K Number
K200492
Date Cleared
2020-04-09

(41 days)

Product Code
Regulation Number
862.1120
Reference & Predicate Devices
Predicate For
N/A
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP AuthorizedThirdpartyExpeditedreview
Intended Use

The i-STAT CG4+ cartridge with the i-STAT 1 System is intended for use in the in vitro quantification of pH, PO2, PCO2, and lactate in arterial or venous whole blood in point of care or clinical laboratory settings.

pH, PO2, and PCO2 measurements are used in the diagnosis, monitoring, and treatment of respiratory disturbances and metabolic and respiratory-based acid-base disturbances.

Lactate measurements are used in (1) the diagnosis and treatment of lactic acidosis in conjunction with measurements of blood acid/base status, (2) monitoring tissue hypoxia and strenuous physical exertion, and (3) diagnosis of hyperlactatemia.

Device Description

The i-STAT CG4+ test cartridge contains test reagents to analyze whole blood at the point of care or in the clinical laboratory for pH. PO2 (partial pressure of oxygen), PCO2 (partial pressure of carbon dioxide), and lactate. The test is contained in a single-use, disposable cartridge. Cartridges require two to three drops of whole blood which are typically applied to the cartridge using a transfer device.

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 cartridge to move fluid across the sensors and generate a quantitative result (within approximately 2 minutes).

The i-STAT 1 System is comprised of the i-STAT 1 analyzer, the i-STAT test cartridges and accessories (i-STAT 1 Downloader/Recharger, electronic simulator and portable printer). The system is designed for use by trained medical professionals at the patient point of care or in the clinical laboratory and is for prescription use only.

AI/ML Overview

Here's a summary of the acceptance criteria and study information for the i-STAT CG4+ Cartridge with the i-STAT 1 System, based on the provided FDA 510(k) summary:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state formal "acceptance criteria" for each performance characteristic in a pass/fail format. Instead, it presents study results and concludes that the device is "substantially equivalent" to predicate devices. However, we can infer some criteria from the reported performance, especially in precision and linearity compared to typical clinical expectations.

Performance CharacteristicAcceptance Criteria (Implied/Inferred)Reported Device Performance
Precision (Aqueous Materials)Acceptable Total CV% (Specific values for each analyte and level)pH: Total CV% ranged from 0.03% to 0.07% across 5 levels. PO2: Total CV% ranged from 1.9% to 3.5% across 5 levels. PCO2: Total CV% ranged from 1.5% to 3.4% across 5 levels. Lactate: Total CV% ranged from 0.4% to 2.7% across 5 levels.
Precision (Whole Blood)Acceptable SD and CV% within specified sample ranges for venous and arterial bloodpH (Venous): SDs from 0.0030 to 0.0064, CV% from 0.04 to 0.09. pH (Arterial): SDs from 0.0047 to 0.0060, CV% from 0.06 to 0.08. PO2 (Venous): SDs from 0.9 to 12.4, CV% from 0.7 to 3.4. PO2 (Arterial): SDs from 0.5 to 8.5, CV% from 1.2 to 4.4. PCO2 (Venous): SDs from 0.29 to 0.77, CV% from 0.8 to 1.7. PCO2 (Arterial): SDs from 0.37 to 0.90, CV% from 0.5 to 2.1. Lactate (Venous): SDs from 0.016 to 0.200, CV% from 1.14 to 2.26. Lactate (Arterial): SDs from 0.018 to 0.036, CV% from 0.42 to 2.49.
LinearityDemonstrated linearity over the reportable range (e.g., r² > 0.99)pH: Slope 0.966, Intercept 0.246, r² 0.9983 PO2: Slope 1.005, Intercept -0.196, r² 0.9988 PCO2: Slope 1.027, Intercept -1.084, r² 0.9978 Lactate: Slope 1.128, Intercept 0.104, r² 0.9966
Limit of Quantitation (LoQ)LoQ to be below the lower limit of the reportable rangepH: Determined LoQ 6.716 (LLR ≤ 7.000) PO2: Determined LoQ 10 mmHg (LLR ≤ 15 mmHg) PCO2: Determined LoQ 9.7 mmHg (LLR ≤ 15.0 mmHg) Lactate: Determined LoQ 0.27 mmol/L (LLR ≤ 0.30 mmol/L)
Limit of Blank (LoB) / Limit of Detection (LoD)LoB and LoD for Lactate to be within acceptable limitsLactate: LoB 0.15 mmol/L, LoD 0.19 mmol/L
Oxygen Sensitivity (Lactate)Insensitive to oxygen changes between 20 to >500 mmHg (equivalence demonstrated)The study demonstrated that the i-STAT Lactate test is insensitive to oxygen changes between 20 to >500 mmHg.
InterferenceNo significant interference (difference between control and test samples within allowed error (Ea)) (Note: Bromide and Glycolic Acid were identified as interferents for Lactate, with specific effects reported)pH, PO2, PCO2: No interference found for Acetaminophen, Atracurium, Calcium, Ethanol, Ibuprofen, Morphine, Potassium, Sodium, Bilirubin, Hemoglobin, Triglyceride, Intralipid, Thiopental. Lactate: No interference for Acetaldehyde, Acetaminophen, N-Acetyl-Cysteine, Ascorbic Acid, β-Hydroxybutyric Acid, Bilirubin, Dopamine, Formaldehyde, Hemoglobin, Hydroxyurea, Pyruvate, Salicylate, Thiocyanate, Triglyceride, Intralipid, Uric Acid. Interference identified for Bromide (decreased results ≥ 40.7 mmol/L) and Glycolic Acid (increased results ≥ 1.18 mmol/L).
Method ComparisonAcceptable correlation with predicate device (e.g., high r-value, slope near 1, intercept near 0)pH: N=316, Slope 1.05, Intercept -0.34, r 0.97 PO2: N=308, Slope 1.03, Intercept -3.96, r 0.99 PCO2: N=327, Slope 1.01, Intercept -1.29, r 0.99 Lactate: N=246, Slope 0.96, Intercept 0.08, r 1.00

