The i-STAT PTP45 cartridge is intended for use in the in vitro quantitative measurement of the extrinsic coagulation pathway when activated by thromboplastin in non-anticoagulated whole blood (venous or capillary), using the i-STAT 1 System. Measurements of prothrombin time are used to aid in the monitoring of patients receiving anticoagulant therapy with coumarin derivatives. The i-STAT PT246 Prothrombin Time test result is reported in seconds and as an International Normalized Ratio (INR). The test is intended for point of care use and is for prescription use only.

Device Description

The i-STAT 1 System consists of the i-STAT 1 analyzer and the i-STAT cartridges. Other components of the i-STAT 1 System are the Electronic Simulator, the i-STAT 1 Downloader/Recharger and the i-STAT Printer. The i-STAT 1 analyzer is a handheld, in vitro diagnostic analytical device designed to run only i-STAT test cartridges. The system is designed for use by trained medical professionals at the patient point of care or in the clinical laboratory and is for prescription use only.

The i-STAT PTPlus cartridge is a coagulation cartridge for determining the time required for complete activation of the extrinsic coagulation cascade. The cartridge contains electrochemical sensors and test reagents that must be mixed with the sample. The reagents include the reactive ingredient to activate the coagulation cascade as well as electrochemical markers that generate a sensor signal when the cascade is fully activated.

The analysis time of the i-STAT PT2405 cartridge is up to 300 seconds (5 minutes). The sample volume required for the i-STAT PT2105 cartridge is approximately 20 ul of whole blood (venous or capillary) without added anticoagulant. The i-STAT PTplus cartridge is a single-use disposable unit that is self-contained. The test reagents and sample fluids do not contact the instrument or user. All the test steps and fluid movements occur within the cartridge.

The i-STAT 1 System has an internal quality control (internal simulator) and an external quality control (Electronic Simulator). The internal and external simulators are used to check the instrument signal-reading function. In addition to the quality controls within the i-STAT 1 System, liquid quality controls are available as an optional quality control methodology to meet the regulatory compliance requirements applicable to the facility where they are to be used.

The liquid quality controls are the i-STAT PT2008 Control Levels 1 and 2 and can be used for the quality control of the i-STAT PT2005 cartridge. The coagulation controls consist of lyophilized citrated human plasma and calcium chloride fluid for reconstitution.

i-STAT PT2145 Control Level 1 has been formulated to produce a normal prothrombin time. Level 2 has been formulated to produce an extended prothrombin time.

Each level of control is packaged as a box of 5 vials containing 1 mL of lyophilized citrated human plasma and 5 vials of 1.5 mL of calcium chloride diluent.

The i-STAT PT2"45 controls are intended for use with the i-STAT PTP"46 cartridge on the i-STAT System, and values assigned to these controls may not be commutable with other commercial methods.

AI/ML Overview

Here's an analysis of the provided FDA 510(k) summary for the i-STAT PTplus Cartridge with the i-STAT 1 System, structured to address your request about acceptance criteria and study proof.

Device: i-STAT PTplus Cartridge with the i-STAT 1 System
Device Name: Prothrombin Time Test
Regulation Number: 21 CFR 864.7750
Regulatory Class: Class II

This document is a 510(k) summary, which focuses on demonstrating substantial equivalence to a predicate device, rather than defining specific pre-defined acceptance criteria in the same way one might for a novel high-risk device or an AI/ML product where clinical endpoints are primary. For an IVD like a PT test, the "acceptance criteria" are generally established through analytical performance metrics that demonstrate equivalence or non-inferiority to a legally marketed predicate and established scientific principles for laboratory tests. The studies predominantly prove analytical performance.

1. Table of Acceptance Criteria and Reported Device Performance

Given this is a 510(k) for an In Vitro Diagnostic (IVD) device, the "acceptance criteria" aren't explicitly stated as pass/fail thresholds against specific performance numbers in the summary. Instead, they are implicitly defined by robust analytical performance demonstrating precision, linearity, traceability, and method comparison with a predicate and a reference method. The goal is to show the new device performs comparably and acceptably for its intended use.

Here, I've interpreted "acceptance criteria" as ranges or levels of performance that are considered acceptable for a prothrombin time test, and then listed the reported device performance.

