Predicate Devices

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The description focuses on the electrochemical detection method and microprocessor control, with no mention of AI or ML algorithms for data processing or interpretation.

Therapeutic

No

Explanation: This device is an in vitro diagnostic test designed to quantify cardiac troponin I (cTnI) to aid in the diagnosis of myocardial infarction (MI). It provides diagnostic information but does not directly treat or prevent a disease, nor does it restore, modify, or correct body function or structure.

Diagnostic

Yes

The "Intended Use / Indications for Use" section explicitly states that the device "is intended to be used as an aid in the diagnosis of myocardial infarction (MI)," which directly defines it as a diagnostic device.

SaMD (Software as a Medical Device)

No

The device is an in vitro diagnostic test that utilizes a physical cartridge containing reagents and a biosensor chip, which interacts with a hardware analyzer (i-STAT 1 System) to perform the test and process signals. This involves significant hardware components and chemical processes, not just software.

IVD (In Vitro Diagnostic)

Based on the provided information, the device is an IVD (In Vitro Diagnostic).

Here's why:

Intended Use/Indications for Use: Explicitly states "in the in vitro quantification of cardiac troponin I (cTnl) in whole blood or plasma samples" and "intended to be used as an aid in the diagnosis of myocardial infarction (MI)." This clearly indicates testing biological samples outside the body for diagnostic purposes.
Device Description: Describes the device as an "in vitro diagnostic test" and details the process of analyzing whole blood or plasma samples using an immunoassay method.
Assay quality control materials: The availability of control materials for use with the cartridge further supports its nature as a diagnostic test.

The information provided aligns perfectly with the definition of an In Vitro Diagnostic device.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

The i-STAT hs-Tnl cartridge with the i-STAT 1 System is in the in vitro quantification of cardiac troponin I (cTnl) in whole blood or plasma samples in point of care or clinical laboratory settings.

The i-STAT hs-Tnl cartridge with the i-STAT 1 System is intended to be used as an aid in the diagnosis of myocardial infarction (MI).

Product codes (comma separated list FDA assigned to the subject device)

MMI, JJE

Device Description

The i-STAT hs-TnI cartridge is an in vitro diagnostic test for the quantitative measurement of cardiac troponin I (cTnI) in whole blood or plasma samples using the i-STAT 1 analyzer in point of care or clinical laboratory settings.

The i-STAT hs-TnI test uses an enzyme-linked immunosorbent assay (ELISA) method with electrochemical detection of the resulting enzyme signal. The test reports a quantitative measurement of the sample concentration of cTnI in units of ng/L in approximately 15 minutes.

The i-STAT hs-TnI immunoassay test method uses anti-cTnI antibodies for labeling and capture. The capture antibodies are coated on para-magnetic microparticles. Both label and capture antibodies are contained within the cartridge on a biosensor chip. The ELISA is initiated when the test cartridge is inserted into the analyzer. The sample is positioned over the biosensor chip to dissolve the reagents. This forms the ELISA sandwich (detection antibodylabel/antigen/capture antibody). The sample and excess antibody-conjugate are then washed off the sensors. An enzyme within the ELISA sandwich generates an electrochemically detectable product. The biosensor chip measures the enzyme product which is proportional to the concentration of cTnI within the sample.

The i-STAT hs-TnI cartridge is a single use test cartridge. The cartridge contains a biosensor chip and all reagents required to execute the test cycle. All fluid movements within the cartridge (test sample or reagent) are automatically controlled by the i-STAT 1 analyzer by electromechanical interaction with the cartridge. The analyzer executes the test cycle, acquires and processes the electrical sensor signals converting the signals into quantitative results. These functions are controlled by a microprocessor.

The i-STAT 1 System is comprised of the i-STAT 1 analyzer and accessories (i-STAT 1 Downloader/Recharger, i-STAT Electronic Simulator, i-STAT Printer and i-STAT 1 9V NiMH Rechargeable Battery).

Assay quality control materials are also available for use with the i-STAT hs-TnI cartridge and include i-STAT hs-TnI Control Level 1. i-STAT hs-TnI Control Level 2. i-STAT hs-TnI Control Level 3, and the i-STAT hs-TnI Calibration Verification Levels 1-3.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Not Found

Indicated Patient Age Range

Not Found

Intended User / Care Setting

point of care or clinical laboratory settings.

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

Not Found

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

A. Analytical Performance
a. Precision/Reproducibility:

i. 20-Day Precision: Evaluated using a panel of six (6) frozen plasma samples across the reportable range. Conducted using three (3) lots of cartridges and multiple analyzers at one (1) site over 20 non-consecutive days with two (2) runs per day by two (2) operators for each cartridge lot. Performance was acceptable, within acceptance criteria for all levels. (Sample sizes 239-240).
ii. Whole Blood and Plasma Precision: Evaluated in point of care settings at three (3) clinical sites using native venous whole blood and plasma specimens prospectively collected in lithium heparin anticoagulant tubes assigned to six (6) cardiac troponin I levels. At each site, a minimum of one (1) whole blood and one (1) plasma specimen per level was tested by one (1) operator using eight (8) cartridges on eight (8) analyzers across three (3) runs (1 replicate/analyzer/run) for a total of 24 replicates per specimen. Precision estimates for both whole blood and plasma were acceptable.
iii. Precision in Control Materials: Evaluated using i-STAT hs-TnI control and calibration verification materials at a single site. Five (5) unique levels of frozen materials were tested in five (5) replicates over five (5) consecutive days (Total 25 replicates per level).
iv. Multi-site Multi-Day Precision: Evaluated using a panel of six (6) frozen plasma samples tested at three (3) clinical sites. Each of the six (6) test materials was tested once per day for five (5) days by two (2) different operators, with each operator using three (3) cartridges on three (3) analyzers. (N=90 per level).

b. Linearity/assay reportable range:

i. Linearity: Established by testing venous whole blood and plasma samples of varying cTnI levels. Whole blood and plasma samples were prepared by combining unaltered/spiked samples in specific ratios to span the reportable range. Regression summary showed R2 of 0.9990 for whole blood and 0.9993 for plasma. Demonstrated linearity over the reportable range (2.9 – 1000.0 ng/L).
ii. Sample Type Comparison: Compared fresh lithium heparin whole blood (WB) and plasma samples. Passing-Bablok regression showed a slope of 1.01 and r of 0.99 for WB vs. Plasma.
iii. High Dose Hook Effect: Evaluated with whole blood and plasma samples spiked up to 500,000 ng/L. No hook effect was observed.

c. Traceability, Calibration and Reference Interval

i. Traceability and Calibration: cTnI values are traceable to i-STAT's working calibrator prepared from human cardiac troponin-ITC complex (NIST SRM2921).
ii. Reference Interval / Reference Range: Reference range study conducted with 895 apparently healthy subjects (18-87 years) from eight (8) clinical sites in the US using venous whole blood specimens. Determined 99th percentile URL for female (13 ng/L), male (28 ng/L), and overall (21 ng/L) populations.

d. Detection Limit

i. Limit of Blank and Detection (LoB/LoD): Evaluated using four (4) cartridge lots for LoB and three (3) for LoD, with altered healthy donor samples. LoB: Whole Blood = 0.78 ng/L, Plasma = 0.57 ng/L. LoD: Whole Blood = 1.61 ng/L, Plasma = 1.05 ng/L.
ii. Limit of Quantitation (LoQ): Evaluated using four (4) cartridge lots and low-level cTnI whole blood and plasma samples. LoQ in whole blood = 2.90 ng/L (20 %CV). Lower limit of reportable range set to 2.9 ng/L.

e. Analytical Specificity

i. Interference: Evaluated performance in presence of potentially interfering endogenous and exogenous substances at two cTnI levels (20 ng/L and 600 ng/L). Bilirubin (Unconjugated), Cefoxitin, Fibrinogen, Rheumatoid Factor (RF), and Total Protein were identified as interferents at certain concentrations.
ii. Cross-reactivity: Evaluated nine (9) potentially cross-reactive endogenous substances at three cTnI concentrations (10%) observed above 57% PCV, and increased bias (>±10%) above 55% PCV.
- 2) Altitude: Evaluated performance at simulated altitudes of 7,500 and 10,000 feet above sea level. Demonstrated equivalent performance to sea level with strong correlation coefficients (r=1.00).

