(268 days)
The i-STAT CG8+ cartridge with the i-STAT 1 System is in the in vitro quantification of sodium and potassium 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 sodium in capillary whole blood in point of care or clinical laboratory settings.
Sodium measurements are used for monitoring electrolyte imbalances.
Potassium measurements are used in the diagnosis and cinical conditions that manifest high and low potassium levels.
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 sodium (Na) in arterial, venous or capillary whole blood and to measure potassium (K) 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+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 instrument interacts with the i-STAT CG8+ cartridge to move fluid across the sensors and generate a quantitative result (within approximately 2 minutes).
This document describes the performance of the i-STAT CG8+ cartridge with the i-STAT 1 System for the in vitro quantification of sodium (Na) and potassium (K) in whole blood. This is a medical device, and the provided text is a 510(k) summary, which is typically submitted to the FDA to demonstrate substantial equivalence to a legally marketed predicate device.
It's important to note that the provided text focuses on the analytical performance of a diagnostic device (measuring concentrations of substances), not an AI-assisted diagnostic device for interpreting images or other complex data. Therefore, many of the requested points regarding AI/MRMC studies, number of experts, adjudication methods, and ground truth establishment for complex AI algorithms are not applicable to this type of device and will not be found in the document.
Here's a breakdown of the requested information based on the provided text, focusing on the analytical performance validation:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state "acceptance criteria" in a single table. Instead, it presents performance characteristic studies (precision, linearity, detection limit, interference, method comparison, and matrix equivalence) with their respective results. The success of these studies implicitly serves as the acceptance criteria for the device to be considered substantially equivalent.
Below is a summary of the reported device performance for key analytical characteristics:
| Performance Metric | Test (Units) | Relevant Range / Levels | Acceptance Criteria (Implied by Study Design & Results) | Reported Device Performance (Summary) |
|---|---|---|---|---|
| Precision | Demonstrated low variability across multiple conditions | |||
| 20-Day Precision | Na (mmol/L) | 5 levels (approx. 99-181 mmol/L) | Low SD and %CV | SD: 0.17-0.32, %CV: 0.16-0.20 (Repeatability); Overall within-lab %CV ≤ 0.20 |
| K (mmol/L) | 5 levels (approx. 2.09-7.99 mmol/L) | Low SD and %CV | SD: 0.007-0.027, %CV: 0.25-0.37 (Repeatability); Overall within-lab %CV ≤ 0.41 | |
| Multi-Site/Operator (Aqueous) | Na (mmol/L) | 5 levels (approx. 100-181 mmol/L) | Low overall %CV | Overall %CV: 0.23-0.32 |
| K (mmol/L) | 5 levels (approx. 2.10-7.89 mmol/L) | Low overall %CV | Overall %CV: 0.39-1.05 | |
| Whole Blood Precision | Na (mmol/L) | Venous (100-180), Arterial (100-180), Capillary (100-180) | Low SD and %CV | Venous: SD 0.30-0.45, %CV 0.24-0.33; Arterial: SD 0.37-0.42, %CV 0.26-0.31; Capillary: SD 0.41-0.62, %CV 0.34-0.44 |
| K (mmol/L) | Venous (2.0-9.0), Arterial (2.0-9.0) | Low SD and %CV | Venous: SD 0.032-0.038, %CV 0.50-1.12; Arterial: SD 0.021-0.041, %CV 0.65-0.79 | |
| Linearity | Slope near 1, Intercept near 0, High R^2 | |||
| Na (mmol/L) | Reportable Range: 100-180 Tested Range: 91.3-209.8 | Meets reportable range | Slope: 1.005, Intercept: -0.525, R^2: 0.9996 | |
| K (mmol/L) | Reportable Range: 2.0-9.0 Tested Range: 1.79-10.04 | Meets reportable range | Slope: 1.011, Intercept: 0.002, R^2: 0.9994 | |
| Detection Limit (LoQ) | At or below lower limit of reportable range | |||
| LoQ | Na (mmol/L) | Reportable Range: 100 | ≤ 100 | Determined LoQ: 92 |
| K (mmol/L) | Reportable Range: 2.0 | ≤ 2.0 | Determined LoQ: 1.6 | |