Performance Metric	Implicit Acceptance Criteria (General for IVD PT Test)	Reported Device Performance (i-STAT PTplus)
Reportable Range (INR)	Must cover clinically relevant range. Predicate range: 0.8-8.0 INR. New device should cover at least this and ideally extend.	0.8 - 8.0 INR (matches predicate in lower-to-mid range, extends higher in seconds)
Reportable Range (seconds)	Must cover clinically relevant range. (Predicate only specifies INR).	8.1 - 80.8 seconds (extends beyond the predicate's specified INR range when converted to seconds).
Precision/Reproducibility	Low coefficient of variation (CV%) and standard deviation (SD) across different levels (normal, therapeutic, high) and testing conditions (within-run, between-run, between-day). Comparable to predicate or established clinical standards.	Liquid Controls (Within-laboratory for INR): L1 (1.03 INR): SD 0.031 (3.0% CV) (Lot A), SD 0.034 (3.3% CV) (Lot B), SD 0.029 (2.8% CV) (Lot C) L2 (2.43 INR): SD 0.090 (3.7% CV) (Lot A), SD 0.090 (4.0% CV) (Lot B), SD 0.058 (2.5% CV) (Lot C) L3 (5.34 INR): SD 0.366 (6.8% CV) (Lot A), SD 0.208 (4.2% CV) (Lot B), SD 0.090 (1.7% CV) (Lot C) Whole Blood (Capillary INR): Non-therapeutic (1.48 INR): SD 0.143 (9.7% CV) Therapeutic (2.82 INR): SD 0.148 (5.2% CV) Very High Therapeutic (5.02 INR): SD 0.201 (4.0% CV) Whole Blood (Venous INR): Non-therapeutic (1.45 INR): SD 0.109 (7.5% CV) Therapeutic (2.85 INR): SD 0.069 (2.4% CV) Very High Therapeutic (5.38 INR): SD 0.088 (1.6% CV)
Method Comparison (vs. Predicate)	High correlation (R value close to 1), slope close to 1, and intercept close to 0, indicating strong agreement with the predicate device.	Venous (INR): N=191, R=0.98, Slope=0.875, Intercept=0.113 Capillary (INR): N=153, R=0.97, Slope=0.885, Intercept=0.104
Method Comparison (vs. Reference)	High correlation (R value close to 1), slope close to 1, and intercept close to 0, indicating strong agreement with the reference method (	Venous (INR): N=211, R=0.92, Slope=1.037, Intercept=0.004 Capillary (INR): N=203, R=0.91, Slope=1.022, Intercept=0.047
Interference	No clinically significant interference from common endogenous/exogenous substances at specified concentrations.	No interference found for most tested substances. Interference identified for Chlorhexidine digluconate (≥ 9.58x10^-4 %), Daptomycin (≥ 0.22 mg/mL), and Oritavancin (≥ 104 mg/L). This "interference" is a finding and typically results in a warning or limitation in the labeling rather than a failure of acceptance criteria if the impact is characterized.
Factor Sensitivity (FII, FV, FVII, FX)	Device should show expected sensitivity to factor deficiencies.	FII - 39.5%; FV - 42.0%; FVII - 21.5%; FX - 22.0% (estimated sensitivity at which the device detects a change)
Fibrinogen Sensitivity	Insensitive to changes in fibrinogen within a specified range.	Insensitive across 63 – 702 mg/dL.
Platelet Sensitivity	Insensitive to changes in platelet count within a specified range.	Insensitive in the range of 70,000 - 670,000/mm².
Hematocrit Sensitivity	Insensitive to changes in hematocrit within a specified range.	Insensitive in the range of 24 to 54% PCV.
Heparin Sensitivity	Insensitive to unfractionated heparin up to a certain concentration.	Insensitive up to 1.0 IU/mL.
Lupus Anticoagulant Sensitivity	May or may not be sensitive; characterization is important for clinical context.	Sensitive to both low and high levels of lupus anticoagulant antibodies.
Reference Range	Established normal range for healthy individuals.	Capillary: 0.9 - 1.3 INR (Mean 1.1 INR), 9.0 - 13.8 seconds (Mean 10.6 seconds) Venous: 0.9 - 1.3 INR (Mean 1.1 INR), 9.2 - 13.0 seconds (Mean 10.6 seconds)

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

Precision/Reproducibility (Liquid Controls): N=104-120 per fluid level per cartridge lot (total of 9 measurements * ~115 samples = ~1035 data points). Data provenance implied as internal laboratory study.
Precision (Whole Blood):
- Capillary: N=58 (non-therapeutic), N=119 (therapeutic), N=9 (very high therapeutic).
- Venous: N=65 (non-therapeutic), N=131 (therapeutic), N=13 (very high therapeutic).
- Data provenance: Samples collected from "three (3) point of care sites" for repeatability analysis. Implied retrospective or prospective collection based on CLSI guidelines.
Method Comparison (vs. Predicate):
- Venous: N=191* (samples with outliers included)
- Capillary: N=153* (samples with outliers included)
- Data provenance: "prospectively collected from subjects undergoing anticoagulant therapy with coumarin derivates and from subjects who were not on anticoagulant therapy at three (3) clinical sites." (Prospective)
Method Comparison (vs. Reference):
- Venous: N=211* (samples with outliers included)
- Capillary: N=203* (samples with outliers included)
- Data provenance: "prospectively collected from subjects undergoing anticoagulant therapy with coumarin derivates and from subjects who were not on anticoagulant therapy at three (3) clinical sites." (Prospective)
Interference: Not explicitly stated N, but implied adequate for the substances tested.
Factor Sensitivity: Not explicitly stated N.
Fibrinogen, Platelet, Hematocrit, Heparin Sensitivity, Lupus Anticoagulant: Not explicitly stated N.
Reference Range:
- Capillary: N=146
- Venous: N=154
- Data provenance: "apparently healthy adult subjects" from "three (3) clinical sites." (Likely Prospective)

