Predicate Devices

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The description focuses on standard in vitro diagnostic technology, including sensors, fluidics, and electrochemical measurements. There is no mention of AI/ML algorithms for data analysis or interpretation.

Therapeutic

No.
The device is an in vitro diagnostic (IVD) medical device used for quantifying ionized calcium and hematocrit to aid in diagnosis, monitoring, and treatment of various conditions; it does not directly provide therapy.

Diagnostic

Yes

Explanation: The "Intended Use / Indications for Use" section explicitly states that the device is "intended for use in the in vitro quantification of ionized calcium and hematocrit in arterial or venous whole blood in point of care or clinical laboratory settings." It further elaborates that these measurements are "used in the diagnosis, monitoring, and treatment of conditions." The "Device Description" also labels it as "an in vitro diagnostic (IVD) medical device."

SaMD (Software as a Medical Device)

No

The device description clearly outlines hardware components including the i-STAT 1 analyzer (a portable blood analyzer), single-use disposable test cartridges (i-STAT cartridges) with sensors, fluid packs, channels, and waste chambers, and accessories like a downloader/recharger, electronic simulator, and printer. This is not a software-only device.

IVD (In Vitro Diagnostic)

Yes, this device is an IVD (In Vitro Diagnostic).

Here's why:

Explicit Statement: The "Device Description" section explicitly states: "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."
Intended Use: The "Intended Use / Indications for Use" section describes the device's purpose as the "in vitro quantification of ionized calcium and hematocrit in arterial or venous whole blood" and "in vitro quantification of hematocrit in capillary whole blood." The term "in vitro" means "in glass" or "outside the body," which is a key characteristic of IVD devices.
Sample Type: The device analyzes whole blood, which is a biological specimen taken from the body for diagnostic testing.
Measurement: It performs quantitative measurements of specific analytes (ionized calcium and hematocrit) in these samples.
Diagnostic Purpose: The results of these measurements are intended to be used in the "diagnosis, monitoring, and treatment of conditions" and to "aid in the determination of normal or abnormal total red cell volume status." This clearly indicates a diagnostic purpose.
Setting: The device is intended for use in "point of care or clinical laboratory settings," which are typical environments for IVD testing.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

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

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

Ionized calcium measurements are used in the diagnosis, monitoring, and treatment of conditions including, but not limited to, parathyroid disease, a variety of bone diseases, chronic renal disease, tetany, and disturbances related to surgical and intensive care.

Hematocrit measurements can aid in the determination and monitoring of normal or abnormal total red cell volume status that can be associated with conditions including anemia, erythrocytosis, and blood loss related to trauma and surgery.

Product codes (comma separated list FDA assigned to the subject device)

JFP, JPI

Device Description

The i-STAT CG8+ cartridge is used with the i-STAT 1 analyzer as part of the i-STAT 1 System and contains test reagents to measure hematocrit (Hct) in arterial, venous or capillary whole blood and to measure ionized calcium (iCa) in arterial and 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 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+ cartridges require two to three drops of whole blood which are 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).