| Analytical Specificity (Interference) | Na & K (mmol/L) | Various substances at toxic/pathological concentrations | Difference between control and test samples within allowable error (±Ea) | Most substances showed no interference. Noted interferences:- Cholesterol: Decreased Na results > 400 mg/dL- Nithiodote (Sodium Thiosulfate): Increased Na results ≥ 2.1 mmol/L |
| Method Comparison | Slope near 1, Intercept near 0, High r | Substantially equivalent to predicate device | ||
| K (mmol/L) vs. Predicate (i-STAT CHEM8+) | Arterial/Venous | n=340 | Strong correlation & agreement | Slope: 1.00, Intercept: 0.00, r: 1.00. Bias at Medical Decision Levels (3.0, 5.8, 7.5): 0.00 |
| Na (mmol/L) vs. Predicate (i-STAT CHEM8+ or epoc Blood Analysis System) | Pooled: Arterial/Venous/Capillary | n=551 (pooled), n=209 (capillary only) | Strong correlation & agreement | Pooled: Slope: 1.00, Intercept: 0.00, r: 0.99. Bias at Medical Decision Levels (115, 135, 150): 0.0. Capillary only: Slope 1.00, Intercept 0.00, r 0.98. Bias 0.0. |
| Matrix Equivalence | Slope near 1, Intercept near 0, High r | Equivalence demonstrated | ||
| Na (mmol/L) | Venous/Arterial non-anticoagulated vs. with anticoagulant | n=295 | Strong correlation & agreement | r: 0.99, Slope: 1.00, Intercept: 0.00 |
| K (mmol/L) | Venous/Arterial non-anticoagulated vs. with anticoagulant | n=292 | Strong correlation & agreement | r: 0.99, Slope: 1.00, Intercept: 0.00 |
2. Sample Size Used for the Test Set and the Data Provenance
The "test set" in this context refers to the samples used in the analytical performance studies. The data provenance is described within each study:
- Precision/Reproducibility (Aqueous materials):
- 20-day precision: N=80 per level (5 levels) for Na and K. Conducted at "one site."
- Multi-site/operator precision: N=90-97 per level (5 levels) for Na and K. Conducted at "three (3) sites."
- Precision (Whole Blood):
- N varies by analyte and sample type/range (e.g., Na venous: 17, 99, 67; Na arterial: 2, 89, 62; Na capillary: 3, 56, 95; K venous: 27, 135, 19; K arterial: 23, 124, 6).
- Whole blood specimens collected "across multiple point of care sites." Capillary specimens involved "two individual fingersticks, collected independently by two operators."
- Linearity:
- Whole blood samples of "varying analyte levels" were used. Specific N not provided for this study.
- Detection Limit (LoQ):
- Whole blood that was altered to a low analyte level. Specific N not provided.
- Analytical Specificity (Interference):
- Whole blood samples were used. Specific N not provided, but interference determined by comparing "control sample" to "test sample."
- Method Comparison:
- K (Arterial/Venous): N=340. "Lithium heparin venous and arterial whole blood specimens collected across multiple point of care sites."
- Na (Pooled: Arterial/Venous/Capillary): N=551. "Venous and arterial" data pooled with "capillary whole blood specimens."
- Na (Capillary only): N=209. "Native and Contrived Capillary Specimens." Bias at Medical Decision Levels for "Native Capillary Specimens" (N=194).
- Matrix Equivalence:
- N=295 for Na, N=292 for K. "non-anticoagulated venous and arterial whole blood specimens."
Data Provenance: The data was collected from "multiple point of care sites" in the precision and method comparison studies. The document does not specify the country of origin or whether the studies were retrospective or prospective, though typical 510(k) studies for new devices are prospective analytical performance studies.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and the Qualifications of Those Experts
This type of device (in vitro diagnostic for chemical analysis) does not typically involve expert readers or adjudication for "ground truth" in the same way an AI imaging algorithm would. The "ground truth" for analytical performance is the reference measurement provided by a comparator method (e.g., the i-STAT CHEM8+ predicate device or "comparative method" lab instrument) or gravimetric/volumetric preparation for linearity and precision studies.