Country of Origin: Not explicitly stated, but "CLSI guidelines" are US-based and "FDA" approval implies US studies or studies compliant with US standards. Assuming US/North American origin.

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

This section is not applicable in the context of this device. This is an In Vitro Diagnostic (IVD) device for measuring a quantitative biomarker (prothrombin time). The "ground truth" for these studies is typically established by:

Reference Methods: Such as the Sysmex CS-2500 instrument in this case, which is a laboratory instrument considered a more definitive measurement.
Predicate Devices: The CoaguChek® XS Plus System, which is a legally marketed device used for comparison to demonstrate equivalence.
Assigned Values for Controls/Calibrators: For analytical precision and linearity.
Clinical Outcomes/Pathology: Not used directly for establishing "ground truth" for the PT measurement itself, but the PT values might be correlated with outcomes in broader clinical studies (which are not detailed here as part of the 510k).

There are no human "experts" rating images or making diagnoses that would require adjudication; the measurements are quantitative.

4. Adjudication Method for the Test Set

Not applicable. As a quantitative IVD, there is no subjective rating or interpretation by multiple readers that would require an adjudication method (like 2+1, 3+1 consensus for imaging studies). Measurements from instruments are taken as-is for statistical analysis.

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

Not applicable. This is an In Vitro Diagnostic (IVD) device, not an AI/ML imaging device that assists human readers. Therefore, an MRMC study and analysis of human reader improvement with AI assistance are not relevant to this submission.

6. Standalone (Algorithm Only) Performance

The device itself (i-STAT PTplus Cartridge with the i-STAT 1 System) is the "standalone" diagnostic method. Its performance is measured directly by comparing its results to a predicate device and a laboratory reference instrument (Sysmex CS-2500). There isn't a separate "algorithm" that generates interpretations for human-in-the-loop use. The reported analytical performance (precision, correlation, etc.) reflects its standalone performance.

7. The Type of Ground Truth Used

The ground truth for evaluating the i-STAT PTplus cartridge performance was established primarily through:

Validated Reference Method: The Sysmex CS-2500 (using Dade Innovin reagent) for venous plasma measurements, considered a reliable laboratory method for PT.
Legally Marketed Predicate Device: The CoaguChek® XS Plus System, used for direct comparison to demonstrate substantial equivalence.
Internal Control Fluids/Levels: For precision studies against known or assigned values.
Clinical Samples: From patients on and not on anticoagulant therapy, characterized by their clinical status.

8. The Sample Size for the Training Set

Not applicable. This device does not use machine learning or AI that requires a "training set" in the traditional sense. It's a chemical and electrochemical analysis system. The development and internal validation of the cartridge's reagents and measurement principles would involve extensive R&D and analytical testing, but this isn't structured as a conventional ML training set.

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

Not applicable. As stated above, there is no AI/ML training set for this device. The "ground truth" for development and validation would involve standard analytical chemistry and medical device engineering practices, using reference materials, spiked samples, and clinical samples analyzed by established laboratory methods.

Summary

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Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, with the letters "FDA" in a blue square. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

July 14, 2023

Abbott Laboratories Melissa Tristani Senior Regulatory Affairs Specialist 400 College Road East Princeton, New Jersey 08540

Re: K220282

Trade/Device Name: i-STAT PTplus Cartridge with the i-STAT I System Regulation Number: 21 CFR 864.7750 Regulation Name: Prothrombin Time Test Regulatory Class: Class II Product Code: GJS Dated: January 31, 2022 Received: February 1, 2022

Dear Melissa Tristani:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. 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 located 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.

Please note that if you modify your IVD in the future to exceed any of the limitations to the exemption found in 21 CFR 864.9(c), your device will require a new 510(k) prior to marketing this device in the United States and will not be exempt from the premarket notification requirements so long as it exceeds the limitations to the exemption found in 21 CFR 864.9.

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

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Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-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 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 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.

