The i-STAT CG4+ cartridge with the i-STAT 1 System is intended for use in the in vitro quantification of pH, partial pressure of oxygen (PO2), and partial pressure of carbon dioxide (PCO2) in arterial, venous, or capillary whole blood in point of care or clinical laboratory settings.

The i-STAT CG4+ cartridge with the i-STAT 1 System is intended for use in the in vitro quantification of lactate in arterial or venous whole blood in point of care or clinical laboratory settings.

pH, PO2, and PCO2 measurements are used in the diagnosis, monitoring, and treatment of respiratory, metabolic, and acid-base disturbances.

Lactate measurements are used in (1) the diagnosis and treatment of lactic acidosis in conjunction with measurements of blood acid/base status, (2) monitoring tissue hypoxia and strenuous physical exertion, and (3) diagnosis of hyperlactatemia.

Device Description

The i-STAT CG4+ cartridge is used with the i-STAT 1 analyzer as part of the i-STAT 1 System to measure pH, partial pressure of oxygen (PO2), and partial pressure of carbon dioxide (PCO2) in arterial, venous or capillary whole blood and to measure lactate (Lac) in arterial or venous whole blood.

The i-STAT 1 System is an in vitro diagnostic (IVD) medical device intended for the quantitative determination of various clinical chemistry tests contained within i-STAT cartridges using whole blood. The i-STAT 1 System consists of a portable blood analyzer (i-STAT 1 analyzer), single-use disposable test cartridges (i-STAT cartridges), liquid quality control and calibration verification materials, and accessories (i-STAT 1 Downloader/Recharger, i-STAT Electronic Simulator and i-STAT 1 Printer). The i-STAT 1 System, including the i-STAT CG4+ cartridge, is designed for use by trained medical professionals in point of care or clinical laboratory settings and is for prescription use only.

The i-STAT CG4+ cartridge contains the required sensors, a fluid pack (calibrant pouch), a sample entry well and closure, fluid channels, waste chamber, and the necessary mechanical features for controlled fluid movement within cartridge. The i-STAT cartridge format allows all the tests in the cartridge to be performed simultaneously. All the test steps and fluid movements occur within the i STAT CG4+ cartridge. The i-STAT 1 analyzer interacts with the i-STAT CG4+ cartridge to move fluid across the sensors and generate a quantitative result. Cartridges require two to three drops of whole blood applied to the cartridge using a transfer device, by the trained user before the cartridge is placed within the analyzer.

The i-STAT 1 analyzer is a handheld, in vitro diagnostic analytical device designed to run only i-STAT test cartridges. The analyzer functions as the main user interface and the electromechanical interface to the test cartridge. All within-cartridge fluid movements, as well as the timing and heating of the test cycle, are automated and controlled without user intervention by system software embedded within the analyzer.

AI/ML Overview

Since the provided text describes a medical device (i-STAT CG4+ cartridge with the i-STAT 1 System), it is an in vitro diagnostic (IVD) device, not an AI/ML diagnostic system. Therefore, many of the typical acceptance criteria and study components for AI/ML devices (e.g., number of experts, adjudication methods, MRMC studies, training set details) are not applicable to this type of device.

This clearance is based on demonstrating substantial equivalence to a predicate device (i-STAT G3+ cartridge) through analytical performance studies, rather than a comparative effectiveness study against human readers or specific performance benchmarks tied to a disease outcome.

Here's an organized breakdown of the acceptance criteria and study information provided for the i-STAT CG4+ cartridge, focusing on what is relevant for an IVD device and clearly indicating where AI/ML-specific criteria do not apply:

Acceptance Criteria and Device Performance for i-STAT CG4+ Cartridge

The acceptance criteria for this in-vitro diagnostic device are based on demonstrating robust analytical performance and substantial equivalence to a legally marketed predicate device (i-STAT G3+ cartridge). The studies focus on precision, linearity, traceability, detection limits, and analytical specificity (interference and oxygen sensitivity), as well as method comparison with established laboratory methods.

1. Table of Acceptance Criteria and Reported Device Performance

The "acceptance criteria" for an IVD device like this are generally implied by the successful demonstration of performance characteristics within clinically acceptable ranges and alignment with the predicate device. The tables below summarize the reported device performance, which implicitly met the internal acceptance criteria for substantial equivalence.

Precision/Reproducibility (Aqueous Materials - Sampled Performance Ranges)

Test (units)	Fluid Level	Reported Repeatability (%CV)	Reported Within-Laboratory (%CV)	Reported Reproducibility (%CV)
pH (pH units)	CV L1-L5	0.03 - 0.13	0.03 - 0.14	0.03 - 0.08
PO2 (mmHg)	CV L1-L5	1.25 - 2.41	1.97 - 2.96	3.07 - 5.89
PCO2 (mmHg)	CV L1-L5	1.10 - 3.10	1.40 - 3.43	1.16 - 2.96
Lactate (mmol/L)	CV L1-L5	0.40 - 3.13	0.69 - 3.47	0.53 - 3.39

Linearity/Assay Reportable Range (Regression Summary)

Test	Units	Reportable Range (Acceptance Criteria)	Range Tested	Slope (Reported)	Intercept (Reported)	R² (Reported)
pH	pH units	6.500 – 7.800	6.4509 – 7.9500	1.012	-0.096	0.9996
PO2	mmHg	5 – 700	3.5 – 723.4	0.990	0.176	0.9970
PCO2	mmHg	5.0 – 130.0	2.59 – 145.97	1.016	-0.513	0.9986
Lactate	mmol/L	0.30 – 20.00	0.276 – 21.502	1.012	0.033	0.9991

Detection Limits (LOQ and LOD)

Test	Units	Lower Limit of Reportable Range (Acceptance Criteria)	LoQ (Reported)	LoB (Reported)	LoD (Reported)
pH	pH units	6.500	6.471	N/A	N/A
PO2	mmHg	5	5	N/A	N/A
PCO2	mmHg	5.0	3.0	N/A	N/A
Lactate	mmol/L	0.30	0.18	0	0.026

Analytical Specificity (Interference): A substance was identified as an interferent if the difference in means (or medians) between the control and test samples was outside of the allowed error (±Ea) for the i-STAT test.

Bromide: Interferent at 37.5 mmol/L (decreased lactate results >10.0 mmol/L).
Glycolic Acid: Interferent at 10.0 mmol/L (increased lactate results >0.8 mmol/L).
Other substances listed (Table 11) showed No Interference.

