LogoFDA 510(k) Search
K Number
K240984
Device Name
i-STAT hs-TnI cartridge with the i-STAT 1 System
Manufacturer
Abbott Point of Care Inc.
Date Cleared
2025-01-03

(268 days)

Product Code
MMI,JJE
Regulation Number
862.1215
Type
Traditional
Panel
Clinical Chemistry
Reference & Predicate Devices
K231974
Predicate For
N/A
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP AuthorizedThirdpartyExpeditedreview
Intended 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).

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.

AI/ML Overview

Acceptance Criteria and Device Performance for i-STAT hs-TnI Cartridge with i-STAT 1 System

This response outlines the acceptance criteria and the study that demonstrates the i-STAT hs-TnI Cartridge with the i-STAT 1 System meets these criteria, based on the provided FDA 510(k) summary.

1. Table of Acceptance Criteria and Reported Device Performance

The provided document doesn't explicitly list "acceptance criteria" in a single, consolidated table with pass/fail remarks. Instead, it presents performance characteristics and states whether the results "met the acceptance criteria" or "demonstrated acceptable performance." Based on this, the table below synthesizes the reported performance against inferred acceptance criteria.

Table: Acceptance Criteria and Reported Device Performance

Performance CharacteristicInferred Acceptance Criteria (e.g., Target Range, Deviation Limit, "Acceptable Performance")Reported Device Performance
Analytical Performance
20-Day Precision (Plasma)Results within acceptance criteria for all levels (e.g., CV% within specified limits, not explicitly stated as numerical values but implied by "demonstrated acceptable performance").All levels demonstrated acceptable performance, with Within-Laboratory CV% ranging from 3.68% to 15.89%. One outlier (0.07%) was excluded.
Whole Blood PrecisionWithin-site precision acceptable for all levels for each specimen type at each site (e.g., CV% within specified limits, not explicitly stated as numerical values but implied by "demonstrated to be acceptable").All levels and sites demonstrated acceptable performance. Within-Site CV% for whole blood ranged from 3.09% to 9.93%.
Plasma PrecisionWithin-site precision acceptable for all levels for each specimen type at each site (e.g., CV% within specified limits, not explicitly stated as numerical values but implied by "demonstrated to be acceptable").All levels and sites demonstrated acceptable performance. Within-Site CV% for plasma ranged from 2.57% to 12.80%. One outlier (0.38%) was excluded.
Precision in Control MaterialsResults demonstrate acceptable precision (e.g., CV% within specified limits, not explicitly stated as numerical values but implied by "acceptable").Within-Laboratory CV% ranged from 3.25% to 7.45%.
Multi-site Multi-Day PrecisionReproducibility within acceptable limits (e.g., CV% within specified limits, not explicitly stated as numerical values but implied by "acceptable").All levels demonstrated acceptable reproducibility. Reproducibility CV% ranged from 3.54% to 4.71%.
LinearityDemonstrated linearity over the reportable range (2.9 – 1000.0 ng/L) with a slope close to 1 and R^2 close to 1, meeting acceptance criteria (not explicitly stated as numerical range, but implied).Whole Blood: Slope = 1.025, Intercept = 0.183, R^2 = 0.9990. Plasma: Slope = 1.043, Intercept = -0.171, R^2 = 0.9993. Both met acceptance criteria over the reportable range.
Sample Type Comparison (WB vs. Plasma)Slope close to 1, Intercept close to 0, and high correlation (r) indicating equivalence.Slope = 1.01, Intercept = 0.603, r = 0.99.
High Dose Hook EffectNo hook effect observed up to 500,000 ng/L.No hook effect was observed for whole blood and plasma samples with cTnI concentrations up to 500,000 ng/L.
Limit of Blank (LoB)Determined from study results, ensuring minimal false positives.Whole Blood LoB: 0.78 ng/L; Plasma LoB: 0.57 ng/L.
Limit of Detection (LoD)Determined from study results, ensuring minimal false negatives.Whole Blood LoD: 1.61 ng/L; Plasma LoD: 1.05 ng/L.
Limit of Quantitation (LoQ)LoQ determined as 20% CV concentration using a precision profile method, with lower limit of reportable range set to the greater of WB and Plasma LoQ.Whole Blood LoQ: 2.90 ng/L. Lower limit of reportable range set to 2.9 ng/L.
Analytical Specificity (Interference)Difference between control and test samples within a pre-determined acceptable range (not explicitly quantified but implied by "No interference").Bilirubin (Unconjugated) showed decreased results > 85.5 µmol/L (5 mg/dL). Cefoxitin showed decreased results > 6564 µmol/L (295 mg/dL) in plasma. Fibrinogen showed decreased results > 0.4 g/dL in plasma. Rheumatoid Factor (RF) showed decreased results > 350 IU/mL in plasma. Total Protein showed decreased results ≥ 8.5 g/dL in plasma. All other listed substances showed no interference.
Analytical Specificity (Cross-reactivity)No cross-reactivity observed at specified concentrations.None of the nine substances tested (e.g., cTnT, CK-MB, Myoglobin, sTnI) were found to cross-react.
Hematocrit SensitivityImprecision not exceeding 10% and bias not exceeding ±10% for whole blood samples.Increased imprecision exceeding 10% for whole blood with hematocrit > 57 %PCV and increased bias exceeding ±10% for whole blood with hematocrit > 55 %PCV.
Altitude PerformanceEquivalent performance (slope close to 1, high correlation r) between simulated altitude (7,500 ft and 10,000 ft) and sea level.All conditions demonstrated equivalent performance: 7,500 ft (WB r=1.00, Plasma r=1.00), 10,000 ft (WB r=1.00, Plasma r=1.00) with slopes close to 1.
Comparison Studies
Matrix Equivalence (Non-Anticoagulated WB vs. Li-Heparin WB)Slope close to 1, Intercept close to 0, and high correlation (r) indicating equivalence.r = 1.00, Slope = 1.04, Intercept = -0.01. Demonstrated to be equivalent.
Matrix Equivalence (Li-Heparin Tube with Separator Gel vs. Li-Heparin Tube)Slope close to 1, Intercept close to 0, and high correlation (r) indicating equivalence for both whole blood and plasma.Whole Blood: r = 1.00, Slope = 1.01, Intercept = -0.15. Plasma: r = 1.00, Slope = 1.01, Intercept = 0.04. Demonstrated to be equivalent.
Clinical Sensitivity (Overall 99th Percentile URL)High sensitivity values, especially in later time points (>1 to 6 hours), with lower limits of 97.5% CI above specific thresholds (not numerically listed, but stated as a target for "acceptable performance").Female: 86.05% (0-1hr) to 95.71% (>3-6hr). Male: 83.08% (0-1hr) to 95.65% (>3-6hr). Plasma values were similar.
Clinical Specificity (Overall 99th Percentile URL)High specificity values above specific thresholds (not numerically listed, but stated as a target for "acceptable performance"). Note: lower specificity in longer time points/lower MI prevalence areas is expected.Female: 89.37% (0-1hr) to 65.91% (>6hr). Male: 78.33% (0-1hr) to 54.29% (>6hr). Plasma values were similar.
Clinical Sensitivity (Sex-Specific 99th Percentile URL)High sensitivity values, especially in later time points (>1 to 6 hours), with lower limits of 97.5% CI above specific thresholds (not numerically listed, but stated as a target for "acceptable performance").Female: 91.47% (0-1hr) to 100.00% (>6hr). Male: 79.23% (0-1hr) to 94.20% (>3-6hr). Plasma values were similar.
Clinical Specificity (Sex-Specific 99th Percentile URL)High specificity values above specific thresholds (not numerically listed, but stated as a target for "acceptable performance"). Note: lower specificity in longer time points/lower MI prevalence areas is expected.Female: 83.23% (0-1hr) to 54.55% (>6hr). Male: 84.17% (0-1hr) to 57.14% (>6hr). Plasma values were similar.