For comprehensive regulatory information about medical devices and radiation-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,

Takeesha Taylor-bell -S

Takeesha Taylor-Bell Deputy Director Division of Immunology and Hematology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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Abbott Point of Care / Traditional 510(k) /
i-STAT PTplus cartridge with the i-STAT 1 System

DEPARTMENT OF HEALTH AND HUMAN SERVICES	Form Approved: OMB No. 0910-0120
Food and Drug Administration	Expiration Date: 06/30/2023

Indications for Use
See PRA Statement below.510(k) Number (if known)

Device Name

i-STAT PTPlus cartridge with the i-STAT 1 System

Indications for Use (Describe)

Type of Use (Select one or both, as applicable)
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."

Page 1 of 1

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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
Owner	Abbott Point of Care Inc.400 College Road EastPrinceton, NJ 08540
Contact	Primary: Melissa TristaniSenior Regulatory Affairs SpecialistPhone: 613-688-5949Secondary contact person for allcommunications: Maria L FigueroaAssociate Director Regulatory AffairsPhone: 609-454-9271
Date Prepared	January 28, 2022

2. Device Information

Proprietary Name	i-STAT PTplus cartridge with the i-STAT 1 System
Common Name	Prothrombin time, PT, analyzer, handheld

Productcode	Device Classificationname	RegulationNumber	Class	Panel
GJS	Test, Time, Prothrombin	864.7750	II	Hematology

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3. Predicate Device

Proprietary Name CoaguChek® XS Plus System

510(k) Number K071041

Productcode	Device Classificationname	RegulationNumber	Class	Panel
GJS	Test, Time, Prothrombin	864.7750	II	Hematology

Device Description 4.

The liquid quality controls are the i-STAT PT2008 Control Levels 1 and 2 and can be used for the quality control of the i-STAT PT2005 cartridge. The coagulation controls

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consist of lyophilized citrated human plasma and calcium chloride fluid for reconstitution.

i-STAT PT2145 Control Level 1 has been formulated to produce a normal prothrombin time. Level 2 has been formulated to produce an extended prothrombin time.

Each level of control is packaged as a box of 5 vials containing 1 mL of lyophilized citrated human plasma and 5 vials of 1.5 mL of calcium chloride diluent.

The i-STAT PT2"45 controls are intended for use with the i-STAT PTP"46 cartridge on the i-STAT System, and values assigned to these controls may not be commutable with other commercial methods.

5. Intended Use Statement

The i-STAT PTplus cartridge is intended for use in the in vitro quantitative measurement of the clot time of the extrinsic coagulation pathway when activated by thromboplastin in non-anticoagulated whole blood (venous or capillary), using the i-STAT 1 System. Measurements of prothrombin time are used to aid in the monitoring of patients receiving anticoagulant therapy with coumarin derivatives. The i-STAT PT20145 Prothrombin Time test result is reported in seconds and as an International Normalized Ratio (INR). The test is intended for point of care use and is for prescription use only.

	Table 1: Summary Comparison
Feature orCharacteristic	Candidate:i-STAT PTplus cartridge with the i-STAT1 System	Predicate:CoaguChek® XS Plus System(K071041)
Intended Use	The i-STAT PTplus cartridge is intended for usein the in vitro quantitative measurement of theclot time of the extrinsic coagulation pathwaywhen activated by thromboplastin in non-anticoagulated whole blood (venous orcapillary), using the i-STAT 1 System.Measurements of prothrombin time are usedto aid in the monitoring of patients receivinganticoagulant therapy with coumarinderivatives. The i-STAT PTplus ProthrombinTime test result is reported in seconds and asan International Normalized Ratio (INR). Thetest is intended for point of care use and is forprescription use only.	Intended for use by professionalhealthcare providers forquantitative prothrombin timetesting for the monitoring ofwarfarin therapy. The system usesfresh capillary or non-anticoagulated venous wholeblood.
ReportableRange	0.8-8.0 INR8.1-80.8 seconds	0.8-8.0 INR
Sample Type	Fresh whole blood from venous or capillarysamples	Same

Summary Comparison of Technological Characteristics 6.

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Table 1: Summary Comparison
Feature orCharacteristic	Candidate:i-STAT PTplus cartridge with the i-STAT1 System	Predicate:CoaguChek® XS Plus System(K071041)
Sample Volume	Approximately 20 µL	Minimum of 10 µL
SamplePreparation	Ready to Use. No sample preparation required.	Same
Traceability	Traceable to the WHO international reference method.	Same
Reagent	Human recombinant thromboplastin.	Same
ElectronicQualityControls	On-board quality control built into the analyzer and external Electronic Simulator.	On-board quality control which uses electrochemical signal to detect test strip integrity.
Liquid QualityControls	Two levels of liquid controls	Same
Principle ofMeasurement	Electrochemical technology with amperometric (electric current) detection of thrombin activity	Same
Analyzer Type	Handheld	Same

Performance Characteristics 7.