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

  • Precision (Aqueous Materials): The "test set" for this was aqueous materials. N values for each level were 80 or 81. Provenance is not explicitly stated beyond "at one site." It's an analytical performance study, not involving human subjects directly.
  • Precision (Whole Blood): The "test set" for this involved whole blood venous and arterial specimens. Sample sizes (N) varied by sample type and range for each analyte (e.g., pH venous <7.30 had N=20). Provenance: "data collected across multiple point of care sites." This implies prospective collection from various clinical settings.
  • Linearity: Whole blood samples of varying analyte levels. Sample sizes are not explicitly stated for individual samples, but the study design evaluated the linearity of the tests using these blood samples. The regression summary provides an R² value for each analyte, indicating the strength of the linear relationship.
  • Limit of Quantitation (LoQ): Whole blood altered to low concentrations. Sample size not specified, but utilized "two cartridge lots for each test."
  • Limit of Blank (LoB) / Limit of Detection (LoD): Whole blood altered to "blank" and "low" lactate concentrations. Sample size not specified, but results based on the maximal value obtained for "each lot tested."
  • Oxygen Sensitivity: Whole blood with high and low ranges of oxygen. Sample size not specified.
  • Interference: Whole blood samples. Sample sizes not specified for individual interfering substances.
  • Method Comparison:
    • pH: N=316
    • PO2: N=308
    • PCO2: N=327
    • Lactate: N=246
      Provenance: "Lithium heparin venous and arterial blood specimens were evaluated." This implies prospective collection or re-analysis of existing clinical samples. Country of origin not specified.

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

This document describes the analytical performance of an in vitro diagnostic device (blood gas and lactate analyzer). The "ground truth" for these types of studies is typically established by comparative methods using highly accurate and precise laboratory-grade instruments or reference methods. It does not involve human expert consensus in the way a medical imaging AI would for diagnosis.

For the method comparison, the comparative methods used were:

  • pH, PO2, and PCO2: Radiometer ABL800 FLEX
  • Lactate: epoc® Blood Analysis System

These are established clinical laboratory devices, and their measurements form the "ground truth" for comparison. The expertise lies in the certified reference materials and the robust design of these predicate devices, which are regularly calibrated and validated. No individual human experts were mentioned to establish "ground truth" for the test set in the traditional sense of consensus reading in AI studies.

4. Adjudication Method for the Test Set

Not applicable to this type of analytical performance study. Adjudication methods (like 2+1, 3+1) are typically used in studies where human interpretation (e.g., radiologist reads) needs to be reconciled to establish a ground truth for evaluating AI systems. Here, the comparison is against established analytical methods.

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 an analytical performance study of an in vitro diagnostic device, not a human-in-the-loop AI system for interpretation. Therefore, no MRMC study or assessment of human reader improvement with AI assistance was performed.

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

This device is an analytical instrument, so its performance is inherently "standalone" in generating a numerical result. The measurements generated (pH, PO2, PCO2, Lactate) are numerical outputs. The studies described (precision, linearity, LoQ, interference, method comparison) directly assess this standalone performance against reference methods or defined standards.