2. Sample Sizes and Data Provenance

  • Test Set Sample Size:

    • 20-Day Precision: 240 replicates per level for 6 plasma samples (total 1440 tests across 3 cartridge lots, 20 days).
    • Whole Blood and Plasma Precision: Min. 24 replicates per level (6 levels) per site (3 sites) for whole blood and plasma specimens. Total number of replicates for whole blood was 576, and for plasma was 576.
    • Precision in Control Materials: 25 replicates per level (5 levels) for control materials.
    • Multi-site Multi-Day Precision: 90 replicates per level (6 plasma samples) (total 540 tests across 3 sites, 5 days, 2 operators).
    • Linearity: Not explicitly stated as a single number but implied by samples covering the reportable range.
    • Sample Type Comparison (WB vs. Plasma): Not explicitly stated, implied by samples covering the reportable range.
    • High Dose Hook Effect: Not explicitly stated.
    • LoB/LoD: Not explicitly stated, but involved 4 healthy donors for each sample type and multiple cartridge lots.
    • LoQ: Not explicitly stated, but involved a low-level cTnI whole blood and plasma samples and 4 cartridge lots.
    • Interference: Tested at two cTnI levels using various interfering substances.
    • Cross-reactivity: Tested at three cTnI concentrations for each cross-reactive substance.
    • Hematocrit Sensitivity: Whole blood samples at two cTnI levels and seven hematocrit levels.
    • Altitude: Not explicitly stated as a single number but involved whole blood and plasma samples at relevant cTnI levels.
    • Matrix Equivalence (Non-Anticoagulated WB vs. Li-Heparin WB): 88 paired specimens (including 8 contrived).
    • Matrix Equivalence (Li-Heparin Tube with Separator Gel vs. Li-Heparin Tube): 87 paired specimens (including 8 contrived).
    • Clinical Sensitivity and Specificity: 3585 subjects presenting to the Emergency Department.

  • Data Provenance:

    • Analytical Performance Studies (Precision, Linearity, Hook Effect, LoB/LoD/LoQ, Interference, Cross-reactivity, Hematocrit, Altitude): These studies used a combination of frozen plasma samples, native venous whole blood and plasma specimens (prospectively collected), whole blood/plasma samples altered via spiking, control materials, and healthy donor samples. The studies were conducted at various clinical sites and internally at Abbott Point of Care.
    • Reference Interval Study: United States (US) based general population, prospectively collected venous whole blood specimens from 895 apparently healthy subjects at 8 clinical sites.
    • Matrix Equivalence Studies: Prospectively collected venous whole blood and plasma specimens from patients in point of care settings at two (2) clinical sites.
    • Clinical Sensitivity and Specificity (Pivotal Study): Prospectively collected venous whole blood and plasma specimens at 28 clinical sites in the United States. These sites were geographically diverse EDs associated with acute care hospitals, medical centers, tertiary care facilities, and primary care clinics.

3. Number of Experts and Qualifications for Ground Truth

  • Clinical Sensitivity and Specificity Study (Pivotal Study):

    • Number of Experts: Not explicitly stated as a specific number, but referred to as "board-certified cardiologists and/or emergency medicine physicians."
    • Qualifications: Board-certified cardiologists and/or emergency medicine physicians. No specific years of experience are detailed.
    • Role: Adjudicated subjects based on the fourth universal definition of MI.

