K Number
K183688
Date Cleared
2020-02-07

(406 days)

Product Code
Regulation Number
862.1665
Reference & Predicate Devices
Predicate For
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP AuthorizedThirdpartyExpeditedreview
Intended Use

The i-STAT CHEM8+ cartridge with the i-STAT 1 System is intended for use in the in vitro quantification of sodium, potassium, chloride and blood urea nitrogen in arterial or venous 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.

Chloride measurements are primarily used in the diagnosis, monitoring, and treatment of electrolyte and metabolic disorders including, but not limited to, cystic fibrosis, diabetic acidosis, and hydration disorders.

Blood urea nitrogen measurements are used for the diagnosis, monitoring, and treatment of certain renal and metabolic diseases.

Device Description

The i-STAT CHEM8+ test cartridge contains test reagents to analyze whole blood at the point of care or in the clinical laboratory for sodium, potassium, chloride and blood urea nitrogen. The test is contained in a single-use, disposable 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

The i-STAT CHEM8+ cartridge with the i-STAT 1 System is intended for in vitro quantification of sodium, potassium, chloride, and blood urea nitrogen (BUN) in arterial or venous whole blood in point-of-care or clinical laboratory settings.

Here's an analysis of the acceptance criteria and the study results:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are implied by the precision and method comparison studies aiming to demonstrate substantial equivalence to a predicate device (Beckman DxC). While explicit "acceptance criteria" are not listed in terms of specific thresholds for precision or correlation, the studies aim to show that the i-STAT CHEM8+ performs comparably to the predicate. The "Reportable Range" serves as one aspect of the acceptance criteria for each analyte.

AnalyteAcceptance Criteria (Reportable Range)Reported Device Performance (Precision) - Aqueous Materials (Total CV)Reported Device Performance (Precision) - Whole Blood (Total %CV) (Range)Reported Device Performance (Method Comparison - Correlation (r))
Sodium100 - 180 mmol/L0.2% - 0.3%0.2% - 0.5%0.96
Potassium2.0 - 9.0 mmol/L0.3% - 0.4%0.0% - 1.9%0.99
Chloride65 - 140 mmol/L0.4% - 0.7%0.2% - 1.2%0.96
BUN3 - 140 mg/dL0.8% - 3.7%0.0% - 9.4%0.99

Interference:

  • Sodium: Increased results ≥ 3.1 mmol/L with Sodium Thiosulfate.
  • Potassium: No identified interferents from the tested substances.
  • Chloride: Increased results ≥ 2.4 mmol/L with Lithium Bromide, Increased results ≥ 4.19 mmol/L with Sodium Thiosulfate.
  • BUN: Increased results ≥ 10.2 mmol/L with Triglyceride.

Limit of Quantitation (LoQ):

  • Sodium: 91 mmol/L
  • Potassium: 1.5 mmol/L
  • Chloride: 56 mmol/L
  • BUN: 1 mg/dL

2. Sample Sizes and Data Provenance

  • Precision (Aqueous Materials):

    • Sample Size: 80 or 81 data points for each of 5 levels per analyte (e.g., 81 for Sodium CV L1, 80 for Sodium CV L4). This study was conducted using multiple instruments and one test cartridge lot (implied prospective, in-house laboratory study).
    • Data Provenance: Not explicitly stated as country of origin, but implies an in-house or specialized laboratory setting. It is a prospective analytical study.
  • Precision (Whole Blood):

    • Sample Size: 21 test results per sample per instrument (total of 21 test results per sample). This study involved at least 3 levels per analyte, 3 point of care sites, and 7 i-STAT 1 Analyzers. The number of unique whole blood samples is not specified, but the total number of measurements is significant (e.g., for Sodium, there are 19 rows of data, each representing a mean derived from 20 or 21 measurements).
    • Data Provenance: Not explicitly stated as country of origin, but indicates multiple point-of-care sites. This is a prospective analytical study.
  • Linearity:

    • Sample Size: Not explicitly stated as a number of individual samples, but involves preparing "whole blood samples of varying analyte levels that spanned the reportable range of the tests."
    • Data Provenance: Implied laboratory-based prospective analytical study.
  • Limit of Quantitation (LoQ):

    • Sample Size: Not explicitly stated, but involved whole blood samples (and plasma for Chloride) altered to low concentrations and two test cartridge lots.
    • Data Provenance: Implied laboratory-based prospective analytical study.
  • Interference:

    • Sample Size: Not explicitly stated ("whole blood samples").
    • Data Provenance: Implied laboratory-based prospective analytical study.
  • Method Comparison:

    • Sample Size:
      • Sodium: N=187
      • Potassium: N=189
      • Chloride: N=176
      • BUN: N=184
    • Data Provenance: Venous and arterial blood specimens were evaluated. Not explicitly stated as country of origin, but indicates clinical laboratory settings. This is a prospective analytical study comparing the i-STAT 1 System to the Beckman DxC.