7. The Type of Ground Truth Used

The ground truth used for performance evaluation was:

  • Certified Reference Materials / Aqueous Controls: For precision studies (aqueous materials).
  • Measurements from Predicate Devices / Comparative Methods: For the method comparison study (Radiometer ABL800 FLEX for pH, PO2, PCO2, and epoc® Blood Analysis System for Lactate). These are considered highly accurate and serve as the clinical reference values.
  • Spiked Samples / Altered Whole Blood Samples: For linearity, LoQ, LoB/LoD, and interference studies, where known concentrations or conditions are created and measured against expected values.

8. The Sample Size for the Training Set

Not applicable. This is an analytical device, not a machine learning or AI algorithm that requires a "training set" in the context of supervised learning. The device is designed based on electrochemical principles, and its performance is validated through traditional analytical studies.

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

Not applicable, as there is no "training set" for this type of device. The device's underlying principles are physics and chemistry-based rather than learned from data.

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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 blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

April 9, 2020

Abbott Point of Care Inc. Susan Tibedo Director, Regulatory Affairs 400 College Road East Princeton, NJ 08540

Re: K200492

Trade/Device Name: i-STAT CG4+ Cartridge with the i-STAT 1 System Regulation Number: 21 CFR 862.1120 Regulation Name: Blood Gases (PCO2, PO2) and Blood pH Test System Regulatory Class: Class II Product Code: CHL, KHP Dated: February 27, 2020 Received: February 28, 2020

Dear Susan Tibedo:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part

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801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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

For comprehensive regulatory information about medical devices and radiation-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,

Marianela Perez-Torres, Ph.D. Acting Deputy Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K200492

Device Name

i-STAT CG4+ cartridge with the i-STAT 1 System

Indications for Use (Describe)

The i-STAT CG4+ cartridge with the i-STAT 1 System is intended for use in the in vitro quantification of pH, PO2, PCO2, and lactate in arterial or venous whole blood in point of care or clinical laboratory settings.

pH, PO2, and PCO2 measurements are used in the diagnosis, monitoring, and treatment of respiratory disturbances and metabolic and respiratory-based acid-base disturbances.

Lactate measurements are used in (1) the diagnosis and treatment of lactic acidosis in conjunction with measurements of blood acid/base status, (2) monitoring tissue hypoxia and strenuous physical exertion, and (3) diagnosis of hyperlactatemia.

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

× Prescription Use (Part 21 CFR 801 Subpart D)

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

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510(k) Summary

The information in this 510(k) summary is being submitted in accordance with the requirements of 21 CFR 807.92.

1.Submitter Information
OwnerAbbott Point of Care Inc.400 College Road EastPrinceton, NJ 08540
ContactPrimary: Susan TibedoDirector Regulatory Affairssusan.tibedo@abbott.comPhone: 609-454-9360
Secondary: Maria FigueroaManager Regulatory Affairsmaria.l.figueroa@abbott.comPhone: 609-454-9271
Date PreparedApril 7, 2020

2. Device Information

Proprietary Namei-STAT CG4+ cartridge with the i-STAT 1 System
Common NameBlood gas test, analyzer, handheld
510(k) NumberK200492
ProductcodeDevice ClassificationnameRegulationNumberClassPanel
CHLElectrode, Ion Specific, pH862.1120IIClinical Chemistry
CHLElectrode, Ion Specific, pCO2862.1120IIClinical Chemistry
CHLElectrode, Ion Specific pO2862.1120IIClinical Chemistry
KHPElectrode, Ion Specific, Lactate862.1450IClinical Chemistry

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3. Predicate Device

Proprietary Name epoc Lactate test, epoc Blood Analysis System

510(k) Number K093297

ProductcodeDevice ClassificationnameRegulationNumberClassPanel
KHPElectrode, Ion Specific,Lactate862.1450IClinical Chemistry

Proprietary Name ABL800 FLEX blood gas, oximetry, electrolyte and metabolite analyzer

510(k) Number K041874

ProductcodeDevice ClassificationnameRegulationNumberClassPanel
CHLElectrode, Ion Specific, pH862.1120IIClinical Chemistry
CHLElectrode, Ion Specific,PCO2862.1120IIClinical Chemistry
CHLElectrode, Ion SpecificPO2862.1120IIClinical Chemistry

4. Device Description

The i-STAT CG4+ test cartridge contains test reagents to analyze whole blood at the point of care or in the clinical laboratory for pH. PO2 (partial pressure of oxygen), PCO2 (partial pressure of carbon dioxide), and lactate. The test is contained in a single-use, disposable cartridge. Cartridges require two to three drops of whole blood which are typically applied to the cartridge using a transfer device.