  • Other Studies: The document does not indicate the involvement of external experts for establishing ground truth for other analytical performance or matrix equivalence studies. Ground truth for these was established through standard laboratory methods, spiked samples, and reference materials.

4. Adjudication Method for the Test Set

  • Clinical Sensitivity and Specificity Study: The adjudication method for the clinical study involved "adjudication by board-certified cardiologists and/or emergency medicine physicians based on the fourth universal definition of MI." The adjudicators were blinded to the i-STAT hs-TnI test results, indicating an independent review process. The specific number of adjudicators per case (e.g., 2+1, 3+1) is not provided, but the mention of plural "physicians" suggests at least two.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

  • The document does not mention a multi-reader multi-case (MRMC) comparative effectiveness study to assess how much human readers improve with AI vs. without AI assistance. The device is an in vitro diagnostic test (IVD) for quantitative measurement of cTnI, not an imaging device or AI-powered diagnostic aide for human interpretation.

6. Standalone (Algorithm Only) Performance Study

  • The performance studies described are inherently standalone for the device itself. The i-STAT hs-TnI cartridge with the i-STAT 1 System is a diagnostic test that provides a quantitative result. The clinical sensitivity and specificity are reported for the device's output (cTnI levels) as an aid in MI diagnosis, without human-in-the-loop interpretation of raw data from the device beyond reading the final numerical result.

7. Type of Ground Truth Used

  • Clinical Sensitivity and Specificity Study: The ground truth for the diagnosis of MI was established by expert consensus (board-certified cardiologists and/or emergency medicine physicians) based on the fourth universal definition of MI. This is a clinical outcome/diagnostic ground truth.
  • Analytical Studies:
    • Precision, Linearity, Hook Effect, LoB/LoD/LoQ, Interference, Cross-reactivity, Hematocrit, Altitude, Matrix Equivalence: Ground truth was established using a combination of:
      • Known concentrations in spiked samples.
      • Reference methods/materials (e.g., NIST SRM2921 for traceability).
      • Standard laboratory measurements and pre-defined expected values for linearity and comparison studies.
      • Clinical classification based on robust biomarker criteria (for the reference interval study of healthy subjects).

8. Sample Size for the Training Set

  • The document describes performance evaluation studies and does not explicitly differentiate a "training set" for an AI/machine learning model. The i-STAT hs-TnI test is an immunoassay (ELISA method with electrochemical detection), not a device based on AI/ML. Therefore, the concept of a "training set" for an algorithm is not directly applicable in the context of this device description. The studies described are for analytical and clinical validation of the assay.

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

  • As stated in point 8, the device is an immunoassay, not an AI/ML system, so there isn't a "training set" in that conventional sense. The "ground truth" for the various analytical and clinical studies (which could be considered analogous to data used for establishing performance) was established as described in point 7.

{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.

OwnerAbbott Point of Care Inc.400 College Road EastPrinceton, NJ 08540
ContactPrimary: Jacquelyn GesumariaManager Regulatory AffairsPhone: 609-454-9384Secondary: Mojgan SoleimaniDirector, Regulatory Strategy and Design QualityPhone: 613-295-0932
Date PreparedJanuary 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

ProductCodeDevice Classification NameRegulationNumberClassPanel
MMICreatinephosphokinase/creatine kinaseor isoenzymes test system862.1215IICH - ClinicalChemistry
JJEDiscrete photometric chemistryanalyzer for clinical use862.2160ICH - ClinicalChemistry

3. Predicate Device

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

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

ProductCodeDevice Classification NameRegulationNumberClassPanel
MMICreatinephosphokinase/creatine kinaseor isoenzymes test system862.1215IICH - ClinicalChemistry

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 orCharacteristicPredicate Device:PATHFAST hs-cTnI-II Test(K231974)Candidate Device:i-STAT hs-Tnl cartridge with thei-STAT 1 System
Intended UsePATHFAST hs-cTnI-II is an in vitrodiagnostic test for the quantitativemeasurement of cardiac Troponin I(cTnI) in heparinized or EDTA wholeblood and plasma. Measurements ofcardiac Troponin I are used to aid inthe diagnosis of acute myocardialinfarction (AMI).PATHFAST hs-cTnI-II is for use inclinical laboratory or point of care(POC) settings.The i-STAT hs-Tnl cartridge with thei-STAT 1 System is intended for use inthe in vitro quantification of cardiactroponin I (cTnI) in whole blood orplasma samples in point of care orclinical laboratory settings.The i-STAT hs-Tnl cartridge with thei-STAT 1 System is intended to be usedas an aid in the diagnosis ofmyocardial infarction (MI).
Intended UseSettingClinical Laboratory and Point of CareSame
DeviceClassificationClass IISame
Product CodeMMISame
RegulationNumber862.1215Same
MeasurandsCardiac Troponin I (cTnI)Same
AssayTechnologyChemiluminescent enzymeimmunoassayEnzyme-linked immunosorbent assay
Assay FormatSingle use cartridgeSame
DetectionTechnologyChemiluminescentElectrochemical
Sample TypeHeparinized and EDTA whole bloodand plasmaWhole blood and plasma
Sample Volume100 μL~22 μL
SamplePreparationReady to UseSame
SampleCollectionWith Na-heparin, Li-heparin or EDTA anticoagulantWith lithium heparin anticoagulant With lithium heparin tube with plasma separator gel Without anticoagulant
Table 1: Similarities and Differences: System (Test and Instrument)
Feature orCharacteristicPredicate Device:PATHFAST hs-cTnI-II Test(K231974)Candidate Device:i-STAT hs-Tnl cartridge with thei-STAT 1 System
Time to ResultWithin 17 minutes~ 15 minutes
ReportableResultQuantitative resultsSame
InstrumentPlatformPATHFAST Analyzeri-STAT 1 analyzer
CalibrationReagent lot: Initially by mastercalibration code, then by user withenclosed calibrators. Recalibrationrequired every four weeks.No calibration needed by the enduser; calibration is pre-set duringmanufacture of the cartridge.
TraceabilityThe calibrator for PATHFAST hs-cTnl istraceable to the reference materialNIST Standard Reference Material forHuman Cardiac Troponin ComplexSRM2921 of the National Institute ofStandard and Technology in USAwhich certified concentration forhuman cTnl.Cardiac troponin I values assigned toi-STAT controls and calibrationverification materials are traceable toi-STAT's working calibrators preparedfrom human cardiac troponin-ITCcomplex (NIST SRM2921).
Assay Cut-off99th percentile cutoff:0.029 ng/mL (29 ng/L)99th percentile cutoff:Female: 13 ng/LMale: 28 ng/LOverall: 21 ng/L
ReportableRange4.1 - 50,000 ng/L2.9 – 1000.0 ng/L
Time to Test/Sample Stability(Time fromcollection tocartridge fill)Whole Blood:With Heparin Anticoagulant:Within 4 hoursWhole Blood:With Lithium HeparinAnticoagulant:Within 4 hoursWithout Anticoagulant:Within 3 minutes
Plasma:With Heparin Anticoagulant:within 24 hoursPlasma:With Lithium HeparinAnticoagulant:within 4 hours
StorageConditionsRefrigerated 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
SampleLevelNMean(ng/L)RepeatabilityBetween-RunBetween-DayWithin-Laboratorya
SD(ng/L)%CVSD(ng/L)%CVSD(ng/L)%CVSD(ng/L)%CV
124011.701.78015.220.4483.830.2972.541.85915.89
1239b11.590.7556.520.1291.110.0260.220.7676.61
224015.620.6193.970.2621.680.2241.440.7094.54
324033.941.1843.490.3330.980.2110.621.2483.68
424084.252.7503.260.1630.190.4030.482.7843.30
5240511.9519.2983.774.8250.943.1890.6220.1463.94
6240786.6535.6364.539.3371.196.2910.8037.3724.75