3. Number of Experts and Qualifications for Ground Truth

This type of device (in vitro diagnostic for laboratory analytes) does not typically involve human expert adjudication for ground truth. The "ground truth" for analytical performance studies is established by:

  • The reference method (Beckman DxC in the method comparison study).
  • Precisely prepared calibrators or control materials with known concentrations (for precision, linearity, LoQ, and interference studies).
  • NIST Standard Reference Materials (SRM) were used for traceability and calibration (NIST SRM 918, 919, 956, 912, 909).

4. Adjudication Method for the Test Set

Not applicable, as this is an analytical device for quantitative measurements, not an imaging device requiring expert clinical interpretation. The ground truth is established by reference measurement systems and documented analytical methods.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done

No, an MRMC study was not done. This type of study is typically for evaluating the performance of diagnostic imaging devices that rely on human interpretation, often with and without AI assistance. This device is an in vitro diagnostic (IVD) analyzer that provides quantitative results.

6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) was done

Yes, the studies presented (precision, linearity, LoQ, interference, and method comparison) represent the standalone performance of the i-STAT CHEM8+ cartridge with the i-STAT 1 System. The device provides a direct quantitative measurement without human interpretation of its internal algorithm's output in the manner implied by "human-in-the-loop performance" for AI/ML devices.

7. The Type of Ground Truth Used

The ground truth for the analytical performance studies was established using:

  • Reference instrumentation run by trained laboratory personnel: For the method comparison, the Beckman DxC clinical analyzer served as the comparative method.
  • Prepared aqueous and whole blood materials with known analyte concentrations: Used for precision, linearity, LoQ, and interference studies.
  • NIST Standard Reference Materials (SRM): Used for traceability and calibration.

8. The Sample Size for the Training Set

Not applicable. This device is a traditional in vitro diagnostic device, not an AI/ML device that requires a "training set" in the machine learning sense. The "training" for such devices typically refers to the development and optimization of the electrochemical sensors and algorithms during the R&D phase, which is not described in terms of a quantifiable "training set size" in a regulatory submission for a traditional IVD.

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

Not applicable, as there is no "training set" in the AI/ML context for this traditional IVD device. The accuracy of the device's measurement principles is established through rigorous analytical verification and validation using reference materials and comparative methods, as detailed in the performance characteristics section.

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

February 7, 2020

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

Re: K183688

Trade/Device Name: i-STAT CHEM8+ 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, CDS, CEM, CGZ Dated: January 9, 2020 Received: January 10, 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

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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 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 (OS) 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,

Kellie Kelm, Ph.D. Acting 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) K183688

Device Name

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

Indications for Use (Describe)

The i-STAT CHEM8+ cartridge with the i-STAT 1 System is intended for use in the in vitro quantification of sodium, potassium, chloride and blood urea nitrogen in arterial or venous 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.

Chloride measurements are primarily used in the diagnosis, monitoring, and treatment of electrolyte and metabolic disorders including, but not limited to, cystic fibrosis, diabetic acidosis, and hydration disorders.

Blood urea nitrogen measurements are used for the diagnosis, monitoring, and treatment of certain renal and metabolic diseases.

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: 609-454-9360Secondary: Maria FigueroaManager Regulatory Affairsmaria.l.figueroa@abbott.comPhone: 609-454-9271
Date PreparedFebruary 5, 2020
510(k) NumberK183688

2. Device Information

Proprietary Namei-STAT CHEM8+ cartridge with i-STAT 1 System
Common NameChemistry test, analyzer, handheld
ProductcodeDevice ClassificationnameRegulationNumberClassPanel
JGSElectrode, Ion Specific,Sodium862.1665IIClinical Chemistry
CEMElectrode, Ion Specific,Potassium862.1600IIClinical Chemistry
CGZElectrode, Ion SpecificChloride862.1170IIClinical Chemistry
CDSElectrode, Ion Specific,Urea Nitrogen862.1770IIClinical Chemistry

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3. Predicate Device

Proprietary Name SYNCHRON Systems Sodium Reagent on UniCel DxC 600/800 SYNCHRON Clinical System

SYNCHRON Systems Potassium Reagent on UniCel DxC 600/800 SYNCHRON Clinical System