A. Analytical Performance

a. Precision/Reproducibility:

Precision 20 days (Liquid Controls) i.
The precision of the prothrombin time test in the i-STAT PT2465 cartridge was evaluated using three (3) lots of i-STAT PT2"16 cartridges and three (3) fluid levels. The fluids included the i-STAT PT2145 Controls (Levels 1 and 2) as well as an internal fluid level (Level 3). The study was performed based on CLSI document EP05-A3: Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline-Third Edition. Each cartridge and fluid level was tested over 20 days by two operators running two test events per day at one site. The results of the 20-day precision study are shown in Table 2 (seconds) and Table 3 (INR).

Table 2: 20 Day Precision Results (seconds)
CartridgeLot	FluidLevel	N	Mean	Within-run		Between-run		Between-day		Within-laboratory
			(sec)	SD(sec)	%CV	SD(sec)	%CV	SD(sec)	%CV	SD (sec)	%CV
A	L1	119	10.38	0.279	2.7	0.019	0.2	0.134	1.3	0.310	3.0
	L2	116	24.51	0.881	3.6	0.227	0.9	0.075	0.3	0.912	3.7
	L3	104	53.95	3.488	6.5	0.986	1.8	0.709	1.3	3.693	6.8

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	Table 2: 20 Day Precision Results (seconds)
CartridgeLot	FluidLevel	N	Mean(sec)	Within-run		Between-run		Between-day		Within-laboratory
				SD(sec)	%CV	SD(sec)	%CV	SD(sec)	%CV	SD (sec)	%CV
B	L1	120	10.36	0.279	2.7	0.065	0.6	0.186	1.8	0.342	3.3
	L2	119	22.82	0.812	3.6	0.272	1.2	0.298	1.3	0.906	4.0
	L3	118	49.54	1.884	3.8	0.734	1.5	0.568	1.1	2.099	4.2
C	L1	120	10.58	0.266	2.5	0.128	1.2	0.004	0.0	0.295	2.8
	L2	120	23.62	0.540	2.3	0.139	0.6	0.189	0.8	0.589	2.5
	L3	117	52.07	0.818	1.6	0.332	0.6	0.211	0.4	0.907	1.7

Table 3: 20-day Precision Results (INR)
CartridgeLot	FluidLevel	N	Mean(INR)	Within-run		Between-run		Between-day		Within-laboratory
				SD(INR)	%CV	SD(INR)	%CV	SD(INR)	%CV	SD(INR)	%CV
A	L1	119	1.03	0.028	2.7	0.002	0.2	0.013	1.3	0.031	3.0
	L2	116	2.43	0.087	3.6	0.022	0.9	0.007	0.3	0.090	3.7
	L3	104	5.34	0.345	6.5	0.098	1.8	0.070	1.3	0.366	6.8
B	L1	120	1.03	0.028	2.7	0.006	0.6	0.018	1.8	0.034	3.3
	L2	119	2.26	0.080	3.6	0.027	1.2	0.029	1.3	0.090	4.0
	L3	118	4.91	0.186	3.8	0.073	1.5	0.056	1.1	0.208	4.2
C	L1	120	1.05	0.026	2.5	0.013	1.2	0.000	0.0	0.029	2.8
	L2	120	2.34	0.053	2.3	0.014	0.6	0.019	0.8	0.058	2.5
	L3	117	5.16	0.081	1.6	0.033	0.6	0.021	0.4	0.090	1.7

ii. Precision (Whole Blood)

Whole blood precision (repeatability) was evaluated using venous and capillary specimens at three (3) ranges: non-therapeutic (INR 0.8 - 1.9), therapeutic (INR 2.0 -4.5), and very high therapeutic (INR 4.6 - 8.0). The repeatability analysis was conducted using the data collected across three (3) point of care sites. Data from duplicate testing in both the capillary method comparison study and the venous method comparison study were used to evaluate whole blood precision. The whole blood precision results for all three (3) sites combined are summarized for capillary whole blood in Table 4 (seconds) and Table 5 (INR) and for venous whole blood are summarized in Table 6 (seconds) and Table 7 (INR).

Site	Interval	N	Mean		Standard Deviation		%CV
			Estimate	95% CI	Estimate	95% CI	Estimate	95% CI
	Non-therapeutic	58*	14.89	14.06 to 15.73	1.414	1.197 to 1.727	9.5	8.0 to 11.6

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Table 4: Capillary Whole Blood PT (seconds) Precision
Site	Interval	N	Mean		Standard Deviation		%CV
			Estimate	95% CI	Estimate	95% CI	Estimate	95% CI
AllSites	Therapeutic	119*	28.51	27.73 to 29.30	1.495	1.327 to 1.713	5.2	4.7 to 6.0
	Very HighTherapeutic	9	50.71	42.88 to 58.54	2.109	1.451 to 3.851	4.2	2.9 to 7.6