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
SiteCardiacTroponinLevelNMin(ng/L)Max(ng/L)Mean(ng/L)RepeatabilitySDCV (%)Between-AnalyzerSDCV (%)Within-SiteSDCV (%)
11244.16.05.160.4578.860.2314.480.5139.93
22417.420.519.130.6813.560.2771.450.7353.84
32327.231.129.031.0563.640.0000.001.0563.64
424205.4263.0244.5013.5255.530.0000.0013.5255.53
524584.8721.2638.5031.3294.910.0000.0031.3294.91
623693.8792.7744.3726.2913.5318.8032.5332.3234.34
2122874.6983.5934.7722.9252.4520.8472.2330.9863.31
2246.69.77.390.5237.080.4395.940.6839.25
32318.922.420.321.0345.090.0000.001.0345.09
42342.148.744.221.3763.110.7081.601.5483.50
52337.242.739.971.4083.520.0000.001.4083.52
62464.877.471.443.1144.360.0000.003.1144.36
3123432.4523.8478.9518.5693.8810.2122.1321.1924.42
224554.9660.2606.6527.6844.5611.4181.8829.9464.94
324724.1844.9795.9333.1254.1615.1751.9136.4364.58
422812.4940.0881.1529.3343.3316.0481.8233.4373.79
52411.413.812.490.6094.870.2131.700.6455.16
62415.919.017.390.7724.440.0000.000.7724.44
412424.427.826.570.7572.850.5592.110.9413.54
22443.752.147.282.1614.570.0000.002.1614.57
323314.2370.4336.5813.9894.162.2330.6614.1664.21
423628.0763.3681.8930.9294.540.0000.0030.9294.54
524630.0800.1742.4336.9964.9823.5753.1843.8695.91
6 a24825.9946.2869.7026.8913.090.0000.0026.8913.09

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
SiteCardiacTroponinLevelNMin(ng/L)Max(ng/L)Mean(ng/L)RepeatabilityBetween -AnalyzerWithin-Site
SDCV (%)SDCV (%)SD
11235.69.56.080.76312.550.1542.530.77812.80
22318.322.120.580.9994.860.0000.000.9994.86
32328.632.430.830.8182.650.4451.440.9323.02
424225.3259.2243.9710.6884.381.1530.4710.7504.41
524548.1662.9602.7032.5725.400.0000.0032.5725.40
623679.6900.1764.5051.2556.707.6521.0051.8236.78
21247.48.68.030.3063.810.0921.140.3203.98
22420.023.822.590.8893.940.1440.640.9003.99
32440.648.944.191.5723.561.2472.822.0074.54
42472.481.176.811.9772.570.0000.001.9772.57
524464.4531.2499.7616.5753.329.7271.9519.2193.85
624624.3924.4712.1752.5917.3819.8812.7956.2237.89
3124591.7759.7680.0140.4295.950.0000.0040.4295.95
221858.5990.1945.6223.4192.4826.2802.7835.2013.72
32411.633.913.654.33031.710.0000.004.33031.71
423b11.613.412.770.3782.960.1301.020.4003.13
52422.933.224.841.9998.050.0000.001.9998.05
6 a23b22.926.324.480.9303.800.0000.000.9303.80
2417.220.618.800.7984.240.0000.000.7984.24
2443.149.947.001.7053.630.5971.271.8073.84
24315.9375.0338.2710.8933.229.0562.6814.1654.19
24631.8737.9672.2924.8133.690.0000.0024.8133.69
24664.0797.1743.0133.4514.506.6940.9034.1144.59
24768.8915.8847.9334.7014.090.0000.0034.7014.09