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 cartridge to move fluid across the sensors and generate a quantitative result (within approximately 2 minutes).

The i-STAT 1 System is comprised of the i-STAT 1 analyzer, the i-STAT test cartridges and accessories (i-STAT 1 Downloader/Recharger, electronic simulator and portable printer). The system is designed for use by trained medical professionals at the patient point of care or in the clinical laboratory and is for prescription use only.

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5. Intended Use Statement

The i-STAT CG4+ cartridge with the i-STAT 1 System is intended for use in the in vitro quantification of pH, PO2, PCO2, and lactate in arterial or venous whole blood in point of care or clinical laboratory settings.

pH, PO2, and PCO2 measurements are used in the diagnosis, monitoring, and treatment of respiratory disturbances and metabolic and respiratory-based acid-base disturbances.

Lactate measurements are used in (1) the diagnosis and treatment of lactic acidosis in conjunction with measurements of blood acid/base status, (2) monitoring tissue hypoxia and strenuous physical exertion, and (3) diagnosis of hyperlactatemia.

Similarities and Differences: System (Test and Instrument) for pH
Feature orCharacteristicPredicate:ABL800 FLEX pH Test(K041874)Candidate: pH test in thei-STAT CG4+ cartridge withthe i-STAT 1 System
Intended UseThe ABL800 FLEX is intended for in vitrotesting of samples of whole blood for theparameters pH, pO2, pCO2, potassium,sodium, calcium, chloride, glucose, lactate,total bilirubin, and co-oximetry parameters(total hemoglobin, oxygen saturation, and thehemoglobin fractions FO2Hb, FCOHb,FMetHb, FHHb, and FHbF). In addition theABL800 FLEX is intended for in vitro testing ofsamples of expired air for the parameters pO2and pCO2. The ABL800 FLEX includes anAutoCheck Module to perform automatedanalysis of quality control fluids.pH is the indispensable measure of acidemiaor alkalemia and is therefore an essential partof the pH/blood gas measurement. Thenormal function of many metabolicprocesses requires a pH to be within arelatively narrow range.The i-STAT CG4+ cartridge withthe i-STAT 1 System is intendedfor use in the in vitro quantificationof pH in arterial or venous wholeblood in point of care or clinicallaboratory settings.pH measurements are used in thediagnosis, monitoring, andtreatment of respiratorydisturbances and metabolic andrespiratory-based acid-basedisturbances.
ReportableRangeTest Range:1 7.0 – 7.7Measuring Range:2 6.300 - 8.000Reportable Range: 7.000 - 7.700
Sample TypeArterial, venous or capillary whole bloodArterial or venous whole blood
Sample VolumeAt least 50 – 70 μL95 μL

6. Summary Comparison of Technological Characteristics

1 The measuring range for a parameter is the range within which the analyzer is physically capable of measuring. The measuring range corresponds to the "range of indication" as defined in the International vocabulary of basic and general terms in metrology" (VIM).

? The test range for a parameter is the range within which accuracy and precision of a measured parameter has been specified and intended to lie within specified limits. The test range corresponds to the "measuring range" as defined in the "International vocabulary of basic and general terms in metrology" (VIM).