SYNCHRON Systems Chloride Reagent on UniCel DxC 600/800 SYNCHRON Clinical System

SYNCHRON Systems BUN Reagent on UniCel DxC 600/800 SYNCHRON Clinical System

510(k) Number K042291

ProductcodeDevice ClassificationnameRegulationNumberClassPanel
JGSElectrode, Ion Specific,Sodium862.1665IIClinical Chemistry
CEMElectrode, Ion Specific,Potassium862.1600IIClinical Chemistry
CGZElectrode, Ion SpecificChloride862.1170IIClinical Chemistry
LFPConductivity Rate, UreaNitrogen862.1770IIClinical Chemistry

4. Device Description

The i-STAT CHEM8+ test cartridge contains test reagents to analyze whole blood at the point of care or in the clinical laboratory for sodium, potassium, chloride and blood urea nitrogen. The test is contained in a single-use, disposable 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 CHEM8+ cartridge with the i-STAT 1 System is intended for use in the in vitro quantification of sodium, potassium, chloride and blood urea nitrogen in arterial or venous 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.

Chloride measurements are primarily used in the diagnosis, monitoring, and treatment of electrolyte and metabolic disorders including, but not limited to, cystic fibrosis, diabetic acidosis, and hydration disorders.

Blood urea nitrogen measurements are used for the diagnosis, monitoring, and treatment of certain renal and metabolic diseases.

