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.

Device Description

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.

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.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the i-STAT cTnI Test, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state formal "acceptance criteria" in a numerical or pass/fail format for clinical performance as might be seen for a new device. Instead, it demonstrates "substantial equivalence" to a predicate device. The performance metrics presented are comparative.

Characteristic	Acceptance Criteria (Implied by Predicate Comparison)	Reported Device Performance (i-STAT cTnI)
Non-Clinical Performance
Hematocrit Insensitivity	Similar to predicate (Dade Behring Stratus CS)	Range of 0-65% PCV
Isoform Detection	Similar relative responses as predicate	Relative responses range from 83% to 122% compared to predicate for various isoforms
Drug Interference	Similar effects as predicate	Similar effects to common medications (especially CV drugs)
Lower Limit of Detection (LLD)	Comparable to predicate (0.03 ng/mL)	0.02 ng/mL
Imprecision (Plasma Controls)	Adequate for low, mid-range, and high results	Level 1: 7.8% CV at 0.53 ng/mL; Level 2: 8.5% CV at 2.17 ng/mL; Level 3: 7.6% CV at 31.82 ng/mL
Clinical Performance (Correlation to Predicate)
i-STAT whole blood vs. Stratus CS plasma
- All samples	Acceptable correlation (e.g., high correlation coefficient, slope near 1, intercept near 0)	N=189; Mean Stratus CS: 4.79; Range: 0-46.27; Slope: 0.883; Intercept: 0.029; Correlation: 0.975; Sy.x: 1.40
- Samples where [cTnI] < 3.0 ng/mL	Acceptable correlation (e.g., high correlation coefficient, slope near 1, intercept near 0)	N=112; Mean Stratus CS: 0.738; Range: 0-2.90; Slope: 0.880; Intercept: -0.036; Correlation: 0.975; Sy.x: 0.15
i-STAT plasma vs. i-STAT whole blood
- All samples	Acceptable correlation (e.g., high correlation coefficient, slope near 1, intercept near 0)	N=188; Mean i-STAT WB: 4.27; Range: 0-37.9; Slope: 0.948; Intercept: 0.052; Correlation: 0.997; Sy.x: 0.55
- Samples where [cTnI] < 3.0 ng/mL	Acceptable correlation (e.g., high correlation coefficient, slope near 1, intercept near 0)	N=118; Mean i-STAT WB: 0.712; Range: 0-2.95; Slope: 1.002; Intercept: -0.010; Correlation: 0.991; Sy.x: 0.097

2. Sample Size Used for the Test Set and Data Provenance

Test Set Sample Size:
- i-STAT whole blood vs. Stratus CS plasma: 189 patient samples (all), 112 samples ([cTnI] < 3.0 ng/mL)
- i-STAT plasma vs. i-STAT whole blood: 188 patient samples (all), 118 samples ([cTnI] < 3.0 ng/mL)
Data Provenance: The studies were conducted at "three external clinical sites." The country of origin is not explicitly stated, but given the manufacturer's location (East Windsor, NJ) and the FDA submission, it is highly likely to be the United States. The data appears to be prospective or collected for the purpose of the study, as it involved "samples from patients who presented to the hospital with acute, severe, and prolonged chest pain" and analyses were performed by both the i-STAT system and the predicate.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts

This type of information is not applicable and therefore not provided in this document. The "ground truth" for this device is established by quantitative measurement and comparison to a legally marketed predicate device (Dade Behring Stratus CS Cardiac Troponin I TestPak), which itself is established as a reliable diagnostic tool. The performance is assessed by comparing quantitative results, not by expert interpretation of images or clinical cases.

4. Adjudication Method for the Test Set

Not applicable. The study compares quantitative measurements of cardiac troponin I from two different laboratory methods, not subjective interpretations 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

Not applicable. This is not an AI-based diagnostic device where human readers interact with AI. It's an in vitro diagnostic test for measuring a biomarker.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Yes, in a way that is relevant to IVD devices. The "standalone" performance for this device is represented by its analytical performance characteristics (like LLD, imprecision, insensitivity to hematocrit, isoform detection, drug interference) and its agreement with the predicate device when testing patient samples without human intervention in the result generation itself. The i-STAT 1 Analyzer performs all analytical steps automatically after sample insertion.

7. The Type of Ground Truth Used

The ground truth is established by the quantitative measurement of cardiac troponin I by a legally marketed predicate device (Dade Behring Stratus CS Cardiac Troponin I TestPak). The study seeks to show substantial equivalence of the i-STAT device's measurements to those of the predicate device. For analytical characteristics, the "ground truth" is based on controlled laboratory experiments (e.g., known hematocrit levels, spiked samples with isoforms or drugs) and established reference methods for LLD and imprecision calculations.

8. The Sample Size for the Training Set

The document does not explicitly mention a "training set" in the context of machine learning or AI models. For an IVD device like this, method development and optimization would typically involve numerous internal R&D experiments rather than a distinct "training set" like in AI. Therefore, this information is not provided and not directly applicable in the AI sense.

9. How the Ground Truth for the Training Set Was Established

As no specific "training set" for an AI model is described, this information is not provided and not applicable in the AI sense. The development of an IVD typically involves extensive analytical testing using reference materials, spiked samples, and clinical samples to optimize reagents, assay parameters, and ensure accurate and precise measurements.

Summary

{0}------------------------------------------------

Image /page/0/Picture/1 description: The image shows the logo for i-STAT Corporation. The logo consists of the text "i-STAT" in a large, bold, sans-serif font. The "i" is lowercase, and there is a hyphen between the "i" and "STAT". Below the main text, in a smaller font, is the word "CORPORATION" in all caps. A thin line is present above the "i-STAT" text.

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: 609-443-9300 FAX: 609-443-9310

Contact:

Gregory W. Shipp, MD Vice-President, Medical Affairs i-STAT Corporation 104 Windsor Center Drive East Windsor, NJ 08520 Phone: 609-443-9300 Fax: 609-443-9310

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:

Description of the Device:

{1}------------------------------------------------

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.

{2}------------------------------------------------

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 vsStratus CS plasma		i-STAT plasma vsi-STAT whole blood
Statistic	Definition	allsamples	sampleswhere[cTnl] < 3.0ng/mL	allsamples	sampleswhere[cTnl] < 3.0ng/mL
N	The number of patientsamples included in the dataset	189	112	188	118
Mean	The average of thecomparative method resultover the sample population	4.79	0.738	4.27	0.712
Range	The range of comparativemethod results obtained overthe sample population	0 - 46.27	0 to 2.90	0 to 37.9	0 to 2.95
Sxx	The pooled estimate of thewithin-sample standarddeviation of the comparativemethod over the samplepopulation	0.28	0.029	0.31	0.048
Syy	The pooled estimate of thewithin-sample standarddeviation of the test methodover the sample population	0.31	0.046	0.36	0.065
Slope	The Deming slope of thecorrelation	0.883	0.880	0.948	1.002
Intercept	The Deming intercept of thecorrelation	0.029	-0.036	0.052	-0.010
Correlation	The correlation coefficientdetermined from regression	0.975	0.975	0.997	0.991
Sy.x	The standard error of theestimate of the regression ofthe regression of y (testmethod) on x (comparativemethod) calculated using theregular 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.

{3}------------------------------------------------

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.

{4}------------------------------------------------

Page 2 -

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,

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

{5}------------------------------------------------

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

✓

prescription

ver - the - counter

Page 1 of 1

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.