Therefore, there is no mention of "experts" (e.g., radiologists) establishing ground truth, nor their qualifications or numbers.
4. Adjudication Method for the Test Set
Not applicable. As noted above, this device does not involve human interpretation requiring adjudication. Performance is assessed by comparing quantitative results from the device against a known reference or comparative method.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
Not applicable. This is not an AI-assisted diagnostic device, nor does it involve human readers interpreting data. It's a quantitative measurement device.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done
This is an algorithm/device-only performance study, as it's a fully automated in vitro diagnostic device. The performance data presented (precision, linearity, method comparison, etc.) reflects the standalone performance of the i-STAT CG8+ cartridge with the i-STAT 1 System. There is no human interpretation component in the measurement or output of the device.
7. The Type of Ground Truth Used
The "ground truth" in these analytical performance studies is established by:
- Reference materials/calibrators: For precision, linearity, and detection limit studies, defined aqueous or whole blood materials with known (or precisely determined) analyte concentrations are used.
- Comparator methods: For method comparison studies, the device's results are compared against a legally marketed predicate device (i-STAT CHEM8+ cartridge on the i-STAT 1 System) or another established "comparative method" (e.g., epoc Blood Analysis System) which serves as the reference, assumed to be accurate.
- Prepared samples: For linearity, samples are prepared with varying analyte levels.
8. The Sample Size for the Training Set
This document does not specify a "training set" size. For traditional in vitro diagnostic devices, there isn't a "training" phase in the machine learning sense. The device's algorithms (for sensor interpretation and calculation) are developed and validated in a more traditional engineering sense, not through iterative machine learning on a large dataset. The studies described are for validation or testing the final product's performance.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there's no "training set" in the context of machine learning for this type of device. The ground truth for development and internal validation of such a device would likely be established through highly controlled laboratory measurements using reference methods and materials.
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Image /page/0/Picture/0 description: The image shows 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, with the letters "FDA" in a blue square. To the right of the blue square 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: K230275
Trade/Device Name: i-STAT CG8+ cartridge with the i-STAT 1 System Regulation Number: 21 CFR 862.1665 Regulation Name: Sodium Test System Regulatory Class: Class II Product Code: JGS, CEM Dated: September 25, 2023 Received: September 26, 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).
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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, 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
Form Approved: OMB No. 0910-0120 Expiration Date: 07/31/2026 See PRA Statement below.
Submission Number (if known)
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 in the in vitro quantification of sodium and potassium 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 sodium in capillary whole blood in point of care or clinical laboratory settings.
Sodium measurements are used for monitoring electrolyte imbalances.
Potassium measurements are used in the diagnosis and cinical conditions that manifest high and low potassium levels.
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.
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*DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW *
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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 EastPrinceton, NJ 08540 |
|---|---|
| Contact | Primary: Brian Ma, PhDPrincipal Specialist Regulatory AffairsPhone: + 1 613-688-5949Secondary: Mojgan SoleimaniAssociate Director Regulatory AffairsPhone: + 1 613-295-0932 |
| Date Prepared | October 27, 2023 |
II. DEVICE INFORMATION
| Proprietary Name | i-STAT CG8+ cartridge with the i-STAT 1 System |
|---|---|
| Common Name | Chemistry test, analyzer, handheld |
| 510(k) Number: | K230275 |
| Product Code | Device ClassificationName | RegulationNumber | Class | Panel |
|---|---|---|---|---|
| JGS | Electrode, IonSpecific, Sodium | 862.1665 | II | Clinical Chemistry |
| CEM | Electrode, IonSpecific, Potassium | 862.1600 | II | Clinical Chemistry |
III. PREDICATE DEVICE
| Proprietary Name | i-STAT CHEM8+ cartridge with the i-STAT 1 System |
|---|---|
| 510(k) Number | K183688 |
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| ProductCode | Device ClassificationName | RegulationNumber | Class | Panel |
|---|---|---|---|---|
| JGS | Electrode, Ion Specific,Sodium | 862.1665 | II | Clinical Chemistry |
| CEM | Electrode, Ion Specific,Potassium | 862.1600 | 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 sodium (Na) in arterial, venous or capillary whole blood and to measure potassium (K) 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+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 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 Sustem is intended for use in the in vitro quantification of sodium and potassium 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 sodium in capillary whole blood in point of care or clinical laboratory settings.
