The i-STAT CG8+ cartridge with the i-STAT 1 System is intended for use in the in vitro quantification of glucose in arterial, venous, or capillary whole blood in point of care or clinical laboratory settings.

Glucose measurements are used in the diagnosis, monitoring, and treatment of carbohydrate metabolism disorders including, but not limited to, diabetes mellitus, neonatal hypoglycemia, and pancreatic islet cell carcinoma.

The i-STAT 1 Analyzer is intended for use in the in vitro quantification of various analytes in whole blood or plasma in point of care or clinical laboratory settings. Analyzers and cartridges should be used by healthcare professionals trained and certified to use the system and should be used according to the facility's policies and procedures.

The i-STAT System is for in vitro diagnostics use. Caution: Federal law restricts this device to sale by or on the order of a licensed practitioner.

Device Description

The i-STAT CG8+ cartridge is used with the i-STAT 1 analyzer as part of the i-STAT 1 System to measure glucose (Glu) in arterial, venous or capillary 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 CG8+ 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 CG8+ 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 movement occur within the i-STAT CG8+ cartridge. Cartridges require two to three drops of whole blood, which are typically 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 instrument interacts with the i-STAT CG8+ cartridge to move fluid across the sensors and generate a quantitative result (within approximately 2 minutes).

AI/ML Overview

The acceptance criteria and study proving the device meets those criteria are detailed below, based on the provided FDA 510(k) summary for the i-STAT CG8+ cartridge with the i-STAT 1 System.

Acceptance Criteria and Reported Device Performance

The acceptance criteria are not explicitly listed in a single table with corresponding performance values in the provided document. Instead, performance expectations are implied through the comparison to the predicate device and the presentation of various study results (precision, linearity, detection limits, interference, sensitivity, and method comparison) against established CLSI guidelines or internal thresholds.

However, based on the provided information, a summary of key performance characteristics and their reported values can be presented as follows:

1. Table of Acceptance Criteria and Reported Device Performance (Implied from Study Results)

Performance Characteristic	Acceptance Criteria (Implied/Standard)	Reported Device Performance (i-STAT CG8+ Glucose Test)
Precision	Consistent and acceptable repeatability, between-run, between-day, between-operator, and within-laboratory/total precision across various glucose levels and sample types, demonstrated through statistical metrics like SD and %CV, in line with CLSI EP05-A3 and internal standards.	20-Day Precision (Aqueous Materials - CV%): Ranges from 0.80% to 1.66% within-laboratory for various levels (28.4 to 576.8 mg/dL). Repeatability %CV is 0.53% to 1.25%.Multi-site/Operator Precision (Aqueous Materials - Overall %CV): Ranges from 0.64% to 1.59% for various levels (28.1 to 578.4 mg/dL).Whole Blood Precision (SD/ %CV): Ranges from 0.66% to 1.46% (%CV) for venous blood (73.9 to 544.3 mg/dL), 0.66% to 0.96% (%CV) for arterial blood (80.8 to 280.7 mg/dL), and 1.34% to 2.16% (%CV) for capillary blood (77.6 to 203.8 mg/dL). Values are well within typical acceptable ranges for point-of-care glucose testing.
Linearity/Reportable Range	Demonstration of linearity across the claimed reportable range (20 – 700 mg/dL), typically assessed by a high correlation coefficient (R²) and slope/intercept close to 1 and 0, respectively.	Reportable Range: 20 – 700 mg/dL.Range Tested: 17.1 – 795.4 mg/dL.Regression Summary: Slope = 0.994, Intercept = -1.385, R² = 0.9993. This indicates excellent linearity across and beyond the reportable range.
Detection Limits (LoQ, LoB, LoD)	Limit of Quantitation (LoQ) at or below the lower limit of the reportable range. Limit of Blank (LoB) and Limit of Detection (LoD) sufficiently low to ensure reliable detection of very low glucose levels.	Determined LoQ: 17 mg/dL (lower limit of reportable range is 20 mg/dL). Meets criteria.Determined LoB: 0.2 mg/dL.Determined LoD: 0.9 mg/dL. These values demonstrate the ability to accurately measure very low glucose concentrations.
Analytical Specificity (Interference)	Minimal or no significant interference from common endogenous and exogenous substances at specified concentrations, as determined by the difference between control and test samples falling within allowable error (±Ea). For identified interferents, a dose-response study is required.	Most substances tested (e.g., Acetaminophen, Acetoacetate, Bilirubin, Cholesterol, Ethanol, Heparin) showed No Interference. Identified Interferents for Glu: • Bromide: Yes, "Use Another Method"• Hydroxyurea: Yes, "Increased results ≥ 0.08 mmol/L"• Isoniazid: Yes, "Increased results ≥ 0.29 mmol/L"(Note: Intralipid 20% showed "Increased results >", but without a specific concentration or 'Yes/No' for interference, it's less clear, though typically levels above ~300 mg/dL (triglycerides) can interfere with glucose assays).
Sensitivity (Oxygen, Hematocrit, Altitude)	Insensitivity to variations in oxygen levels, hematocrit levels, and altitude within specified clinical ranges, demonstrating comparable performance under these varied conditions.	Oxygen Sensitivity: Insensitive to oxygen levels between 20 and 503 mmHg. (95% CI of difference within ±Ea).Hematocrit Sensitivity: Insensitive to hematocrit levels between 15% to 75% PCV. (Difference vs. mid-hematocrit within ±Ea).Altitude: Equivalent performance at ~10,000 feet above sea level, with a correlation coefficient (r) of 1.00 and a slope of 0.96 (95% CI: 0.957 to 0.971), meeting acceptance criteria.
Method Comparison (vs. Predicate)	Substantial equivalence to the predicate device in arterial, venous, and capillary whole blood, demonstrated by Passing-Bablok regression with a high correlation coefficient (r) close to 1, and slope/intercept close to 1 and 0 respectively.	Venous/Arterial/Capillary Whole Blood (Pooled Data):N: 547Slope: 0.98Intercept: 1.62r: 1.00This demonstrates strong agreement with the comparative methods (i-STAT CHEM8+ and epoc Blood Analysis System), supporting substantial equivalence.
Matrix Equivalence	Demonstration of equivalence between non-anticoagulated and anticoagulated whole blood specimens for Glucose.	Non-anticoagulated vs. Anticoagulated Whole Blood:N: 297r: 1.00Slope: 1.00Intercept: 0.00This indicates excellent matrix equivalence.

Note: The acceptance criteria are largely implied by the successful completion and positive results of studies designed according to CLSI (Clinical and Laboratory Standards Institute) guidelines, such as EP05-A3, EP06-Ed2, EP17-A2, EP07-ED3, EP37-ED1, EP09c-ED3, and EP35. Meeting the statistical benchmarks (e.g., specific SD, %CV, R², slope, intercept ranges, or being within "allowable error") for these guidelines indicates that the device's performance is acceptable for its intended use.

Study Details

Here's a breakdown of the study details based on the provided document:

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

Precision Studies:
- 20-day Precision (Aqueous): N=80 samples per level.
- Multi-site/Operator Precision (Aqueous): N=90-96 samples per level (across 3 sites).
- Whole Blood Precision: Venous (N=29-102 per range), Arterial (N=5-105 per range), Capillary (N=15-107 per range).
Linearity: Whole blood samples of varying glucose levels. Specific N not provided for this section, but typically multiple points across the range are tested.
Detection Limits (LoQ, LoB, LoD): Whole blood samples (altered to low/blank glucose levels). Specific N not provided.
Analytical Specificity (Interference): Whole blood samples. Specific N for each substance not provided, but the study was extensive (Table 8 lists many substances).
Other Sensitivity Studies:
- Oxygen Sensitivity: Whole blood samples.
- Hematocrit Sensitivity: Whole blood samples (at low, mid, high hematocrit levels).
- Altitude: Whole blood samples.
Method Comparison (with predicate device):
- N = 547 (pooled data from arterial, venous, and capillary whole blood specimens).
Matrix Equivalence:
- N = 297 (venous and arterial whole blood specimens).
Data Provenance:
- The document states "collected across multiple point of care sites" for whole blood precision and method comparison studies. It also mentions "at one site" for the 20-day precision study and "at three (3) sites" for the multi-site precision study.
- The document does not explicitly state the country of origin of the data or whether the studies were retrospective or prospective. However, clinical studies for 510(k) submissions are typically prospective, especially those involving patient samples collected concurrently with the study.