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Not Found

Indicated Patient Age Range

Not Found

Intended User / Care Setting

trained medical professionals in point of care or clinical laboratory settings

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

Not Found

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

A. Analytical Performance
a. Precision/Reproducibility:
i. Precision 20 days (Aqueous materials)
* Study Type: Precision/Reproducibility (20-day precision testing based on CLSI document EP05-A3)
* Sample Size: 80-82 measurements per level for iCa and Hct.
* Key Results: Evaluated repeatability, between-run, between-day, and within-laboratory precision for iCa (5 levels) and Hct (4 levels). Results are summarized in Table 2, showing low SD and %CV values across all levels and components, indicating good precision.
ii. Multi-site and operator-to-operator precision (Aqueous materials)
* Study Type: Multi-site and operator-to-operator precision (Multi-day precision testing)
* Sample Size: 90-97 measurements per level for iCa, 90 measurements per level for Hct.
* Key Results: Performed at 3 sites by 2 operators over 5 days using 6 i-STAT 1 Analyzers. Calculated within-run, between-day, between-operator, within-site (total), between-site, and overall variance components. Results in Table 3 show consistent precision across sites and operators.
iii. Precision (Whole Blood)
* Study Type: Precision (Whole Blood)
* Sample Size: Varied per sample type and range (e.g., iCa venous whole blood: 5 to 95 samples; Hct venous whole blood: 7 to 88 samples; Hct arterial whole blood: 2 to 104 samples; Hct capillary whole blood: 17 to 109 samples).
* Key Results: Evaluated whole blood precision using lithium heparin collected specimens across multiple point of care sites. Results in Table 4 show mean, SD, and %CV for different ranges for venous, arterial, and capillary whole blood for both iCa and Hct.

b. Linearity/assay reportable range:
i. Linearity
* Study Type: Linearity (based on CLSI EP06-Ed2)
* Key Results: Demonstrated linearity of iCa and Hct tests over their reportable ranges. Regression summary (Table 5) shows high R values (0.9981 for iCa, 0.9992 for Hct), indicating good linearity.

c. Detection Limit
i. Limit of Quantitation (LoQ)
* Study Type: Limit of Quantitation (LoQ) (based on CLSI EP17-A2)
* Key Results: Determined LoQ for iCa and Hct tests to be at or below the lower limit of their reportable ranges (Table 6: iCa LoQ 0.15 mmol/L vs. lower limit 0.25 mmol/L; Hct LoQ 13 %PCV vs. lower limit 15 %PCV).
ii. Limit of Blank and Detection (LoB/LoD)
* Study Type: Limit of Blank (LoB) and Limit of Detection (LoD) (based on CLSI EP17-A2)
* Key Results: Determined LoB and LoD for iCa and Hct (Table 7: iCa LoB 0.119 mmol/L, LoD 0.125 mmol/L; Hct LoB 0 %PCV, LoD 0.4 %PCV).

d. Analytical Specificity
i. Interference
* Study Type: Interference (based on CLSI EP07-ED3)
* Key Results: Evaluated potentially interfering substances. Identified several interferents for iCa (Lactate, Leflunomide, Magnesium, Nithiodote, Teriflunomide, Thiocyanate) and Hct (Bromide, Total Protein). A dose-response was performed for identified interferents. Results are summarized in Table 8.

B. Comparison Studies
a. Method Comparison with Comparator Device
* Study Type: Method Comparison (based on CLSI EP09c-ED3)
* Sample Size: iCa: 343 specimens (venous and arterial whole blood); Hct: 535 specimens (venous, arterial, and capillary whole blood pooled), 208 capillary (native and contrived), 193 native capillary.
* Key Results:
* iCa: Compared against i-STAT CHEM8+. Passing-Bablok analysis for pooled venous and arterial data showed Slope 1.02, Intercept -0.02, r 0.99 (Table 9). Biases at medical decision levels were minimal.
* Hct: Compared against i-STAT CHEM8+ (arterial/venous) and Epoc Blood Analysis System (capillary). Passing-Bablok analysis for pooled data showed Slope 1.000, Intercept -1.00, r 0.98 (Table 10). For capillary specimens only, Slope 1.000, Intercept 0.00, r 0.97 (Table 11). Biases at medical decision levels for native capillary specimens were 0.0 (Table 12).

b. Matrix Equivalence
* Study Type: Matrix Equivalence (based on CLSI EP35)
* Sample Size: iCa: 298 specimens; Hct: 293 specimens.
* Key Results: Compared non-anticoagulated venous and arterial whole blood (candidate) to balanced heparin or lithium heparin anticoagulated samples (primary). Passing-Bablok analysis showed high correlation (r = 0.99 for both iCa and Hct) and slopes near 1 (1.00 for iCa and Hct) and intercepts near 0 (0.01 for iCa and 0.00 for Hct), demonstrating matrix equivalence (Table 13).