B. Comparison Studies

a. Matrix Equivalence - Non-Anticoagulated Whole Blood: Compared performance of non-anticoagulated whole blood (candidate) to lithium heparinized whole blood (primary). 88 paired specimens (including 8 contrived). Passing-Bablok regression showed slope of 1.04 and r of 1.00, demonstrating equivalence.
b. Matrix Equivalence - Lithium Heparin Tube with Separator Gel (Whole Blood and Plasma): Compared whole blood and plasma collected with separator gel (candidate) to lithium heparin tubes (primary). 87 paired specimens each for whole blood and plasma (including 8 contrived). Passing-Bablok regression showed slope of 1.01 and r of 1.00 for both, demonstrating equivalence.

C. Clinical Sensitivity and Specificity

Pivotal study: Prospective study at 28 clinical sites with 3585 subjects presenting to ED with chest discomfort/ischemic symptoms for MI diagnosis. Adjudicated by cardiologists/emergency medicine physicians blinded to i-STAT hs-TnI results. MI prevalence was 6.8% for females and 11.6% for males.
Clinical Performance: Analyzed using overall (21 ng/L) and sex-specific (female 13 ng/L, male 28 ng/L) 99th percentile URLs for clinical sensitivity, specificity, PPV, and NPV.
- Overall 99th percentile URL (21 ng/L):
  - Female: Sensitivity 86.05% (0-1 hr) to 95.71% (>3-6 hr), Specificity 89.37% (0-1 hr) to 65.91% (>6 hr), NPV 98.86% (0-1 hr) to 96.67% (>6 hr).
  - Male: Sensitivity 83.08% (0-1 hr) to 95.65% (>3-6 hr), Specificity 78.33% (0-1 hr) to 54.29% (>6 hr), NPV 97.16% (0-1 hr) to 95.00% (>6 hr).
- Sex-specific 99th percentile URL (female 13 ng/L, male 28 ng/L):
  - Female: Sensitivity 91.47% (0-1 hr) to 100.00% (>6 hr), Specificity 83.23% (0-1 hr) to 54.55% (>6 hr), NPV 99.25% (0-1 hr) to 100.00% (>6 hr).
  - Male: Sensitivity 79.23% (0-1 hr) to 94.20% (>3-6 hr), Specificity 84.17% (0-1 hr) to 57.14% (>6 hr), NPV 96.77% (0-1 hr) to 95.24% (>6 hr).

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Clinical Performance for i-STAT 1 System in whole blood using overall 99th percentile URL (21 ng/L)

Female, 0 to 1 hour: Sensitivity 86.05%, Specificity 89.37%, PPV 37.50%, NPV 98.86%
Female, >1 to 3 hours: Sensitivity 92.44%, Specificity 89.70%, PPV 38.87%, NPV 99.41%
Female, >3 to 6 hours: Sensitivity 95.71%, Specificity 85.78%, PPV 41.88%, NPV 99.47%
Female, >6 hours: Sensitivity 93.75%, Specificity 65.91%, PPV 50.00%, NPV 96.67%
Male, 0 to 1 hour: Sensitivity 83.08%, Specificity 78.33%, PPV 34.18%, NPV 97.16%
Male, >1 to 3 hours: Sensitivity 92.37%, Specificity 77.95%, PPV 35.28%, NPV 98.74%
Male, >3 to 6 hours: Sensitivity 95.65%, Specificity 74.32%, PPV 40.99%, NPV 98.92%
Male, >6 hours: Sensitivity 91.67%, Specificity 54.29%, PPV 40.74%, NPV 95.00%

Clinical Performance for i-STAT 1 System in whole blood using sex-specific 99th percentile URL (female 13 ng/L, male 28 ng/L)

Female, 0 to 1 hour: Sensitivity 91.47%, Specificity 83.23%, PPV 28.78%, NPV 99.25%
Female, >1 to 3 hours: Sensitivity 96.64%, Specificity 82.14%, PPV 27.71%, NPV 99.71%
Female, >3 to 6 hours: Sensitivity 97.14%, Specificity 77.83%, PPV 31.92%, NPV 99.61%
Female, >6 hours: Sensitivity 100.00%, Specificity 54.55%, PPV 44.44%, NPV 100.00%
Male, 0 to 1 hour: Sensitivity 79.23%, Specificity 84.17%, PPV 40.39%, NPV 96.77%
Male, >1 to 3 hours: Sensitivity 90.68%, Specificity 83.90%, PPV 42.29%, NPV 98.58%
Male, >3 to 6 hours: Sensitivity 94.20%, Specificity 82.97%, PPV 50.78%, NPV 98.71%
Male, >6 hours: Sensitivity 91.67%, Specificity 57.14%, PPV 42.31%, NPV 95.24%

Clinical Performance for i-STAT hs-Tnl cartridge with i-STAT 1 System in plasma using overall 99th percentile URL (21 ng/L)

Female, 0 to 1 hour: Sensitivity 86.72%, Specificity 89.23%, PPV 37.25%, NPV 98.92%
Female, >1 to 3 hours: Sensitivity 92.37%, Specificity 89.65%, PPV 38.52%, NPV 99.41%
Female, >3 to 6 hours: Sensitivity 94.29%, Specificity 85.76%, PPV 41.51%, NPV 99.29%
Female, >6 hours: Sensitivity 93.75%, Specificity 68.18%, PPV 51.72%, NPV 96.77%
Male, 0 to 1 hour: Sensitivity 83.08%, Specificity 78.17%, PPV 33.96%, NPV 97.16%
Male, >1 to 3 hours: Sensitivity 92.31%, Specificity 77.10%, PPV 34.29%, NPV 98.73%
Male, >3 to 6 hours: Sensitivity 95.65%, Specificity 73.24%, PPV 40.00%, NPV 98.91%
Male, >6 hours: Sensitivity 91.67%, Specificity 54.29%, PPV 40.74%, NPV 95.00%

Clinical Performance for i-STAT 1 System in plasma using sex-specific 99th percentile URL (female 13 ng/L, male 28 ng/L)

Female, 0 to 1 hour: Sensitivity 92.19%, Specificity 82.27%, PPV 27.70%, NPV 99.31%
Female, >1 to 3 hours: Sensitivity 96.61%, Specificity 81.68%, PPV 27.01%, NPV 99.71%
Female, >3 to 6 hours: Sensitivity 97.14%, Specificity 77.18%, PPV 31.34%, NPV 99.60%
Female, >6 hours: Sensitivity 100.00%, Specificity 54.55%, PPV 44.44%, NPV 100.00%
Male, 0 to 1 hour: Sensitivity 79.23%, Specificity 83.26%, PPV 39.02%, NPV 96.74%
Male, >1 to 3 hours: Sensitivity 90.60%, Specificity 82.74%, PPV 40.46%, NPV 98.55%
Male, >3 to 6 hours: Sensitivity 94.20%, Specificity 80.27%, PPV 47.10%, NPV 98.67%
Male, >6 hours: Sensitivity 91.67%, Specificity 54.29%, PPV 40.74%, NPV 95.00%

Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.