Altitude Study (Correlation Coefficient and Slope Acceptance)

Test	Correlation Coefficient (r) Acceptance	Reported r	Slope Acceptance	Reported Slope
pH	Close to 1.00	1.00	Close to 1.00	1.00
PO2	Close to 1.00	1.00	Close to 1.00	1.03
PCO2	Close to 1.00	1.00	Close to 1.00	0.96
Lactate	Close to 1.00	1.00	Close to 1.00	1.00
All reported values met the implied acceptance criteria for correlation and slope, demonstrating equivalent performance at altitude.

Method Comparison (Bias at Medical Decision Levels)
Bias at medical decision levels (MDL) needs to be clinically acceptable.

pH: Biases ranging from -0.0080 to -0.0166 at various MDLs.
PO2: Biases ranging from -0.6 to -3.3 at various MDLs.
PCO2: Biases ranging from 0.67 to 3.49 at various MDLs.
Lactate: Bias of -0.140 at 5.00 mmol/L MDL.
These biases met the implicit acceptance criteria for substantial equivalence to the comparative methods.

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

For an IVD device, there isn't a "test set" in the AI/ML sense, but rather a series of analytical performance studies using different types of samples.

Precision (Aqueous Materials):
- 20-Day Precision: 83-84 replicates (N) per fluid level per test.
- Multi-site Multi-day Precision: 90-91 replicates (N) per fluid level per test across 3 point-of-care sites.
Precision (Whole Blood):
- Clinical Precision: N varied by sample range and test, ranging from 3 to 154 for various analytes and sample types (venous, arterial, capillary).
- Within-Sample (Native Capillary): 60 test results (30 subjects, duplicate tests).
- Within-Sample (Contrived Capillary): N=32 for L1 pH/PO2/PCO2, N=22 for L2 pH/PO2/PCO2 (from 27 subjects, duplicate tests).
Linearity: Whole blood samples of varying analyte levels. Specific N not provided per sample, but regression analysis was performed.
Detection Limit (LoQ/LoB/LoD): Whole blood samples (altered to low/blank analyte levels).
Interference: Whole blood samples (spiked with potentially interfering substances).
Oxygen Sensitivity: Whole blood samples (altered to 4 lactate levels).
Altitude: Whole blood samples (relevant analyte levels).
Method Comparison:
- Arterial/Venous/Capillary pooled for pH, PO2, PCO2: 551-557 specimens.
- Arterial/Venous pooled for Lactate: 345 specimens.
- Capillary only for pH, PO2, PCO2: 184-193 specimens (native and contrived).
- Native Capillary (Bias at MDL): 175-178 specimens.
Matrix Equivalence: 228-289 specimens (arterial/venous whole blood, with and without anticoagulant).

Data Provenance:

The studies were conducted by Abbott Point of Care Inc. and at "multiple point of care sites" for clinical precision and method comparison.
The exact country of origin is not specified but implied to be across various clinical settings where the device might be used.
The studies appear to be prospective analytical studies designed to evaluate device performance under controlled conditions, not retrospective real-world data collection.

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

Not Applicable. For an IVD device, the "ground truth" is established through the measurement by a comparative/reference method (e.g., RAPIDPoint 500/500e, or the i-STAT G3+ predicate device), not through human expert consensus or labeling. The device's performance is compared against these established analytical methods.

4. Adjudication Method for the Test Set

Not Applicable. Adjudication methods (like 2+1, 3+1) are for establishing ground truth from multiple human readers/experts, which is not relevant for calibrating the analytical performance of an IVD device.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No. MRMC studies are typically performed for AI/ML diagnostic aids where the AI is intended to assist a human reader, and the study measures the improvement in human reader performance (e.g., diagnostic accuracy, sensitivity, specificity) with and without AI assistance. This device is an analytical instrument for quantitative determination of blood gases and lactate, not an AI/ML diagnostic aid.

6. If a Standalone (i.e., Algorithm Only Without Human-in-the-Loop Performance) Was Done

Yes (in principle). The listed performance studies (precision, linearity, detection limits, interference, method comparison) assessed the analytical performance of the device itself (i-STAT CG4+ cartridge with the i-STAT 1 System) independent of a human's interpretative role. The device measures and provides a numerical output for pH, PO2, PCO2, and Lactate. The "human-in-the-loop" here is the operator performing the test, not interpreting an AI-generated image or signal.

7. The Type of Ground Truth Used

The "ground truth" for the performance evaluation of this IVD device was established in two primary ways:

Reference Materials: Traceability to NIST SRMs (for pH, PO2, PCO2) or a manufacturer's working calibrator (for Lactate). These are analytical standards.
Comparative Methods: Established and legally marketed laboratory instruments (e.g., RAPIDPoint 500/500e for pH/PO2, and the i-STAT G3+ predicate device for PCO2 and the i-STAT CG4+ (K200492) for Lactate).
Defined Concentrations: For linearity, LoQ, LoB, LoD, interference, and oxygen sensitivity studies, samples were prepared with known or targeted analyte concentrations.

This is distinct from clinical diagnostic "ground truth" which might come from pathology, long-term outcomes, or expert consensus in fields like radiology.

8. The Sample Size for the Training Set

Not Applicable. This is an IVD device that does not use AI/ML, so there is no concept of a "training set" for an algorithm. The device measures chemical analytes via established electrochemical principles.

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

Not Applicable. As there is no training set for an AI/ML algorithm, this question is not relevant.

Summary

FDA 510(k) Clearance Letter - i-STAT CG4+ Cartridge

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May 2, 2025

Abbott Point of Care Inc.
Brian Ma, Ph.D.
Principal Specialist, Regulatory Affairs
400 College Road East
Princeton, New Jersey 08540

Re: K244014
Trade/Device Name: i-STAT CG4+ cartridge with the i-STAT 1 System
Regulation Number: 21 CFR 862.1120
Regulation Name: Blood Gases (PCO2, PO2) And Blood pH Test System
Regulatory Class: Class II
Product Code: CHL, KHP
Dated: April 4, 2025
Received: April 4, 2025

Dear Brian Ma:

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.

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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 (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-safety-reporting-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-devices/device-advice-comprehensive-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-devices/medical-device-safety/medical-device-reporting-mdr-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/medical-devices/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

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the DICE website (https://www.fda.gov/medical-devices/device-advice-comprehensive-regulatory-assistance/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 Director
Division of Chemistry and Toxicology Devices
OHT7: Office of In Vitro Diagnostics
Office of Product Evaluation and Quality
Center for Devices and Radiological Health

Enclosure

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

Form Approved: OMB No. 0910-0120
Expiration Date: 07/31/2026
See PRA Statement below.

