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

K223755 · Abbott Point of Care, Inc. · CGA · Sep 11, 2023 · Clinical Chemistry

Device Facts

• Record ID: K223755
• Device Name: i-STAT G cartridge with the i-STAT 1 System
• Applicant: Abbott Point of Care, Inc.
• Product Code: CGA · Clinical Chemistry
• Decision Date: Sep 11, 2023
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1345
• Device Class: Class 2
• Attributes: Pediatric

Intended Use

The i-STAT G 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, idiopathic hypoglycemia, and pancreatic islet cell carcinoma.

Device Story

The i-STAT G cartridge is a single-use, disposable test cartridge used with the i-STAT 1 handheld analyzer. It accepts 2-3 drops of whole blood (arterial, venous, or capillary) via a transfer device. The cartridge contains sensors, a fluid pack, and channels for controlled fluid movement. The analyzer moves the sample across the sensors to perform an amperometric measurement of oxidized hydrogen peroxide produced by glucose oxidase activity. Results are generated in approximately 2 minutes. Used in point-of-care or clinical laboratory settings by trained medical professionals. The output provides quantitative glucose levels to assist clinicians in diagnosing and managing metabolic disorders. The device benefits patients by providing rapid, actionable diagnostic information at the point of care.

Clinical Evidence

Bench testing only. Precision studies (internal and multi-site) evaluated repeatability and reproducibility across 5 concentration levels, showing within-lab CVs < 2.2%. Linearity was confirmed across 20-700 mg/dL (R²=0.999). Interference testing established limits for exogenous/endogenous substances. Method comparison (n=164 venous, n=173 arterial, n=234 capillary) against predicate and epoc systems showed high correlation (r=1.00 for all) and slope/intercept values near 1.0/0.0, respectively. No clinical trials were required.

Technological Characteristics

Handheld in vitro diagnostic system. Amperometric biosensor technology using glucose oxidase. Single-use disposable cartridge containing fluid pack, sensors, and waste chamber. Supports arterial, venous, and capillary whole blood. Connectivity via i-STAT 1 analyzer accessories (Downloader/Recharger). Calibration is 1-point on-board. Operates at room temperature or refrigerated storage.

Indications for Use

Indicated for patients requiring glucose quantification in arterial, venous, or capillary whole blood for diagnosis, monitoring, and treatment of carbohydrate metabolism disorders, including diabetes mellitus, neonatal hypoglycemia, idiopathic hypoglycemia, and pancreatic islet cell carcinoma.

Regulatory Classification

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.

Special Controls

*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.

Predicate Devices

• i-STAT CHEM8+ cartridge with the i-STAT 1 System (K210958, K183678)

Reference Devices

• epoc Blood Analysis System

Submission Summary (Full Text)

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

September 11, 2023

Mojgan Soleimani Associate Director Regulatory Affairs Abbott Point of Care Inc. 400 College Road East Princeton, New Jersey 08540

Re: K223755

Trade/Device Name: i-STAT G 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 Dated: August 8, 2023 Received: August 9, 2023

#### Dear Mojgan Soleimani:

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 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR

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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 ([e-mail]) or phone [phone] 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) K223755

Device Name i-STAT G cartridge on the i-STAT 1 System

#### Indications for Use (Describe)

The i-STAT G 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.

| Type of Use (Select one or both, as applicable) |
|----------------------------------------------------------------------------------------------------------------------------------------|
| <span style="white-space: nowrap;"> <span style="font-size: 16px;">☑</span> Prescription Use (Part 21 CFR 801 Subpart D) </span> |
| <span style="white-space: nowrap;"> <span style="font-size: 16px;">☐</span> Over-The-Counter Use (21 CFR 801 Subpart C) </span> |

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Image /page/3/Picture/0 description: The image shows the Abbott logo. The logo consists of a blue abstract shape on the left and the word "Abbott" in black on the right. The abstract shape is a stylized letter "A" with rounded corners. The word "Abbott" is in a bold, sans-serif font.