K231974

Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).

Not Found

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.

Summary

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January 3, 2025

Image /page/0/Picture/1 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA logo on the right. The FDA logo features the letters 'FDA' in a blue square, followed by the words 'U.S. FOOD & DRUG ADMINISTRATION' in blue text.

Abbott Point of Care Inc. Jacquelyn Gesumaria Manager Regulatory Affairs 400 College Road East Princeton, New Jersey 08540

Re: K240984

Trade/Device Name: i-STAT hs-TnI Cartridge with the i-STAT 1 System Regulation Number: 21 CFR 862.1215 Regulation Name: Creatine Phosphokinase/Creatine Kinase Or Isoenzymes Test System Regulatory Class: Class II Product Code: MMI, JJE Dated: November 29, 2024 Received: December 2, 2024

Dear Jacquelyn Gesumaria:

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 (the 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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

U.S. Food & Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993 www.fda.gov

1

Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).

Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30. Design controls; 21 CFR 820.90. Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

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 Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safetyreporting-combination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.

All medical devices, including Class I and unclassified devices and combination product device constituent parts are required to be in compliance with the final Unique Device Identification System rule ("UDI Rule"). The UDI Rule requires, among other things, that a device bear a unique device identifier (UDI) on its label and package (21 CFR 801.20(a)) unless an exception or alternative applies (21 CFR 801.20(b)) and that the dates on the device label be formatted in accordance with 21 CFR 801.18. The UDI Rule (21 CFR 830.300(a) and 830.320(b)) also requires that certain information be submitted to the Global Unique Device Identification Database (GUDID) (21 CFR Part 830 Subpart E). For additional information on these requirements, please see the UDI System webpage at https://www.fda.gov/medical-device-advicecomprehensive-regulatory-assistance/unique-device-identification-system-udi-system.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

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For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Paula V. Caposino -S

Paula Caposino, Ph.D. Deputy Division Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K240984

Device Name

i-STAT hs-TnI cartridge with the i-STAT 1 System

Indications for Use (Describe)

The i-STAT hs-Tnl cartridge with the i-STAT 1 System is in the in vitro quantification of cardiac troponin I (cTnl) in whole blood or plasma samples in point of care or clinical laboratory settings.

The i-STAT hs-Tnl cartridge with the i-STAT 1 System is intended to be used as an aid in the diagnosis of myocardial infarction (MI).

Type of Use (Select one or both, as applicable)
X Prescription Use (Part 21 CFR 801 Subpart D)	Over-The-Counter Use (21 CFR 801 Subpart C)

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Image /page/4/Picture/0 description: The image shows the Abbott logo. The logo consists of a blue stylized letter "a" on the left and the word "Abbott" in black bold font on the right. The blue "a" is made up of three horizontal lines connected by a vertical line on the left.

510(k) Summary

The information in this 510(k) summary is being submitted in accordance with the requirements of 21 CFR 807.92.

Submitter Information 1.

| Owner | Abbott Point of Care Inc.
400 College Road East
Princeton, NJ 08540 |
|---------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Contact | Primary: Jacquelyn Gesumaria
Manager Regulatory Affairs
Phone: 609-454-9384

Secondary: Mojgan Soleimani
Director, Regulatory Strategy and Design Quality
Phone: 613-295-0932 |
| Date Prepared | January 03, 2025 |

2. Device Information

Proprietary Names: i-STAT hs-TnI Cartridge with the i-STAT 1 System

Common Name: High Sensitivity Cardiac Troponin-I (hs-TnI)

510(k) Number: K240984

| Product
Code | Device Classification Name | Regulation
Number | Class | Panel |
|-----------------|------------------------------------------------------------------------|----------------------|-------|----------------------------|
| MMI | Creatine
phosphokinase/creatine kinase
or isoenzymes test system | 862.1215 | II | CH - Clinical
Chemistry |
| JJE | Discrete photometric chemistry
analyzer for clinical use | 862.2160 | I | CH - Clinical
Chemistry |

3. Predicate Device

PATHFAST hs-cTnI-II Test Proprietary Name: 510(k) Number: K231974

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| Product
Code | Device Classification Name | Regulation
Number | Class | Panel |
|-----------------|------------------------------------------------------------------------|----------------------|-------|----------------------------|
| MMI | Creatine
phosphokinase/creatine kinase
or isoenzymes test system | 862.1215 | II | CH - Clinical
Chemistry |

4. Device Description

The i-STAT hs-TnI cartridge is an in vitro diagnostic test for the quantitative measurement of cardiac troponin I (cTnI) in whole blood or plasma samples using the i-STAT 1 analyzer in point of care or clinical laboratory settings.

The i-STAT hs-TnI test uses an enzyme-linked immunosorbent assay (ELISA) method with electrochemical detection of the resulting enzyme signal. The test reports a quantitative measurement of the sample concentration of cTnI in units of ng/L in approximately 15 minutes.

The i-STAT hs-TnI immunoassay test method uses anti-cTnI antibodies for labeling and capture. The capture antibodies are coated on para-magnetic microparticles. Both label and capture antibodies are contained within the cartridge on a biosensor chip. The ELISA is initiated when the test cartridge is inserted into the analyzer. The sample is positioned over the biosensor chip to dissolve the reagents. This forms the ELISA sandwich (detection antibodylabel/antigen/capture antibody). The sample and excess antibody-conjugate are then washed off the sensors. An enzyme within the ELISA sandwich generates an electrochemically detectable product. The biosensor chip measures the enzyme product which is proportional to the concentration of cTnI within the sample.

The i-STAT hs-TnI cartridge is a single use test cartridge. The cartridge contains a biosensor chip and all reagents required to execute the test cycle. All fluid movements within the cartridge (test sample or reagent) are automatically controlled by the i-STAT 1 analyzer by electromechanical interaction with the cartridge. The analyzer executes the test cycle, acquires and processes the electrical sensor signals converting the signals into quantitative results. These functions are controlled by a microprocessor.

The i-STAT 1 System is comprised of the i-STAT 1 analyzer and accessories (i-STAT 1 Downloader/Recharger, i-STAT Electronic Simulator, i-STAT Printer and i-STAT 1 9V NiMH Rechargeable Battery).

Assay quality control materials are also available for use with the i-STAT hs-TnI cartridge and include i-STAT hs-TnI Control Level 1. i-STAT hs-TnI Control Level 2. i-STAT hs-TnI Control Level 3, and the i-STAT hs-TnI Calibration Verification Levels 1-3.

5. Intended Use Statement

i-STAT hs-TnI Cartridge

The i-STAT hs-TnI cartridge with the i-STAT 1 System is intended for use in the in vitro quantification of cardiac troponin I (cTnI) in whole blood or plasma samples in point of care or clinical laboratory settings.

6

The i-STAT hs-TnI cartridge with the i-STAT 1 System is intended to be used as an aid in the diagnosis of myocardial infarction (MI).

Table 1: Similarities and Differences: System (Test and Instrument)
Feature or
Characteristic	Predicate Device:
PATHFAST hs-cTnI-II Test
(K231974)	Candidate Device:
i-STAT hs-Tnl cartridge with the
i-STAT 1 System
Intended Use	PATHFAST hs-cTnI-II is an in vitro
diagnostic test for the quantitative
measurement of cardiac Troponin I
(cTnI) in heparinized or EDTA whole
blood and plasma. Measurements of
cardiac Troponin I are used to aid in
the diagnosis of acute myocardial
infarction (AMI).

