Who is the manufacturer of i-STAT hs-TnI cartridge with the i-STAT 1 System?

Abbott Point of Care, Inc. filed the 510(k) submission for i-STAT hs-TnI cartridge with the i-STAT 1 System (K240984).

What is the FDA product code for i-STAT hs-TnI cartridge with the i-STAT 1 System?

MMI. It is classified under 21 CFR 862.1215 as a Class 2 device in the Clinical Chemistry panel.

What is the regulatory pathway for i-STAT hs-TnI cartridge with the i-STAT 1 System?

510(k) clearance (submission type: Traditional).

What are the predicate devices for i-STAT hs-TnI cartridge with the i-STAT 1 System?

PATHFAST hs-cTnI-II Test (K231974).

Who can help prepare an FDA 510(k) submission like i-STAT hs-TnI cartridge with the i-STAT 1 System?

Innolitics — a medical-device software consultancy — provides regulatory and engineering support for FDA 510(k) submissions. See https://innolitics.com/services/510ks/ or contact https://innolitics.com/contact.

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

K240984 · Abbott Point of Care, Inc. · MMI · Jan 3, 2025 · Clinical Chemistry

Device Facts

Record ID	K240984
Device Name	i-STAT hs-TnI cartridge with the i-STAT 1 System
Applicant	Abbott Point of Care, Inc.
Product Code	MMI · Clinical Chemistry
Decision Date	Jan 3, 2025
Decision	SESE
Submission Type	Traditional
Regulation	21 CFR 862.1215
Device Class	Class 2

Intended Use

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. 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).

Device Story

The i-STAT hs-TnI cartridge is a single-use, in vitro diagnostic test for quantitative measurement of cardiac troponin I (cTnI) in whole blood or plasma. Used in point-of-care or clinical laboratory settings, the cartridge is inserted into the i-STAT 1 analyzer. The device utilizes an enzyme-linked immunosorbent assay (ELISA) with electrochemical detection. Capture antibodies are coated on para-magnetic microparticles within the biosensor chip. Upon insertion, the sample dissolves reagents, forming an ELISA sandwich (detection antibody-label/antigen/capture antibody). The analyzer automatically controls fluid movement, washes the sensors, and measures the enzyme product, which is proportional to cTnI concentration. Results are reported in ng/L in approximately 15 minutes. The output aids healthcare providers in diagnosing myocardial infarction (MI), facilitating rapid clinical decision-making and patient management.

Clinical Evidence

Clinical performance was evaluated in a pivotal study of 3,585 subjects presenting to the ED with ACS symptoms. MI prevalence was 6.8% (female) and 11.6% (male). Sensitivity and specificity were assessed using overall (21 ng/L) and sex-specific (female 13 ng/L, male 28 ng/L) 99th percentile URLs. Sensitivity ranged from 79.23% to 100% across time points and populations; specificity ranged from 54.29% to 89.70%. Analytical performance included 20-day precision (CV 3.30-15.89%), linearity (R2 0.999), and LoQ (2.9 ng/L).

Technological Characteristics

Single-use disposable cartridge containing electrochemical sensors and reagents (antibodies, alkaline phosphatase conjugate, heparin). Analyte detection via ELISA with electrochemical signal transduction. Dimensions/form factor: handheld cartridge for i-STAT 1 analyzer. Connectivity: infrared transceiver for data transfer. Sterilization: not specified. Software: embedded firmware in i-STAT 1 analyzer for automated fluid control and signal processing.

Indications for Use

Indicated for use in patients presenting to the emergency department with signs and symptoms suggestive of acute coronary syndrome (ACS) to aid in the diagnosis of myocardial infarction (MI).

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

PATHFAST hs-cTnI-II Test (K231974)

Related Devices

K031739 — I-STAT CARDIAC TROPONIN (CTNI) TEST · I-Stat Corporation · Sep 2, 2003
K172787 — Access hsTnl · Beckman Coulter, Inc. · Jun 14, 2018
K202525 — Alinity i STAT High Sensitivity Troponin-I · Abbott Laboratories Diagnostics Division · May 19, 2022

Submission Summary (Full Text)

{0}------------------------------------------------ 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. {2}------------------------------------------------ 3 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 {3}------------------------------------------------ ## 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) | #### CONTINUE ON A SEPARATE PAGE IF NEEDED. This section applies only to requirements of the Paperwork Reduction Act of 1995. #### *DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.* The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to: > Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov "An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number." {4}------------------------------------------------ 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 {5}------------------------------------------------ | 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. 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). | | Intended Use Setting | Clinical Laboratory and Point of Care | Same | | Device Classification | Class II | Same | | Product Code | MMI | Same | | Regulation Number | 862.1215 | Same | | Measurands | Cardiac Troponin I (cTnI) | Same | | Assay Technology | Chemiluminescent enzyme immunoassay | Enzyme-linked immunosorbent assay | | Assay Format | Single use cartridge | Same | | Detection Technology | Chemiluminescent | Electrochemical | | Sample Type | Heparinized and EDTA whole blood and plasma | Whole blood and plasma | | Sample Volume | 100 μL | ~22 μL | | Sample Preparation | Ready to Use | Same | | Sample Collection | With Na-heparin, Li-heparin or EDTA anticoagulant | With lithium heparin anticoagulant With lithium heparin tube with plasma separator gel Without anticoagulant | | 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 | | Time to Result | Within 17 minutes | ~ 15 minutes | | Reportable Result | Quantitative results | Same | | Instrument Platform | PATHFAST Analyzer | i-STAT 1 analyzer | | Calibration | Reagent lot: Initially by master calibration code, then by user with enclosed calibrators. Recalibration required every four weeks. | No calibration needed by the end user; calibration is pre-set during manufacture of the cartridge. | | Traceability | The calibrator for PATHFAST hs-cTnl is traceable to the reference material NIST Standard Reference Material for Human Cardiac Troponin Complex SRM2921 of the National Institute of Standard and Technology in USA which certified concentration for human cTnl. | Cardiac troponin I values assigned to i-STAT controls and calibration verification materials are traceable to i-STAT's working calibrators prepared from human cardiac troponin-ITC complex (NIST SRM2921). | | Assay Cut-off | 99th percentile cutoff: 0.029 ng/mL (29 ng/L) | 99th percentile cutoff: Female: 13 ng/L Male: 28 ng/L Overall: 21 ng/L | | Reportable Range | 4.1 - 50,000 ng/L | 2.9 – 1000.0 ng/L | | Time to Test/ Sample Stability (Time from collection to cartridge fill) | Whole Blood: With Heparin Anticoagulant: Within 4 hours | Whole Blood: With Lithium Heparin Anticoagulant: Within 4 hours Without Anticoagulant: Within 3 minutes | | | Plasma: With Heparin Anticoagulant: within 24 hours | Plasma: With Lithium Heparin Anticoagulant: within 4 hours | | Storage Conditions | Refrigerated at 2 to 8°C (35 to 46°F) until expiration date. | Refrigerated at 2 to 8°C (35 to 46°F) until expiration date. Room Temperature at 18-30°C (64- 86°F) for up to 14 days | #### Summary Comparison of Technological Characteristics 6. {7}------------------------------------------------ {8}------------------------------------------------ #### 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. {12}------------------------------------------------ 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 | {13}------------------------------------------------ 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) <125 pg/mL (for subjects younger than 75 years) or < 450 pg/mL (for subjects 75 years or older), glomerular filtration rate (eGFR) values ≥ 60 mL/min, and Hemoglobin A1c (HbA1c) ≤ 6.5%. Subjects were excluded based on the following criteria: BMI < 16.0 or > 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/…