# 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.<br>400 College Road East<br>Princeton, NJ 08540 |
|---------------|----------------------------------------------------------------------------------------------|
| Contact | Primary: Mojgan Soleimani<br>Associate Director Regulatory Affairs<br>Phone: [phone] |
| | Secondary: Robert Gregg<br>Director Regulatory Affairs<br>Phone: [phone] |
| Date Prepared | September 11, 2023 |

#### II. DEVICE INFORMATION

| Proprietary Name | i-STAT G cartridge with the i-STAT 1 System |
|------------------|---------------------------------------------|
| Common Name | Glucose test, analyzer, handheld |
| 510(k) Number: | K223755 |

| Product<br>Code | Device Classification Name | Regulation<br>Number | Class | Panel |
|-----------------|----------------------------|----------------------|-------|--------------------|
| CGA | Glucose oxidase, Glucose | 862.1345 | II | Clinical Chemistry |

#### III. PREDICATE DEVICE

Proprietary Name

i-STAT CHEM8+ cartridge with the i-STAT 1 System

510(k) Number

K210958 (K183678)

| Product<br>Code | Device Classification<br>Name | Regulation<br>Number | Class | Panel |
|-----------------|-------------------------------|----------------------|-------|--------------------|
| CGA | Glucose oxidase, Glucose | 862.1345 | II | Clinical Chemistry |

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## IV. DEVICE DESCRIPTION

The i-STAT G cartridge is used with the i-STAT 1 analyzer as part of the i-STAT 1 System to measure glucose in arterial, venous, or capillary whole blood for the diagnosis, monitoring, and treatment of metabolism disorders including, but not limited to, diabetes mellitus, neonatal hypoglycemia, idiopathic hypoglycemia, and pancreatic islet cell carcinoma.

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 Sustem, including the i-STAT G 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 G cartridge contains the required sensors and 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 the cartridge. The test is contained in a single-use, disposable cartridge. All the test steps and fluid movements occur within the i-STAT G cartridge. 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 interacts with the cartridge to move fluid across the sensors and generate a quantitative result (within approximately 2 minutes).

#### V. INTENDED USE STATEMENT

The i-STAT G 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, idiopathic hypoglycemia, and pancreatic islet cell carcinoma.

| Similarities and Differences (Test and Instrument) | | |
|----------------------------------------------------|-------------------|-------------------|
| | Candidate Devices | Predicate Devices |