PATHFAST hs-cTnI-II is for use in
clinical laboratory or point of care
(POC) settings. | The i-STAT hs-Tnl cartridge with the
i-STAT 1 System is intended for use in
the in vitro quantification of cardiac
troponin I (cTnI) in whole blood or
plasma samples in point of care or
clinical laboratory settings.

Summary Comparison of Technological Characteristics 6.

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7. Performance Characteristics

A. Analytical Performance

a. Precision/Reproducibility:

i. 20-Day Precision
The precision performance of the i-STAT hs-TnI test in the i-STAT hs-TnI cartridge with the i-STAT 1 Sustem was evaluated using a panel of six (6) frozen plasma samples with concentrations across the reportable range of the test. This 20-day precision study was based on the Clinical and Laboratory Standards Institute (CLSI) guideline EP05-A3: Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline – Third Edition. The study was conducted using three (3) lots of i-STAT hs-TnI cartridges and multiple i-STAT 1 analyzers at one (1) site. Testing was conducted over 20 non-consecutive days, two (2) runs per day, by two (2) operators for each cartridge lot. The results for the study are shown below in Table 2.

The within-laboratory precision of the i-STAT hs-TnI test in the i-STAT hs-TnI cartridge on the i-STAT 1 System demonstrated acceptable performance as the results are shown to be within the acceptance criteria for all levels.

Table 2: 20-Day Precision Results for the i-STAT hs-Tnl cartridge with the i-STAT 1 System
Sample
Level	N	Mean
(ng/L)	Repeatability		Between-Run		Between-Day		Within-Laboratorya
			SD
(ng/L)	%CV	SD
(ng/L)	%CV	SD
(ng/L)	%CV	SD
(ng/L)	%CV
1	240	11.70	1.780	15.22	0.448	3.83	0.297	2.54	1.859	15.89
1	239b	11.59	0.755	6.52	0.129	1.11	0.026	0.22	0.767	6.61
2	240	15.62	0.619	3.97	0.262	1.68	0.224	1.44	0.709	4.54
3	240	33.94	1.184	3.49	0.333	0.98	0.211	0.62	1.248	3.68
4	240	84.25	2.750	3.26	0.163	0.19	0.403	0.48	2.784	3.30
5	240	511.95	19.298	3.77	4.825	0.94	3.189	0.62	20.146	3.94
6	240	786.65	35.636	4.53	9.337	1.19	6.291	0.80	37.372	4.75

a Includes repeatability, between-run and between-day variability.

b One falsely elevated outlier was excluded. The observed outlier rate in this study was 0.07% (1/1440).

ii. Whole Blood and Plasma Precision

The precision performance of the i-STAT hs-TnI test in the i-STAT hs-TnI cartridge with the i-STAT 1 System was evaluated in point of care settings at three (3) clinical sites following a modified design based on CLSI EP05-A3: Evaluation of Quantitative Measurement Procedures; Approved Guideline – Third Edition. The precision performance was evaluated using native venous whole blood and plasma specimens prospectively collected in lithium heparin anticoagulant tubes assigned to six (6) cardiac troponin I levels spanning the reportable range of the i-STAT hs-TnI test.

9

At each site, a minimum of one (1) whole blood and one (1) plasma specimen was tested per level by one (1) operator using eight (8) i-STAT hs-TnI cartridges on eight (8) i-STAT 1 analyzers across three (3) runs (1 replicate/analyzer/run) for a total of 24 replicates per specimen. Spiked specimens constituted 4.16% (1/24) of total whole blood specimens and 4.54% (1/22) of total plasma specimens used in precision analysis.

The within-site precision of the i-STAT hs-TnI test in the i-STAT hs-TnI cartridge with the i-STAT 1 System was demonstrated to be acceptable as the results are within the acceptance criteria for all levels for each specimen type at each site. The precision estimates for the i-STAT hs-TnI test in whole blood are shown in Table 3 and for plasma are shown in Table 4.

Table 3: Whole Blood Precision Results for the i-STAT hs-Tnl cartridge with the i-STAT 1 System
Site	Cardiac
Troponin
Level	N	Min
(ng/L)	Max
(ng/L)	Mean
(ng/L)	Repeatability
SD	CV (%)	Between-Analyzer
SD	CV (%)	Within-Site
SD	CV (%)
1	1	24	4.1	6.0	5.16	0.457	8.86	0.231	4.48	0.513	9.93
	2	24	17.4	20.5	19.13	0.681	3.56	0.277	1.45	0.735	3.84
	3	23	27.2	31.1	29.03	1.056	3.64	0.000	0.00	1.056	3.64
	4	24	205.4	263.0	244.50	13.525	5.53	0.000	0.00	13.525	5.53
	5	24	584.8	721.2	638.50	31.329	4.91	0.000	0.00	31.329	4.91
	6	23	693.8	792.7	744.37	26.291	3.53	18.803	2.53	32.323	4.34
2	1	22	874.6	983.5	934.77	22.925	2.45	20.847	2.23	30.986	3.31
	2	24	6.6	9.7	7.39	0.523	7.08	0.439	5.94	0.683	9.25
	3	23	18.9	22.4	20.32	1.034	5.09	0.000	0.00	1.034	5.09
	4	23	42.1	48.7	44.22	1.376	3.11	0.708	1.60	1.548	3.50
	5	23	37.2	42.7	39.97	1.408	3.52	0.000	0.00	1.408	3.52
	6	24	64.8	77.4	71.44	3.114	4.36	0.000	0.00	3.114	4.36
3	1	23	432.4	523.8	478.95	18.569	3.88	10.212	2.13	21.192	4.42
	2	24	554.9	660.2	606.65	27.684	4.56	11.418	1.88	29.946	4.94
	3	24	724.1	844.9	795.93	33.125	4.16	15.175	1.91	36.436	4.58
	4	22	812.4	940.0	881.15	29.334	3.33	16.048	1.82	33.437	3.79
	5	24	11.4	13.8	12.49	0.609	4.87	0.213	1.70	0.645	5.16
	6	24	15.9	19.0	17.39	0.772	4.44	0.000	0.00	0.772	4.44
4	1	24	24.4	27.8	26.57	0.757	2.85	0.559	2.11	0.941	3.54
	2	24	43.7	52.1	47.28	2.161	4.57	0.000	0.00	2.161	4.57
	3	23	314.2	370.4	336.58	13.989	4.16	2.233	0.66	14.166	4.21
	4	23	628.0	763.3	681.89	30.929	4.54	0.000	0.00	30.929	4.54
	5	24	630.0	800.1	742.43	36.996	4.98	23.575	3.18	43.869	5.91
	6 a	24	825.9	946.2	869.70	26.891	3.09	0.000	0.00	26.891	3.09

ª Specimen from one (1) subject was spiked with ≤ 5% v/v recombinant cardiac troponin I antigen.