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

For this type of in vitro diagnostic device (quantitative glucose measurement), the "ground truth" for the test set is established by comparative reference methods, not by expert consensus or interpretations of images by radiologists.
The document mentions "a comparative method" (i-STAT CHEM8+ and epoc Blood Analysis System for glucose) for the method comparison study. These are legally marketed, validated laboratory or point-of-care devices that serve as the reference standard for measuring glucose.
No human experts (like radiologists in an imaging study) are used to establish "ground truth" for quantitative lab tests in this context. Their role might be in collecting samples by healthcare professionals, but not in determining the true value of the analyte.

4. Adjudication Method for the Test Set

Adjudication methods (e.g., 2+1, 3+1) are primarily relevant for imaging studies where human readers interpret data, and discrepancies need to be resolved.
For quantitative in vitro diagnostic tests like glucose measurement, adjudication of results in the traditional sense is not applicable. The "ground truth" is determined by the output of a reference instrument or method, and performance is assessed by statistical agreement between the new device and the reference.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done, If so, What was the Effect Size of How Much Human Readers Improve with AI vs without AI Assistance

No, an MRMC comparative effectiveness study was not done.
This device is an in vitro diagnostic for quantitative measurement of glucose, not an AI-based imaging or diagnostic device that assists human readers. Therefore, the concept of human readers improving with AI assistance is not relevant to this submission.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was Done

Yes, the performance characteristics described (precision, linearity, detection limits, interference, sensitivity) represent the standalone performance of the device (i-STAT CG8+ cartridge with i-STAT 1 System).
The method comparison study also evaluates the device's performance against a reference method independently. Human involvement is primarily in operating the device and collecting samples, not in interpreting or enhancing the device's quantitative output.

7. The Type of Ground Truth Used

The ground truth for the device's performance evaluation was established using comparative reference methods (e.g., i-STAT CHEM8+ glucose test, epoc Blood Analysis System) which are considered established and validated methods for glucose quantification.
This is akin to using a gold standard laboratory test result for comparison.

8. The Sample Size for the Training Set

The provided document is a 510(k) summary for a point-of-care in vitro diagnostic device, not an AI/Machine Learning device.
Therefore, there is no "training set" in the context of machine learning model development. The device relies on electrochemical detection mechanisms and pre-calibrated algorithms, not on statistical models trained on large datasets in the way AI applications do.
The studies described are for validation (test set), not training.

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

As explained in point 8, there is no "training set" for this device in the machine learning sense.
The fundamental principles and calibration of the glucose sensor (glucose oxidase-based amperometric peroxide detection) are based on established chemical and electrochemical principles in analytical chemistry, refined and validated during product development.

Summary

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July 28, 2023

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

Re: K223710

Trade/Device Name: i-STAT CG8+ cartridge with the i-STAT 1 System Regulation Number: 21 CFR 862.1345 Regulation Name: Glucose Test System Regulatory Class: Class II Product Code: CGA, JJE Dated: June 28, 2023 Received: June 28, 2023

Dear Jacquelyn Gesumaria:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (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.

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.

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

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

Sincerely,

Paula V. Caposino -S

Paula Caposino, Ph.D. Acting 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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Indications for Use

510(k) Number (if known) K223710

Device Name

i-STAT CG8+ cartridge with the i-STAT 1 System

Indications for Use (Describe)

The i-STAT System is for in vitro diagnostics use. Caution: Federal law restricts this device to sale by or on the order of a licensed practitioner.

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)

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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.