Indications for Use

Submission Number (if known)
K244014

Device Name
i-STAT CG4+ cartridge with the i-STAT 1 System

Indications for Use (Describe)

The i-STAT CG4+ cartridge with the i-STAT 1 System is intended for use in the in vitro quantification of lactate in arterial or venous whole blood in point of care or clinical laboratory settings.

pH, PO2, and PCO2 measurements are used in the diagnosis, monitoring, and treatment of respiratory, metabolic, and acid-base disturbances.

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
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"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."

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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.

1. Submitter Information

Owner: Abbott Point of Care Inc.
400 College Road East
Princeton, NJ 08540

Contact: Primary: Brian Ma, PhD
Principal Specialist, Regulatory Affairs
Phone: 613-688-5949

Secondary: Mojgan Soleimani
Director, Regulatory Strategy and Design Quality Assurance
Phone: 613-295-0932

Date Prepared: May 2, 2025

2. Device Information

Proprietary Name: i-STAT CG4+ cartridge with the i-STAT 1 System
Common Name: Blood gas test, lactate test, analyzer, handheld
510(k) Number: K244014

Product Code	Device Classification Name	Regulation Number	Class	Panel
CHL	Electrode measurement, blood gases (PCO2, PO2) and blood pH	862.1120	II	Clinical Chemistry
KHP	Acid, lactic, enzymatic method	862.1450	I	Clinical Chemistry

3. Predicate Device

Proprietary Name: i-STAT G3+ cartridge with the i-STAT 1 System
510(k) Number: K223857

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Product Code	Device Classification Name	Regulation Number	Class	Panel
CHL	Electrode measurement, blood gases (PCO2, PO2) and blood pH	862.1120	II	Clinical Chemistry

4. Device Description

5. Intended Use Statement

The i-STAT CG4+ cartridge with the i-STAT 1 System is intended for use in the in vitro quantification of lactate in arterial or venous whole blood in point of care or clinical laboratory settings.

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pH, PO2, and PCO2 measurements are used in the diagnosis, monitoring, and treatment of respiratory, metabolic, and acid-base disturbances.

6. Summary Comparison of Technological Characteristics

Table 1: Similarities and Differences: System (Test and Instrument)

Feature or Characteristic	Candidate Device: i-STAT CG4+ cartridge with the i-STAT 1 System	Predicate Device: i-STAT G3+ cartridge with the i-STAT 1 System (K223857)
Intended Use	The i-STAT CG4+ cartridge with the i-STAT 1 System is intended for use in the in vitro quantification of pH, partial pressure of oxygen (PO2), and partial pressure of carbon dioxide (PCO2) in arterial, venous, or capillary whole blood in point of care or clinical laboratory settings.The i-STAT CG4+ cartridge with the i-STAT 1 System is intended for use in the in vitro quantification of lactate in arterial or venous whole blood in point of care or clinical laboratory settings.pH, PO2, and PCO2 measurements are used in the diagnosis, monitoring, and treatment of respiratory, metabolic, and acid-base disturbances.Lactate measurements are used in (1) the diagnosis and treatment of lactic acidosis in conjunction with measurements of blood acid/base status, (2) monitoring tissue hypoxia and strenuous physical exertion, and (3) diagnosis of hyperlactatemia.	The i-STAT G3+ cartridge with the i-STAT 1 System is intended for use in the in vitro quantification of pH, partial pressure of oxygen (PO2), and partial pressure of carbon dioxide (PCO2) in arterial, venous, or capillary whole blood in point of care or clinical laboratory settings.pH, PO2, and PCO2 measurements are used in the diagnosis, monitoring, and treatment of respiratory, metabolic, and acid-base disturbances.
Device Classification(s)	Class II - PCO2, PO2, pHClass I - Lactate	Class II - PCO2, PO2, pH
Product Code(s)	CHL, KHP	CHL
Regulation Number(s)	862.1120, 862.1450	862.1120

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Feature or Characteristic	Candidate Device: i-STAT CG4+ cartridge with the i-STAT 1 System	Predicate Device: i-STAT G3+ cartridge with the i-STAT 1 System (K223857)
Reportable Range	pH: 6.500 – 7.800PO2: 5 – 700 mmHg, 0.7 – 93.3 kPaPCO2: 5 – 130 mmHg, 0.67 – 17.33 kPaLactate: 0.30 – 20.00 mmol/L, 2.7 – 180.2 mg/dL	pH: SamePO2: SamePCO2: Same
Sample Type	pH, PO2, PCO2: Arterial, venous or capillary whole bloodlactate: Arterial or venous whole blood	pH, PO2, PCO2: Same
Sample Volume	95 µL	Same
Sample Preparation	Ready to Use	Same
Sample Collection	pH, PO2, PCO2:• Without anticoagulant (for arterial and venous whole blood sample types)• With balanced heparin anticoagulant or lithium heparin anticoagulant (for arterial, venous, and capillary whole blood sample types)lactate:• Without anticoagulant (for arterial and venous whole blood sample types)• With balanced heparin anticoagulant or lithium heparin anticoagulant (for arterial and venous whole blood sample types)	pH, PO2, PCO2: Same

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Feature or Characteristic	Candidate Device: i-STAT CG4+ cartridge with the i-STAT 1 System	Predicate Device: i-STAT G3+ cartridge with the i-STAT 1 System (K223857)
Traceability	pH: Traceable to NIST SRMs 186-I, 186-II, 185 and 187PO2, PCO2: Traceable to NIST SRMs via commercially available certified specialty medical gas tanksLactate: Certified Standard Reference Material not available at present; traceable to i-STAT manufacturer's working calibrator (MWC) prepared from sodium L-lactate (Sigma-Aldrich Fluka, >99 % purity)	pH: SamePO2, PCO2: Same
Calibration	1-point on-board contained within cartridge	Same