10

Table 4: Plasma Precision Results for the i-STAT hs-Tnl cartridge with the i-STAT 1 System
Site	Cardiac
Troponin
Level	N	Min
(ng/L)	Max
(ng/L)	Mean
(ng/L)	Repeatability	Between -
Analyzer		Within-Site
							SD	CV (%)	SD	CV (%)	SD
1	1	23	5.6	9.5	6.08	0.763	12.55	0.154	2.53	0.778	12.80
	2	23	18.3	22.1	20.58	0.999	4.86	0.000	0.00	0.999	4.86
	3	23	28.6	32.4	30.83	0.818	2.65	0.445	1.44	0.932	3.02
	4	24	225.3	259.2	243.97	10.688	4.38	1.153	0.47	10.750	4.41
	5	24	548.1	662.9	602.70	32.572	5.40	0.000	0.00	32.572	5.40
	6	23	679.6	900.1	764.50	51.255	6.70	7.652	1.00	51.823	6.78
2	1	24	7.4	8.6	8.03	0.306	3.81	0.092	1.14	0.320	3.98
	2	24	20.0	23.8	22.59	0.889	3.94	0.144	0.64	0.900	3.99
	3	24	40.6	48.9	44.19	1.572	3.56	1.247	2.82	2.007	4.54
	4	24	72.4	81.1	76.81	1.977	2.57	0.000	0.00	1.977	2.57
	5	24	464.4	531.2	499.76	16.575	3.32	9.727	1.95	19.219	3.85
	6	24	624.3	924.4	712.17	52.591	7.38	19.881	2.79	56.223	7.89
3	1	24	591.7	759.7	680.01	40.429	5.95	0.000	0.00	40.429	5.95
	2	21	858.5	990.1	945.62	23.419	2.48	26.280	2.78	35.201	3.72
	3	24	11.6	33.9	13.65	4.330	31.71	0.000	0.00	4.330	31.71
	4	23b	11.6	13.4	12.77	0.378	2.96	0.130	1.02	0.400	3.13
	5	24	22.9	33.2	24.84	1.999	8.05	0.000	0.00	1.999	8.05
	6 a	23b	22.9	26.3	24.48	0.930	3.80	0.000	0.00	0.930	3.80
		24	17.2	20.6	18.80	0.798	4.24	0.000	0.00	0.798	4.24
		24	43.1	49.9	47.00	1.705	3.63	0.597	1.27	1.807	3.84
		24	315.9	375.0	338.27	10.893	3.22	9.056	2.68	14.165	4.19
		24	631.8	737.9	672.29	24.813	3.69	0.000	0.00	24.813	3.69
		24	664.0	797.1	743.01	33.451	4.50	6.694	0.90	34.114	4.59
		24	768.8	915.8	847.93	34.701	4.09	0.000	0.00	34.701	4.09

ª Specimen from one (1) subject was spiked with ≤ 5% v/v recombinant cardiac troponin l antigen.

b One falsely elevated outlier was excluded. The observed outlier rate in this study was 0.38% (2/521).

iii. Precision in Control Materials

The precision performance of the i-STAT hs-TnI test in the i-STAT hs-TnI cartridge with the i-STAT 1 System was evaluated using i-STAT hs-TnI control and calibration verification materials at a single site. The study was based on CLSI EP15-A3: User Verification of Precision and Estimation of Bias; Approved Guideline – Third Edition. The study was conducted using one (1) lot of i-STAT hs-ThI cartridges and five (5) unique levels of frozen i-STAT hs-TnI control materials tested in five (5) replicates over five (5) consecutive days. The precision of the i-STAT hs-TnI test was evaluated using one (1) lot each of i-STAT hs-TnI Controls Levels 1 and 2 (L1 and L2) and one (1) lot each of i-STAT hs-TnI Calibration Verification Set Levels 1, 2, and 3 (CV1, CV2, and CV3).

The mean, standard deviation (SD) and coefficient of variation (CV) are presented below in Table 5.

11

| Table 5: Precision Results in Control Materials for the i-STAT hs-Tnl cartridge with the i-STAT 1

System
Fluid
Level*	Mean
(ng/L)	N	Repeatability		Between-Day		Within-Laboratory
			SD (ng/L)	%CV	SD (ng/L)	%CV	SD (ng/L)	%CV
CV1	2.85	25	0.202	7.07	0.066	2.33	0.212	7.45
L1	20.43	25	0.640	3.13	0.178	0.87	0.664	3.25
L2	98.46	25	3.108	3.16	0.924	0.94	3.242	3.29
CV2 / L3	592.85	25	28.288	4.77	12.617	2.13	30.974	5.22
CV3	1174.29	25	55.117	4.69	15.296	1.30	57.200	4.87

Since i-STAT hs-Tnl Calibration Level 2 (CV2) and i-STAT hs-Tnl Control Level 3 (L3) share the same target and have identical formulations, the i-STAT hs-Tnl test results from CV2 were used to assess the precision in L3.

iv. Multi-site Multi-Day Precision

The multiday precision performance of the i-STAT hs-TnI test in the i-STAT hs-TnI cartridge with the i-STAT 1 System was evaluated using a panel of six (6) frozen plasma samples, which included six (6) cardiac troponin I levels which were tested in point of care settings at three (3) clinical sites. At each site, each of the six (6) test materials was tested once per day for five (5) days by two (2) different operators, with each operator using three (3) i-STAT hs-TnI cartridges on three (3) i-STAT 1 analyzers. The study followed a 3x5x2x3 design based on CLSI EP05-43: Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline – Third Edition. The results of the multi-day precision testing of the i-STAT hs-TnI test in the i-STAT hs-TnI cartridge on the i-STAT 1 System are shown in Table 6 for all sites combined.

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Image /page/12/Picture/0 description: The image shows the Abbott logo. The logo consists of a blue abstract shape on the left and the word "Abbott" in black on the right. The blue shape is a stylized letter "a".

Table 6: Multi-Site Multi-Day Precision Results for the i-STAT hs-Tnl cartridge with the i-STAT 1 System (ng/L)
Level	N	Min	Max	Mean	Repeatability		Between-Day	Between-
Operator		Within-Site		Between-Site		Reproducibility
					SD
(95% CI)	%CV	SD
(95% CI)	%CV	SD
(95% CI)	%CV	SD
(95% CI)	%CV	SD
(95% CI)	%CV	SD
(95% CI)	%CV
1	90	11.5	15.1	13.03	0.599
(0.554,
0.653)	4.60	0.135
(0.097,
0.223)	1.04	0.000
(0.000,
0.000)	0.00	0.614
(0.568,
0.669)	4.71	0.000
(0.000,
0.000)	0.00	0.614
(0.568,
0.668)	4.71
2	90	16.1	19.2	17.68	0.564
(0.521,
0.614)	3.19	0.225
(0.162,
0.372)	1.28	0.200
(0.151,
0.296)	1.13	0.639
(0.582,
0.710)	3.62	0.000
(0.000,
0.000)	0.00	0.639
(0.582,
0.710)	3.62
3	90	35.2	41.3	38.49	1.306
(1.206,
1.423)	3.39	0.192
(0.138,
0.317)	0.50	0.329
(0.249,
0.487)	0.86	1.360
(1.257,
1.482)	3.54	0.000
(0.000,
0.000)	0.00	1.360
(1.258,
1.481)	3.54
4	90	81.6	100.3	90.33	3.300
(3.048,
3.596)	3.65	0.917
(0.658,
1.515)	1.02	1.114
(0.842,
1.648)	1.23	3.602
(3.307,
3.955)	3.99	1.179
(0.614,
7.407)	1.31	3.789
(3.308,
4.437)	4.20
5	90	482.5	590.3	543.24	19.253
(17.786,
20.985)	3.54	4.407
(3.160,
7.275)	0.81	9.074
(6.856,
13.419)	1.67	21.735
(19.785,
24.116)	4.00	0.000
(0.000,
0.000)	0.00	21.735
(19.798,
24.096)	4.00
6	90	714.3	874.4	791.67	26.656
(24.626,
29.054)	3.37	5.316
(3.812,
8.776)	0.67	0.000
(0.000,
0.000)	0.00	27.181
(25.154,
29.567)	3.43	17.311
(9.013,
108.794)	2.19	32.225
(24.793,
46.052)	4.07

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Image /page/13/Picture/0 description: The image shows the Abbott logo. The logo consists of a blue, stylized letter "a" in a square shape, followed by the word "Abbott" in bold, black font. The logo is simple and modern, and the colors are eye-catching.