I. SUBMITTER INFORMATION

Owner	Abbott Point of Care Inc.400 College Road EastPrinceton, NJ 08540
Contact	Primary: Jacquelyn GesumariaPrincipal Specialist Regulatory AffairsPhone: 609-454-9384Secondary: Mojgan SoleimaniAssociate Director Regulatory AffairsPhone: 613-295-0932
Date Prepared	June 28, 2023

II. DEVICE INFORMATION

Proprietary Name	i-STAT CG8+ cartridge with the i-STAT 1 System
Common Name	Chemistry test, analyzer, handheld
510(k) Number	K223710

Product Code	Device ClassificationName	RegulationNumber	Class	Panel
CGA	Glucose Oxidase,Glucose	862.1345	II	Clinical Chemistry

III. PREDICATE DEVICE

K210958 (K183678) 510(k) Number

ProductCode	Device ClassificationName	RegulationNumber	Class	Panel
CGA	Glucose Oxidase, Glucose	862.1345	II	Clinical Chemistry

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IV. DEVICE DESCRIPTION

The i-STAT CG8+ cartridge is used with the i-STAT 1 analyzer as part of the i-STAT 1 System to measure glucose (Glu) in arterial, venous or capillary whole blood.

V. INTENDED USE STATEMENT

The i-STAT System is for in vitro diagnostics use. Caution: Federal law restricts this device to sale by or on the order of a licensed practitioner.

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VI. SUMMARY COMPARISON OF TECHNOLOGICAL CHARACTERISTICS

	Table 1: Similarities and Differences (Test and Instrument)
Feature orCharacteristic	Candidate Devices:i-STAT CG8+ cartridge with the i-STAT 1System, i-STAT Glucose test	Predicate Device:i-STAT CHEM8+ cartridge with the i-STAT 1System, i-STAT Glucose test (K210958)
Intended Use	The i-STAT CG8+ cartridge with thei-STAT 1 System is intended for use in thein vitro quantification of glucose in arterial,venous or capillary whole blood in point ofcare or clinical laboratory settings.Glucose measurements are used in thediagnosis, monitoring, and treatment ofcarbohydrate metabolism disordersincluding, but not limited to, diabetesmellitus, neonatal hypoglycemia,idiopathic hypoglycemia, and pancreaticislet cell carcinoma.	The i-STAT CHEM8+ cartridge with thei-STAT 1 System is intended for use in thein vitro quantification of sodium,potassium, chloride, ionized calcium,glucose, blood urea nitrogen, creatinine,hematocrit, and total carbon dioxide inarterial or venous whole blood in point ofcare or clinical laboratory settings.Glucose measurements are used in thediagnosis, monitoring, and treatment ofcarbohydrate metabolism disordersincluding, but not limited to, diabetesmellitus, neonatal hypoglycemia, idiopathichypoglycemia, and pancreatic islet cellcarcinoma.
DeviceClassification	Same	Class II
Product Code	Same	CGA
RegulationNo.	Same	862.1345
ReportableRange	Same	1.1 – 38.9 mmol/L20 – 700 mg/dL0.20 - 7.00 g/L
Sample Type	Arterial, venous, or capillary whole blood	Arterial and venous whole blood
SampleVolume	Same	95 µL
SamplePreparation	Same	Ready to Use
Samplecollection	Same	• Without anticoagulant• With balanced heparin anticoagulant orlithium heparin anticoagulant
Traceability	Same	NIST SRM965
Calibration	Same	1-point on-board contained withincartridge

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Table 1: Similarities and Differences (Test and Instrument)
Feature or Characteristic	Candidate Devices:i-STAT CG8+ cartridge with the i-STAT 1 System, i-STAT Glucose test	Predicate Device:i-STAT CHEM8+ cartridge with the i-STAT 1 System, i-STAT Glucose test (K210958)
Time to Test(Sample Stability)	Without anticoagulant:Arterial and venous within 3 minutesWith anticoagulant:Capillary within 3 minutesArterial and venous within 30 minutes	Without anticoagulant:Arterial and venous within 3 minutesWith anticoagulant:Arterial and venous within 30 minutes
Principle of Measurement	Same	Glu: Glucose oxidase based amperometric peroxide detection
Reagent Format	Same	Cartridge
Reagent Storage and Stability	Refrigerated at 2 to 8°C (35 to 46°F) until expiration dateRoom Temperature at 18-30°C (64-86°F) for 2 months	Refrigerated at 2 to 8°C (35 to 46°F) until expiration dateRoom Temperature at 18-30°C (64-86°F) for 14 days
Analyzer Type	Same	Handheld

PERFORMANCE CHARACTERISTICS VII.