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Key metrics reported are precision (SD, %CV), linearity (Slope, Intercept, R), detection limits (LoQ, LoB, LoD), and method comparison statistics (Slope, Intercept, r, Bias at Medical Decision Level).

Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.

K191360

Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).

Not Found

Regulation Number and Section

§ 862.1145 Calcium test system.

(a)
Identification. A calcium test system is a device intended to measure the total calcium level in serum. Calcium measurements are used in the diagnosis and treatment of parathyroid disease, a variety of bone diseases, chronic renal disease and tetany (intermittent muscular contractions or spasms).(b)
Classification. Class II.

Summary

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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.

October 27, 2023

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

Re: K230300

Trade/Device Name: i-STAT CG8+ cartridge with the i-STAT 1 System Regulation Number: 21 CFR 862.1145 Regulation Name: Calcium Test System Regulatory Class: Class II Product Code: JFP, JPI Dated: September 28, 2023 Received: September 29, 2023

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.

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).

1

Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safetyreporting-combination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

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 Acting Deputy Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Ouality Center for Devices and Radiological HealthEnclosure

Enclosure

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Indications for Use

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

Submission Number (if known)

K230300

Device Name

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

Indications for Use (Describe)

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

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

lonized calcium measurements are used in the diagnosis, monitoring, and treatment of conditions including, but not limited to, parathyroid disease, a variety of bone disease, chronic renal disease, tetany, and disturbances related to surgical and intensive care.

Hematocrit measurements can aid in the determination of normal or abnormal total red cell volume status that can be associated with conditions including anemia, erythrocytosis, and blood loss related to trauma and surgery.

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

Prescription Use (Part 21 CFR 801 Subpart D)

Over-The-Counter Use (21 CFR 801 Subpart C)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

3

Image /page/3/Picture/0 description: The image contains the logo for Abbott. The logo consists of a blue, stylized letter "a" on the left, followed by the word "Abbott" in bold, black font on the right. The blue "a" symbol is a modern, geometric design, while the word "Abbott" is in a classic, serif typeface.

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 East
Princeton, NJ 08540 |
|---------------|-----------------------------------------------------------------------------------------------|
| Contact | Primary: Brian Ma, PhD
Principal Specialist Regulatory Affairs
Phone: +1613-688-5949 |
| | Secondary: Mojgan Soleimani
Associate Director Regulatory Affairs
Phone: +1613-295-0932 |
| Date Prepared | October 27, 2023 |

II. DEVICE INFORMATION

Proprietary Name	i-STAT CG8+ cartridge with the i-STAT 1 System
Common Name	Chemistry test, hematology test, analyzer, handheld
510(k) Number	K230300

| Product Code | Device Classification
Name | Regulation
Number | Class | Panel |
|--------------|-------------------------------------|----------------------|-------|--------------------|
| JFP | Electrode, Ion
Specific, Calcium | 862.1145 | II | Clinical Chemistry |
| JPI | Device, Hematocrit,
Measuring | 864.6400 | II | Hematology |

III. PREDICATE DEVICE

Proprietary Name	i-STAT CHEM8+ cartridge with the i-STAT 1 System
510(k) Number	K191360

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| Product
Code | Device Classification
Name | Regulation
Number | Class | Panel |
|-----------------|-------------------------------------|----------------------|-------|--------------------|
| JFP | Electrode, Ion Specific,
Calcium | 862.1145 | II | Clinical Chemistry |

IV. DEVICE DESCRIPTION

The i-STAT CG8+ cartridge is used with the i-STAT 1 analyzer as part of the i-STAT 1 System and contains test reagents to measure hematocrit (Hct) in arterial, venous or capillary whole blood and to measure ionized calcium (iCa) in arterial and 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 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+ cartridges require two to three drops of whole blood which are 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).

