.997 | 0.991 |
| Sy.x | The standard error of the<br>estimate of the regression of<br>the regression of y (test<br>method) on x (comparative<br>method) calculated using the<br>regular regression slope | 1.40 | 0.15 | 0.55 | 0.097 |

## Conclusions:

Based on clinical and non-clinical data the i-STAT cardiac troponin I test is insensitive to hematocrit level from 0 - 65 %PCV, detects isoforms of cTnl in a similar manner as the Stratus CS cardiac troponin I test, shows similar interference effects to common drugs as the Stratus CS cardiac troponin I test, and has a lower limit of detection (LLD) of 0.02 ng/mL. Studies using plasma controls indicate adequate imprecision for low, mid-range, and high results. Clinical data indicates acceptable correlation to the predicate device.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

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 seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" arranged around the perimeter. Inside the circle is a stylized symbol resembling three overlapping human figures or waves, rendered in black against a white background.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

SEP - 2 2003

Gregory Shipp, M.D. Vice President, Medical Affairs i-STAT Corporation 104 Windsor Center Drive East Windsor, New Jersey 08520

Re: k031739

> Trade/Device Name: i-STAT® cTnI Test Regulation Number: 21 CFR § 862.1215 Regulation Name: Immunoassay Method, Troponin Subunit Regulatory Class: II Product Code: MMI Dated: June 3, 2003 Received: June 4, 2003

Dear Dr. Shipp:

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 (OS) regulation (21 CFR Part 820). 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.

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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 [phone]. 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 [phone] or [phone] or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.

Sincerely yours,

steven Sutman

Steven I. Gutman, M.D., M.B.A. Director Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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#### Indications for use 3

510(k) Number (if known): K03 1739

Device Name: i-STAT Cardiac Troponin I test

The i-STAT Cardiac Troponin I (cTnl) test is an in vitro diagnostic test for the quantitative measurement of cardiac troponin I in heparinized whole blood or plasma. Measurements of cardiac troponin I are used in the diagnosis and treatment of myocardial infarction and as an aid in the risk stratification of patients with acute coronary syndromes with respect to their relative risk of mortality.

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

Concurrence of CDRH, Office of Device Evaluation (ODE) (Per 21 CFR 801.109)

Sean Cooper
Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K031739

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