A. Analytical Performance

a. Precision/Reproducibility:

i. Precision 20 days (Aqueous materials)
The precision of the i-STAT Glucose (Glu) test in the i-STAT CG8+ cartridge on the i-STAT 1 System was evaluated using five (5) levels of aqueous material. This 20day multi-day precision testing was based on CLSI document EP05-A3: Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline – Third Edition. The study was conducted using multiple analyzers and two (2) test cartridge lots over 20 days at one 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 CG8+ cartridge on the i-STAT 1 System are shown in Table 2.

Table 2: Results of 20-Day Precision of the i-STAT CG8+ Cartridge on the i-STAT 1 Analyzer
Test(units)	FluidLevel	N	Mean	Repeatability		Between-run		Between-day		Within-Laboratory
				SD	%CV	SD	%CV	SD	%CV	SD	%CV
Glu(mg/dL)	CV L1	80	28.4	0.36	1.25	0.20	0.69	0.24	0.85	0.47	1.66
	CV L2	80	42.0	0.36	0.87	0.29	0.70	0.23	0.56	0.52	1.25
	CV L3	80	124.7	0.66	0.53	0.55	0.44	0.52	0.42	1.00	0.80
	CV L4	80	279.4	1.47	0.53	1.79	0.64	1.26	0.45	2.63	0.94
	CV L5	80	576.8	4.70	0.81	2.35	0.41	2.91	0.50	6.01	1.04

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

Multi-day precision testing was performed at three (3) sites using a panel of aqueous solutions containing five (5) levels of glucose. At each site, each level was tested once a day by two (2) operators for five (5) days on six (6) i-STAT 1 Analyzers using i-STAT CG8+ cartridges. Within-run, between-day, betweenoperator and within-site (total) variance components were calculated by site. These components were also calculated for all sites combined and provided in the Table 3 below.

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Table 3: Multi-Day Precision of the i-STAT CG8+ Cartridge on the i-STAT 1 Analyzer
Test(units)	FluidLevel	N	Mean	Within-Run		Between-Day		Between-Operator		Within-Site (Total)		Between-Site		Overall
				SD	%CV	SD	%CV	SD	%CV	SD	%CV	SD	%CV	SD	%CV
Glu(mg/dL)	CV L1	91	28.1	0.39	1.40	0.16	0.55	0.08	0.29	0.43	1.54	0.11	0.41	0.45	1.59
	CV L2	90	41.4	0.50	1.21	0.12	0.30	0.17	0.41	0.54	1.32	0.00	0.00	0.54	1.32
	CV L3	96	124.5	0.64	0.52	0.47	0.38	0.08	0.06	0.8	0.64	0.00	0.00	0.80	0.64
	CV L4	90	280.3	1.42	0.51	0.33	0.12	0.22	0.08	1.47	0.53	0.44	0.16	1.54	0.55
	CV L5	90	578.4	4.25	0.73	1.78	0.31	0.00	0.00	4.61	0.80	0.00	0.00	4.61	0.80

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iii. Precision (Whole Blood)

Whole blood precision of the i-STAT Glucose test in the i-STAT CG8+ cartridge on the i-STAT 1 System was evaluated using arterial, venous, and capillary whole blood specimens collected with lithium heparin. The whole blood precision was assessed using the duplicate test results collected across multiple point of care sites. The mean values for each sample were divided into subintervals for each sample type across the reportable range for the i-STAT Glucose test. The results are summarized in Table 4.