b. Linearity/assay reportable range:

i. Linearity

The linearity of the i-STAT hs-TnI test in the i-STAT hs-TnI cartridge on the i-STAT 1 System was established by testing venous whole blood and plasma samples of varying levels of cardiac troponin I. The study was designed based on CLSI EP06-Ed2: Evaluation of the Linearity of Quantitative Measurement Procedures, 2nd Edition. The study was conducted using whole blood samples of varying cardiac troponin I levels prepared by combining an unaltered whole blood sample and a whole blood sample spiked with a human sourced previously frozen plasma sample containing a high level of native cardiac troponin I in specific ratios to span the reportable range. Plasma samples of varying cardiac troponin I levels were prepared by combining plasma obtained via centrifugation from an unaltered whole blood sample and a plasma sample spiked with human sourced previously frozen plasma sample containing a high level of native cardiac troponin I in specific ratios to span the reportable range. The expected values for cardiac troponin I were determined for the lowest and highest levels as measured by the i-STAT hs-TnI cartridge on the i-STAT 1 analyzer and mathematically calculated for intermediate levels using admixture ratios.

The regression summary of the results obtained in the i-STAT hs-TnI cartridge (y-axis) versus the expected values (x-axis) is provided in Table 7 below. The results of the linearity study for the i-STAT hs-TnI test in the i-STAT hs-TnI cartridge on the i-STAT 1 Sustem met the acceptance criteria and demonstrated linearity over the reportable range of the test for both whole blood and plasma.

Table 7: Linearity Study Results for the i-STAT hs-Tnl cartridge with the i-STAT 1 System
Assay	Sample Type	Test Sample
Range (ng/L)	Reportable
Range (ng/L)	Slope	Intercept
(ng/L)	R2
hs-Tnl	Whole Blood	1.1 – 1070.0	2.9 – 1000.0	1.025	0.183	0.9990
	Plasma	1.4 – 1050.8	2.9 – 1000.0	1.043	-0.171	0.9993

ii. Sample Type Comparison

Comparison studies were performed based on CLSI EP35: Assessment of Equivalence or Suitability of Specimen Types for Medical Laboratory Measurement Procedures, 1st ed. using fresh lithium heparin whole blood (WB) and plasma samples with the i-STAT hs-TnI cartridge on i-STAT 1 analyzers. The relationship between the two sample types is summarized in Table 8 below using a Passing-Bablok regression.

Table 8: Comparison of Whole Blood vs. Plasma Sample Type
for the i-STAT hs-Tnl cartridge with the i-STAT 1 System
Sample Type Comparison	Slope	Intercept	r
WB vs. Plasma	1.01	0.603	0.99

14

iii. High Dose Hook Effect

The i-STAT hs-TnI test in the i-STAT hs-TnI cartridge on the i-STAT 1 System was evaluated for high dose hook effect. The testing was conducted using venous whole blood and plasma samples collected with lithium heparin and altered via spiking with recombinant human cardiac troponin ITC-complex and serial dilution to obtain cardiac troponin I levels up to 500.000 ng/L. The whole blood and plasma samples were tested alongside the highest level calibrator, MWC7, which cardiac troponin I level exceeds the upper limit of the reportable range of 1000.0 ng/L. The high dosage hook effect was evaluated by verifying that the measured i-STAT hs-TnI results of the test samples was greater than that of the MWC7 calibrator.

Hook effect was not observed for the i-STAT hs-TnI test in the i-STAT hs-TnI cartridge with the i-STAT 1 Sustem using whole blood and plasma samples with cardiac troponin I concentrations up to 500,000 ng/L.

c. Traceability, Calibration and Reference Interval

i. Traceability and Calibration

The i-STAT hs-TnI test for cardiac troponin-I measures the amount of substance concentration in plasma or the plasma fraction of whole blood for in vitro diagnostic use. Cardiac troponin-I values assigned to i-STAT controls and calibration materials are traceable to i-STAT's working calibrator prepared from human cardiac troponin-ITC complex (NIST SRM2921).

i-STAT System controls and calibration verification materials are validated for use only with the i-STAT System and assigned values may not be commutable with other methods.

ii. Reference Interval / Reference Range

A reference range study was conducted with a United States (US) based general population. Venous whole blood specimens were collected from 895 apparently healthy subjects between the ages of 18 and 87 years at point-of-care settings in eight (8) clinical sites. Subjects included met the following biomarker criteria: N-terminal pro-B-type natriuretic peptide (NT-proBNP) 35.0 kg/m², Type 1 or Type 2 diabetes, hospitalization within the previous 3 months, personal history of heart disease or vascular conditions (e.g. high blood pressure requiring medication, heart attack (acute myocardial infarction), angina), stent procedure or percutaneous cardiac intervention, angioplasty or balloon angioplasty, coronary artery bypass graft, surgery for a circulation problem (e.g., leg), statin use within the last 6 months, or known pregnancy or within 6 weeks postpartum.

The venous whole blood and plasma specimens were tested with the i-STAT hs-ThI cartridge with the i-STAT 1 System to determine the 99th percentile upper reference limit (URL) and associated 90% confidence intervals for the female, male, and overall population.

Based on the test results from whole blood specimen testing, the 99th percentile URL of an apparently healthy population for the i-STAT hs-TnI test was determined as presented in Table 9.

15

| Table 9: 99th Percentile URL and 90% Confidence Intervals for the Female, Male and

Overall Population for the i-STAT hs-Tnl cartridge with the i-STAT 1 System
Sex	N	99th Percentile Upper
Reference Limit (ng/L)	90% Cl (ng/L)
Female	490	13	(10, 17)
Male	404	28	(19, 58)
Overall	895	21	(14, 30)

Note: The overall and female 90th percentile URL values were determined using all data. The male 90th percentile URL value was determined using data with one outlier excluded.

d. Detection Limit

i. Limit of Blank and Detection (LoB/LoD)
The study was based on CLSI EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline – Second Edition.

The LoB and LoD of the i-STAT hs-TnI test in the i-STAT hs-TnI cartridge was evaluated on the i-STAT 1 analyzer using four (4) i-STAT hs-TnI cartridge lots for LoB testing and three (3) i-STAT hs-TnI cartridge lots for LoD testing. Whole blood and plasma samples from four (4) healthy donors were altered to blank cardiac troponin I levels for LoB testing. Whole blood and plasma samples from four (4) healthy donors with low level cardiac troponin I levels were used for LoD testing.

The LoB and LoD were determined based on the maximal LoB and LoD value obtained for each lot tested.

The determined LoB and LoD for i-STAT hs-TnI test in the i-STAT hs-TnI cartridge on the i-STAT 1 System are shown in Table 10.

| Table 10: LoB and LoD Results for the i-STAT hs-

Tnl cartridge with the i-STAT 1 System
Sample Type	LoB (ng/L)	LoD (ng/L)
Whole Blood	0.78	1.61
Plasma	0.57	1.05

ii. Limit of Quantitation (LoQ)

The study was based on the CLSI EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures: Approved Guideline – Second Edition.

The LoQ of the i-STAT hs-TnI test in the i-STAT hs-TnI cartridge was evaluated on the i-STAT 1 analyzer using four (4) i-STAT hs-TnI cartridge lots and whole blood and plasma samples containing a low-level of cardiac troponin I. The LoQ for the i-STAT hs-TnI test in the i-STAT hs-TnI cartridge with the i-STAT 1 System was determined for whole blood and plasma, as shown in Table 11.

The lower limit of the reportable range was set to be the greater of the LoQ values for whole blood and plasma.