VI. SUMMARY COMPARISON OF TECHNOLOGICAL CHARACTERISTICS

| Similarities and Differences (Test and Instrument) | | |
|--------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Feature or<br>Characteristic | Candidate Device:<br>Glucose test in the <i>i-STAT G</i> cartridge<br>with the <i>i-STAT 1 System</i> | Predicate Device:<br>Glucose test in the <i>i-STAT CHEM8+</i><br>cartridge with the <i>i-STAT 1 System</i><br>K210958 (K183678) |
| Intended Use | The <i>i-STAT G</i> cartridge with the <i>i-STAT 1 System</i> is intended for use in the <i>in vitro</i> quantification of glucose in arterial, venous, or capillary whole blood in point of care or clinical laboratory settings. | The <i>i-STAT CHEM8+</i> cartridge with the <i>i-STAT 1 System</i> is intended for use in the <i>in vitro</i> quantification of sodium, potassium, chloride, ionized calcium, glucose, blood urea nitrogen, creatinine, hematocrit, and total carbon dioxide in |
| Similarities and Differences (Test and Instrument) | | |
| Feature or<br>Characteristic | Candidate Device:<br>Glucose test in the i-STAT G cartridge<br>with the i-STAT 1 System | Predicate Device:<br>Glucose test in the i-STAT CHEM8+<br>cartridge with the i-STAT 1 System<br>K210958 (K183678) |
| | Glucose measurements are used in the<br>diagnosis, monitoring, and treatment<br>of carbohydrate metabolism disorders<br>including, but not limited to, diabetes<br>mellitus, neonatal hypoglycemia,<br>idiopathic hypoglycemia, and<br>pancreatic islet cell carcinoma. | arterial or venous whole blood in point of<br>care or clinical laboratory settings.<br><br>The glucose test in the i-STAT CHEM8+<br>cartridge with the i-STAT 1 System is<br>intended for use in the <i>in vitro</i><br>quantification of glucose in arterial or<br>venous whole blood in point of care or<br>clinical laboratory settings.<br><br>Glucose measurements are used in the<br>diagnosis, monitoring, and treatment of<br>carbohydrate metabolism disorders<br>including, but not limited to, diabetes<br>mellitus, neonatal hypoglycemia,<br>idiopathic hypoglycemia, and pancreatic<br>islet cell carcinoma. |
| Device<br>Classification | Same | Class II |
| Product Code | Same | CGA |
| Regulation<br>Number | Same | 862.1345 |
| Reportable<br>Range | Same | 1.1 – 38.9 mmol/L<br>20 – 700 mg/dL<br>0.20 – 7.00 g/L |
| Sample Type | Arterial, venous or capillary whole<br>blood | Arterial or venous whole blood |
| Sample<br>Volume | 65 μL | 95 μL |
| Sample<br>Preparation | Same | Ready to use |
| Sample<br>Collection | | • Without anticoagulant<br>• With balanced heparin anticoagulant<br>or lithium anticoagulant |
| | Arterial and<br>venous<br>Without anticoagulant | |
| | Arterial and<br>Venous<br>With balanced heparin,<br>lithium, K2 or K3 EDTA<br>anticoagulant | |
| | Capillary<br>With balanced heparin<br>or lithium anticoagulant | |
| Similarities and Differences (Test and Instrument) | | |
| Feature or Characteristic | Candidate Device:<br>Glucose test in the i-STAT G cartridge<br>with the i-STAT 1 System | Predicate Device:<br>Glucose test in the i-STAT CHEM8+ cartridge<br>with the i-STAT 1 System<br>K210958 (K183678) |
| Traceability | Same | NIST SRM 965 |
| Calibration | Same | 1-point on-board contained within cartridge |
| Time to Test / Sample Stability<br>(Time from collection to sample fill) | Without anticoagulant:<br>Arterial and venous within 3 minutes<br><br>With anticoagulant:<br>Capillary within 3 minutes<br>Arterial and venous within 30 minutes | Without anticoagulant:<br>Arterial and venous within 3 minutes<br><br>With anticoagulant:<br>Arterial and venous within 30 minutes |
| Principle of Measurement | Same | Amperometric measurement of oxidized hydrogen peroxide produced by glucose oxidase activity |
| Reagent Format | Same | Cartridge |
| Reagent Storage and Stability | Same | Refrigeration at 2°C to 8°C (35-46°F) until expiration date;<br>Room Temperature at 18°C to 30°C (64–86 °F) for 14 days |
| Analyzer Type | Same | Handheld |

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#### VII. PERFORMANCE CHARACTERISTICS

#### A. Analytical Performance

#### a. Precision/Reproducibility:

#### i. Precision 20 days (aqueous materials)

The precision of the i-STAT Glucose test in the i-STAT G cartridge with the i-STAT 1 System was evaluated using five (5) levels of aqueous material. This single-site 20-day 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 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 are shown in Table 1.

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Table 1: Results of 20-Day precision of the i-STAT Glucose test on the i-STAT 1 analyzer using i-STAT Calibration Verification set (mg/dL)

| Fluid Level | N | Mean<br>(mg/dL) | Repeatability | | Between-run | | Between-day | | Within-Laboratory | |
|-------------|----|-----------------|---------------|------|-------------|------|-------------|------|-------------------|------|
| | | | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| CV L1 | 80 | 25.0 | 0.43 | 1.71 | 0.06 | 0.23 | 0.34 | 1.36 | 0.55 | 2.19 |
| CV L2 | 80 | 38.5 | 0.38 | 0.99 | 0.22 | 0.58 | 0.21 | 0.54 | 0.49 | 1.27 |
| CV L3 | 80 | 119.1 | 0.69 | 0.58 | 0.21 | 0.18 | 0.31 | 0.26 | 0.78 | 0.66 |
| CV L4 | 80 | 272.2 | 1.42 | 0.52 | 0.40 | 0.15 | 0.76 | 0.28 | 1.66 | 0.61 |
| CV L5 | 80 | 565.5 | 4.33 | 0.77 | 2.71 | 0.48 | 1.78 | 0.32 | 5.41 | 0.96 |

#### 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 material containing five (5) levels of glucose. At each site, testing was performed 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 G cartridges. Within-run, between-day, between-operator and within-site (total) variance components were calculated by site. These components were also calculated for all sites combined and provided in the Table 2 below.