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Similarities and Differences: System (Test and Instrument) for Sodium
Feature orCharacteristicPredicateSYNCHRON Systems SodiumReagent on UniCel DxC 600/800SYNCHRON Clinical System(K042291)CandidateSodium Test with i-STAT 1System
Intended UseThe sodium test systems are intendedfor the quantitative determination ofsodium concentration in humanserum, plasma or urine.Sodium measurements are used in thediagnosis and treatment ofaldosteronism (excessive secretion ofhormone aldosterone), diabetesinsipidus, adrenal hypertension,Addison's disease, dehydration,inappropriate antidiuretic hormonesecretion, or other diseases involvingelectrolyte imbalance.The i-STAT CHEM8+ cartridge withthe i-STAT 1 System is intended foruse in the in vitro quantification ofsodium, potassium, chloride and bloodurea nitrogen in arterial or venouswhole blood in point of care or clinicallaboratory settings.Sodium measurements are used formonitoring electrolyte imbalances.
Reportable Range100-200 mmol/L (Serum or Plasma)10-300 mmol/L (Urine)Sodium: 100-180 mmol/L (mEq/L)
Sample TypeSerum, plasma, urineArterial or venous whole blood
Sample Volume0.5 mL (500 $ μ $ L)95 $ μ $ L
PreparationSample tubes prepared and thenprocessed within analyzerReady to Use
TraceabilityCalibrationNIST SRM 919Must be conducted every 24 hours andwith each new reagentNIST SRM 9561-point on-board contained within thecartridge
Time to Test(Sample Stability)Serum or plasma: Within 8 hours atroom temperature, or up to 48 hours ifstored at +2°C to +8°CUrine: Within 2 hours of collectionHeparinized samples: within 30minutes of collection
Principle ofMeasurementIon selective electrodeIon selective electrode
Reagent FormatReagent handling system, storedwithin analyzerCartridge
Reagent Storageand StabilityRoom temperature2°C to 8°C (35-46°F)
Similarities and Differences: System (Test and Instrument) for Potassium
Feature orCharacteristicPredicateSYNCHRON Systems PotassiumReagent on UniCel DxC 600/800SYNCHRON Clinical System(K042291)CandidatePotassium Test with i-STAT 1System
Intended UseThe potassium test systems areintended the quantitativedetermination of potassiumconcentration in human serum, plasmaor urine.Potassium measurements are used inthe diagnosis and treatment ofhypokalemia (metabolic alkalosis,metabolic acidosis or the absence ofacid-base disturbances), hyperkalemia(over administration of potassium,acidosis, or crush injuries), renalfailure, Addison's disease or otherdiseases involving electrolyteimbalance.The i-STAT CHEM8+ cartridge withthe i-STAT 1 System is intended foruse in the in vitro quantification ofsodium, potassium, chloride and bloodurea nitrogen in arterial or venouswhole blood in point of care or clinicallaboratory settingsPotassium measurements are used inthe diagnosis and monitoring ofdiseases and clinical conditions thatmanifest high and low potassiumlevels.
Reportable Range1-15.0 mmol/L (Serum or Plasma)2.0 - 9.0 mmol/L (mEq/L)
Sample TypeSerum, plasma, urineArterial or venous whole blood
Sample Volume0.5 mL (500 µL)95 µL
SamplePreparationSample tubes prepared and thenprocessed within analyzerReady to Use
TraceabilityNIST SRM 918NIST SRM 956
CalibrationMust be conducted every 24 hours andwith each new reagent1-point on-board contained within thecartridge
Time to Test(Sample Stability)Serum or plasma: Within 8 hours atroom temperature, or up to 48 hours ifstored at +2°C to +8°CUrine: Within 2 hours of collectionNon-anticoagulated samples: within 3minutes of collectionHeparinized samples: within 30minutes of collection
Principle ofMeasurementIon selective electrodeIon selective electrode
Reagent FormatReagent handling system, storedwithin analyzerCartridge
Reagent Storageand StabilityRoom temperature2°C to 8°C (35-46°F)
Analyzer TypeFloor ModelHandheld
Similarities and Differences: System (Test and Instrument) for Chloride
Feature orCharacteristicPredicateSYNCHRON Systems ChlorideReagent on UniCel DxC 600/800SYNCHRON Clinical System(K042291)CandidateChloride Test with i-STAT 1System
Intended UseThe chloride test systems are intendedfor the quantitative determination ofchloride concentration in human serum,plasma, urine or cerebrospinal fluid(CSF).Chloride measurements are used in thediagnosis and treatment of electrolyteand metabolic disorders such as cysticfibrosis and diabetic acidosis.The i-STAT CHEM8+ cartridgewith the i-STAT 1 System isintended for use in the in vitroquantification of sodium, potassium,chloride and blood urea nitrogen inarterial or venous whole blood inpoint of care or clinical laboratorysettings.Chloride measurements are primarilyused in the diagnosis, monitoring,and treatment of electrolyte andmetabolic disorders including, butnot limited to, cystic fibrosis,diabetic acidosis, and hydrationdisorders.
Reportable Range50-200 mmol/L (Serum or Plasma)65-140 mmol/L (mEq/L)
Sample TypeSerum, plasma, urineArterial or, venous whole blood
Sample Volume0.5 mL (500 µL)95 µL
SampleSample tubes prepared and thenReady to Use
Preparationprocessed within analyzer
TraceabilityNIST SRM 918/919NIST SRM 956
CalibrationMust be conducted every 24 hours andwith each new reagent1-point on-board contained withinthe cartridge
Time to Test(Sample Stability)Serum or plasma: Within 8 hours atroom temperature, or up to 48 hours ifstored at +2°C to +8°CUrine: Within 2 hours of collectionNon-anticoagulated samples: within3 minutes of collectionHeparinized samples: within 30minutes of collection
Principle ofMeasurementIon selective electrodeIon selective electrode
Reagent FormatReagent handling system, stored withinanalyzerCartridge
Reagent Storageand StabilityRoom temperature2°C to 8°C (35-46°F)
Analyzer TypeFloor ModelHandheld
Feature orCharacteristicPredicateSYNCHRON Systems BUNReagent on UniCel DxC 600/800SYNCHRON Clinical System(K042291)CandidateBUN Test with i-STAT 1System
Intended UseThe blood urea nitrogen (BUN) testsystems are intended for thequantitative determination of ureanitrogen or urea concentration inhuman serum, plasma or urine.Urea nitrogen or urea measurements areused in the diagnosis and treatment ofcertain renal and metabolic diseases.The i-STAT CHEM8+ cartridge withthe i-STAT 1 System is intended foruse in the in vitro quantification ofsodium, potassium, chloride andblood urea nitrogen in arterial orvenous whole blood in point of careor clinical laboratory settingsBlood urea nitrogen measurementsare used for the diagnosis,monitoring, and treatment of certainrenal and metabolic diseases.
Reportable Range1-150 mg/dL (Serum or Plasma)10-1500 mg/dL (Urine)3-140 mg/dL
Sample TypeSerum, plasma, urineArterial or venous whole blood
Sample Volume0.5 mL (500 μL)95 µL
Sample PreparationSample tubes prepared and thenprocessed within analyzerReady to Use
TraceabilityNIST SRM 912NIST SRM 909
CalibrationMust be conducted every 24 hours andwith each new reagent1-point on-board contained withinthe cartridge
Time to Test(Sample Stability)Serum or plasma: Within 8 hours atroom temperature, or up to 48 hours at+2°C to +8°CUrine: Within 2 hours of collectionNon-anticoagulated samples: within3 minutes of collectionHeparinized samples: within 30minutes of collection
Principle ofMeasurementConductivityIon selective electrode
Reagent FormatReagent handling system, stored withinanalyzerCartridge
Reagent Storageand Stability2°C to 8°C (35-46°F)2°C to 8°C (35-46°F)
Analyzer TypeFloor ModelHandheld
    1. Summary Comparison of Technological Characteristics