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 1System
FluidLevel*Mean(ng/L)NRepeatabilityBetween-DayWithin-Laboratory
SD (ng/L)%CVSD (ng/L)%CVSD (ng/L)%CV
CV12.85250.2027.070.0662.330.2127.45
L120.43250.6403.130.1780.870.6643.25
L298.46253.1083.160.9240.943.2423.29
CV2 / L3592.852528.2884.7712.6172.1330.9745.22
CV31174.292555.1174.6915.2961.3057.2004.87
  • 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)
LevelNMinMaxMeanRepeatabilityBetween-DayBetween-OperatorWithin-SiteBetween-SiteReproducibility
SD(95% CI)%CVSD(95% CI)%CVSD(95% CI)%CVSD(95% CI)%CVSD(95% CI)%CVSD(95% CI)%CV
19011.515.113.030.599(0.554,0.653)4.600.135(0.097,0.223)1.040.000(0.000,0.000)0.000.614(0.568,0.669)4.710.000(0.000,0.000)0.000.614(0.568,0.668)4.71
29016.119.217.680.564(0.521,0.614)3.190.225(0.162,0.372)1.280.200(0.151,0.296)1.130.639(0.582,0.710)3.620.000(0.000,0.000)0.000.639(0.582,0.710)3.62
39035.241.338.491.306(1.206,1.423)3.390.192(0.138,0.317)0.500.329(0.249,0.487)0.861.360(1.257,1.482)3.540.000(0.000,0.000)0.001.360(1.258,1.481)3.54
49081.6100.390.333.300(3.048,3.596)3.650.917(0.658,1.515)1.021.114(0.842,1.648)1.233.602(3.307,3.955)3.991.179(0.614,7.407)1.313.789(3.308,4.437)4.20
590482.5590.3543.2419.253(17.786,20.985)3.544.407(3.160,7.275)0.819.074(6.856,13.419)1.6721.735(19.785,24.116)4.000.000(0.000,0.000)0.0021.735(19.798,24.096)4.00
690714.3874.4791.6726.656(24.626,29.054)3.375.316(3.812,8.776)0.670.000(0.000,0.000)0.0027.181(25.154,29.567)3.4317.311(9.013,108.794)2.1932.225(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
AssaySample TypeTest SampleRange (ng/L)ReportableRange (ng/L)SlopeIntercept(ng/L)R2
hs-TnlWhole Blood1.1 – 1070.02.9 – 1000.01.0250.1830.9990
Plasma1.4 – 1050.82.9 – 1000.01.043-0.1710.9993

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 ComparisonSlopeInterceptr
WB vs. Plasma1.010.6030.99

{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 andOverall Population for the i-STAT hs-Tnl cartridge with the i-STAT 1 System
SexN99th Percentile UpperReference Limit (ng/L)90% Cl (ng/L)
Female49013(10, 17)
Male40428(19, 58)
Overall89521(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 TypeLoB (ng/L)LoD (ng/L)
Whole Blood0.781.61
Plasma0.571.05

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 withthe i-STAT 1 SystemLoQ*(ng/L)Lower Limit of theReportable Range (ng/L)
Whole Blood2.902.9
  • 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 Concentration1Interference (Yes/No)
Substanceumol/Lmg/dL, unlessspecified2Whole BloodPlasmaOverallComment
Acetaminophen103015.6NoNoNo
Acetylsalicylic Acid1673.01NoNoNo
Alkaline Phosphatase3060 (U/L)NoNoNo
(ALP)
Allopurinol4416.00NoNoNo
cartridge
Test Concentration1Interference (Yes/No)
Substanceμmol/Lmg/dL, unlessspecified2Whole BloodPlasmaOverallComment
Ambroxola96540NoNoNo
Ampicillin2157.51NoNoNo
Ascorbic Acid2985.25NoNoNo
Atenolol33.80.900NoNoNo
Bilirubin (Conjugated)47540.0NoNoNo
Bilirubin (Unconjugated)68440.0YesYesYesDecreased 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).
Biotin14.30.349NoNoNo
Bivalirudina18.33.99NoNoNo
Caffeine55610.8NoNoNo
Carvedilola37015NoNoNo
Cefoxitin15500697NoYesYesDecreased results > 6564 μmol/L (295 mg/dL)
Cholesterol10300398NoNoNo
Clopidogrela1807.5NoNoNo
Cocainea11.4060.346NoNoNo
Cyclosporine1.500.180NoNoNo
Diclofenac81.02.58NoNoNo
Digoxin0.04990.00390NoNoNo
Dopamine4.060.0770NoNoNo
Doxycycline40.52.08NoNoNo
Enalaprilat2.350.0903NoNoNo
Enoxaparina500 IU/dL5NoNoNo
Epinephrinea1.70.037NoNoNo
Eptifibatidea110.90NoNoNo
Erythromycin18813.8NoNoNo
Ethanol130000599NoNoNo
FibrinogenaN/A1 g/dLNoYesYesDecreased results > 0.4 g/dL. The reference range per literature for Fibrinogen is 0.2-0.4 g/dL3.
Fondaparinuxa2.30.40NoNoNo
Furosemide48.11.59NoNoNo
SubstanceTest Concentration1Interference (Yes/No)Comment
μmol/Lmg/dL, unless specified2Whole BloodPlasmaOverall
HemoglobinN/A1000NoNoNo
Human Anti-MouseAntibody (HAMA)a3000 (ng/mL)NoNoNo
Ibuprofen106021.9NoNoNo
Intralipid (Intralipid20%)aN/A3144NoNoNo
Isosorbide Dinitrate25.10.593NoNoNo
Levodopa38.00.749NoNoNo
Lithium Heparina~3160 IU/dLNoNoNo
Methyldopa1072.55NoNoNo
Methylprednisolone20.90.783NoNoNo
Metronidazole71912.3NoNoNo
Nicotine5.970.0969NoNoNo
Nifedipine1.700.0589NoNoNo
Nitrofurantoin8.940.213NoNoNo
Nystatina181.416.80NoNoNo
Oxytetracyclinea241.2NoNoNo
Phenobarbital297069.0NoNoNo
Phenylbutazone104032.1NoNoNo
Phenytoin2386.00NoNoNo
Pravastatin0.4880.0218NoNoNo
Primidone2615.70NoNoNo
Rheumatoid Factor(RF)a500 IU/mLNoYesYesDecreased results>350 IU/mL
Rifampicin58.34.80NoNoNo
Salicylic Acid2073.31NoNoNo
Simvastatin0.1990.00833NoNoNo
Sodium Heparin330 IU/dLNoNoNo
Theophylline3336.00NoNoNo
Tissue PlasminogenActivator (TPA)aN/A0.23NoNoNo
Total Protein(Human SerumAlbumin)N/A15 g/dLNoYesYesDecreased results ≥ 8.5 g/dL.The reference range per CLSIEP37 for Total Protein is 6.4-8.3 g/dL.
Triglyceride169401500NoNoNo
Trimethoprim1454.21NoNoNo
Verapamil3.510.172NoNoNo
Warfarin2437.49NoNoNo

