(228 days)
Not Found
No
The summary describes a standard in vitro diagnostic system based on electrochemical sensors and fluidics, with no mention of AI or ML in the device description, intended use, or performance studies.
No
The device is described as 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." It measures glucose, which is used in diagnosis, monitoring, and treatment, but the device itself is not a therapeutic intervention.
Yes
The device explicitly states in its intended use, "Glucose measurements are used in the diagnosis, monitoring, and treatment of carbohydrate metabolism disorders". This directly indicates a diagnostic purpose. Additionally, the device is described as an "in vitro diagnostic (IVD) medical device".
No
The device description clearly states that the i-STAT 1 System consists of a portable blood analyzer (hardware), single-use disposable test cartridges (hardware), and accessories (hardware). The software is part of a system that includes significant hardware components.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Explicit Statement: The "Intended Use / Indications for Use" section explicitly states: "The i-STAT System is for in vitro diagnostics use."
- Device Description: The "Device Description" section also 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 device is intended for the "in vitro quantification of glucose in arterial, venous, or capillary whole blood." This involves testing biological samples outside of the body, which is the definition of in vitro diagnostics.
- Purpose: The glucose measurements are used in the "diagnosis, monitoring, and treatment of carbohydrate metabolism disorders," which are clinical purposes.
All of these points clearly indicate that the i-STAT CG8+ cartridge with the i-STAT 1 System is an In Vitro Diagnostic device.
N/A
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 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.
Product codes
CGA, JJE
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).
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
Healthcare professionals trained and certified to use the system 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)
Analytical Performance
- Precision/Reproducibility:
- 20 days (Aqueous materials): Evaluated using five (5) levels of aqueous material over 20 days, multiple analyzers, and two (2) test cartridge lots. Measured repeatability, between-run, between-day, and within-laboratory precision.
- Multi-site and operator-to-operator precision (Aqueous materials): Performed at three (3) sites using a panel of aqueous solutions (five levels of glucose). Each level tested once a day by two (2) operators for five (5) days on six (6) i-STAT 1 Analyzers. Calculated within-run, between-day, between-operator, and within-site variance components.
- Precision (Whole Blood): Evaluated using arterial, venous, and capillary whole blood specimens collected with lithium heparin. Assessed using duplicate test results from multiple point of care sites.
- Linearity/assay reportable range:
- Linearity: Evaluated by preparing whole blood samples of varying glucose levels. Demonstrated linearity over the reportable range (20 – 700 mg/dL). Slope: 0.994, Intercept: -1.385, R2: 0.9993.
- Detection Limit:
- Limit of Quantitation (LoQ): Determined using two (2) i-STAT CG8+ cartridge lots and whole blood altered to a low glucose level. Determined LoQ: 17 mg/dL.
- Limit of Blank and Detection (LoB/LoD): Determined using two (2) i-STAT CG8+ cartridge lots, whole blood altered to blank glucose level for LoB and two low levels for LoD. LoB: 0.2 mg/dL, LoD: 0.9 mg/dL.
- Analytical Specificity:
- Interference: Evaluated using whole blood samples based on CLSI EP07-ED3. Substances identified as interferents if performance was outside allowable error. Bromide (Use Another Method) and Hydroxyurea (Increased results ≥ 0.08 mmol/L), Isoniazid (Increased results ≥ 0.29 mmol/L) showed interference.
- Other sensitivity studies:
- Oxygen Sensitivity Study: Evaluated with low and high oxygen levels using whole blood samples altered to four glucose levels. Insensitive to oxygen levels between 20 and 503 mmHg.
- Hematocrit Sensitivity: Evaluated at three (3) hematocrit levels (low, mid, high) at four (4) glucose levels. Insensitive to hematocrit levels between 15% to 75% packed cell volume (PCV).
- Altitude: Performed at approximately 10,000 feet above sea level. Correlation coefficient: 1.00 (95% CI: 1.000 to 1.000), Slope: 0.96 (95% CI: 0.957 to 0.971). Demonstrated equivalent performance.
Comparison Studies
- Method Comparison with Predicate Device:
- Sample Size: N=547 (Arterial/Venous/Capillary whole blood specimens).
- Study Type: Passing-Bablok linear regression analysis.
- Key Results: For Glu, Slope: 0.98, Intercept: 1.62, r: 1.00.
- Matrix Equivalence:
- Sample Size: N=297.
- Study Type: Passing-Bablok linear regression analysis comparing non-anticoagulated venous and arterial whole blood to samples collected with balanced heparin or lithium heparin.
- Key Results: For Glu, Slope: 1.00, Intercept: 0.00, r: 1.00.
Conclusion: The studies demonstrate that the performance of the i-STAT Glucose test in the i-STAT CG8+ cartridge with the i-STAT 1 System is substantially equivalent to the predicate device.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Not Found. Precision metrics (SD, %CV, etc.) and regression analysis results (Slope, Intercept, R2, r) are provided.
Predicate Device(s)
Reference Device(s)
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information
Not Found
§ 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.
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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 side of the logo is the Department of Health & Human Services logo. To the right of the HHS logo is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.
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
1
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
2
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 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.
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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3
Image /page/3/Picture/0 description: The image shows the Abbott logo. On the left is a blue stylized letter A. To the right of the letter is the word "Abbott" in black, bold 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.