Table 2: Results of point of care multi-day precision of i-STAT Glucose test on the i-STAT 1 analyzer using i-STAT TriControls Calibration Verification set (mg/dL)

| Fluid Level | 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 |
| CV L1 | 89 | 573.1 | 2.63 | 0.46 | 1.20 | 0.21 | 0.00 | 0.00 | 2.89 | 0.50 | 0.00 | 0.00 | 2.89 | 0.50 |
| CV L2 | 90 | 266.3 | 0.71 | 0.27 | 0.37 | 0.14 | 0.16 | 0.06 | 0.82 | 0.31 | 0.05 | 0.02 | 0.82 | 0.31 |
| CV L3 | 90 | 133.7 | 0.57 | 0.43 | 0.12 | 0.09 | 0.18 | 0.13 | 0.61 | 0.46 | 0.00 | 0.00 | 0.61 | 0.46 |
| CV L4 | 90 | 46.1 | 0.33 | 0.72 | 0.31 | 0.67 | 0.04 | 0.09 | 0.46 | 0.99 | 0.15 | 0.32 | 0.48 | 1.04 |
| CV L5 | 90 | 33.7 | 0.57 | 1.68 | 0.00 | 0.00 | 0.14 | 0.40 | 0.58 | 1.73 | 0.00 | 0.00 | 0.58 | 1.73 |

#### iii. Precision (whole blood)

Whole blood precision of the i-STAT Glucose test in the i-STAT G 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. For each sample type, samples were grouped into subintervals based on their mean values. The results are summarized in Table 3.

| Test<br>(units) | Sample Type | Sample Range | N | Mean | SD | %CV |
|--------------------|--------------------|--------------|----|-------|------|------|
| Glucose<br>(mg/dL) | Venous whole blood | 20-90 | 38 | 75.0 | 0.32 | 0.43 |
| | | >90-150 | 67 | 109.6 | 0.39 | 0.35 |
| | | >150-250 | 32 | 195.8 | 0.73 | 0.37 |

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| | | >250-400 | 15 | 315.0 | 1.17 | 0.37 |
|--|-----------------------|----------|----|-------|------|------|
| | | >400-700 | 12 | 559.0 | 2.01 | 0.36 |
| | Arterial whole blood | 20-90 | 9 | 82.4 | 0.33 | 0.40 |
| | | >90-150 | 94 | 125.0 | 0.57 | 0.46 |
| | | >150-250 | 64 | 182.0 | 0.54 | 0.30 |
| | | >250-700 | 6 | 357.0 | 0.91 | 0.26 |
| | Capillary whole blood | 20-90 | 33 | 70.9 | 1.92 | 2.71 |
| | | >90-150 | 53 | 116.0 | 2.44 | 2.10 |
| | | >150-250 | 37 | 196.6 | 4.40 | 2.24 |
| | | >250-700 | 16 | 297.1 | 4.09 | 1.38 |

#### b. Linearity/assay reportable range:

#### i. Linearity

The study was designed based on CLSI EP06-Ed2: Evaluation of Linearity of Quantitative Measurement Procedures - Second Edition.

The linearity of the i-STAT Glucose test in the i-STAT G cartridge with the i-STAT 1 System was evaluated by preparing whole blood samples of varying glucose levels across the reportable range for the test. The i-STAT Glucose test in the i-STAT G cartridge on the i-STAT 1 System demonstrated linearity over the reportable range of 20 - 700 mg/dL. 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 4.

| Test | Units | Reportable Range | Range Tested | Slope | Intercept | R2 |
|---------|-------|------------------|--------------|-------|-----------|-------|
| Glucose | mg/dL | 20-700 | 15.3 – 793.3 | 1.002 | -1.258 | 0.999 |

#### c. Detection Limit

#### Limit of Quantitation (LoQ) i.

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 G cartridge was evaluated on the i-STAT 1 analyzer using two (2) cartridge lots and whole blood that was altered to a low glucose level. The LoQ for the i-STAT Glucose test was determined to be 14 mg/dL, which is below the lower limit of the reportable range for the i-STAT Glucose test as shown in Table 5.

| Table 5: LoQ result for the i-STAT Glu test in the i-STAT G cartridge | | |
|-----------------------------------------------------------------------|-------------------------------------|----------|
| Test | Lower limit of the reportable range | LoQ |
| Glucose | 20 mg/dL | 14 mg/dL |