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 <5.0 ng/L, 20 ng/L, and 600 ng/L) by comparing the performance of a test sample spiked with a potentially crossreactive substance and a control sample spiked with an equal volume of blank plasma diluent as per CLSI EP07 ED3.

None (0) of the nine (9) substances tested were found to cross-react with the i-STAT hs-TnI test in the i-STAT hs-TnI cartridge with the i-STAT 1 System when tested in whole blood and plasma.

Table 13: Cross-Reactivity Testing for the i-STAT hs-Tnl cartridge with the i-STAT 1 System
SubstanceSubstance TestConcentration (ng/L)Outcome (Cross-Reactivity/No Cross-Reactivity)
Actin1,000,000No Cross-Reactivity
Human Cardiac Troponin T (cTnT)1,000,000No Cross-Reactivity
Human Creatine Kinase MyocardialBand (CK-MB)1,000,000No Cross-Reactivity
Human Myoglobin1,000,000No Cross-Reactivity
Human Myosin LC (Light Chain)1,000,000No Cross-Reactivity
Human Skeletal Troponin I (sTnI)1,000,000No Cross-Reactivity
Human Skeletal Troponin T (sTnT)1,000,000No Cross-Reactivity
Human Troponin C (TnC)1,000,000No Cross-Reactivity
Tropomyosin1,000,000No Cross-Reactivity

Other sensitivity studies iii.

1) Hematocrit Sensitivity

The effect of hematocrit on the i-STAT hs-TnI test in the i-STAT hs-TnI cartridge with the i-STAT Sustem was assessed across a hematocrit range of 15-60% packed cell volume (PCV). The study was conducted using three (3) lots of i-STAT hs-ThI cartridges, i-STAT 1 analyzers and whole blood samples tested at two (2) cardiac troponin I levels (approximately 20 ng/L and 600 ng/L). Each cardiac troponin I level was evaluated at seven (7) hematocrit levels, with the nominal hematocrit level as control condition and the higher and lower hematocrit levels as test conditions.

The results of the study for the i-STAT hs-TnI test in the i-STAT hs-TnI cartridge with the i-STAT Sustem demonstrated increased imprecision exceeding 10% for whole blood samples with hematocrit values above 57 %PCV and increased bias exceeding ±10% for whole blood samples with hematocrit values above 55 %PCV.

{20}------------------------------------------------

2) Altitude

The performance of the i-STAT hs-TnI test in the i-STAT hs-TnI cartridge on the i-STAT 1 Sustem at two altitude conditions, approximately 7,500 and 10,000 feet above sea level, was evaluated in two separate test events using whole blood and plasma samples at relevant cardiac troponin I levels across the reportable range for the i-STAT hs-TnI test.

At each test event, the i-STAT hs-TnI results obtained from the i-STAT hs-TnI cartridges on the i-STAT 1 analyzer within a hypobaric chamber simulating approximately 7,500 feet (at test event 1) and 10,000 feet (at test event 2) above sea level (test conditions) were compared to the i-STAT hs-TnI results from testing outside of the chamber at sea level (comparator condition). A Passing-Bablok regression analysis comparing the test conditions to the comparator condition was performed based on the CLSI guidance EP09c: Measurement Procedure Comparison and Bias Estimation using Patient Samples, 3rd ed.

The results of the study demonstrated equivalent performance between the i-STAT hs-TnI cartridges tested at both a simulated altitude of 7.500 and 10.000 feet above sea level (test conditions) and the i-STAT hs-TnI cartridges tested at sea level (comparator condition) when evaluated with the i-STAT 1 Sustem using both whole blood and plasma samples. The results are summarized in Table 14 below.

Table 14: Altitude Study Results for the i-STAT hs-Tnl cartridge with the i-STAT 1 System
AltitudeConditionSample TyperCorrelation Coefficient (r)95% CISlopeSlope95% CI
7,500 ft.Whole Blood1.00(0.997, 0.998)0.99(0.983, 1.005)
Plasma1.00(0.998, 0.999)1.00(0.994, 1.013)
10,000 ftWhole Blood1.00(0.994, 0.997)1.02(1.003, 1.042)
Plasma1.00(0.995, 0.998)1.04(1.012, 1.050)

f. Assay Cut-Off

Refer to the Reference Range Section.