Table 4: Whole Blood Precision of arterial, venous, and capillary whole blood for the i-STATGlucose test in the i-STAT CG8+ cartridge on the i-STAT 1 Analyzer
Test(units)	Sample Type	Sample Range	N	Mean	SD	%CV
Glu(mg/dL)	Venous Whole Blood	20-90	29	73.9	0.86	1.17
		>90-150	102	111.7	1.08	0.96
		>150-250	27	173.4	1.82	1.05
		>250-400	13	308.5	2.08	0.67
		>400-700	9	544.3	7.92	1.46
Glu(mg/dL)	Arterial Whole Blood	20-90	5	80.8	0.77	0.96
		>90-150	105	113.6	0.75	0.66
		>150-250	35	178.0	1.55	0.87
		>250-400	8	280.7	2.19	0.78
Glu(mg/dL)	Capillary Whole Blood	20-90	32	77.6	1.08	1.39
		>90-150	107	108.3	2.34	2.16
		>150-700	15	203.8	2.74	1.34

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 Glucose test in the i-STAT CG8+ cartridge with the i-STAT 1 System was evaluated by preparing whole blood samples of varying glucose levels. The i-STAT Glucose test in the i-STAT CG8+ cartridge demonstrated linearity over the reportable range for each i-STAT test. Regression summary of the response for the i-STAT Glucose test versus the concentration of the whole blood samples of varying glucose levels is provided in Table 5.

Table 5: Regression Summary for the i-STAT Glucose test in the i-STAT CG8+ Cartridge on thei-STAT 1 Analyzer
Test	Units	Reportable Range	Range Tested	Slope	Intercept	R2
Glu	mg/dL	20 – 700	17.1 – 795.4	0.994	-1.385	0.9993

c. 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 Glucose test in the i-STAT CG8+ cartridge was evaluated on the i-STAT 1 analyzer using two (2) i-STAT CG8+ cartridge lots and whole blood

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that was altered to a low glucose level. The LoQ for the i-STAT Glucose test in the i-STAT CG8+ cartridge was determined to be at or below the lower limit of the reportable range for the i-STAT Glucose test as shown in Table 6.

Table 6: Summary of LoQ Results for i-STAT Glucose Test in the i-STAT CG8+Cartridge
Test (units)	Lower limit of thereportable range	Determined LoQ
Glu (mg/dL)	20	17

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 Glucose (Glu) test in the i-STAT CG8+ cartridge was evaluated on the i-STAT 1 analyzer using two (2) i-STAT CG8+ cartridge lots. Whole blood was altered to a blank glucose level for LoB testing. Whole blood was altered to two (2) low levels of glucose 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 Glucose test in the i-STAT CG8+ cartridge on the i-STAT 1 analyzer is shown in the Table 7.

Table 7: Summary of LoB and LoD Results
Test (units)	LoB	LoD
Glu (mg/dL)	0.2	0.9

d. Analytical Specificity

i. Interference

The study was based on CLSI EP07-ED3: Interference Testing in Clinical Chemistry, Third Edition.

The interference performance of the i-STAT Glucose test in the i-STAT CG8+ 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 between the control and test samples was outside of the allowable error (+Ea) for the i-STAT Glucose test. For an identified interferent, a dose-response was performed to determine the degree of interference as a function of the substance concentration.

Table 8 contains the lists of potentially interfering substances tested and the interference results for the i-STAT CG8+ cartridge.