V. INTENDED USE STATEMENT

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

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

Ionized calcium measurements are used in the diagnosis, monitoring, and treatment of conditions including, but not limited to, parathyroid disease, a variety of bone diseases, chronic renal disease, tetany, and disturbances related to surgical and intensive care.

Hematocrit measurements can aid in the determination and monitoring of normal or abnormal total red cell volume status that can be associated with conditions including anemia, erythrocytosis, and blood loss related to trauma and surgery.

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VI. SUMMARY COMPARISON OF TECHNOLOGICAL CHARACTERISTICS

Table 1: Similarities and Differences (Test and Instrument): iCa and Hct in Whole Blood
Feature or
Characteristic	Candidate Devices:
iCa and Hct Tests in the:
i-STAT CG8+ cartridge
with the i-STAT 1 System	Predicate Device:
iCa Test in the:
i-STAT CHEM8+ cartridge
with the i-STAT 1 System
(K191360)
Intended Use	The i-STAT CG8+ cartridge with the
i-STAT 1 System is intended for use in the
in vitro quantification of ionized calcium
and hematocrit in arterial or venous
whole blood in point of care or clinical
laboratory settings.

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

Ionized calcium measurements are used
in the diagnosis, monitoring, and
treatment of conditions including, but not
limited to, parathyroid disease, a variety
of bone diseases, chronic renal disease,
tetany, and disturbances related to
surgical and intensive care.

Hematocrit measurements can aid in the
determination and monitoring of normal
or abnormal total red cell volume status
that can be associated with conditions
including anemia, erythrocytosis, and
blood loss related to trauma and surgery. | The i-STAT CHEM8+ cartridge with the i-
STAT 1 System is intended for use in the in
vitro quantification of ionized calcium in
arterial or venous whole blood in point of
care or clinical laboratory settings.

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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 Ionized Calcium (iCa) test in the i-STAT CG8+ cartridge on the i-STAT 1 System was evaluated using five (5) levels of aqueous material. The precision of the i-STAT Hematocrit (Hct) test in the i-STAT CG8+ cartridge on the i-STAT 1 System was evaluated using four (4) levels of aqueous materials. This 20-day precision testing was based on CLSI document EP05-A3: Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline - Third Edition. Each study was conducted using multiple analyzers and one (1) test cartridge lot over at least 20 days at one site. Repeatability, betweenrun, 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)	Fluid
Level	N	Mean	Repeatability		Between-run		Between-day		Within-Laboratory
				SD	%CV	SD	%CV	SD	%CV	SD	%CV
iCa
(mmol/L)	CV L1	80	2.280	0.0129	0.57	0.0050	0.22	0.0036	0.16	0.0144	0.63
	CV L2	80	1.517	0.0073	0.48	0.0023	0.15	0.0020	0.13	0.0080	0.52
	CV L3	80	1.282	0.0080	0.63	0.0020	0.15	0.0018	0.14	0.0085	0.66
	CV L4	80	0.763	0.0034	0.44	0.0018	0.23	0.0010	0.13	0.0039	0.51
	CV L5	80	0.260	0.0018	0.68	0.0007	0.27	0.0006	0.22	0.0020	0.76
Hct
(%PCV)	CV L2	81	22.0	0.38	1.74	0.12	0.54	0.11	0.48	0.42	1.89
	CV L3	80	35.0	0.41	1.17	0.14	0.40	0.11	0.32	0.45	1.27
	CV L4	80	56.4	0.22	0.40	0.12	0.21	0.10	0.18	0.27	0.48
	CV L5	82	66.3	0.24	0.35	0.02	0.03	0.06	0.09	0.24	0.37