Sodium measurements are used for monitoring electrolyte imbalances.
Potassium measurements are used in the diagnosis and monitoring of diseases and clinical conditions that manifest high and low potassium levels.
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VI. SUMMARY COMPARISON OF TECHNOLOGICAL CHARACTERISTICS
| Feature orCharacteristic | Candidate Devices:Na and K Tests in the:i-STAT CG8+ cartridgewith the i-STAT 1 System | Predicate Device:Na and K Tests in the:i-STAT CHEM8+ cartridgewith the i-STAT 1 System(K183688) |
|---|---|---|
| Intended Use | i-STAT CG8+ cartridgeThe i-STAT CG8+ cartridge with thei-STAT 1 System is intended for use in thein vitro quantification of sodium andpotassium in arterial or venous wholeblood in point of care or clinical laboratorysettings.The i-STAT CG8+ cartridge with the i-STAT1 System is intended for use in the in vitroquantification of sodium in capillary wholeblood in point of care or clinical laboratorysettings.Sodium measurements are used formonitoring electrolyte imbalances.Potassium measurements are used in thediagnosis and monitoring of diseases andclinical conditions that manifest high andlow potassium levels. | i-STAT CHEM8+ cartridgeThe i-STAT CHEM8+ cartridge with thei-STAT 1 System is intended for use in thein vitro quantification of sodium,potassium, chloride and blood ureanitrogen in arterial or venous whole bloodin point of care or clinical laboratorysettings.Sodium measurements are used formonitoring electrolyte imbalances.Potassium measurements are used in thediagnosis and monitoring of diseases andclinical conditions that manifest high andlow potassium levels. |
| DeviceClassification | Same | Class II |
| Product Code | Same | JGS (Na)CEM (K) |
| RegulationNo. | Same | 862.1665 (Na)862.1600 (K) |
| ReportableRange | Same | Na 100 – 180 mmol/L (mEq/L)K 2.0 - 9.0 mmol/L (mEq/L) |
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| Feature orCharacteristic | Candidate Devices:Na and K Tests in the:i-STAT CG8+ cartridgewith the i-STAT 1 System | Predicate Device:Na and K Tests in the:i-STAT CHEM8+ cartridgewith the i-STAT 1 System(K183688) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Sample Type | Na | Arterial, venous or capillarywhole bloodArterial or venous wholeblood | Arterial and venous whole blood | |||||||||
| SampleVolume | Same | 95 µL | ||||||||||
| SamplePreparation | Same | Ready to Use | ||||||||||
| Samplecollection | Na K Withoutanticoagulant Arterial or venous With balancedheparinanticoagulant orlithium heparinanticoagulant Arterial,venous,orcapillary Arterialor venous | With balanced heparin anticoagulant orlithium heparin anticoagulant | ||||||||||
| Traceability | Same | Na, K NIST SRM956 | ||||||||||
| Calibration | Same | 1-point on-board contained withincartridge | ||||||||||
| Principle ofMeasurement | Same | Na, K: Ion-selective electrodepotentiometry | ||||||||||
| ReagentFormat | Same | Cartridge | ||||||||||
| ReagentStorage andStability | Refrigerated at 2-8°C (35-46°F) untilexpiration dateRoom Temperature at 18-30°C (64-86°F)for 2 months | Refrigerated at 2 to 8°C (35 to 46°F) untilexpiration dateRoom Temperature at 18-30°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 Sodium (Na) and Potassium (K) tests in the i-STAT CG8+ cartridge on the i-STAT 1 System was evaluated using five (5) levels of aqueous material. This 20-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 20 days at one site. Repeatability, between-run, between-day, and within-laboratory precision were estimated for each level. The results of the 20-day precision study for the i-STAT CG8+ cartridge on the i-STAT 1 System are shown in Table 2.