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Similarities and Differences: System (Test and Instrument) for pH
Feature orCharacteristicPredicate:ABL800 FLEX pH Test(K041874)Candidate: pH test in thei-STAT CG4+ cartridge withthe i-STAT 1 System
SamplePreparationReady to UseReady to Use
TraceabilityBMS™ Mk2NIST SRM 186-I, 186-II, 185, and187
Calibration1-point intervals 30 min, 1 hour, 2 hours1-point on-board contained withinthe cartridge
Time to Test(SampleStability)Analyze heparinized samples within 30minutes after collectionHeparinized samples: within 10minutes of collection
Principle ofMeasurementIon selective electrodeIon selective electrode
Reagent FormatReagent handling system, stored withinanalyzerCartridge
Analyzer TypeFloor ModelHandheld
Similarities and Differences: System (Test and Instrument) for PO2
Feature orCharacteristicPredicate:ABL800 FLEX pO2 Test(K041874)Candidate: PO2 test in thei-STAT CG4+ cartridge withthe i-STAT 1 System
Intended UseThe ABL800 FLEX is intended for in vitrotesting of samples of whole blood for theparameters pH, pO2, pCO2, potassium,sodium, calcium, chloride, glucose, lactate,total bilirubin, and co-oximetry parameters(total hemoglobin, oxygen saturation, and thehemoglobin fractions FO2Hb, FCOHb,FMetHb, FHHb, and FHbF). In addition theABL800 FLEX is intended for in vitro testingof samples of expired air for the parameterspO2 and pCO2. The ABL800 FLEX includesan AutoCheck Module to perform automatedanalysis of quality control fluids.The arterial oxygen tension is an indicator ofthe oxygen uptake in the lungs.The i-STAT CG4+ cartridge withthe i-STAT 1 System is intendedfor use in the in vitro quantificationof PO2 in arterial or venous wholeblood in point of care or clinicallaboratory settings.PO2 measurements are used in thediagnosis, monitoring, andtreatment of respiratorydisturbances and metabolic andrespiratory-based acid-basedisturbances.
ReportableRangeTest Range:115 - 530 mmHgMeasuring Range:20.0 - 800 mmHg0.00 – 107 kPaReportable Range:15 – 530 mmHg2.00 - 70.49 kPa
Sample TypeArterial, venous or capillary whole bloodArterial or venous whole blood
Sample VolumeAt least 50 - 70 μL95 μL
SamplePreparationReady to UseReady to Use
TraceabilityNIST certified Standard Reference MaterialsNIST standard reference materialsvia commercially available certifiedspecialty medical gas standards
Calibration1-point intervals 30 min, 1 hour, 2 hours1-point on-board contained withinthe cartridge
Time to Test(Sample Stability)Analyze heparinized samples within 30minutes after collectionHeparinized samples: within 10minutes of collection
Principle ofMeasurementAmperometric measurement of oxygenreduction currentAmperometric measurement ofoxygen reduction current
Reagent FormatReagent handling system, stored withinanalyzerCartridge
Analyzer TypeFloor ModelHandheld
Similarities and Differences: System (Test and Instrument) for PCO2
Feature orCharacteristicPredicate:ABL800 FLEX pCO2 Test(K041874)Candidate: PCO2 test in thei-STAT CG4+ cartridge withthe i-STAT 1 System
Intended UseThe ABL800 FLEX is intended for in vitrotesting of samples of whole blood for theparameters pH, pO2, pCO2, potassium,sodium, calcium, chloride, glucose, lactate,total bilirubin, and co-oximetry parameters(total hemoglobin, oxygen saturation, and thehemoglobin fractions FO2Hb, FCOHb,FMetHb, FHHb, and FHbF). In addition theABL800 FLEX is intended for in vitro testingof samples of expired air for the parameterspO2 and pCO2. The ABL800 FLEX includesan AutoCheck Module to perform automatedanalysis of quality control fluids.pCO2 is a direct reflection of the adequacy ofalveolar ventilation in relation to themetabolic rate.The i-STAT CG4+ cartridge withthe i-STAT 1 System is intendedfor use in the in vitro quantificationof PCO2 in arterial or venous wholeblood in point of care or clinicallaboratory settings.PCO2 measurements are used inthe diagnosis, monitoring, andtreatment of respiratorydisturbances and metabolic andrespiratory-based acid-basedisturbances.
ReportableRangeTest Range:115 – 150 mmHgMeasuring Range:25.0 – 250 mmHg0.67 – 33.3 kPaReportable Range:15.0 – 130.0 mmHg2.00 –17.29 kPa
Sample TypeArterial, venous or capillary whole bloodArterial or venous whole blood
Sample VolumeAt least 50 – 70 μL95 μL
SamplePreparationReady to UseReady to Use
TraceabilityNIST certified Standard Reference MaterialsNIST standard reference materialsvia commercially available certifiedspecialty medical gas standards
Calibration1-point intervals 30 min, 1 hour, 2 hours1-point on-board contained withinthe cartridge
Time to Test(Sample Stability)Analyze heparinized samples within 30minutes after collectionHeparinized samples: within 10minutes of collection
Principle ofMeasurementIon selective electrodeIon selective electrode
Reagent FormatReagent handling system, stored withinanalyzerCartridge
Analyzer TypeFloor ModelHandheld
Similarities and Differences: System (Test and Instrument) for Lactate
Feature orCharacteristicPredicate:epoc Lactate Test with epoc BloodAnalysis System(K093297)Candidate: Lactate test in thei-STAT CG4+ cartridge withthe i-STAT 1 System
Intended UseThe Lactate test, as part of the epoc BloodAnalysis System, is intended for use bytrained medical professionals as an in vitrodiagnostic device for the quantitative testingof samples of heparinized or un-anticoagulated arterial, venous or capillarywhole blood in the laboratory or at the pointof care in hospitals, nursing homes or otherclinical institutions.Lactate measurements from the epoc BloodAnalysis System are used to evaluate theacid-base status and are used in thediagnosis and treatment of lactic acidosis(abnormally high acidity of the blood.)The i-STAT CG4+ cartridge withthe i-STAT 1 System is intendedfor use in the in vitro quantificationof lactate in arterial or venouswhole blood in point of care orclinical laboratory settings.Lactate measurements are used in(1) the diagnosis and treatment oflactic acidosis in conjunction withmeasurements of blood acid/basestatus, (2) monitoring tissuehypoxia and strenuous physicalexertion, and (3) diagnosis ofhyperlactatemia.
ReportableRangeReportable Range:0.30 – 20.00 mmol/L2.7 – 180.2 mg/dL0.03 – 1.80 g/LReportable Range:0.30 – 20.00 mmol/L2.7 – 180.2 mg/dL
Sample TypeArterial, venous or capillary whole bloodArterial or venous whole blood
Sample VolumeAt least 92 µL95 µL
SamplePreparationReady to UseReady to Use
TraceabilityCertified standard reference material notavailable at presentCertified standard referencematerial not available at present
Calibration1-point on-board contained within the card1-point on-board contained withinthe cartridge
Time to Test(Sample Stability)Immediately after collection or in less than 5minutesImmediately after collection
Principle ofMeasurementAmperometric measurement of oxidizedhydrogen peroxide produced by lactateoxidase activityAmperometric measurement ofoxidized hydrogen peroxideproduced by lactate oxidaseactivity
Reagent FormatTest cardCartridge
Analyzer TypeHandheldHandheld