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 ionized calcium and a second panel of aqueous solutions containing five (5) levels of hematocrit. 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)	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
iCa
(mmol/L)	CV L1	91	2.323	0.0147	0.63	0.0104	0.45	0.0000	0.00	0.018	0.77	0.0079	0.34	0.0196	0.84
	CV L2	90	1.535	0.0078	0.51	0.0043	0.28	0.0000	0.00	0.0089	0.58	0.0018	0.12	0.0091	0.59
	CV L3	97	1.288	0.0068	0.53	0.0000	0.00	0.0013	0.10	0.0069	0.53	0.0000	0.00	0.0069	0.53
	CV L4	90	0.762	0.0049	0.64	0.0000	0.00	0.0000	0.00	0.0049	0.64	0.0008	0.10	0.0049	0.65
	CV L5	90	0.260	0.0011	0.41	0.0000	0.00	0.0000	0.00	0.0011	0.41	0.0000	0.00	0.0011	0.41
Hct
(%PCV)	CV L1	90	12.2	0.34	2.75	0.18	1.45	0.11	0.89	0.39	3.24	0.12	0.97	0.41	3.38
	CV L2	90	22.1	0.35	1.57	0.00	0.00	0.13	0.57	0.37	1.67	0.20	0.92	0.42	1.90
	CV L3	90	35.1	0.36	1.03	0.00	0.00	0.08	0.22	0.37	1.06	0.11	0.31	0.39	1.10
	CV L4	90	56.3	0.45	0.80	0.09	0.16	0.00	0.00	0.46	0.81	0.27	0.48	0.53	0.95
	CV L5	90	66.1	0.31	0.47	0.17	0.26	0.06	0.10	0.36	0.54	0.14	0.21	0.38	0.58

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iii. Precision (Whole Blood)

Whole blood precision of the i-STAT Ionized Calcium and Hematocrit tests in the i-STAT CG8+ cartridge on the i-STAT 1 System was evaluated using whole blood specimens 1 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 each i-STAT test. The results are summarized in Table 4.

cartridge on the i-STAT 1 Analyzer
Test
(units)	Sample Type	Sample Range	N	Mean	SD	%CV
iCa
(mmol/L)	Venous Whole Blood	0.25-0.75	5	0.468	0.0045	0.96
		>0.75-1.20	95	1.123	0.0094	0.84
		>1.20-1.50	77	1.281	0.0165	1.29
		>1.50-2.50	7	2.179	0.0214	0.98
	Arterial Whole Blood	0.25-0.75	0	N/A	N/A	N/A
		>0.75-1.20	92	1.144	0.0063	0.55
		>1.20-1.50	58	1.282	0.0114	0.89
		>1.50-2.50	3	1.797	0.0100	0.56
Hct
(%PCV)	Venous Whole Blood	15-35	88	27.3	0.45	1.63
		>35-50	75	39.4	2.20	5.59
		>50-75	7	60.1	0.46	0.77
	Arterial Whole Blood	15-35	104	26.3	0.55	2.08
		>35-50	45	38.9	0.48	1.24
		>50-75	2	50.0	0.00	0.00
	Capillary Whole Blood	15-35	28	29.5	1.23	4.18
		>35-50	109	41.1	1.10	2.68
		>50-75	17	53.5	0.95	1.78

Table 4: Whole Blood Precision of arterial, venous, and capillary whole blood for i-STAT CG8+

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

	Table 5: Regression Summary for the i-STAT iCa and Hct tests in the i-STAT CG8+ Cartridge on
	the i-STAT 1 Analyzer
Test	Units	Reportable Range	Range Tested	Slope	Intercept	R
iCa	mmol/L	0.25 - 2.50	0.204 - 2.832	1.016	0.019	0.9981

1 The capillary whole blood clinical precision study design included the performance of two individual fingersticks, collected independently by two operators into two separate capillary tubes and tested on two (2) i-STAT CG8+ cartridges.