| Table 2: Results of 20-Day Precision of the i-STAT CG8+ Cartridge on the i-STAT 1 Analyzer | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Test(units) | FluidLevel | N | Mean | Repeatability | Between-run | Between-day | Within-Laboratory | ||||
| SD | %CV | SD | %CV | SD | %CV | SD | %CV | ||||
| CV L1 | 80 | 99.3 | 0.17 | 0.17 | 0.09 | 0.09 | 0.05 | 0.05 | 0.19 | 0.20 | |
| Na(mmol/L) | CV L2 | 80 | 121.4 | 0.20 | 0.16 | 0.06 | 0.05 | 0.05 | 0.04 | 0.22 | 0.18 |
| CV L3 | 80 | 134.8 | 0.22 | 0.16 | 0.06 | 0.05 | 0.06 | 0.05 | 0.23 | 0.17 | |
| CV L4 | 80 | 161.3 | 0.27 | 0.16 | 0.12 | 0.07 | 0.07 | 0.04 | 0.30 | 0.19 | |
| CV L5 | 80 | 181.1 | 0.32 | 0.18 | 0.12 | 0.06 | 0.09 | 0.05 | 0.35 | 0.19 | |
| K(mmol/L) | CV L1 | 80 | 2.09 | 0.008 | 0.37 | 0.003 | 0.16 | 0.001 | 0.04 | 0.009 | 0.41 |
| CV L2 | 80 | 2.87 | 0.007 | 0.25 | 0.002 | 0.09 | 0.002 | 0.08 | 0.008 | 0.28 | |
| CV L3 | 80 | 3.76 | 0.012 | 0.31 | 0.004 | 0.10 | 0.006 | 0.15 | 0.014 | 0.36 | |
| CV L4 | 80 | 6.41 | 0.021 | 0.33 | 0.008 | 0.12 | 0.012 | 0.18 | 0.025 | 0.39 | |
| CV L5 | 80 | 7.99 | 0.027 | 0.33 | 0.010 | 0.13 | 0.014 | 0.18 | 0.032 | 0.40 |
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 sodium and potassium. 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, 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 3 below.
| Table 3: Multi-Day Precision of the i-STAT CG8+ Cartridge on the i-STAT 1 Analyzer | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Test(units) | FluidLevel | N | Mean | Within-Run | Between-Day | Between-Operator | Within-Site (Total) | Between-Site | Overall | ||||||
| SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | ||||
| Na(mmol/L) | CV L1 | 91 | 100.0 | 0.29 | 0.29 | 0.12 | 0.12 | 0.08 | 0.08 | 0.32 | 0.32 | 0.00 | 0.00 | 0.32 | 0.32 |
| CV L2 | 90 | 121.9 | 0.28 | 0.23 | 0.04 | 0.04 | 0.00 | 0.00 | 0.29 | 0.23 | 0.00 | 0.00 | 0.29 | 0.23 | |
| CV L3 | 97 | 134.9 | 0.34 | 0.25 | 0.00 | 0.00 | 0.06 | 0.04 | 0.34 | 0.25 | 0.03 | 0.02 | 0.34 | 0.26 | |
| CV L4 | 90 | 161.2 | 0.46 | 0.29 | 0.00 | 0.00 | 0.00 | 0.00 | 0.46 | 0.29 | 0.21 | 0.13 | 0.51 | 0.32 | |
| CV L5 | 90 | 181.1 | 0.37 | 0.21 | 0.04 | 0.02 | 0.00 | 0.00 | 0.38 | 0.21 | 0.18 | 0.10 | 0.42 | 0.23 | |
| K(mmol/L) | CV L1 | 91 | 2.10 | 0.010 | 0.50 | 0.000 | 0.01 | 0.000 | 0.00 | 0.01 | 0.50 | 0.000 | 0.01 | 0.010 | 0.50 |
| CV L2 | 90 | 2.81 | 0.026 | 0.91 | 0.000 | 0.00 | 0.012 | 0.44 | 0.028 | 1.01 | 0.008 | 0.28 | 0.029 | 1.05 | |
| CV L3 | 97 | 3.70 | 0.014 | 0.38 | 0.000 | 0.00 | 0.003 | 0.09 | 0.014 | 0.39 | 0.000 | 0.00 | 0.014 | 0.39 | |
| CV L4 | 90 | 6.32 | 0.044 | 0.70 | 0.000 | 0.00 | 0.005 | 0.08 | 0.044 | 0.70 | 0.008 | 0.12 | 0.045 | 0.71 | |