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#### 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 test in the i-STAT G cartridge were evaluated on the i-STAT 1 analyzer using two (2) cartridge lots. Whole blood was altered to a blank glucose level for LoB testing and two (2) low glucose levels for LoD testing. The LoB and LoD were determined based on the maximal LoB or LoD value obtained for each lot tested. The LoB and LoD for the i-STAT Glucose test on the i-STAT 1 analyzer was determined as shown in the Table 6 below.

| Table 6: Summary of LoB and LoD results for the i-STAT G cartridge | | |
|--------------------------------------------------------------------|---------|-----------|
| Test | LoB | LoD |
| Glucose | 0 mg/dL | 0.7 mg/dL |

## 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 G cartridge on the i STAT 1 analyzer with the i-STAT 1 System was evaluated using whole blood samples at low and high glucose levels for all substances. The effect of each substance was evaluated by comparing the test results 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 or 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 glucose allowable error (±Ea). For an identified interferent, a dose-response analysis was performed to determine the degree of interference as a function of the substance concentration.

Table 7 contain the lists of potentially interfering substances tested for the i-STAT Glucose test and the interference results.

| Table 7: Potentially interfering substances and test concentrations for the i-STAT Glucose | | | | | |
|--------------------------------------------------------------------------------------------|----------------------------------------|---------------------------------------|------|--------------------------|-------------------------------------|
| test in the i-STAT G cartridge | | | | | |
| Substance | Substance<br>Concentration<br>(mmol/L) | Substance<br>Concentration<br>(mg/dL) | Test | Interference<br>(Yes/No) | Comment |
| Acetaldehyde | 0.045 | 0.2 | Glu | No | |
| Acetaminophen | 1.03 | 15.6 | Glu | No | |
| Acetoacetate<br>(Lithium Acetoacetate) | 2.0 | 20 | Glu | No | |
| Table 7: Potentially interfering substances and test concentrations for the i-STAT Glucose | | | | | |
| test in the i-STAT G cartridge | | | | | |
| Substance | Substance<br>Concentration<br>(mmol/L) | Substance<br>Concentration<br>(mg/dL) | Test | Interference<br>(Yes/No) | Comment |
| Acetyl Cysteine<br>(N-Acetyl-L-<br>Cysteine) | 0.92 | 15.0 | Glu | No | |
| Ammonium<br>(Ammonium<br>Chloride) | 2.0 | 10.7 | Glu | No | |
| Ascorbic Acid<br>(L-Ascorbic<br>Acid) | 0.298 | 5.25 | Glu | No | |
| β-<br>Hydroxybutyric<br>Acid | 6.0 | 62.46 | Glu | No | |
| Bilirubin | 0.684 | 40 | Glu | No | |
| Bromide | 2.5 | 21.7 | Glu | No | |
| (Lithium<br>Bromide) | 37.5 | 325.7 | Glu | Yes | Use another method. |
| Cholesterol | 10.3 | 400 | Glu | No | |
| Creatinine | 1.326 | 15 | Glu | No | |
| Dopamine<br>(Dopamine<br>Hydrochloride) | 4.06 µmol/L | 0.0621 | Glu | No | |
| Ethanol | 130 | 600 | Glu | No | |
| Fluoride<br>(Lithium<br>Fluoride) | 0.0632 | 0.12 | Glu | No | |
| Formaldehyde | 0.133 | 0.399 | Glu | No | |
| Fructose | 1 | 18 | Glu | No | |
| Galactose | 3.33 | 60 | Glu | No | |
| Gentamicin<br>(Gentamicin<br>Sulfate) | 0.0628 | 3 | Glu | No | |
| Gentisic Acid | 0.0973 | 1.5 | Glu | No | |
| Glucosamine<br>(Glucosamine<br>Hydrochloride) | 0.030 | 0.647 | Glu | No | |
| Glutathione,<br>reduced | 3 | 3 mEq/L | Glu | No | |
| Glycolic Acid | 10.0 | 76.05 | Glu | No | |
| Guaifenesin | 0.0227 | 0.45 | Glu | No | |
| Hemoglobin | 10 g/L | 1000 | Glu | No | |
| Heparin<br>(Sodium<br>Heparin) | 3.30 U/mL | 330 U/dL | Glu | No | |
| Hydroxyurea | 0.405 | 3.08 | Glu | Yes | Increased results ≥ 0.08<br>mmol/L. |
| Ibuprofen | 1.06 | 21.9 | Glu | No | |
| Intralipid 20% | N/A | 3151 | Glu | No | |