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| | Table 5: Regression Summary for the i-STAT iCa and Hct tests in the i-STAT CG8+ Cartridge on
the i-STAT 1 Analyzer | | | | | | | | | |
|------|-----------------------------------------------------------------------------------------------------------------------|------------------|--------------|-------|-----------|--------|--|--|--|--|
| Test | Units | Reportable Range | Range Tested | Slope | Intercept | R | | | | |
| Hct | %PCV | 15 — 75 | 12.7 - 78.3 | 1.031 | -0.592 | 0.9992 | | | | |

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 Ionized Calcium and Hematocrit tests 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 that was altered to a low analyte level for each i-STAT test. The LoQ for the i-STAT Ionized Calcium and Hematocrit tests in the i-STAT CG8+ cartridge 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 6.

Table 6: Summary of LoQ Results for i-STAT Tests in the i-STAT CG8+ Cartridge
Test (units)	Lower limit of the reportable range	Determined LoQ
iCa (mmol/L)	0.25	0.15
Hct (%PCV)	15	13

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 Ionized Calcium (iCa) and Hematocrit (Hct) tests in the i-STAT CG8+ cartridge were evaluated on the i-STAT 1 analyzer using two (2) i-STAT CG8+ cartridge lots for each test. Whole blood was altered to blank ionized calcium and hematocrit levels for LoB testing. Whole blood was altered to two (2) low levels of ionized calcium and four (4) low levels of hematocrit 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 i-STAT Ionized Calcium and Hematocrit tests in the i-STAT CG8+ cartridge on the i-STAT 1 analyzer are shown in the Table 7.

Table 7: Summary of LoB and LoD Results
Test
(units)	i-STAT CG8+ Cartridge
LoB	i-STAT CG8+ Cartridge
LoD
iCa (mmol/L)	0.119	0.125
Hct (%PCV)	0	0.4

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 Ionized Calcium and Hematocrit tests in the i-STAT CG8+ cartridge on the i-STAT 1 analyzer with the i-STAT 1 System

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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 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 list of potentially interfering substances tested and the interference results for the i-STAT CG8+ cartridge.

i-STAT CG8+ Cartridge
Substance 2	mmol/L
(unless specified)	mg/dL
(unless specified)	i-STAT Test	Interference
(Yes/No)	Comments
Acetaminophen	1.03	15.6	iCa	No
Acetyl Cysteine
(N-Acetyl-L-Cysteine)	0.92	15	iCa	No
Ascorbic Acid
(L-Ascorbic Acid)	0.298	5.25	iCa	No
β-Hydroxybutyric Acid3	6.0	62.46	iCa	No
Bilirubin	0.684	40	iCa
Hct	No
No
Bromide 3
(Lithium Bromide)	2.5
37.5	21.7
325.7	iCa
Hct	No
Yes
			iCa
Hct	Yes
Yes	Use Another Method
Cholesterol	11.0	425	iCa	No
Hemoglobin	10 g/L	1000	iCa	No
	N/A	3447	iCa	No
Intralipid 20%		2325	Hct	No
Iodide (Sodium Iodide)3	2.99	44.82	iCa	No
Lactate
(Lithium Lactate)	10	90	iCa	Yes	Decreased results ≥ 6 mmol/L
Leflunomide	0.722	19.5	iCa	Yes	Decreased results ≥ 0.345 mmol/L
Magnesium
(Magnesium Chloride)	4.1	10	iCa	Yes	Increased results ≥ 3.5 mmol/L
Nithiodote
(Sodium Thiosulfate)3	16.7	264.04	Hct
iCa	No
Yes
					Decreased results ≥ 5.3 mmol/L
Potassium (Potassium
Chloride)	8	59.6	iCa	No
Salicylate
(Lithium Salicylate)	0.207	2.86	iCa	No
Sodium
(Sodium Chloride)	170	993.48	iCa	No
Table 8: Potentially Interfering Substances and Test Concentrations for the i-STAT tests in the
i-STAT CG8+ Cartridge
Substance 2	Test Concentration
	mmol/L
(unless
specified)	mg/dL
(unless
specified)	i-STAT
Test	Interference
(Yes/No)	Comments
Teriflunomide 3	0.722	19.5	iCa	Yes	Decreased results
≥ 0.049 mmol/L
Thiocyanate (Lithium
Thiocyanate)	0.898	5.22	iCa	Yes	Decreased results
≥ 0.898 mmol/L
Total Protein (Human
Serum Albumin)	15 g/dL	150 g/L	Hct	Yes	Increased results ≥
9.5 g/dL
Triglyceride	16.94	1500	iCa
Hct	No
White Blood Cells	50,000
WBC/μL	N/A	Hct	No