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Feature or Characteristic	Candidate Device: i-STAT CG4+ cartridge with the i-STAT 1 System	Predicate Device: i-STAT G3+ cartridge with the i-STAT 1 System (K223857)
Time to Test/Sample Stability (Time from collection to sample fill)	Without anticoagulant:pH, PO2, PCO2 (arterial and venous): within 3 minutesLactate (arterial and venous): ImmediatelyWith anticoagulant:pH, PO2, PCO2 (arterial and venous): within 10 minutespH, PO2, PCO2 (capillary): within 3 minutesLactate (arterial and venous): Immediately	Without anticoagulant:pH, PO2, PCO2 (arterial and venous): SameWith anticoagulant:pH, PO2, PCO2 (arterial and venous): SamepH, PO2, PCO2 (capillary): Same
Principle of Measurement	pH, PCO2: Potentiometric measurement between active working sensor and independent reference sensor.PO2: Amperometric measurement of oxygen reduction current.Lactate: Amperometric measurement of oxidized hydrogen peroxide produced by lactate oxidase activity.	pH, PCO2: SamePO2: Same
Reagent Format	Cartridge	Same
Storage Conditions	Refrigerated at 2 to 8°C (35 to 46°F) until expiration date.Room Temperature at 18-30°C (64-86°F) for 2 months.	Same
Analyzer Type	Handheld	Same

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7. Performance Characteristics

A. Analytical Performance

a. Precision/Reproducibility:

i. Precision 20 days (Aqueous Materials)

The precision of the i-STAT pH, PO2, PCO2, and Lactate tests in the i-STAT CG4+ cartridge with the i-STAT 1 System was evaluated using five (5) levels of aqueous materials. The study followed the standard single-site 20x2x2 experimental design based on guidance provided in CLSI document EP05-A3: Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline – Third Edition. The study was conducted using multiple analyzers and one (1) test cartridge lot over at least 20 days at one (1) site. Repeatability, between-run, between-day, and within-laboratory precision were estimated for each level. The results of the 20-day precision study for the i-STAT CG4+ cartridge on the i-STAT 1 System are shown in Table 2.

Table 2: 20-Day Precision of i-STAT CG4+ Cartridge on the i-STAT 1 Analyzer

Test (units)	Fluid Level	Mean	N	Repeatability		Between-run		Between-day		Within-Laboratory
				SD	%CV	SD	%CV	SD	%CV	SD	%CV
pH (pH units)	CV L1	6.5701	84	0.00359	0.05	0.00280	0.04	0.00034	0.01	0.00457	0.07
	CV L2	7.0259	84	0.00178	0.03	0.00105	0.01	0.00068	0.01	0.00218	0.03
	CV L3	7.4532	83	0.00231	0.03	0.00051	0.01	0.00052	0.01	0.00242	0.03
	CV L4	7.6338	84	0.00961	0.13	0.00325	0.04	0.00266	0.03	0.01049	0.14
	CV L5	7.9653	84	0.00236	0.03	0.00081	0.01	0.00165	0.02	0.00299	0.04
PO2 (mmHg)	CV L1	71.0	84	1.71	2.41	0.65	0.92	1.03	1.45	2.10	2.96
	CV L2	82.6	84	1.74	2.11	0.58	0.70	0.45	0.54	1.89	2.29
	CV L3	108.9	83	1.86	1.71	1.00	0.91	0.67	0.62	2.22	2.03
	CV L4	138.8	84	2.52	1.82	0.90	0.65	1.12	0.81	2.90	2.09
	CV L5	372.9	84	4.66	1.25	5.29	1.42	2.07	0.56	7.35	1.97
PCO2 (mmHg)	CV L1	89.41	84	1.251	1.40	0.626	0.70	0.354	0.40	1.443	1.61
	CV L2	56.28	84	0.621	1.10	0.338	0.60	0.165	0.29	0.726	1.29
	CV L3	29.37	83	0.365	1.24	0.128	0.43	0.141	0.48	0.412	1.40
	CV L4	22.69	84	0.707	3.11	0.196	0.86	0.191	0.84	0.758	3.34
	CV L5	12.19	84	0.377	3.10	0.131	1.07	0.123	1.01	0.418	3.43
Lactate (mmol/L)	CV L1	19.791	84	0.1827	0.92	0.0869	0.44	0.0226	0.11	0.2035	1.03
	CV L2	7.874	84	0.0592	0.75	0.0302	0.38	0.0123	0.16	0.0676	0.86
	CV L3	2.110	83	0.0128	0.61	0.0051	0.24	0.0046	0.22	0.0146	0.69
	CV L4	0.820	84	0.0135	1.64	0.0036	0.44	0.0049	0.60	0.0148	1.80
	CV L5	0.410	84	0.0128	3.13	0.0028	0.70	0.0055	1.35	0.0142	3.47

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ii. Multi-site and operator-to-operator precision (Aqueous materials)

Multi-day precision testing was performed at three (3) point of care sites using a panel of aqueous material containing five (5) levels of pH, PO2, PCO2, and lactate. The study followed a 3x5x2x3 design based on guidance provided in CLSI EP05-A3: Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline – Third Edition. At each site, each level was tested once per day by two (2) operators for five (5) days on six (6) i-STAT 1 analyzers using one (1) lot of i-STAT CG4+ cartridges. Repeatability, between-day, between-operator, within-site, between-site variance components, and reproducibility were calculated for all sites combined and provided in the Table 3 below.

Table 3: Multi-Site Multi-Day Precision of i-STAT CG4+ Cartridge on the i-STAT 1 Analyzer