16

| Table 11: LoQ Results for the i-STAT hs-Tnl cartridge with
the i-STAT 1 System | LoQ*
(ng/L) | Lower Limit of the
Reportable Range (ng/L) |
|-----------------------------------------------------------------------------------|----------------|-----------------------------------------------|
| Whole Blood | 2.90 | 2.9 |

LoQ determined as 20 %CV concentration using a precision profile method.

The 10 %CV concentration was determined to be 6.88 ng/L for whole blood and 3.70 ng/L for plasma.

e. Analytical Specificity

i. Interference

The performance of the i-STAT hs-TnI test in the i-STAT hs-TnI cartridge when tested in the presence of potentially interfering endogenous and exogenous substances was evaluated using whole blood and plasma samples. The study design was based on CLSI EP07-ED3: Interference Testing in Clinical Chemistry, , 3" ed. Each potentially interfering substance was tested at the concentration recommended in CLSI EP 37: Supplemental Tables for Interference Testing in Clinical Chemistry, 1st ed., as applicable.

The effect of each potentially interfering substance was evaluated at two cardiac troponin I levels (approximately 20 ng/L and 600 ng/L) by comparing the test results from a control sample, spiked with blank solvent, with the results from a test sample spiked with the potentially interfering substance.

A substance was identified as an interferent if the difference between the control and test samples was outside of a pre-determined acceptable range for the assay. Table 12 below contains the list of potentially interfering substances tested for the i-STAT hs-TnI test in the i-STAT hs-TnI cartridge and the interference results.

Table 12: Evaluation of Potentially Interfering Endogenous and Exogenous Substances for the i-STAT hs-Tnl cartridge

	Test Concentration1		Interference (Yes/No)
Substance	umol/L	mg/dL, unless
specified2	Whole Blood	Plasma	Overall	Comment
Acetaminophen	1030	15.6	No	No	No
Acetylsalicylic Acid	167	3.01	No	No	No
Alkaline Phosphatase	3060 (U/L)		No
No	No
(ALP)
Allopurinol	441	6.00	No	No	No
cartridge
	Test Concentration1		Interference (Yes/No)
Substance	μmol/L	mg/dL, unless
specified2	Whole Blood	Plasma	Overall	Comment
Ambroxola	965	40	No	No	No
Ampicillin	215	7.51	No	No	No
Ascorbic Acid	298	5.25	No	No	No
Atenolol	33.8	0.900	No	No	No
Bilirubin (Conjugated)	475	40.0	No	No	No
Bilirubin (Unconjugated)	684	40.0	Yes	Yes	Yes	Decreased results > 85.5 μmol/L (5 mg/dL). The reference range per CLSI EP37 for Bilirubin (Unconjugated) is 0-34 μmol/L (0.0-2.0 mg/dL).
Biotin	14.3	0.349	No	No	No
Bivalirudina	18.3	3.99	No	No	No
Caffeine	556	10.8	No	No	No
Carvedilola	370	15	No	No	No
Cefoxitin	15500	697	No	Yes	Yes	Decreased results > 6564 μmol/L (295 mg/dL)
Cholesterol	10300	398	No	No	No
Clopidogrela	180	7.5	No	No	No
Cocainea	11.406	0.346	No	No	No
Cyclosporine	1.50	0.180	No	No	No
Diclofenac	81.0	2.58	No	No	No
Digoxin	0.0499	0.00390	No	No	No
Dopamine	4.06	0.0770	No	No	No
Doxycycline	40.5	2.08	No	No	No
Enalaprilat	2.35	0.0903	No	No	No
Enoxaparina	500 IU/dL	5	No	No	No
Epinephrinea	1.7	0.037	No	No	No
Eptifibatidea	11	0.90	No	No	No
Erythromycin	188	13.8	No	No	No
Ethanol	130000	599	No	No	No
Fibrinogena	N/A	1 g/dL	No	Yes	Yes	Decreased results > 0.4 g/dL. The reference range per literature for Fibrinogen is 0.2-0.4 g/dL3.
Fondaparinuxa	2.3	0.40	No	No	No
Furosemide	48.1	1.59	No	No	No
Substance	Test Concentration1		Interference (Yes/No)			Comment
	μmol/L	mg/dL, unless specified2	Whole Blood	Plasma	Overall
Hemoglobin	N/A	1000	No	No	No
Human Anti-Mouse
Antibody (HAMA)a		3000 (ng/mL)	No	No	No
Ibuprofen	1060	21.9	No	No	No
Intralipid (Intralipid
20%)a	N/A	3144	No	No	No
Isosorbide Dinitrate	25.1	0.593	No	No	No
Levodopa	38.0	0.749	No	No	No
Lithium Heparina		~3160 IU/dL	No	No	No
Methyldopa	107	2.55	No	No	No
Methylprednisolone	20.9	0.783	No	No	No
Metronidazole	719	12.3	No	No	No
Nicotine	5.97	0.0969	No	No	No
Nifedipine	1.70	0.0589	No	No	No
Nitrofurantoin	8.94	0.213	No	No	No
Nystatina	181.4	16.80	No	No	No
Oxytetracyclinea	24	1.2	No	No	No
Phenobarbital	2970	69.0	No	No	No
Phenylbutazone	1040	32.1	No	No	No
Phenytoin	238	6.00	No	No	No
Pravastatin	0.488	0.0218	No	No	No
Primidone	261	5.70	No	No	No
Rheumatoid Factor
(RF)a	500 IU/mL		No	Yes	Yes	Decreased results

350 IU/mL |
| Rifampicin | 58.3 | 4.80 | No | No | No | |
| Salicylic Acid | 207 | 3.31 | No | No | No | |
| Simvastatin | 0.199 | 0.00833 | No | No | No | |
| Sodium Heparin | | 330 IU/dL | No | No | No | |
| Theophylline | 333 | 6.00 | No | No | No | |
| Tissue Plasminogen
Activator (TPA)a | N/A | 0.23 | No | No | No | |
| Total Protein
(Human Serum
Albumin) | N/A | 15 g/dL | No | Yes | Yes | Decreased results ≥ 8.5 g/dL.
The reference range per CLSI
EP37 for Total Protein is 6.4-
8.3 g/dL. |
| Triglyceride | 16940 | 1500 | No | No | No | |
| Trimethoprim | 145 | 4.21 | No | No | No | |
| Verapamil | 3.51 | 0.172 | No | No | No | |
| Warfarin | 243 | 7.49 | No | No | No | |

1 Test concentrations were as recommended in CLSI EP37, Supplemental Tables for Interference Testing in Clinical Chemistry, 1st Edition, or from literature.

2 For substances with recommended test concentrations listed in CLSI EP37 ED01, the concentration in mg/dL was calculated using the molecular weight of the substance tested listed by the supplier and not CLSI. For substances without CLSI recommended test concentrations, the concentration in umol/L was calculated using the molecular weight of the form of the substance.

17

Table 12: Evaluation of Potentially Interfering Endogenous and Exogenous Substances for the i-STAT hs-Tnl cartridge

3 B.E. Statland, Clinical Decision Levels for Lab Tests, 2nd Edition (1987), Medical Economics Books.

18

Table 12: Evaluation of Potentially Interfering Endogenous and Exogenous Substances for the i-STAT hs-Tnl cartridge

ª The test concentration for this substance is not included in CLSI guideline EP37 1ぷ edition.