Table 8: Potentially Interfering Substances and Test Concentrations for the i-STAT tests in the

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

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

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B. Comparison Studies

a. Method Comparison with Comparator Device

Method comparison for 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. For ionized calcium and hematocrit, the first replicate result from the i-STAT 1 analyzer was compared to the mean 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 hematocrit was performed using the singlicate result from the i-STAT 1 analyzer versus the singlicate result of the comparative method.

The venous and arterial data were pooled, and a Passing-Bablok linear regression analysis was performed using the i-STAT Ionized Calcium results from the i-STAT CG8+ cartridges on the i-STAT 1 analyzer versus the comparative method results. Method comparison results comparing the i-STAT Ionized Calcium performance on the i-STAT 1 analyzer to comparative method for arterial and venous 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 the i-STAT iCa test in the i-STAT CG8+ Cartridge with

i-STAT 1 System
Test
(units)	Comparative
Method
Arterial/Venous	N	Slope	Intercept	r	Medical
Decision
Level	Bias at Medical
Decision Level
iCa
(mmol/L)	i-STAT CHEM8+	343	1.02	-0.02	0.99	0.37
0.82	-0.009
0.003

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

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Method comparison results comparing the i-STAT Hematocrit performance on the i-STAT 1 analyzer to the comparative method 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 the i-STAT Hct test in the i-STAT CG8+ 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
Hct
(%PCV)	i-STAT
CHEM8+	Epoc
Blood
Analysis
System	535	1.000	-1.00	0.98	33	-1.0
		Blood					53	-1.0
		Analysis					56	-1.0
		System					70	-1.0

The method comparison results for capillary whole blood specimens only for the i-STAT Hematocrit test are shown in Table 11.

Table 11: Results for i-STAT CG8+ Cartridge with i-STAT 1 System - Native and Contrived Capillary Specimens
Test
(units)	N	Slope	Intercept	r	Range
Hct
(%PCV)	208	1.000	0.00	0.97	18-73

Bias at the medical decision levels for native capillary whole blood specimens only for the i-STAT Hematocrit test are shown in Table 12.

Table 12: Results for i-STAT CG8+ 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


Hct
(%PCV)	193	23	68	33	0.0	(-1.0, 0.0)
				53	0.0	(-1.0, 0.0)
				56	0.0	(-1.0, 0.0)
				70	0.0	(-1.0, 0.0)

b. Matrix Equivalence

A matrix equivalence study was conducted to evaluate the performance of the i-STAT Ionized Calcium and Hematocrit tests in the i-STAT CG8+ cartridge on the i-STAT 1 System using non-anticoagulated 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 each test in the i-STAT CG8+ cartridge was assessed by comparing arterial or venous whole blood specimens collected without

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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 13. In the table, N is the number of specimens in the data set, and r is the correlation coefficient.

Table 13: Matrix Equivalence Results
Test (units)	N	Candidate
Specimen Range	Primary Specimen
Range	r	Slope	Intercept
iCa (mmol/L)	298	0.44-2.43	0.45-2.42	0.99	1.00	0.01
Hct (%PCV)	293	15-73	15-73	0.99	1.000	0.00

CONCLUSION

VIII.

The results of these studies demonstrate that performance of the i-STAT Ionized Calcium and Hematocrit tests in the i-STAT CG8+ cartridge with the i-STAT 1 System are substantially equivalent to the predicate device.