Test (units)	Fluid Level	N	Mean	Repeatability		Between-Day		Between-Operator		Within-Site		Between-Site		Reproducibility
				SD	%CV	SD	%CV	SD	%CV	SD	%CV	SD	%CV	SD	%CV
pH (pH units)	CV L1	90	6.5725	0.00404	0.06	0.00111	0.02	0.00281	0.04	0.00504	0.08	0.00147	0.02	0.00525	0.08
	CV L2	90	7.0266	0.00204	0.03	0.00133	0.02	0.00124	0.02	0.00274	0.04	0.00201	0.03	0.00340	0.05
	CV L3	90	7.4540	0.00139	0.02	0.00062	0.01	0.00119	0.02	0.00193	0.03	0.00080	0.01	0.00209	0.03
	CV L4	90	7.6373	0.00194	0.03	0.00046	0.01	0.00096	0.01	0.00222	0.03	0.00142	0.02	0.00263	0.03
	CV L5	90	7.9681	0.00194	0.02	0.00062	0.01	0.00093	0.01	0.00224	0.03	0.00107	0.01	0.00248	0.03
PO2 (mmHg)	CV L1	91	76.9	2.80	3.64	0.95	1.23	2.63	3.42	3.96	5.15	2.20	2.87	4.53	5.89
	CV L2	90	87.4	2.02	2.31	0.86	0.98	2.13	2.44	3.06	3.50	2.56	2.93	3.99	4.57
	CV L3	90	113.4	2.34	2.06	0.57	0.50	1.57	1.38	2.87	2.53	3.08	2.71	4.21	3.71
	CV L4	90	141.4	2.63	1.86	1.50	1.06	1.15	0.82	3.24	2.29	3.47	2.45	4.74	3.35
	CV L5	90	366.0	6.26	1.71	2.92	0.80	7.53	2.06	10.21	2.79	4.66	1.27	11.23	3.07
PCO2 (mmHg)	CV L1	90	89.41	1.365	1.53	0.501	0.56	0.710	0.79	1.618	1.81	0.000	0.00	1.618	1.81
	CV L2	90	57.20	0.508	0.89	0.287	0.50	0.311	0.54	0.661	1.16	0.000	0.00	0.661	1.16
	CV L3	90	29.99	0.289	0.96	0.169	0.56	0.063	0.21	0.341	1.14	0.140	0.47	0.368	1.23
	CV L4	90	23.03	0.336	1.46	0.092	0.40	0.000	0.00	0.348	1.51	0.054	0.24	0.353	1.53
	CV L5	90	12.18	0.361	2.96	0.000	0.00	0.000	0.00	0.361	2.96	0.000	0.00	0.361	2.96
Lactate (mmol/L)	CV L1	91	18.928	0.1905	1.01	0.0573	0.30	0.0000	0.00	0.199	1.05	0.0000	0.00	0.1990	1.05
	CV L2	90	7.636	0.0423	0.55	0.0216	0.28	0.0126	0.16	0.0491	0.64	0.0000	0.00	0.0491	0.64
	CV L3	90	2.087	0.0084	0.40	0.0033	0.16	0.0022	0.11	0.0093	0.44	0.0061	0.29	0.0111	0.53
	CV L4	90	0.838	0.0090	1.08	0.0088	1.05	0.0023	0.28	0.0128	1.53	0.0053	0.63	0.0139	1.65
	CV L5	90	0.433	0.0124	2.87	0.0056	1.29	0.0012	0.27	0.0137	3.16	0.0053	1.21	0.0146	3.39

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iii. Precision (Whole Blood)

The precision of the i-STAT pH, PO2, PCO2 and Lactate tests in the i-STAT CG4+ cartridge on the i-STAT 1 System was evaluated using anticoagulated arterial, venous, and capillary¹ whole blood specimens. The whole blood precision was assessed using duplicate test results collected across multiple point of care sites. For each sample type, the specimens were grouped into subintervals of the test reportable range for analysis. The results are summarized in Table 4.

Table 4: Whole blood precision of arterial, venous, and capillary whole blood for i-STAT CG4+ cartridge on the i-STAT 1 analyzer

Test (units)	Sample Type	Sample Range	N	Mean	SD	%CV
pH (pH units)	Venous Whole Blood	6.500-7.300	9	7.0265	0.00235	0.03
		>7.300 – 7.450	154	7.3745	0.00668	0.09
		>7.450-7.800	12	7.5355	0.00732	0.10
	Arterial Whole Blood	6.500-7.300	9	7.2229	0.00262	0.04
		>7.300 – 7.450	124	7.3816	0.00486	0.07
		>7.450-7.800	43	7.4763	0.00690	0.09
	Capillary Whole Blood	6.500-7.300	3	7.2477	0.01355	0.19
		7.300-7.450	121	7.4099	0.02084	0.28
		>7.450-7.800	32	7.4781	0.02609	0.35
PO2 (mmHg)	Venous Whole Blood	10-40	125	26.2	0.91	3.49
		>40-50	21	43.1	0.98	2.26
		>50-100	24	59.3	1.32	2.23
		>100-250	3	227.7	2.65	1.16
		>250-700	8	508.4	6.96	1.37
	Arterial Whole Blood	>50-100	108	73.2	1.29	1.76
		>100-250	66	135.9	2.90	2.13
		>250-700	3	381.3	8.94	2.35
	Capillary Whole Blood	10-40	15	33.8	4.30	12.74
		>40-50	34	46.0	3.84	8.35
		>50-100	112	63.4	6.04	9.52
		>100-250*	5	166.4	12.98	7.80
		>250-700	8	489.6	8.53	1.74
PCO2 (mmHg)	Venous Whole Blood	5.0-35.0	23	30.17	0.379	1.26
		>35.0-50.0	119	46.48	0.639	1.38
		>50.0-62.5	31	57.05	0.687	1.20
		>62.5-130.0	10	117.05	1.650	1.41
	Arterial Whole Blood	5.0-35.0	48	33.24	0.393	1.18
		>35.0-50.0	105	44.55	0.641	1.44
		>50.0-62.5	16	61.33	1.100	1.79
		>62.5-130.0	6	77.18	1.080	1.40

¹ The capillary whole blood clinical precision study design involved collection of capillary blood (from either two fingersticks or a single heelstick) into two (2) anticoagulated capillary tubes and each tube was used to fill a single i-STAT CG4+ cartridge.

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Test (units)	Sample Type	Sample Range	N	Mean	SD	%CV
	Capillary Whole Blood	5.0-35.0	47	32.31	1.736	5.37
		>35.0-50.0	105	40.00	2.258	5.64
		>50.0-62.5	3	58.35	1.967	3.37
		>62.5-130.0	1	68.20	2.263	3.32
Lactate (mmol/L)	Venous Whole Blood	0.30-1.00	100	0.639	0.0127	1.99
		>1.00-5.00	81	1.549	0.0206	1.33
		>5.00-20.00	20	12.476	0.0756	0.61
	Arterial Whole Blood	0.30-1.00	55	0.653	0.0138	2.11
		>1.00-5.00	76	1.771	0.0184	1.04
		>5.00-20.00	3	8.120	0.0252	0.31

*A potential outlier due to preanalytical handling was identified for one (1) subject; PO2 precision for capillary whole blood in sample range 100-250 mmHg with this subject excluded (N=4) is as follows: Mean = 177.8 mmHg; SD = 5.50, %CV=3.09

iv. Precision (Within-Sample, Capillary Specimens)

Whole blood within sample precision of the i-STAT pH, PO2, and PCO2 tests in the i-STAT CG4+ cartridge on the i-STAT 1 System was evaluated using native and contrived pooled capillary whole blood samples.

Native capillary whole blood samples collected from 30 subjects via fingerstick punctures and tested in duplicate at Abbott Point of Care were assessed for within sample precision. Results are summarized in Table 5.