19

ii. Cross-reactivity

The i-STAT hs-TnI test in the i-STAT hs-TnI cartridge on the i-STAT 1 System was evaluated in the presence of potentially cross-reactive endogenous substances in whole blood and plasma samples based on CLSI guidance EP07-ED3: Interference Testing in Clinical Chemistry, 3d edition. The effect of each potentially interfering substance listed below in Table 13 was evaluated at three (3) cardiac troponin I concentrations (approximately 1 to 3 | 1799 | 119 | 1680 | 92.44 | 86.25 | 89.70 | 88.16 | 38.87 | 33.38 | 99.41 | 98.88 |
| | >3 to 6 | 724 | 70 | 654 | 95.71 | 88.14 | 85.78 | 82.89 | 41.88 | 34.51 | 99.47 | 98.45 |
| | >6 | 60 | 16 | 44 | 93.75 | 71.67 | 65.91 | 51.14 | 50.00 | 33.15 | 96.67 | 83.33 |
| Male | 0 to 1 | 1090 | 130 | 960 | 83.08 | 75.70 | 78.33 | 75.62 | 34.18 | 29.17 | 97.16 | 95.73 |
| | >1 to 3 | 1025 | 118 | 907 | 92.37 | 86.14 | 77.95 | 75.14 | 35.28 | 30.16 | 98.74 | 97.63 |
| | >3 to 6 | 439 | 69 | 370 | 95.65 | 87.98 | 74.32 | 69.64 | 40.99 | 33.69 | 98.92 | 96.88 |
| | >6 | 47 | 12 | 35 | 91.67 | 64.61 | 54.29 | 38.19 | 40.74 | 24.51 | 95.00 | 76.39 |

Table 19: Clinical performance for the i-STAT 1 System in whole blood using the sex-specific 99th percentile URL (female 13 ng/L, male 28 ng/L)

| | Time Point
(hours) | | MI | | Sensitivity (%) | | Specificity (%) | | PPV (%) | | NPV (%) | |
|--------|-----------------------|------|-----|--------|-----------------|-----------------------------------------|-----------------|-----------------------------------------|----------|-----------------------------------------|----------|-----------------------------------------|
| Sex | | N | | Non-MI | | | | | | | | |
| | | | | | Estimate | Lower Limit
of One Sided
97.5% CI | Estimate | Lower Limit of
One Sided
97.5% CI | Estimate | Lower Limit of
One Sided
97.5% CI | Estimate | Lower Limit
of One Sided
97.5% CI |
| Female | 0 to 1 | 1870 | 129 | 1741 | 91.47 | 85.38 | 83.23 | 81.40 | 28.78 | 24.61 | 99.25 | 98.66 |
| Female | >1 to 3 | 1799 | 119 | 1680 | 96.64 | 91.68 | 82.14 | 80.24 | 27.71 | 23.62 | 99.71 | 99.26 |
| Female | >3 to 6 | 724 | 70 | 654 | 97.14 | 90.17 | 77.83 | 74.49 | 31.92 | 26.03 | 99.61 | 98.58 |
| Female | >6 | 60 | 16 | 44 | 100.00 | 80.64 | 54.55 | 40.07 | 44.44 | 29.54 | 100.00 | 86.20 |
| Male | 0 to 1 | 1090 | 130 | 960 | 79.23 | 71.47 | 84.17 | 81.72 | 40.39 | 34.56 | 96.77 | 95.34 |
| Male | >1 to 3 | 1025 | 118 | 907 | 90.68 | 84.08 | 83.90 | 81.37 | 42.29 | 36.36 | 98.58 | 97.47 |
| Male | >3 to 6 | 439 | 69 | 370 | 94.20 | 86.02 | 82.97 | 78.81 | 50.78 | 42.22 | 98.71 | 96.74 |
| Male | >6 | 47 | 12 | 35 | 91.67 | 64.61 | 57.14 | 40.86 | 42.31 | 25.54 | 95.24 | 77.33 |

24

Table 20: Clinical performance for the i-STAT hs-Tnl cartridge with i-STAT 1 System in plasma using the overall 99th percentile URL (21 ng/L)
Sex	Time Point
(hours)	N	MI	Non-MI	Sensitivity (%)		Specificity (%)		PPV (%)		NPV (%)
					Estimate	Lower Limit
of One Sided
97.5% CI	Estimate	Lower Limit
of One Sided
97.5% CI	Estimate	Lower Limit
of One Sided
97.5% CI	Estimate	Lower Limit
of One Sided
97.5% CI
Female	0 to 1	1865	128	1737	86.72	79.76	89.23	87.69	37.25	31.95	98.92	98.27
	>1 to 3	1799	118	1681	92.37	86.14	89.65	88.10	38.52	33.04	99.41	98.88
	>3 to 6	723	70	653	94.29	86.21	85.76	82.87	41.51	34.14	99.29	98.19
	>6	60	16	44	93.75	71.67	68.18	53.44	51.72	34.43	96.77	83.81
Male	0 to 1	1092	130	962	83.08	75.70	78.17	75.45	33.96	28.98	97.16	95.73
	>1 to 3	1021	117	904	92.31	86.02	77.10	74.25	34.29	29.26	98.73	97.60
	>3 to 6	439	69	370	95.65	87.98	73.24	68.51	40.00	32.83	98.91	96.83
	>6	47	12	35	91.67	64.61	54.29	38.19	40.74	24.51	95.00	76.39

Table 21: Clinical performance for the i-STAT 1 System in plasma using the sex-specific 99th percentile URL (female 13 ng/L, male 28 ng/L)

| Sex | Time Point
(hours) | N | MI | Non-MI | Sensitivity (%) | | Specificity (%) | | PPV (%) | | NPV (%) | |
|--------|-----------------------|------|-----|--------|-----------------|-------|-----------------|-----------------------------------------|----------|-----------------------------------------|----------|-----------------------------------------|
| | | | | | | | Estimate | Lower Limit
of One Sided
97.5% CI | Estimate | Lower Limit
of One Sided
97.5% CI | Estimate | Lower Limit
of One Sided
97.5% CI |
| Female | 0 to 1 | 1865 | 128 | 1737 | 92.19 | 86.22 | 82.27 | 80.40 | 27.70 | 23.66 | 99.31 | 98.73 |
| | >1 to 3 | 1799 | 118 | 1681 | 96.61 | 91.61 | 81.68 | 79.76 | 27.01 | 23.00 | 99.71 | 99.26 |
| | >3 to 6 | 723 | 70 | 653 | 97.14 | 90.17 | 77.18 | 73.81 | 31.34 | 25.53 | 99.60 | 98.57 |
| | >6 | 60 | 16 | 44 | 100.00 | 80.64 | 54.55 | 40.07 | 44.44 | 29.54 | 100.00 | 86.20 |
| Male | 0 to 1 | 1092 | 130 | 962 | 79.23 | 71.47 | 83.26 | 80.77 | 39.02 | 33.33 | 96.74 | 95.30 |
| | >1 to 3 | 1021 | 117 | 904 | 90.60 | 83.95 | 82.74 | 80.14 | 40.46 | 34.69 | 98.55 | 97.42 |
| | >3 to 6 | 439 | 69 | 370 | 94.20 | 86.02 | 80.27 | 75.91 | 47.10 | 38.96 | 98.67 | 96.63 |
| | >6 | 47 | 12 | 35 | 91.67 | 64.61 | 54.29 | 38.19 | 40.74 | 24.51 | 95.00 | 76.39 |

25

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8. Conclusion

The results of the studies demonstrate that the analytical and clinical performance of the candidate device, i-STAT hs-TnI test in the i-STAT hs-ThI cartridge with the i-STAT 1 System is acceptable, and therefore safe and effective for the intended use of the device.

The results of these studies demonstrate that performance of the i-STAT hs-TnI test in the i-STAT hs-TnI cartridge with the i-STAT 1 System is substantially equivalent to the predicate device.