| CV L5 | 90 | 7.89 | 0.038 | 0.48 | 0.000 | 0.00 | 0.006 | 0.07 | 0.038 | 0.48 | 0.011 | 0.14 | 0.040 | 0.50 |
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iii. Precision (Whole Blood)
Whole blood precision of the i-STAT Sodium and Potassium 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 results are summarized in Table 4.
| cartridge on the i-STAT 1 Analyzer | ||||||
|---|---|---|---|---|---|---|
| Test(units) | Sample Type | Sample Range | N | Mean | SD | %CV |
| Na(mmol/L) | Venous Whole Blood | 100-130 | 17 | 122.6 | 0.30 | 0.24 |
| Venous Whole Blood | >130-140 | 99 | 137.5 | 0.45 | 0.33 | |
| Venous Whole Blood | >140-180 | 67 | 146.2 | 0.43 | 0.30 | |
| Na(mmol/L) | Arterial Whole Blood | 100-130 | 2 | 128.0 | 0.00 | 0.00 |
| Arterial Whole Blood | >130-140 | 89 | 137.4 | 0.42 | 0.31 | |
| Arterial Whole Blood | >140-180 | 62 | 142.9 | 0.37 | 0.26 | |
| Na(mmol/L) | Capillary Whole Blood | 100-130 | 3 | 120.8 | 0.41 | 0.34 |
| Capillary Whole Blood | >130-140 | 56 | 138.1 | 0.61 | 0.44 | |
| Capillary Whole Blood | >140-180 | 95 | 142.4 | 0.62 | 0.44 | |
| K(mmol/L) | Venous Whole Blood | 2.0-3.5 | 27 | 3.22 | 0.036 | 1.12 |
| Venous Whole Blood | >3.5-5.0 | 135 | 4.12 | 0.038 | 0.92 | |
| Venous Whole Blood | >5.0-9.0 | 19 | 6.49 | 0.032 | 0.50 | |
| K(mmol/L) | Arterial Whole Blood | 2.0-3.5 | 23 | 3.21 | 0.021 | 0.65 |
| Arterial Whole Blood | >3.5-5.0 | 124 | 4.11 | 0.032 | 0.79 | |
| Arterial Whole Blood | >5.0-9.0 | 6 | 5.67 | 0.041 | 0.72 | |
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 Sodium and Potassium 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 Sodium and Potassium 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 Na and K tests in the i-STAT CG8+ Cartridge onthe i-STAT 1 Analyzer | ||||||
|---|---|---|---|---|---|---|
| Test | Units | Reportable Range | Range Tested | Slope | Intercept | R2 |
| Na | mmol/L | 100 – 180 | 91.3 – 209.8 | 1.005 | -0.525 | 0.9996 |
| K | mmol/L | 2.0 – 9.0 | 1.79 – 10.04 | 1.011 | 0.002 | 0.9994 |
1 The capillary whole blood clinical precision study design involved 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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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 Sodium and Potassium 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 Sodium and Potassium 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 |
| Na (mmol/L) | 100 | 92 |
| K (mmol/L) | 2.0 | 1.6 |
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 Sodium and Potassium tests 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 test. For an identified interferent, a dose-response was performed to determine the degree of interference as a function of the substance concentration.