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| Table 7: Potentially interfering substances and test concentrations for the i-STAT Glucose | | | | | | | |
|--------------------------------------------------------------------------------------------|----------------------------------------|---------------------------------------|------|--------------------------|-------------------------------------|--|--|
| test in the i-STAT G cartridge | | | | | | | |
| Substance | Substance<br>Concentration<br>(mmol/L) | Substance<br>Concentration<br>(mg/dL) | Test | Interference<br>(Yes/No) | Comment | | |
| Isoniazid | 0.438 | 6 | Glu | Yes | Increased results ≥ 0.29<br>mmol/L. | | |
| Lactate<br>(Lithium<br>Lactate) | 10 | 90 | Glu | No | | | |
| Maltose | 10.5 | 360 | Glu | No | | | |
| Mannose | 1 | 18.02 | Glu | No | | | |
| Nithiodote<br>(Sodium<br>Thiosulfate) | 16.7 | 264.04 | Glu | No | | | |
| pH | 8.0 pH units | N/A | Glu | No | | | |
| Pyruvate<br>(Lithium<br>Pyruvate) | 0.570 | 5 | Glu | No | | | |
| Salicylate<br>(Lithium<br>Salicylate) | 0.207 | 2.86 | Glu | No | | | |
| Thiocyanate<br>(Lithium<br>Thiocyanate) | 0.898 | 5.22 | Glu | No | | | |
| Triglyceride | 16.94 | 1500 | Glu | No | | | |
| Uric Acid | 1.4 | 23.5 | Glu | No | | | |
| Xylose | 3 | 45.04 | Glu | No | | | |

#### ii. Other sensitivity studies

#### 1) Oxygen Sensitivity

The effect of oxygen on the i-STAT Glucose test in the i-STAT G 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 across 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 i-STAT Glucose test in the i-STAT G cartridge with the i-STAT 1 System is insensitive to oxygen levels between 21 and 515 mmHg.

#### 2) Hematocrit Sensitivity

The effect of hematocrit on the i-STAT Glucose test in the i-STAT G cartridge with the i-STAT 1 System was assessed. 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 G 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

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and the mid hematocrit level was within the allowable error (±Ea). The study demonstrated that i-STAT Glucose test in the i-STAT G cartridge with the i-STAT 1 System is insensitive to hematocrit levels between 15% to 75% packed cell volume (PCV).

### 3) Altitude

The performance of the i-STAT Glucose test in the i-STAT G cartridge on the i-STAT 1 analyzer was evaluated at an altitude of approximately 10,000 feet above sea level using whole blood samples across the reportable range. The glucose test results obtained from the i-STAT G cartridges (candidate device) were compared to the glucose test results obtained from the i-STAT CHEM8+ cartridges on the i-STAT 1 analyzer (comparator device). Passing-Bablok regression analyses between the 1st replicate of the candidate device (v-axis) and mean of the comparator device (x-axis) were performed based on the CLSI cc: 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 8 below.

Table 8: Summary of altitude study results for the i-STAT G cartridge Correlation Coefficient (r) Slope Test 95% Cl 95% Cl r Slope

0.97

0.964 to 0.972

#### B. Comparison Studies

Glucose

#### a. Method Comparison with Comparator Device

1.00

Method comparison was demonstrated in studies based on CLSI EP09c-ED3: Measurement Procedure Comparison and Bias Estimation Using Patient Samples -Third Edition. Lithium heparin arterial and venous whole blood specimens collected across multiple point of care sites were evaluated using the first replicate result from the i-STAT G cartridge on the i-STAT 1 analyzer versus the mean result from the i-STAT CHEM8+ cartridge on the i-STAT 1 analyzer.

1.000 to 1.000

In addition, two (2) capillary whole blood specimens collected from skin punctures with balanced heparin capillary tubes from each study subject across multiple point of care sites were evaluated using the singlicate result from the i-STAT G cartridge on the i-STAT 1 analyzer versus the singlicate result from the epoc Blood Analysis System.