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Table 8: Potentially Interfering Substances and Test Concentrations for the i-STAT Glucose test inthe i-STAT CG8+ Cartridge
	Test Concentration
Substance 1	mmol/L(unlessspecified)	mg/dL(unlessspecified)	i-STATTest	Interference(Yes/No)	Comments
Acetaldehyde 2	0.045	0.2	Glu	No
Acetaminophen	1.03	15.6	Glu	No
Acetoacetate(LithiumAcetoacetate)	2.0	20	Glu	No
Acetyl Cysteine (N-Acetyl-L-Cysteine)	0.92	15	Glu	No
Ammonium(AmmoniumChloride) 2	2.0	10.7	Glu	No
Ascorbic Acid (L-Ascorbic Acid)	0.298	5.25	Glu	No
β-HydroxybutyricAcid 2	6.0	62.46	Glu	No
Bilirubin	0.684	40	Glu	No
	2.5	21.7	Glu	No
Bromide 2(Lithium Bromide)	37.5	325.7	Glu	Yes	Use AnotherMethod
Cholesterol	10.3	400	Glu	No
Creatinine	1.326	15	Glu	No
Dopamine(DopamineHydrochloride)	4.06μmol/L	0.0621	Glu	No
Ethanol	130	600	Glu	No
Fluoride (LithiumFluoride)	0.0632	0.12	Glu	No
Formaldehyde 2	0.133	0.399	Glu	No
Fructose	1	18	Glu	No
Galactose	3.33	60	Glu	No
Gentamicin(Gentamicin Sulfate)	0.0628	3	Glu	No
Gentisic Acid	0.0973	1.5	Glu	No
Glucosamine(GlucosamineHydrochloride) 2	0.030	0.647	Glu	No
Glutathione, reduced 3	3	3 mEq/L	Glu	No
Glycolic Acid 2	10.0	76.05	Glu	No
Guaifenesin	0.0227	0.45	Glu	No
Hemoglobin	10 g/L	1000	Glu	No
Heparin (SodiumHeparin)	3.30 U/mL	330 U/dL	Glu	No
Hydroxyurea	0.405	3.08	Glu	Yes	Increased results ≥0.08 mmol/L
Ibuprofen	1.06	21.9	Glu	No
Table 8: Potentially Interfering Substances and Test Concentrations for the i-STAT Glucose test in
the i-STAT CG8+ Cartridge
Substance 1	Test Concentrationmmol/L(unlessspecified)	mg/dL(unlessspecified)	i-STATTest	Interference(Yes/No)	Comments
Intralipid 20%	N/A	2891	Glu	No	Increased results >
Isoniazid	0.438	6	Glu	Yes	Increased results ≥0.29 mmol/L
Lactate (LithiumLactate)	10	90	Glu	No
Maltose	10.5	360	Glu	No
Mannose 2	1	18.02	Glu	No
Nithiodote (SodiumThiosulfate) 2	16.7	264.04	Glu	No
pH	8.0 pHunits	N/A	Glu	No
Pyruvate (LithiumPyruvate)	0.570	5	Glu	No
Salicylate (LithiumSalicylate)	0.207	2.86	Glu	No
Thiocyanate (LithiumThiocyanate)	0.898	5.22	Glu	No
Triglyceride	16.94	1500	Glu	No
Uric Acid	1.4	23.5	Glu	No
Xylose 2	3	45.04	Glu	No

1 The compound tested to evaluate the interfering substance is presented in parenthesis.

² The test concentration for this substance is not included in CLSI guideline EP37 1st edition.

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ii. Other sensitivity studies

1) Oxygen Sensitivity Study

The effect of oxygen on the i-STAT Glucose test in the i-STAT CG8+ cartridge on the i-STAT 1 System was evaluated with low and high oxygen levels using whole blood samples altered to four (4) glucose levels the reportable range of the i-STAT Glucose test. 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 Glucose test in the i-STAT CG8+ cartridge on the i-STAT 1 System perform is insensitive to oxygen levels between 20 and 503 mmHg.

2) Hematocrit Sensitivity

A hematocrit sensitivity study was conducted to evaluate the performance of the i-STAT Glucose test in the i-STAT CG8+ cartridge with the i-STAT 1 Sustem to assess the effect of hematocrit. Three (3) hematocrit levels (low, mid and high) were evaluated at four (4) glucose levels across the reportable range of the i-STAT Glucose test in the i-STAT CG8+ cartridge. The hematocrit sensitivity at each glucose level was assessed by comparing the results at the low and high hematocrit level to the mid hematocrit level. Equivalency was assessed by determining whether the difference between the low and high hematocrit level and the mid hematocrit level was within the allowable error (±Ea). The study demonstrated that i-STAT Glucose test in the i-STAT CG8+ cartridge with the i-STAT 1 System is insensitive to hematocrit levels between 15% to 75% packed cell volume (PCV).