Table 7 contains the list of potentially interfering substances tested and the interference results for the i-STAT CG8+ cartridge.
| Table 7: Potentially Interfering Substances and Test Concentrations for the i-STAT Sodium andPotassium tests in the i-STAT CG8+ Cartridge | |||||
|---|---|---|---|---|---|
| Substance 2 | Test Concentration | i-STAT Test | Interference (Yes/No) | Comments | |
| mmol/L(unless specified) | mg/dL(unless specified) | ||||
| Acetaminophen | 1.03 | 15.6 | Na | No | |
| K | No | ||||
| Acetyl Cysteine | 0.92 | 15 | Na | No | |
| Table 7: Potentially Interfering Substances and Test Concentrations for the i-STAT Sodium and Potassium tests in the i-STAT CG8+ Cartridge | |||||
| Substance 2 | Test Concentration | i-STAT Test | Interference (Yes/No) | Comments | |
| mmol/L (unless specified) | mg/dL (unless specified) | ||||
| (N-Acetyl-L-Cysteine) | K | No | |||
| Acetylsalicylic Acid | 0.167 | 3.0 | Na | No | |
| Ammonium (Ammonium Chloride) 3 | 2.0 | 10.7 | Na | No | |
| K | No | ||||
| Ascorbic Acid (L-Ascorbic Acid) | 0.298 | 5.25 | Na | No | |
| K | No | ||||
| Benzalkonium (Benzalkonium Chloride) 3 | 0.03 | 1.13 | K | No | |
| β-Hydroxybutyric Acid 3 | 6.0 | 62.46 | Na | No | |
| K | No | ||||
| Bilirubin | 0.684 | 40 | Na | No | |
| K | No | ||||
| Bromide 3 (Lithium Bromide) | 2.5 | 21.7 | Na | No | |
| K | No | ||||
| 37.5 | 325.7 | Na | No | Use Another Method | |
| K | No | ||||
| Calcium (Calcium Chloride) | 5.0 | 20 | Na | No | |
| K | No | ||||
| Chloride (Lithium Chloride) | 3.2 | 13.6 | Na | No | |
| K | No | ||||
| Cholesterol | 11.0 | 425 | Na | Yes | Decreased results > 400 mg/dL |
| K | No | ||||
| Hemoglobin | 10 g/L | 1000 | Na | No | |
| K | No | ||||
| Heparin (Sodium Heparin) | 3.30 U/mL | 330 U/dL | Na | No | |
| Ibuprofen | 1.06 | 21.9 | Na | No | |
| Intralipid 20% | N/A | 2395 | Na | No | |
| 3216 | K | No | |||
| Lactate (Lithium Lactate) | 10 | 90 | Na | No | |
| K | No | ||||
| Magnesium (Magnesium Chloride) | 4.1 | 10 | Na | No | |
| K | No | ||||
| Nithiodote (Sodium Thiosulfate) 3 | 16.7 | 264.04 | Na | Yes | Increased results ≥ 2.1 mmol/L |
| K | No | ||||
| Salicylate (Lithium Salicylate) | 0.207 | 2.86 | Na | No | |
| K | No | ||||
| Triglyceride | 16.94 | 1500 | Na | No | |
| K | No | ||||
| Uric Acid | 1.4 | 23.5 | Na | No |
2 The compound tested to evaluate the interfering substance is presented in parenthesis.
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Table 7: Potentially Interfering Substances and Test Concentrations for the i-STAT Sodium and
B. Comparison Studies
3 The test concentration for this substance is not included in CLSI guideline EP37 1st edition.
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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 sodium and potassium, 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 sodium 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 Potassium 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 Potassium performance on the i-STAT 1 analyzer to comparative methods for arterial and venous are as shown in Table 8. In the table. N is the number of specimens in the data set, and r is the correlation coefficient.