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1 The measuring range for a parameter is the range within which the analyzer is physically capable of measuring. The measuring range corresponds to the "range of indication" as defined in the International vocabulary of basic and general terms in metrology" (VIM).

² The test range for a parameter is the range within which accuracy and precision of a measured parameter has been specified and intended to lie within specified limits. The test range corresponds to the "measuring range" as defined in the "International vocabulary of basic and general terms in metrology" (VIM).

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1 The measuring range for a parameter is the range within which the analyzer is physically capable of measuring. The measuring range corresponds to the "range of indication" as defined in the International vocabulary of basic and general terms in metrology" (VIM).

² The test range for a parameter is the range within which accuracy and precision of a measured parameter has been specified and intended to lie within specified limits. The test range corresponds to the "measuring range" as defined in the "International vocabulary of basic and general terms in metrology" (VIM).

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7. Performance Characteristics Analytical Performance

a. Precision

Precision 20 days (Aqueous Materials)

The precision of the i-STAT pH, PO2, PCO2, and Lactate tests in the i-STAT CG4+ blue cartridge with the i-STAT 1 System was evaluated using 5 levels of aqueous materials. This 20-day multi-day precision testing was based on CLSI document EP05-A3: Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline-Third Edition. The study was conducted using multiple instruments and one test cartridge lot over 20 days at one site. Total precision ( 'within-laboratory'), withinrun, between-run, and between-day were estimated for each level. The results of the 20day precision study are shown in Table 1.

Table 1: 20-Day Precision of i-STAT pH, PO2, PCO2, and Lactate tests on the i-STAT 1Analyzer
i-STATTestFluidLevelNMeanTotalWithin-runBetween-runBetween-day
SD%CVSD%CVSD%CVSD%CV
pHCV L1806.52150.004350.070.003470.050.002280.030.001290.02
CV L2817.01990.002870.040.002520.040.000400.010.001320.02
CV L3807.47580.002790.040.002500.030.000980.010.000750.01
CV L4807.75510.002410.030.002090.030.000710.010.000970.01
CV L5807.98620.003690.050.003220.040.001180.010.001350.02
PO2(mmHg)CV L18070.22.453.52.083.00.701.01.081.5
CV L28185.72.693.12.402.80.760.90.931.1
CV L380120.42.662.22.251.91.181.00.810.7
CV L480152.93.022.01.881.21.781.21.551.0
CV L580363.46.981.94.151.15.071.42.400.7
PCO2(mmHg)CV L18087.081.3491.50.9161.10.8721.00.4700.5
CV L28159.480.9211.50.8721.50.2280.40.1900.3
CV L38029.240.6752.30.6172.10.2270.80.1510.5
CV L48021.140.5522.60.5212.50.1410.70.1180.6
CV L58015.050.5063.40.4733.10.1380.90.1140.8
Lactate(mmol/L)CV L18018.4480.16550.90.15050.80.02660.10.06340.3
CV L2807.9670.04950.60.04590.60.01320.20.01280.2
CV L3792.2510.00820.40.00730.30.00300.10.00210.1
CV L4800.9240.01221.30.01081.20.00380.40.00410.4
CV L5800.4970.01332.70.01232.50.00330.70.00370.7