The arterial, venous, and capillary whole blood data were pooled, and a Passing-Bablok linear regression analysis was performed using the results from the i-STAT G 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 9. In the table, N is the number of specimens in the data set, and r is the correlation coefficient.

Table 9: Method comparison results for i-STAT G cartridge with i-STAT 1 System

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| Test | Comparative Method | | N | Slope | Intercept | r |
|------|--------------------|-------------------------------|-----|-------|-----------|------|
| | Arterial/Venous | Capillary | | | | |
| Glu | i-STAT CHEM8+ | epoc Blood Analysis<br>System | 571 | 1.00 | 1.85 | 1.00 |

A Passing-Bablok linear regression analysis was performed using the results of each sample from the i-STAT G 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 G cartridge with i-STAT 1 System by<br>sample type | | | | | | |
|---------------------------------------------------------------------------------------------------|-------------|----------------------------|-----|-------|-----------|------|
| Test | Sample Type | Comparative Method | N | Slope | Intercept | |
| | Sample Type | Comparative Method | N | Slope | Intercept | r |
| Glu | Arterial | i-STAT CHEM8+ | 173 | 1.00 | 1.00 | 1.00 |
| | Venous | i-STAT CHEM8+ | 164 | 1.00 | 1.50 | 1.00 |
| | Capillary | epoc Blood Analysis System | 234 | 1.00 | 2.00 | 1.00 |

## b. Matrix Equivalence

A matrix equivalence study was conducted to evaluate the performance of the i-STAT Glucose test in the i-STAT G cartridge on the i-STAT 1 analyzer using nonanticoagulated arterial or venous whole blood specimens compared to heparinized whole blood specimens. The study design and analysis method were based on CLSI EP35: Assessment of Equivalence or Suitability of Specimen Types for Medical Laboratory Measurement Procedures – First Edition. The matrix equivalence was assessed by comparing arterial or venous 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 G 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 | | | | | |
|--------------------------------------|-------------------------------------|-----------------------------------|------|-------|-----------|
| N | Candidate Specimen Range<br>(mg/dL) | Primary Specimen Range<br>(mg/dL) | r | Slope | Intercept |
| 158 | 42-679 | 42-681 | 1.00 | 1.00 | 0.00 |

#### c. EDTA Matrix Equivalence

A study was conducted to evaluate matrix equivalency between whole blood sample collected in lithium heparin (primary specimen type) and ethylenediaminetetraacetic acid (K2EDTA and K3EDTA) anticoagulants (candidate specimen types) and tested with the i-STAT Glucose test in the i-STAT G cartridge on the i-STAT 1 analyzer. The

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study design was based on CLSI EP35: Assessment of Equivalence or Suitability of Specimen Types for Medical Laboratory Measurement Procedures – First Edition. Each specimen was tested in duplicate using two (2) i-STAT G cartridges with i-STAT 1 analyzers. A Passing-Bablok regression analysis was performed using the first valid result of the K2EDTA and K3EDTA anticoagulated specimen types versus the first valid result of the specimens with lithium heparin. The regression analysis results are summarized in Table 12 and Table 13.

| Table 12: Passing-Bablok regression summary for K₂EDTA vs lithium heparin | | | | | |
|---------------------------------------------------------------------------|-----------------------------------------------|--------------------------------------------|------|-------|-----------|
| N | K₂EDTA<br>Candidate Specimen Range<br>(mg/dL) | LiHep<br>Primary Specimen Range<br>(mg/dL) | r | Slope | Intercept |
| 43 | 30.3 – 522.9 | 29.5 – 510.9 | 1.00 | 1.03 | -1.037 |

| Table 13: Passing-Bablok regression summary for K3EDTA vs lithium heparin | | | | | |
|---------------------------------------------------------------------------|-----------------------------------------------|--------------------------------------------|------|-------|-----------|
| N | K3EDTA<br>Candidate Specimen Range<br>(mg/dL) | LiHep<br>Primary Specimen Range<br>(mg/dL) | r | Slope | Intercept |
| 43 | 30.4 – 520.6 | 29.5 – 510.9 | 1.00 | 1.03 | 0.015 |

#### CONCLUSION VIII.

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