B. Comparison Studies

a. Matrix Equivalence - Non-Anticoagulated Whole Blood

A matrix equivalence study was conducted to evaluate the performance of the i-STAT hs-TnI test on the i-STAT hs-ThI cartridge on the i-STAT 1 Sustem using venous whole blood specimens collected in syringes without anticoagulant and specimens collected in lithium heparin tubes. The study was conducted using venous whole blood specimens prospectively collected from patients in point of care settings at two (2) clinical sites.

The study design and analysis method were based on recommendations from CLSI guideline EP35: Assessment of Equivalence or Suitability of Specimen Types for Medical Laboratory Measurement Procedures, 1st ed.

The matrix equivalence of the i-STAT hs-TnI test on the i-STAT hs-TnI cartridge using the i-STAT 1 analyzer between venous whole blood specimens collected in syringes without anticoagulant (candidate) and specimens collected in a lithium heparin tube (primary) was assessed using regression analyses comparing the candidate specimen type to the primary specimen type.

{21}------------------------------------------------

Each specimen was tested in duplicate using two (2) i-STAT hs-TnI cartridges with two (2) i-STAT 1 analyzers. A Passing-Bablok linear regression analysis was performed using the first replicate result from the candidate (y-axis) versus the first replicate result from the primary specimen (x-axis). The regression analysis results are summarized in Table 15. In the table. N is the number of paired specimens in the data set, and r is the correlation coefficient.

The performance of the venous whole blood specimens collected in syringes without anticoagulant (candidate) and whole blood specimens collected in a lithium heparin tube (primary) was demonstrated to be equivalent when tested using the i-STAT hs-TnI cartridge on the i-STAT 1 System.

Table 15: i-STAT hs-TnI Cartridge Matrix Equivalence Results – Non-anticoagulated Whole Blood vs.
Lithium Heparinized Whole Blood
N*Candidate SpecimenRange (ng/L)Primary SpecimenRange (ng/L)rSlopeIntercept
883.1 - 952.53.0 - 989.61.001.04-0.01
  • Includes 8 contrived whole blood specimens spiked with ≤ 5% v/v recombinant cardiac troponin I antigen tested internally at Abbott Point of Care.

b. Matrix Equivalence - Lithium Heparin Tube with Separator Gel (Whole Blood and Plasma)

A matrix equivalence study was conducted to evaluate the performance of the i-STAT hs-TnI test on the i-STAT hs-TnI cartridge on the i-STAT 1 System using venous whole blood and plasma specimens collected in a lithium heparin tube with a gel separator and specimens collected in lithium heparin tubes. The study was conducted using venous whole blood and plasma specimens prospectively collected from patients in point of care settings at two (2) clinical sites.

The study design and analysis method were based on recommendations from the Clinical and Laboratory Standards Institute (CLSI) guideline EP35: Assessment of Equivalence or Suitability of Specimen Types for Medical Laboratory Measurement Procedures, 1st ed.

The matrix equivalence was assessed by comparing whole blood and plasma specimens collected in lithium heparin tube with separator gel (candidate) to the specimens collected in a lithium heparin tube (primary) using regression analyses comparing the candidate specimen type to the primary specimen type.

Each specimen was tested in duplicate using two (2) i-STAT hs-TnI cartridges with two (2) i-STAT 1 analyzers. A Passing-Bablok linear regression analysis was performed using the first replicate result from the candidate (y-axis) versus the first replicate result from the primary specimen (x-axis). The regression analysis results are summarized in Table 16. In the table, N is the number of paired specimens in the data set, and r is the correlation coefficient.

The performance of the i-STAT hs-TnI test in the i-STAT hs-TnI cartridge on the i-STAT 1 analyzer when tested using the candidate and primary specimens for both whole blood and plasma was demonstrated to be equivalent.

Table 16: i-STAT hs-Tnl Cartridge Matrix Equivalence Results – Lithium Heparin Tube with Separator
Gel vs. Lithium Heparin Tube (Whole Blood and Plasma)
Sample TypeN*Candidate SpecimenRange (ng/L)Primary SpecimenRange (ng/L)SlopeIntercept
Whole Blood872.9 - 935.13.0 - 930.51.001.01-0.15

{22}------------------------------------------------

Table 16: i-STAT hs-Tnl Cartridge Matrix Equivalence Results – Lithium Heparin Tube with Separator
Gel vs. Lithium Heparin Tube (Whole Blood and Plasma)
Sample TypeN*Candidate Specimen Range (ng/L)Primary Specimen Range (ng/L)rSlopeIntercept
Plasma873.4 – 942.93.4 – 930.91.001.010.04
  • Includes 8 contrived whole blood and plasma spiked with ≤ 5% v/v recombinant cardiac troponin I antigen tested internally at Abbott Point of Care.

C. Clinical Sensitivity and Specificity

A pivotal study using prospectively collected venous whole blood and plasma specimens was conducted at 28 clinical sites to assess diagnostic accuracy of the i-STAT hs-TnI test in the i-STAT hs-TnI cartridge with the i-STAT 1 System. The facilities used and the study staff that performed the testing were representative of point of care end-users.

Venous whole blood specimens collected into lithium heparin tubes from 3585 subjects presenting to the Emergency Department (ED) with chest discomfort or equivalent ischemic symptoms consistent with Acute Coronary Syndrome (ACS) were included in the clinical performance evaluation.

The study sites represented geographically diverse EDs associated acute care hospitals, medical centers, tertiary care facilities, and primary care clinics with patient populations representing regional, urban, and rural areas of the United States. Subjects were adjudicated by boardcertified cardiologists and/or emergency medicine physicians based on the fourth universal definition of MI. The adjudicators were blinded to the i-STAT hs-TnI test results. The observed MI prevalence in this study was 6.8% for females and 11.6% for males, as shown in Table 17 below.