| Table 8: Method Comparison Results for the i-STAT K test in the i-STAT CG8+ Cartridge with i-STAT 1System | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Test | ComparativeMethod | N | Slope | Intercept | r | Xmin | Xmax | MedicalDecisionLevel | Bias atMedicalDecisionLevel |
| (units) | Arterial/Venous | ||||||||
| K(mmol/L) | i-STAT CHEM8+ | 340 | 1.00 | 0.00 | 1.00 | 2.4 | 8.8 | 3.05.87.5 | 0.000.000.00 |
The venous, arterial, and capillary whole blood data were pooled, and a Passing-Bablok linear regression analysis was performed using the i-STAT Sodium 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 Sodium performance on the i-STAT 1 analyzer to the comparative method 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.
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| Table 9: Method Comparison Results for for the i-STAT Na test in the i-STAT CG8+ Cartridge with i-STAT 1 System | ||||||||
|---|---|---|---|---|---|---|---|---|
| Comparative Method | Medical | Bias at | ||||||
| Test(units) | Arterial/Venous | Capillary | N | Slope | Intercept | r | DecisionLevel | MedicalDecisionLevel |
| Na(mmol/L) | i-STATCHEM8+ | epoc BloodAnalysisSystem | 551 | 1.00 | 0.00 | 0.99 | 115 | 0.0 |
| 135 | 0.0 | |||||||
| 150 | 0.0 | |||||||
The method comparison results for capillary whole blood specimens only for the i-STAT Sodium test are shown in Table 10.
| Table 10: Results for i-STAT CG8+ Cartridge with i-STAT 1 System – Native and ContrivedCapillary Specimens | ||||||
|---|---|---|---|---|---|---|
| Test(units) | N | Slope | Intercept | r | Range | |
| Na(mmol/L) | 209 | 1.00 | 0.00 | 0.98 | 101 - 172 | |
Bias at the medical decision levels for native capillary whole blood specimens only for the i-STAT Sodium test are shown in Table 11.
| Table 11: Results for i-STAT CG8+ Cartridge with i-STAT 1 System - Native Capillary SpecimensBias at Medical Decision Levels | |||||
|---|---|---|---|---|---|
| Test(units) | N | Medical DecisionLevel | Bias | ||
| Estimate 95% CI | |||||
| Na(mmol/L) | 194 | 115 | 0.0 (-1.0, 0.0) | ||
| 135 | 0.0 (-1.0, 0.0) | ||||
| 150 | 0.0 (-1.0, 0.0) | ||||
b. Matrix Equivalence
A matrix equivalence study was conducted to evaluate the performance of the i-STAT Sodium and Potassium tests in the i-STAT CG8+ cartridge on the i-STAT 1 System
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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 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 12. In the table, N is the number of specimens in the data set, and r is the correlation coefficient.
| Table 12: Matrix Equivalence Results | ||||||
|---|---|---|---|---|---|---|
| Test (units) | N | CandidateSpecimen Range | Primary SpecimenRange | r | Slope | Intercept |
| Na (mmol/L) | 295 | 102-178 | 102-178 | 0.99 | 1.00 | 0.00 |
| K (mmol/L) | 292 | 2.4-8.7 | 2.4-8.7 | 0.99 | 1.00 | 0.00 |
VIII. CONCLUSION
The results of these studies demonstrate that performance of the i-STAT Sodium and Potassium tests in the i-STAT CG8+ cartridge with the i-STAT 1 System is substantially equivalent to the predicate device.
§ 862.1665 Sodium test system.
(a)
Identification. A sodium test system is a device intended to measure sodium in serum, plasma, and urine. Measurements obtained by this device are used in the diagnosis and treatment of aldosteronism (excessive secretion of the hormone aldosterone), diabetes insipidus (chronic excretion of large amounts of dilute urine, accompanied by extreme thirst), adrenal hypertension, Addison's disease (caused by destruction of the adrenal glands), dehydration, inappropriate antidiuretic hormone secretion, or other diseases involving electrolyte imbalance.(b)
Classification. Class II.