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Precision (Whole Blood)

Whole blood precision was evaluated using whole blood venous and arterial specimens collected with lithium heparin. The repeatability analysis was conducted using the data collected across multiple point of care sites. The mean values for each sample were divided into subintervals for each sample type. The results are provided in Table 2 below:

Table 2: Precision for venous and arterial whole blood
i-STATTestUnitsSample TypeSampleRangeNMeanSDCV (%)
pHpH unitsVenousWhole Blood<7.30207.2020.00640.09
7.30-7.45777.3740.00600.08
>7.4577.5850.00300.04
pHpH unitsArterialWhole Blood<7.30227.2590.00590.087.30-7.451197.3890.00600.08>7.45367.4940.00470.06PO2mmHgVenousWhole Blood<505928.80.93.050 - 1002758.22.03.4100 - 2504188.61.40.7>2506450.012.42.8PO2mmHgArterialWhole Blood<50240.30.51.250-1006577.53.44.4100 - 25078156.63.72.4>25033355.68.52.4PCO2mmHgVenousWhole Blood<35616.830.291.735 - 62.58346.230.771.7>62.52691.610.730.8PCO2mmHgArterialWhole Blood<353331.230.511.635-62.514042.650.902.1>62.5474.360.370.5Lactatemmol/LVenousWhole Blood<1.0500.700.0162.261.0-5.0621.830.0211.14>5.01112.880.2001.55Lactatemmol/LArterialWhole Blood<1.0570.720.0182.491.0-5.0421.870.0201.08>5.088.550.0360.42
pHpH unitsArterialWhole Blood<7.30227.2590.00590.08
7.30-7.451197.3890.00600.08
>7.45367.4940.00470.06
PO2mmHgVenousWhole Blood<505928.80.93.0
50 - 1002758.22.03.4
100 - 2504188.61.40.7
>2506450.012.42.8
PO2mmHgArterialWhole Blood<50240.30.51.2
50-1006577.53.44.4
100 - 25078156.63.72.4
>25033355.68.52.4
PCO2mmHgVenousWhole Blood<35616.830.291.7
35 - 62.58346.230.771.7
>62.52691.610.730.8
PCO2mmHgArterialWhole Blood<353331.230.511.6
35-62.514042.650.902.1
>62.5474.360.370.5
Lactatemmol/LVenousWhole Blood<1.0500.700.0162.26
1.0-5.0621.830.0211.14
>5.01112.880.2001.55
Lactatemmol/LArterialWhole Blood<1.0570.720.0182.49
1.0-5.0421.870.0201.08
>5.088.550.0360.42

b. Linearity

The study was designed based on CLSI EP06-A: Evaluation of the Linearity of Quantitative Measurement Procedures.

The linearity of the i-STAT pH, PO2, PCO2, and Lactate tests in the i-STAT CG4+ blue 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 pH, PO2, PCO2, and Lactate tests 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 3.

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Table 3: Regression Summary for the i-STAT PO2, PCO2, pH and Lactate tests on thei-STAT 1 Analyzer
i-STATTestUnitsReportableRangeRange TestedSlopeInterceptr2
pHpH units7.0 - 7.76.889 - 7.9790.9660.2460.9983
PO2mmHg15 - 53010.69 - 608.491.005-0.1960.9988
PCO2mmHg15 - 13010.75 - 151.021.027-1.0840.9978
Lactatemmol/L0.30 - 20.000.222 - 21.7421.1280.1040.9966

c. 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 pH, PO2, PCO2, and Lactate tests in the i-STAT CG4+ blue cartridge were evaluated on the i-STAT 1 analyzer using whole blood that was altered to low pH (< 7 pH units), PO2 (< 15 mmHg), PCO2 (< 15 mmHg), and lactate (0.22 -0.29 mmol/L) concentrations and two cartridge lots for each test. The LoQ for each of the i-STAT pH, PO2, PCO2, and Lactate tests was determined to be below the lower limit of the reportable range for each of the i-STAT tests as shown in Table 4.

Table 4: LoQ Results for the i-STAT PO2, PCO2, pH andLactate tests on the i-STAT 1 Analyzer
i-STAT TestLower limit of the rangeDetermined LoQ
pH (pH units)≤ 7.000 pH units6.716
PO2 (mmHg)≤ 15 mmHg10
PCO2 (mmHg)≤ 15.0 mmHg9.7
Lactate (mmol/L)≤ 0.30 mmol/L0.27

d. 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 Lactate test in the i-STAT CG4+ blue cartridge were evaluated on the i-STAT 1 analyzer using whole blood that was altered to a "blank" lactate concentration for LoB testing and two "low" lactate concentrations 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 Lactate test on the i-STAT 1 Analyzer are shown in the Table 5 below.