400 College Road East
Princeton, NJ 08540 |
|---------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Contact | Primary: Jacquelyn Gesumaria
Principal Specialist Regulatory Affairs
Phone: 609-454-9384
Secondary: Mojgan Soleimani
Associate Director Regulatory Affairs
Phone: 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 Classification
Name | Regulation
Number | Class | Panel |
|--------------|-------------------------------|----------------------|-------|--------------------|
| CGA | Glucose Oxidase,
Glucose | 862.1345 | II | Clinical Chemistry |
III. PREDICATE DEVICE
K210958 (K183678) 510(k) Number
| Product
Code | Device Classification
Name | Regulation
Number | Class | Panel |
|-----------------|-------------------------------|----------------------|-------|--------------------|
| CGA | Glucose Oxidase, Glucose | 862.1345 | II | Clinical Chemistry |
4
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.
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).
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 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.
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.
5
VI. SUMMARY COMPARISON OF TECHNOLOGICAL CHARACTERISTICS
| 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) | ||||||||||
| Intended Use | 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, | ||||||||||
| idiopathic hypoglycemia, and pancreatic | ||||||||||
| islet cell carcinoma. | The i-STAT CHEM8+ cartridge with the | |||||||||
| i-STAT 1 System is intended for use in the | ||||||||||
| in vitro quantification of sodium, | ||||||||||
| potassium, chloride, ionized calcium, | ||||||||||
| glucose, blood urea nitrogen, creatinine, | ||||||||||
| hematocrit, and total carbon dioxide in | ||||||||||
| arterial or venous 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 | ||||||||||
| Classification | Same | Class II | ||||||||
| Product Code | Same | CGA | ||||||||
| Regulation | ||||||||||
| No. | Same | 862.1345 | ||||||||
| Reportable | ||||||||||
| Range | Same | 1.1 – 38.9 mmol/L | ||||||||
| 20 – 700 mg/dL | ||||||||||
| 0.20 - 7.00 g/L | ||||||||||
| Sample Type | Arterial, venous, or capillary whole blood | Arterial and venous whole blood | ||||||||
| Sample | ||||||||||
| Volume | Same | 95 µL | ||||||||
| Sample | ||||||||||
| Preparation | Same | Ready to Use | ||||||||
| Sample | ||||||||||
| collection | Same | • Without anticoagulant | ||||||||
| • With balanced heparin anticoagulant or | ||||||||||
| lithium heparin anticoagulant | ||||||||||
| Traceability | Same | NIST SRM965 | ||||||||
| Calibration | Same | 1-point on-board contained within | ||||||||
| cartridge |
6
| 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 minutes | ||
| With anticoagulant: | ||
| Capillary within 3 minutes | ||
| Arterial and venous within 30 minutes | Without anticoagulant: | |
| Arterial and venous within 3 minutes | ||
| With 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 date | |
| Room Temperature at 18-30°C (64-86°F) for 2 months | Refrigerated at 2 to 8°C (35 to 46°F) until expiration date | |
| Room 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) | Fluid | ||||||||||
| Level | 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 |
7
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.
8
| 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 | ||||
| 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 |
9
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-STAT
| Glucose 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 the
| i-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 the | |
| reportable 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 in
| the i-STAT CG8+ Cartridge | ||||||
|---|---|---|---|---|---|---|
| Test Concentration | ||||||
| Substance 1 | mmol/L | |||||
| (unless | ||||||
| specified) | mg/dL | |||||
| (unless | ||||||
| specified) | i-STAT | |||||
| Test | Interference | |||||
| (Yes/No) | Comments | |||||
| Acetaldehyde 2 | 0.045 | 0.2 | Glu | No | ||
| Acetaminophen | 1.03 | 15.6 | Glu | No | ||
| Acetoacetate | ||||||
| (Lithium | ||||||
| Acetoacetate) | 2.0 | 20 | Glu | No | ||
| Acetyl Cysteine (N- | ||||||
| Acetyl-L-Cysteine) | 0.92 | 15 | Glu | No | ||
| Ammonium | ||||||
| (Ammonium | ||||||
| Chloride) 2 | 2.0 | 10.7 | Glu | No | ||
| Ascorbic Acid (L- | ||||||
| Ascorbic Acid) | 0.298 | 5.25 | Glu | No | ||
| β-Hydroxybutyric | ||||||
| Acid 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 Another | |
| Method | ||||||
| Cholesterol | 10.3 | 400 | Glu | No | ||
| Creatinine | 1.326 | 15 | Glu | No | ||
| Dopamine | ||||||
| (Dopamine | ||||||
| Hydrochloride) | 4.06 | |||||
| μmol/L | 0.0621 | Glu | No | |||
| Ethanol | 130 | 600 | Glu | No | ||
| Fluoride (Lithium | ||||||
| Fluoride) | 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 | ||||||
| (Glucosamine | ||||||
| Hydrochloride) 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 (Sodium | ||||||
| Heparin) | 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 Concentration | |||||
| mmol/L | ||||||
| (unless | ||||||
| specified) | mg/dL | |||||
| (unless | ||||||
| specified) | i-STAT | |||||
| Test | 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 (Lithium | ||||||
| Lactate) | 10 | 90 | Glu | No | ||
| Maltose | 10.5 | 360 | Glu | No | ||
| Mannose 2 | 1 | 18.02 | Glu | No | ||
| Nithiodote (Sodium | ||||||
| Thiosulfate) 2 | 16.7 | 264.04 | Glu | No | ||
| pH | 8.0 pH | |||||
| units | N/A | Glu | No | |||
| Pyruvate (Lithium | ||||||
| Pyruvate) | 0.570 | 5 | Glu | No | ||
| Salicylate (Lithium | ||||||
| Salicylate) | 0.207 | 2.86 | Glu | No | ||
| Thiocyanate (Lithium | ||||||
| Thiocyanate) | 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 Analysis | ||||
| System | 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 Specimen | ||||
| Range | Primary Specimen | |||||
| Range | 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.