*Results with outliers included

Table 5: Capillary Whole Blood PT INR Precision
Site	Interval	N	Mean		Standard Deviation		%CV
			Estimate	95% Cl	Estimate	95% Cl	Estimate	95% Cl
AllSites	Non-therapeutic	58*	1.48	1.39 to 1.56	0.143	0.121 to 0.174	9.7	8.2 to 11.8
	Therapeutic	119*	2.82	2.74 to 2.90	0.148	0.131 to 0.169	5.2	4.6 to 6.0
	Very HighTherapeutic	9	5.02	4.24 to 5.80	0.201	0.139 to 0.368	4.0	2.8 to 7.3

*Results with outliers included

Table 6: Venous Whole Blood PT (seconds) Precision
Site	Interval	N	Mean		Standard Deviation		%CV
			Estimate	95% Cl	Estimate	95% Cl	Estimate	95% Cl
AllSites	Non-therapeutic	65*	14.69	13.95 to 15.43	1.047	0.894 to 1.263	7.1	6.1 to 8.6
	Therapeutic	131	28.78	27.97 to 29.59	0.660	0.589 to 0.751	2.3	2.0 to 2.6
	Very HighTherapeutic	13*	54.37	48.44 to 60.31	0.785	0.569 to 1.264	1.4	1.0 to 2.3

*Results with outliers included

Table 7: Venous Whole Blood PT INR Precision
Site	Interval	N	Mean		Standard Deviation		%CV
			Estimate	95% CI	Estimate	95% CI	Estimate	95% CI
AllSites	Non-therapeutic	65*	1.45	1.38 to 1.53	0.109	0.093 to 0.131	7.5	6.4 to 9.0
	Therapeutic	131	2.85	2.77 to 2.93	0.069	0.061 to 0.078	2.4	2.1 to 2.7
	Very HighTherapeutic	13*	5.38	3.80 to 5.97	0.088	0.064 to 0.141	1.6	1.2 to 2.6

*Results with outliers included

b. Linearity/assay reportable range:

i. Linearity
Not applicable.
ii. Reportable range
The reportable range of the prothrombin time test in the i-STAT PT2015 cartridge with the i-STAT 1 System was determined through a method comparison study by using venous and capillary whole blood specimens from subjects undergoing anticoagulant therapy with coumarin derivatives and from subjects who were not on anticoagulant therapy. The result of the reportable range is shown in

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Table 8.

Table 8: Reportable Range
Test /Abbreviation	Units	ReportableRange
Prothrombin Time(PTplus)	INR	0.8 – 8.0
	seconds	8.1 – 80.8

c. Traceability, Stability, Expected values (controls, calibrators, or methods):

i. Traceability

i-STAT prothrombin time values are traceable to the World Health Organization (WHO) international reference measurement procedures using an International Reference Preparation (IRP) recommended by the WHO.

d. Detection Limit

i. Limit of Quantitation (LoQ) Not applicable
ii. Limit of Blank and Detection (LoB/LoD) Not applicable.
iii. Other

1) Factor Sensitivity

The factor sensitivity for factors FII, FV, FV, FVII and FX was determined using samples prepared by proportionately combining pooled normal plasma, red blood cells and factor-deficient plasma with various percent (%) factor activity ranging from 20%-100%. The factor sensitivity for the i-STAT PTPlus test was estimated to be FII - 39.5%; FV - 42.0%; FVII - 21.5%; FX - 22.0%.

e. Analytical Specificity

i. Interference

The interference performance of the prothrombin time test in the i-STAT PT2ulus cartridge with the i-STAT 1 System was evaluated in the presence of potentially interfering endogenous or exogenous substances based on CLSI EP07-A2: Interference Testing in Clinical Chemistry, 2nd Edition, CLSI EP07-ED3, and supplement document EP37-ED1. The effect of each substance at each prothrombin time level (normal and therapeutic) was evaluated by comparing the performance of a test sample spiked to a high concentration of the substance and a control sample spiked with an equal volume of solvent. For an identified interferent, a doseresponse was performed to determine the degree of interference as a function of the substance concentration. Table 9 contains the list of substances tested and the interference results.