Table 5: Whole blood precision (within sample) of native capillary whole blood for i-STAT CG4+ cartridge on the i-STAT 1 analyzer

Test	Units	N	Mean	SD	%CV
pH	pH units	60	7.4848	0.01688	0.23
PO2	mmHg	60	143.1	4.55	3.18
PCO2	mmHg	60	30.34	1.505	4.96

Capillary whole blood samples collected from an additional 27 subjects used to prepare two levels of PO2 (16 for low and 11 for high) at Abbott Point of Care were assessed for within sample precision by testing each sample in duplicate. Results for the contrived capillary whole blood samples are summarized in Table 6.

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Table 6: Whole blood precision (within sample) of contrived capillary whole blood for i-STAT CG4+ cartridge on the i-STAT 1 analyzer

Test	Units	Sample Level	N	Mean	SD	%CV
pH	pH units	L1	32	7.3111	0.00996	0.14
		L2	22	7.3176	0.01572	0.21
PO2	mmHg	L1	32	43.4	0.51	1.18
		L2	22	427.4	5.86	1.37
PCO2	mmHg	L1	32	40.45	0.387	0.96
		L2	22	36.16	0.178	0.49

b. Linearity/assay reportable range:

i. Linearity

The study was designed based on CLSI EP06-Ed2: Evaluation of the Linearity of Quantitative Measurement Procedures – Second Edition. The linearity of the i-STAT pH, PO2, PCO2, and Lactate tests in the i-STAT CG4+ cartridge with the i-STAT 1 System were evaluated by preparing whole blood samples of varying analyte levels for each i-STAT test. The i-STAT pH, PO2, PCO2, and Lactate tests in the i-STAT CG4+ cartridge demonstrated linearity across the reportable range for each test. The regression summary of the results from each i-STAT test versus the expected values of the whole blood samples is provided in Table 7.

Table 7: Regression summary for the i-STAT pH, PO2, PCO2, and Lactate tests in the CG4+ cartridge on the i-STAT 1 analyzer

Test	Units	Reportable Range	Range Tested	Slope	Intercept	R²
pH	pH units	6.500 – 7.800	6.4509 – 7.9500	1.012	-0.096	0.9996
PO2	mmHg	5 – 700	3.5 – 723.4	0.990	0.176	0.9970
PCO2	mmHg	5.0 – 130.0	2.59 – 145.97	1.016	-0.513	0.9986
Lactate	mmol/L	0.30 – 20.00	0.276 – 21.502	1.012	0.033	0.9991

c. Traceability, Calibration and Reference Range

i. Traceability and Calibration

The measured analytes in the i-STAT CG4+ cartridge are traceable to the following reference materials or methods. The i-STAT 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.

pH values assigned to the i-STAT System controls and calibration verification materials are traceable to the U.S. National Institute of Standards and Technology (NIST) standard reference materials SRMs 186-I, 186-II, 185, and 187.

PO2 values assigned to the i‑STAT System controls and calibration verification materials are traceable to U.S. National Institute of Standards and Technology (NIST) standard reference materials via commercially available certified specialty medical gas standards.

PCO2 values assigned to the i‑STAT System controls and calibration verification materials are traceable to U.S. National Institute of Standards and Technology (NIST)

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standard reference materials via commercially available certified specialty medical gas standards.

Lactate: Presently, no international conventional reference measurement procedure or international conventional calibrator for lactate is available. Lactate values assigned to the i-STAT System controls and calibration verification materials are traceable to i-STAT System working calibrator prepared from sodium L-lactate (Sigma-Aldrich Fluka, >99 % purity).

ii. Reference Range

Reference ranges for the i-STAT CG4+ cartridge are based on literature reference and are listed in Table 8 below.

Table 8: Reference Ranges

Test	Units	Reportable Range	Reference Range
			Arterial	Venous
pH	pH units	6.50 – 7.80	7.35 – 7.45¹	7.31 – 7.41*
PO2	mmHg	5 – 700	80 – 105²**	–
	kPa	0.7 – 93.3	10.7 – 14.0²**	–
PCO2	mmHg	5 – 130	35 – 45¹	41 – 51¹
	kPa	0.67 – 17.33	4.67 – 6.00	5.47 – 6.80
Lactate	mmol/L	0.30 – 20.00	0.36 – 1.25³***	0.90 – 1.70³***
	mg/dL	2.7 – 180.2	3.2 – 11.3³***	8.1 – 15.3³***

*Calculated from Siggard-Andersen nomogram.
**The reference ranges shown are for a healthy population. Interpretation of blood gas measurements depend on the underlying condition (e.g., patient temperature, ventilation, posture and circulatory status).
***The i-STAT reference ranges for whole blood listed above are similar to reference ranges derived from serum or plasma measurements with standard laboratory methods.

¹ Painter, P. C., Cope, J. Y., and Smith, J. L. (1994) "Reference Ranges, Table 41-20" In Teitz Textbook of Clinical Chemistry, 2nd Ed. Burtis CA, Ashwood ER, eds. W.B. Saunders, Philadelphia.
² Statland, B. E. (1987) Clinical Decision Levels for Lab Tests, 2nd Ed., Medical Economics Books, Oradell, N.J.
³ Sacks, D. B. (1994) Carbohydrates In Teitz Textbook of Clinical Chemistry, 2nd Ed. Burtis CA, Ashwood ER, eds. W.B. Saunders, Philadelphia.

d. Detection Limit

i. 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 pH, PO2, PCO2, and Lactate tests in the i-STAT CG4+ cartridge were evaluated on the i-STAT 1 analyzer using two (2) i-STAT CG4+ cartridge lots, and whole blood that was altered to a low analyte level for each i-STAT test. The LoQ for each of the i-STAT tests was determined to be at or below the lower limit of the reportable range for each of the i-STAT tests as shown in Table 9.

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Table 9: Summary of LoQ results for the pH, PO2, PCO2, and lactate tests in the i-STAT CG4+ cartridge on the i-STAT 1 analyzer

Test	Units	Lower limit of the reportable range	LoQ
pH	pH units	6.500	6.471
PO2	mmHg	5	5
PCO2	mmHg	5.0	3.0
Lactate	mmol/L	0.30	0.18

ii. 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 Lactate test in the i-STAT CG4+ cartridge were evaluated on the i-STAT 1 analyzer using two (2) i-STAT CG4+ cartridge lots. Whole blood was altered to achieve a blank lactate level for LoB testing and two (2) low lactate levels for LoD testing. The LoB and LoD were determined based on the maximal LoB or LoD value obtained for each lot tested. The determined LoB and LoD for the i-STAT Lactate test on the i-STAT 1 analyzer are shown in the Table 10 below.