Table 5: Summary of LoB and LoD Results for the i-STATLactate test on the i-STAT 1 Analyzer
i-STAT TestLODLOB
0.15 mmol/L0.19 mmol/LLactate

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e. Oxygen Sensitivity for the Lactate Test

The effect on oxygen on the i-STAT Lactate test in the i-STAT CG4+ blue cartridge was evaluated with high and low ranges of oxygen. The equivalency between the high and low conditions was determined by a two-sample equivalence test using the analyte allowable error (Ea) relative to the analyte control mean/median results.

The study demonstrated that the i-STAT Lactate test in the i-STAT CG4+ blue cartridge is insensitive to oxygen changes between 20 to >500 mmHg.

f. Interference

The interference performance of the i-STAT pH, PO2, PCO2, and Lactate tests in the i-STAT CG4+ blue cartridge on the i-STAT 1 analyzer 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 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 allowed error (Ea) for the i-STAT test.

Table 6 and Table 7 contain the lists of potentially interfering substances tested for the i-STAT pH, PO2, PCO2, and Lactate tests and the interference results.

Table 6: Potentially Interfering Substances and Test Concentration for pH, PO2, and PCO2
i-STATTestSubstanceTest ConcentrationInterference(Yes/No)InterferenceResults
mmol/Lmg/dL
Acetaminophen1.0315.6No
Atracurium10.02873.57No
Calcium5.020No
Ethanol130600No
PO2PCO2pHIbuprofen1.0621.9No
Morphine0.02730.78No
Potassium859.6No
Sodium170993.48No
Bilirubin0.68440No
Hemoglobin10 g/L1000No
Triglyceride16.941500No
IntralipidN/A2493No
Thiopental166040.2No

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

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Table 7: Potentially Interfering Substances and Test Concentration for Lactate
i-STATTestSubstanceTest ConcentrationInterference(Yes/No)InterferenceResults
LactateAcetaldehyde145 μmol/L0.20No
Acetaminophen1.0315.6No
N-Acetyl-Cysteine0.9215.0No
Ascorbic Acid0.2985.25No
β-Hydroxybutyric Acid1662No
Bilirubin0.68440No
Bromide140.7325.7YesDecreased results≥ 40.7 mmol/L
Dopamine4.06 μmol/L0.0621No
Formaldehyde10.1330.399No
Glycolic Acid110.076.1YesIncreased results≥ 1.18 mmol/L
Hemoglobin10 g/L1000No
Hydroxyurea0.4053.08No
Pyruvate0.5705No
Salicylate0.2072.86No
Thiocyanate0.8985.22No
Triglyceride16.941500No
IntralipidN/A3423No
Uric Acid1.423.5No

Comparison Study

g. Method Comparison with Predicate Device

Method comparison data was demonstrated in a study based on CLSI guideline EP09c-ED3. Lithium heparin venous and arterial blood specimens were evaluated and analyzed on the i-STAT 1 analyzer against whole blood specimens tested on the comparative method. For pH, PO2, and PCO2, a Passing Bablok linear regression analysis was performed using the first replicate result from the i-STAT CG4+ cartridge with the i-STAT 1 System versus the singlicate result of Radiometer ABL800 FLEX. For lactate, the first replicate result from the i-STAT CG4+ cartridge with the i-STAT 1 System was compared to the mean result of epoc® Blood Analysis System.

The results of the method comparison of venous whole blood and arterial whole blood samples is presented in Table 8.

Table 8: Method Comparison Results for venous and arterial whole blood
i-STAT TestNSlopeInterceptr
pH3161.05-0.340.97
PO 23081.03-3.960.99
PCO 23271.01-1.290.99
Lactate2460.960.081.00

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8. Conclusion

The results of these studies demonstrate that performance of the i-STAT pH, PO2, PCO2, and Lactate tests in the i-STAT CG4+ blue cartridge with the i-STAT 1 System are substantially equivalent to the comparative method.

§ 862.1120 Blood gases (P

CO2 , PO2 ) and blood pH test system.(a)
Identification. A blood gases (PCO2 , PO2 ) and blood pH test system is a device intended to measure certain gases in blood, serum, plasma or pH of blood, serum, and plasma. Measurements of blood gases (PCO2 , PO2 ) and blood pH are used in the diagnosis and treatment of life-threatening acid-base disturbances.(b)
Classification. Class II.