Table 17: MI prevalence in the i-STAT hs-TnI cartridge Pivotal Study
SexMisNon-MIsTotal Subjects% MI Prevalence
Female subjects157213822956.8
Male subjects1501140129011.6

An analysis for both females and males was performed using overall (21 ng/L) and sex-specific (female 13 ng/L, male 28 ng/L) 99th percentile URL to demonstrate the clinical performance (clinical sensitivity, clinical specificity, positive predictive value (PPV) and negative predictive value (NPV)) of the i-STAT hs-TnI test in the i-STAT hs-TnI cartridge with the i-STAT 1 Sustem to aid in the diagnosis of MI. The results are summarized in Table 18 through Table 21 below.

NOTE: Of the specimens collected at greater than or equal to 6 hours, specimens were collected within 9 hours from presentation to the ED, except for 6 specimens from 3 female subjects collected within 10 hours from presentation to the ED, and 4 specimens from a male subject collected within 23 and 25 hours.

{23}------------------------------------------------

Image /page/23/Picture/0 description: The image shows the Abbott logo. The logo consists of a stylized letter "A" in blue, followed by the word "Abbott" in black, bold font. The "A" is made up of three horizontal bars, with the top bar being the shortest and the bottom bar being the longest. The logo is simple and modern, and it is easily recognizable.

Table 18: Clinical performance for the i-STAT 1 System in whole blood using the overall 99th percentile URL (21 ng/L)

SexTime Point(hours)NMINon-MISensitivity (%)Specificity (%)PPV (%)NPV (%)
EstimateLower Limitof One Sided97.5% CIEstimateLower Limit ofOne Sided97.5% CIEstimateLower Limit ofOne Sided97.5% CIEstimateLower Limitof One Sided97.5% CI
Female0 to 11870129174186.0579.0289.3787.8437.5032.1898.8698.20
>1 to 31799119168092.4486.2589.7088.1638.8733.3899.4198.88
>3 to 67247065495.7188.1485.7882.8941.8834.5199.4798.45
>660164493.7571.6765.9151.1450.0033.1596.6783.33
Male0 to 1109013096083.0875.7078.3375.6234.1829.1797.1695.73
>1 to 3102511890792.3786.1477.9575.1435.2830.1698.7497.63
>3 to 64396937095.6587.9874.3269.6440.9933.6998.9296.88
>647123591.6764.6154.2938.1940.7424.5195.0076.39

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)MISensitivity (%)Specificity (%)PPV (%)NPV (%)
SexNNon-MI
EstimateLower Limitof One Sided97.5% CIEstimateLower Limit ofOne Sided97.5% CIEstimateLower Limit ofOne Sided97.5% CIEstimateLower Limitof One Sided97.5% CI
Female0 to 11870129174191.4785.3883.2381.4028.7824.6199.2598.66
Female>1 to 31799119168096.6491.6882.1480.2427.7123.6299.7199.26
Female>3 to 67247065497.1490.1777.8374.4931.9226.0399.6198.58
Female>6601644100.0080.6454.5540.0744.4429.54100.0086.20
Male0 to 1109013096079.2371.4784.1781.7240.3934.5696.7795.34
Male>1 to 3102511890790.6884.0883.9081.3742.2936.3698.5897.47
Male>3 to 64396937094.2086.0282.9778.8150.7842.2298.7196.74
Male>647123591.6764.6157.1440.8642.3125.5495.2477.33

{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)
SexTime Point(hours)NMINon-MISensitivity (%)Specificity (%)PPV (%)NPV (%)
EstimateLower Limitof One Sided97.5% CIEstimateLower Limitof One Sided97.5% CIEstimateLower Limitof One Sided97.5% CIEstimateLower Limitof One Sided97.5% CI
Female0 to 11865128173786.7279.7689.2387.6937.2531.9598.9298.27
>1 to 31799118168192.3786.1489.6588.1038.5233.0499.4198.88
>3 to 67237065394.2986.2185.7682.8741.5134.1499.2998.19
>660164493.7571.6768.1853.4451.7234.4396.7783.81
Male0 to 1109213096283.0875.7078.1775.4533.9628.9897.1695.73
>1 to 3102111790492.3186.0277.1074.2534.2929.2698.7397.60
>3 to 64396937095.6587.9873.2468.5140.0032.8398.9196.83
>647123591.6764.6154.2938.1940.7424.5195.0076.39

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)

SexTime Point(hours)NMINon-MISensitivity (%)Specificity (%)PPV (%)NPV (%)
EstimateLower Limitof One Sided97.5% CIEstimateLower Limitof One Sided97.5% CIEstimateLower Limitof One Sided97.5% CI
Female0 to 11865128173792.1986.2282.2780.4027.7023.6699.3198.73
>1 to 31799118168196.6191.6181.6879.7627.0123.0099.7199.26
>3 to 67237065397.1490.1777.1873.8131.3425.5399.6098.57
>6601644100.0080.6454.5540.0744.4429.54100.0086.20
Male0 to 1109213096279.2371.4783.2680.7739.0233.3396.7495.30
>1 to 3102111790490.6083.9582.7480.1440.4634.6998.5597.42
>3 to 64396937094.2086.0280.2775.9147.1038.9698.6796.63
>647123591.6764.6154.2938.1940.7424.5195.0076.39

{25}------------------------------------------------

Image /page/25/Picture/0 description: The image shows the Abbott logo. The logo consists of a stylized letter "a" in a blue box on the left, and the word "Abbott" in black, bold letters on the right. The logo is simple and modern, and it is easily recognizable.

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.

§ 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.