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3) Altitude

The performance of the i-STAT Glucose test in the i-STAT CG8+ 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 glucose levels across the reportable range for the i-STAT Glucose test. The glucose test results obtained from the i-STAT CG8+ cartridges (candidate device) were compared to the glucose test results obtained from the i-STAT CHEM8+ (blue) cartridges on the i-STAT 1 analyzer (comparator device). 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: Measurement Procedure Comparison and Bias Estimation using Patient Samples, 3rd ed. The results of the correlation coefficient and slope met acceptance criteria and demonstrated equivalent performance between the candidate and comparator conditions at approximately 10,000 feet above sea level. The results are summarized in Table 9.

Table 9: Summary of Altitude Study Results for the i-STAT CG8+ Cartridge
Test	Correlation Coefficient (r)		Slope
	r	95% CI	Slope	95% CI
Glu	1.00	1.000 to 1.000	0.96	0.957 to 0.971

B. Comparison Studies

a. Method Comparison with predicate device

Method comparison for arterial, venous, and capillary whole blood specimens on the i-STAT CG8+ 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.

Lithium heparin venous and arterial whole blood specimens collected across multiple point of care sites were evaluated using i-STAT CG8+ cartridges on the i-STAT 1 analyzer against whole blood specimens tested on a comparative method. The first replicate glucose result from the i-STAT 1 analyzer was compared to the mean glucose result from the comparative method.

Two (2) capillary whole blood specimens collected from skin puncture with balanced heparin capillary tubes from each study subject across multiple point of care sites were evaluated and analyzed in singlicate on the i-STAT 1 analyzer against the comparative method. A Passing-Bablok linear regression analysis for glucose was performed using the singlicate result from the i-STAT 1 analyzer versus the singlicate result of the comparative method.

The venous, arterial, and capillary whole blood data were pooled, and a Passing-Bablok linear regression analysis was performed using the results from the i-STAT CG8+ cartridges on the i-STAT 1 analyzer versus the comparative method results.

Method comparison results for arterial, venous, and capillary whole blood specimens are shown in Table 10. In the table, N is the number of specimens in the data set, and r is the correlation coefficient.

Table 10: Method Comparison Results for i-STAT CG8+ Cartridge with i-STAT 1 System
Test	Comparative Method		N	Slope	Intercept	r
	Arterial/Venous	Capillary
Glu	i-STAT CHEM8+	epoc Blood AnalysisSystem	547	0.98	1.62	1.00

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b. Matrix Equivalence

A matrix equivalence study was conducted to evaluate the performance of the i-STAT Glucose test in the i-STAT CG8+ cartridge on the i-STAT 1 System using nonanticoagulated venous and arterial whole blood specimens. The study design and analysis method were based on recommendations from the Clinical and Laboratory Standards Institute (CLSI) guideline EP35: Assessment of Equivalence or Suitability of Specimen Types for Medical Laboratory Measurement Procedures, 1st ed. The matrix equivalence of the i-STAT Glucose test in the i-STAT CG8+ 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 CG8+ 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 mean result from the primary specimen (x-axis). The regression analysis results are summarized in Table 11. In the table, N is the number of specimens in the data set, and r is the correlation coefficient.

Table 11: Matrix Equivalence Results
Test (units)	N	Candidate SpecimenRange	Primary SpecimenRange	r	Slope	Intercept
Glu (mg/dL)	297	39-688	39-671	1.00	1.00	0.00

CONCLUSION VIII.

The results of these studies demonstrate that performance of the i-STAT Glucose test in the i-STAT CG8+ cartridge with the i-STAT 1 System are substantially equivalent to the predicate device.

Regulation Number and Section

§ 862.1345 Glucose test system.

(a)
Identification. A glucose test system is a device intended to measure glucose quantitatively in blood and other body fluids. Glucose measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus, neonatal hypoglycemia, and idiopathic hypoglycemia, and of pancreatic islet cell carcinoma.(b)
Classification. Class II (special controls). The device, when it is solely intended for use as a drink to test glucose tolerance, is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.