Table 10: Summary of LoB and LoD results for the lactate test in the i-STAT CG4+ cartridge on the i-STAT 1 analyzer

Test	Units	LoB	LoD
Lactate	mmol/L	0	0.026

e. Analytical Specificity

i. Interference

The interference performance of the i-STAT pH, PO2, PCO2, and Lactate tests in the i-STAT CG4+ cartridge on the i STAT 1 analyzer with the i-STAT 1 System was evaluated using whole blood samples based on CLSI EP07-ED3: Interference Testing in Clinical Chemistry, Third Edition. The effect of each substance was evaluated by comparing the performance of a control sample, spiked with blank solvent solution, with the test results from a test sample spiked with the potentially interfering substance at the toxic/pathological concentration based on CLSI EP37-ED1: Supplemental Tables for Interference Testing in Clinical Chemistry, First Edition, as applicable. A substance was identified as an interferent if the difference in means (or medians) between the control and test samples was outside of the allowed error (±Ea) for the i-STAT test. For an identified interferent, a dose-response was performed to determine the degree of interference as a function of the substance concentration. Table 11 contains the lists of potentially interfering substances tested and the interference results for the i-STAT CG4+ cartridge.

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Table 11: Potentially Interfering Substances and Test Concentrations for the pH, PO2, PCO2, and Lactate Tests in the i-STAT CG4+ Cartridge on the i-STAT 1 Analyzer

Substance²	Substance Concentration		i-STAT Test	Interference (Yes/No)	Comments
	mmol/L (unless specified)	mg/dL (unless specified)
Acetaldehyde³	0.045	0.2	Lactate	No
Acetaminophen	1.03	15.6	pH	No
			PO2	No
			PCO2	No
			Lactate	No
Acetyl Cysteine (N-Acetyl-Cysteine)	0.92	15.0	Lactate	No
Ascorbic Acid (L-Ascorbic Acid)	0.298	5.25	Lactate	No
Atracurium (Atracurium Besylate)³	0.0287	3.57	pH	No
			PO2	No
			PCO2	No
β-Hydroxybutyric Acid³	6.0	62.46	Lactate	No
Bilirubin	0.684	40	pH	No
			PO2	No
			PCO2	No
			Lactate	No
Bromide³ (Lithium Bromide)	2.5	21.7	Lactate	No
	37.5	325.7	Lactate	Yes	Use another method. Decreased results >10.0 mmol/L bromide.
Calcium (Calcium Chloride)	5.0	20	pH	No
			PO2	No
			PCO2	No
Dopamine (Dopamine Hydrochloride)	4.06 µmol/L	0.0621	Lactate	No
Ethanol	130	600	pH	No
			PO2	No
			PCO2	No
Formaldehyde³	0.133	0.399	Lactate	No
Glycolic Acid³	10.0	76.05	Lactate	Yes	Increased results >0.8 mmol/L glycolic acid.

² The compound tested to evaluate the interfering substance is presented in parenthesis.
³ The test concentration for this substance is not included in CLSI guideline EP37 1st edition.

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Substance²	Substance Concentration		i-STAT Test	Interference (Yes/No)
	mmol/L (unless specified)	mg/dL (unless specified)
Hemoglobin	10 g/L	1000	pH	No
			PO2	No
			PCO2	No
			Lactate	No
Hydroxyurea	0.405	3.08	Lactate	No
Ibuprofen	1.06	21.9	pH	No
			PO2	No
			PCO2	No
Intralipid 20%	N/A	2684	pH	No
			PO2	No
			PCO2	No
		3579	Lactate	No
Morphine (Morphine Sodium Salt)	0.0273	0.78	pH	No
			PO2	No
			PCO2	No
Potassium (Potassium Chloride)	8	59.6	pH	No
			PO2	No
			PCO2	No
Pyruvate (Lithium Pyruvate)	0.570	5	Lactate	No
Salicylate (Lithium Salicylate)	0.207	2.86	Lactate	No
Sodium (Sodium Chloride)	170	993.48	pH	No
			PO2	No
			PCO2	No
Thiocyanate (Lithium Thiocyanate)	0.898	5.22	Lactate	No
Thiopental	1.66	40.2	pH	No
			PO2	No
			PCO2	No
Triglyceride	16.94	1500	pH	No
			PO2	No
			PCO2	No
			Lactate	No
Uric Acid	1.4	23.5	Lactate	No

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ii. Other sensitivity studies

1) Oxygen Sensitivity for the i-STAT Lactate Test

The effect of oxygen on the i-STAT Lactate test in the i-STAT CG4+ cartridge on the i-STAT 1 System was evaluated with low and high oxygen levels using whole blood samples altered to four (4) lactate levels across the test reportable range. The equivalency between the high and low oxygen conditions was determined if the 95% confidence interval (CI) of the difference in means (or medians) was within the allowable error (±Ea). The study demonstrated that the i-STAT Lactate test in the i-STAT CG4+ cartridge on the i-STAT 1 System perform is insensitive to oxygen levels between 28 and 521 mmHg.

2) Altitude

The performance of the i-STAT pH, PO2, PCO2, and Lactate tests in the i-STAT CG4+ cartridge on the i STAT 1 analyzer at an altitude of approximately 10,000 feet above sea level was evaluated using whole blood samples at relevant analyte levels across the reportable range for each test. The pH, PO2, PCO2 and lactate results obtained from the i-STAT CG4+ cartridges (candidate device) were compared to the results obtained from the i-STAT CG4+ cartridges (blue) on the i-STAT 1 analyzer (K200492; comparator device) condition. Passing-Bablok regression analyses between the first replicate of the candidate device (y-axis) and mean of the comparator device (x-axis) were performed based on the CLSI EP09c-ED3: Measurement Procedure Comparison and Bias Estimation using Patient Samples– Third Edition. The results of the correlation coefficient and slope met acceptance criteria and demonstrate equivalent performance between the candidate and comparator condition at approximately 10,000 feet above sea level. The results are summarized in Table 12 below.

Table 12: Summary of Altitude Study Results

Test	Correlation Coefficient (r)		Slope
	r	95% CI	Slope	95% CI
pH	1.00	0.999 to 1.000	1.00	0.995 to 1.005
PO2	1.00	0.997 to 0.999	1.03	1.014 to 1.049
PCO2	1.00	0.999 to 0.999	0.96	0.949 to 0.967
Lactate	1.00	0.999 to 1.000	1.00	0.992 to 1.003

B. Comparison Studies

a. Method Comparison

Method comparison for arterial, venous, and capillary whole blood specimens on the i-STAT CG4+ cartridge with the i-STAT 1 System was demonstrated in studies based on CLSI EP09c-ED3: Measurement Procedure Comparison and Bias Estimation Using Patient Samples – Third Edition.