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Table 9: Potentially Interfering Substances and Test Concentration
Substance	TestConcentration	TestConcentration(mg/dL)	Interference(Yes/No)	InterferenceResult
Acetaminophen	1324 µmol/L	$2.0x10^1$	No
AcetylsalicylicAcid	3.62 mmol/L	$6.5x10^1$	No
Ascorbic Acid	342 µmol/L	6.0	No
Atorvastatin	750 µg/L	$7.5x10^{-2}$	No
UnconjugatedBilirubin	684 µmol/L	$4.0x10^1$	No
ConjugatedBilirubin	475 µmol/L	$4.0x10^1$	No
Chlorhexidinedigluconate	0.1%*	$1.0x10^{-3}$	Yes	Increased results≥ $9.58x10^{-4}$ %
Daptomycin	0.55 mg/mL	$5.5x10^1$	Yes	Increased results≥ 0.22 mg/mL
Enoxaparin	2.0 IU/mL*	2.0	No
Epsilon-aminocaproicacid	0.39 mg/mL	$3.9x10^1$	No
Fondaparinux	3.78 mg/L*	$3.8x10^{-1}$	No
Hemoglobin	10 g/L	$1.0x10^3$	No
Ibuprofen	2425 µmol/L	$5.0x10^1$	No
Oritavancin	414 mg/L*	$4.1x10^1$	Yes	Increased results≥ 104 mg/L
Prasugrel	265.5 ng/mL*	$2.7x10^{-2}$	No
TranexamicAcid	45 µg/mL*	$4.5x10^6$	No
Triglycerides	37 mmol/L	$3.2x10^3$	No
Uric Acid	1.4 mmol/L	$2.4x10^1$	No

No CLSI EP07-A2, EP07-ED3, or EP37-ED1 recommended test concentration available.

ii. Other sensitivity studies

1) Fibrinogen Sensitivity

Fibrinogen sensitivity was evaluated across five (5) fibrinogen levels. The study demonstrated that the prothrombin time test in the i-STAT PTPlus cartridge with the i-STAT 1 System is insensitive to fibrinogen across a concentration range of 63 – 702 mg/dL. In addition, results from the clinical method comparison study (including subjects receiving coumarin therapy as well as subjects not receiving coumarin therapy) supports insensitivity to fibrinogen in the range of 63 – 702 mg/dL.

2) Platelet Sensitivity

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Platelet sensitivity was evaluated at three (3) platelet levels (low, nominal, and high). The study demonstrated that the prothrombin time test in the i-STAT PTplus cartridge with the i-STAT 1 System is insensitive to platelets in the range of 70,000 - 670,000/mm². In addition, results from the clinical method comparison study (including subjects receiving coumarin therapy as well as subjects not receiving coumarin therapy) supports insensitivity to platelets in the range of 70,000 - 670,000/mm3.

3) Hematocrit Sensitivity

Hematocrit sensitivity was evaluated at three (3) hematocrit levels (low, nominal, and high). The study demonstrated that the prothrombin time test in the i-STAT PTplus cartridge with the i-STAT 1 System is insensitive to hematocrit in the range of 24 to 54% packed cell volume (PCV). In addition, results from the clinical method comparison study (including subjects receiving coumarin therapy as well as subjects not receiving coumarin therapy) supports insensitivity to hematocrit in the range of 24 to 54% PCV.

4) Heparin Sensitivitv

Sensitivity to unfractionated heparin was evaluated at two (2) heparin levels. The study demonstrated that the prothrombin time test in the i-STAT PT2/us cartridge with the i-STAT 1 System is insensitive to unfractionated heparin concentrations up to 1.0 IU/mL.

5) Sensitivity for Lupus Anticoagulant

Sensitivity to lupus anticoagulant antibodies (LA) was evaluated using two (2) levels (low and high) of positive LA and one (1) level of negative LA (control). The study demonstrated that the prothrombin time test in the i-STAT PT2/us cartridge with the i-STAT 1 System is sensitive to both low and high levels of lupus anticoagulant antibodies.

f. Assay cut-off

Not applicable.

B. Comparison Studies

a. Method Comparison with predicate device

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method were based on recommendations from CLSI EP09c Measurement Procedure Comparison and Bias Estimation Using Patient Samples, 3rd ed. Passing-Bablok regression analysis was performed for the first replicate of the i-STAT prothrombin time result versus the singlicate result from the CoaguChek. The results of the method comparison of venous whole blood and capillary whole blood samples are presented in Table 10 (seconds) and Table 11 (INR).

Table 10: Method Comparison Results for i-STAT PTplus Cartridge with i-STAT 1 System vs. CoaguChek® XS System
(Seconds)

Matrix	N	i-STAT 1 PT (sec) Range	CoaguChek PT (sec) Range	Correlation coefficient (R) Estimate	95% CI	Slope Estimate	95% CI	Intercept Estimate	95% CI
Venous	191*	8.5 – 67.9	10.8 – 84.6	0.98	0.97 to 0.98	0.736	0.715 to 0.757	1.352	0.708 to 1.920
Capillary	153*	8.6 – 61.9	11.1 – 83.7	0.97	0.96 to 0.98	0.743	0.711 to 0.776	1.051	0.309 to 1.892

Results with outliers included

Table 11: Method Comparison Results for i-STAT PTP48 Cartridge with i-STAT 1 System vs. CoaguChek® XS System (INR)