Heparinized arterial and venous whole blood specimens collected across multiple point of care sites were evaluated using i-STAT CG4+ cartridges on the i-STAT 1 analyzer against whole blood specimens tested on a comparative method. For pH and PO2, a Passing-Bablok linear regression analysis was performed using the first replicate result from the i-STAT 1 analyzer versus the singlicate result from the comparative method. For PCO2 and lactate, the

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first replicate result from the i-STAT 1 analyzer was compared to the mean result from the comparative method.

Two (2) capillary specimens collected from skin puncture with balanced heparin capillary tubes from each study subject across multiple point of care sites. One (1) tube was used to test in singlicate on the i‑STAT 1 analyzer and the other tube was used to test in singlicate on the comparative method.

The arterial, venous, and capillary data were pooled, and a Passing-Bablok linear regression analysis for pH, PO2, and PCO2 was performed using the singlicate result from the i-STAT CG4+ cartridge versus the result from the comparative method.

The method comparison results for arterial, venous, and capillary whole blood specimens are shown in Table 13. In the table, N is the number of specimens in the data set, and r is the correlation coefficient.

Table 13: Method Comparison Results for the pH, PO2, and PCO2 tests on the i-STAT CG4+ Cartridge with i-STAT 1 System

Test (units)	Comparative Method		N	Slope	Intercept	r	Medical Decision Level	Bias at Medical Decision Level
	Arterial/Venous	Capillary
pH (pH units)	RAPIDPoint 500/500e	RAPIDPoint 500/500e	551	1.00	-0.01	0.98	7.30	-0.0080
							7.35	-0.0080
							7.40	-0.0080
PO2 (mmHg)	RAPIDPoint 500/500e	RAPIDPoint 500/500e	557	1.01	-1.29	0.99	30	-0.9
							45	-0.7
							60	-0.6
PCO2 (mmHg)	i-STAT G3+	i-STAT G3+	475	1.03	-0.30	0.99	35.0	0.67
							45.0	0.95
							50.0	1.08
							70.0	1.64

The arterial and venous data were pooled, and a Passing-Bablok linear regression analysis for Lactate was performed using the singlicate result from the i-STAT CG4+ cartridge versus the result from the comparative method. The method comparison results for arterial and venous whole blood specimens are shown in Table 14.

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Table 14: Method Comparison Results for the Lactate test on the i-STAT CG4+ Cartridge with i-STAT 1 System

Test (units)	Comparative Method	N	Slope	Intercept	r	Medical Decision Level	Bias at Medical Decision Level
Lactate (mmol/L)	i-STAT CG4+ (K200492)	345	1.00	0.00	1.00	5.00	-0.140

The method comparison results for capillary whole blood specimens only for pH, PO2, and PCO2 are shown in Table 15.

Table 15: Results for i-STAT CG4+ Cartridge with i-STAT 1 System- Native and Contrived Capillary Specimens

Test (units)	N	Slope	Intercept	r	Xmin	Xmax
pH (pH units)	193	1.01	-0.08	0.97	6.607	7.709
PO2 (mmHg)	192	1.08	-5.47	0.99	14.0	554.0
PCO2 (mmHg)	184	1.05	-0.54	0.98	8.9	125.8

Bias at the medical decision levels for native capillary whole blood specimens only for pH, PO2, and PCO2 are shown in Table 16.

Table 16: Results for i-STAT CG4+ Cartridge with i-STAT 1 System- Native Capillary Specimens Bias at Medical Decision Levels

Test (units)	N	Range Min	Range Max	Medical Decision Level	Bias
					Estimate	95% CI
pH (pH units)	178	7.259	7.531	7.30	-0.0166	(-0.0341, 0.0007)
				7.35	-0.0104	(-0.0207, 0.0000)
				7.40	-0.0041	(-0.0095, 0.0013)
PO2 (mmHg)	178	31	139	30	-3.3	(-6.1, -0.4)
				45	-2.1	(-3.7, -0.4)
				60	-0.9	(-2.1, 0.0)
PCO2 (mmHg)	175	23.1	78.6	35.0	1.18	(0.48, 1.75)
				45.0	1.84	(1.04, 2.46)
				50.0	2.17	(1.15, 3.03)
				70.0	3.49	(1.40, 5.49)

b. Matrix Equivalence

A matrix equivalence study was conducted to evaluate the performance of the i-STAT pH, PO2, PCO2 and Lactate tests in the i STAT CG4+ cartridge on the i STAT 1 System using non-

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anticoagulated arterial and venous whole blood specimens. The study design and analysis method were based on recommendations from CLSI EP35: Assessment of Equivalence or Suitability of Specimen Types for Medical Laboratory Measurement Procedures, First Edition. The matrix equivalence of each test in the i-STAT CG4+ cartridge was assessed by comparing arterial or venous whole blood specimens collected without anticoagulant (candidate specimen type) to samples collected with balanced heparin or lithium heparin anticoagulant (primary specimen type). Each specimen was tested in duplicate using two (2) i-STAT CG4+ 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 17. In the table, N is the number of specimens in the data set, and r is the correlation coefficient.

Table 17: Matrix Equivalence Results

Test (units)	N	Candidate Specimen Range	Primary Specimen Range	r	Slope	Intercept
pH (pH units)	228	7.176-7.567	7.192-7.549	0.96	1.00	0.00
PO2 (mmHg)	228	15-197	15-197	0.99	1.01	-0.53
PCO2 (mmHg)	228	26.3-77.4	26.8-77.0	0.97	1.03	-1.58
Lactate (mmol/L)	289	0.31-19.42	0.30-19.43	1.00	1.00	-0.02

8. Conclusion

The results of these studies demonstrate that performance of the i-STAT pH, PO2, PCO2, and Lactate tests in the i-STAT CG4+ cartridge with the i-STAT 1 System are substantially equivalent to the predicate device.

Regulation Number and Section

§ 862.1120 Blood gases (P

CO2 , PO2 ) and blood pH test system.(a)
Identification. A blood gases (PCO2 , PO2 ) and blood pH test system is a device intended to measure certain gases in blood, serum, plasma or pH of blood, serum, and plasma. Measurements of blood gases (PCO2 , PO2 ) and blood pH are used in the diagnosis and treatment of life-threatening acid-base disturbances.(b)
Classification. Class II.