Matrix	N	i-STAT 1INR Range	CoaguChekINR Range	Correlation coefficient(R)		Slope		Intercept
				Estimate	95% CI	Estimate	95% CI	Estimate	95% CI
Venous	191*	0.8 – 6.7	0.9 – 7.0	0.98	0.97 to 0.98	0.875	0.857 to 0.906	0.113	0.045 to 0.157
Capillary	153*	0.8 – 6.1	0.8 – 7.0	0.97	0.96 to 0.98	0.885	0.846 to 0.923	0.104	0.009 to 0.171

*Results with outliers included

b. Method comparison with reference device

Venous and capillary whole blood specimens were prospectively collected from subjects undergoing anticoagulant therapy with coumarin derivates and from subjects who were not on anticoagulant therapy at three (3) clinical sites. Both venous and capillary specimens were tested in duplicate on the i-STAT 1 Analyzer and citrated plasma from the venous whole blood specimens was tested in duplicate on the Sysmex CS-2500 reference instrument using Dade Innovin reagent. The study design and analysis method were based on recommendations from CLSI EP09c Measurement Procedure Comparison and Bias Estimation Using Patient Samples, 3rd ed. Passing-Bablok regression analysis was performed for the first replicate of the i-STAT prothrombin time result versus the first replicate result from the Sysmex CS-2500. The results of the method comparison of venous whole blood and capillary whole blood samples is presented in Table 12 (seconds) and Table 13 (INR).

				Table 12: Method Comparison Results for i-STAT 1 System vs. Sysmex CS-2500 (seconds)

Matrix	N	i-STAT 1PT (sec)Range	SysmexPT (sec)Range	Correlation coefficient(R)Estimate	Correlation coefficient(R)95% CI	SlopeEstimate	Slope95% CI	InterceptEstimate	Intercept95% CI
Venous	211*	8.5 – 80.5	9.7 – 83.1	0.92	0.90 to 0.94	1.037	0.994 to 1.082	-0.591	-1.500 to 0.151
Capillary	203*	8.6 – 80.5	9.7 – 83.1	0.91	0.88 to 0.93	1.023	0.979 to 1.070	-0.189	-1.052 to 0.641

*Results with outliers included

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Table 13: Method Comparison Results for i-STAT PTplus Cartridge with i-STAT 1 System vs. Sysmex CS-2500 (INR)
Matrix	N	i-STAT 1INRRange	SysmexINRRange	Correlation coefficient(R)/Estimate	Correlation coefficient(R)/95% CI	SlopeEstimate	Slope95% CI	InterceptEstimate	Intercept95% CI
Venous	211*	0.8 – 8.0	0.9 – 8.1	0.92	0.90 to 0.94	1.037	1.000 to 1.078	0.004	-0.079 to 0.075
Capillary	203*	0.8 – 8.0	0.9 – 8.1	0.91	0.89 to 0.93	1.022	0.984 to 1.061	0.047	-0.029 to 0.127

*Results with outliers included

C. Expected Values/Reference range

a. Reference range

A reference interval study was conducted with venous and capillary samples from apparently healthy adult subjects. Venous specimens were tested in singlicate and after testing venous blood, a capillary specimen from the subject was collected via fingerstick. Testing was performed with three cartridges lots on the i-STAT 1 System at three (3) clinical sites. Reference intervals for INR and seconds in venous and capillary samples were determined according to the CLSI Guideline EP28-A3c Defining, Establishing, and Verifying, Reference Intervals in the Clinical Laboratory: Approved Guideline -Third Edition. The reference intervals established for each capillary and venous sample type are summarized in Table 14.

Table 14: Reference Range for i-STAT PTPlus Cartridge with i-STAT 1 System
Specimen Type	N	Unit	Mean	Range
Capillary	146	INR*	1.1	0.9 - 1.3
		Seconds**	10.6	9.0 - 13.8
Venous	154	INR*	1.1	0.9 - 1.3
		Seconds**	10.6	9.2 - 13.0

*Pooled by sample type across all sites.

** Due to the rounding of parameters in the equation to convert INR to seconds, small differences in seconds can be observed.

8. Conclusion

The results of these studies demonstrate that performance of the prothrombin time test in the i-STAT PT2445 cartridge with the i-STAT 1 System are substantially equivalent to the predicate device.

Regulation Number and Section

§ 864.7750 Prothrombin time test.

(a)
Identification. A prothrombin time test is a device used as a general screening procedure for the detection of possible clotting factor deficiencies in the extrinsic coagulation pathway, which involves the reaction between coagulation factors III and VII, and to monitor patients receiving coumarin therapy (the administration of one of the coumarin anticoagulants in the treatment of venous thrombosis or pulmonary embolism).(b)
Classification. Class II (performance standards).