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7. Performance Characteristics

Analytical Performance

  • a. Precision

Precision 20 days (Aqueous Materials)

The precision of the i-STAT Potassium, Chloride, and BUN Tests on the i-STAT 1 Analyzer were 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

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was conducted using multiple instruments and one test cartridge lot over 20 days at one site. Total precision ('within-laboratory', Sr), within-run, (Sr), between-run, (Sm) and between-day, (Saa) were estimated for each level. The results of the 20-day precision study are shown in Table 1.

Table 1: 20-day Precision Study Results (i-STAT 1 Analyzer)
i-STATTestFluidLevelNMeanSTTotalWithin-runBetween-runBetween-day
CVT(%)SrCVr(%)SrrCVrr(%)SddCVdd(%)
Sodium(mmol/L)CV L181100.00.270.30.250.30.070.10.070.1
CV L281121.60.350.30.330.30.090.10.100.1
CV L381134.80.310.20.280.20.090.10.100.1
CV L480160.40.410.30.390.20.100.10.100.1
CV L5801780.420.20.400.20.100.10.110.1
Potassium(mmol/L)CV L1812.070.0060.30.0060.30.0010.050.0020.1
CV L2812.830.0110.40.0110.40.0030.10.0020.1
CV L3813.690.0100.30.0080.20.0040.10.0030.1
CV L4806.170.0180.30.0170.30.0020.030.0070.1
CV L5807.750.0330.40.0270.30.0170.20.0090.1
Chloride(mmol/L)CV L18170.90.470.70.430.60.120.20.120.2
CV L28176.20.530.70.500.70.130.20.130.2
CV L38189.20.330.40.290.30.080.10.120.1
CV L480107.90.430.40.400.40.110.10.120.1
CV L580122.30.480.40.440.40.150.10.120.1
BUN(mg/dL)CV L181107.30.910.80.810.80.410.40.040.04
CV L28159.70.921.50.861.40.230.40.200.3
CV L38110.50.121.10.111.00.050.50.030.3
CV L4808.10.182.20.172.10.030.40.050.6
CV L5804.10.153.70.143.40.041.00.030.7

Precision (Whole Blood)

The whole blood precision of the i-STAT Sodium, Potassium, Chloride, and BUN Tests on i-STAT 1 Analyzer were evaluated using venous whole blood (native or altered) samples targeted to three levels within the test reportable range.

One test cartridge lot was used across 3 point of care sites. At each site, each sample was tested 3 times on each of 7 i-STAT 1 Analyzers (total of 21 test results per sample per instrument). The results of the whole blood precision using the i-STAT 1 Analyzer are shown in Table 2.

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Table 2: Whole Blood Precision Results - i-STAT 1 Wireless Analyzer
i-STATTestLevelSiteNMeanWithin-AnalyzerTotal
SD%CVSDSD 95% CI%CV%CV 95% CI
≤ 1340121110.30.490.40.490.39 to 0.780.40.4 to 0.7
0221123.90.380.30.380.31 to 0.570.30.3 to 0.5
0321108.30.440.40.490.39 to 0.840.50.4 to 0.8
Sodium(mmol/L)0121139.20.580.40.580.48 to 0.830.40.3 to 0.6
0121138.00.220.20.220.17 to 0.350.20.1 to 0.3
0121136.50.650.50.680.54 to 1.130.50.4 to 0.8
0220138.30.450.30.450.36 to 0.730.30.3 to 0.5
0214141.80.460.30.460.38 to 0.810.30.3 to 0.6
0221141.90.310.20.310.25 to 0.480.20.2 to 0.3
0221140.00.380.30.380.31 to 0.630.30.2 to 0.5
135-1450221138.90.440.30.480.38 to 0.830.30.3 to 0.6
0221138.30.530.40.530.44 to 0.760.40.3 to 0.5
0321140.90.310.20.360.29 to 0.640.30.2 to 0.5
0321141.00.220.20.220.17 to 0.350.20.1 to 0.2
0321142.10.310.20.310.25 to 0.480.20.2 to 0.3
0321143.00.220.20.220.17 to 0.350.20.1 to 0.2
0321139.80.440.30.440.35 to 0.710.30.3 to 0.5
≥ 1460121150.10.620.40.620.51 to 0.880.40.3 to 0.6
0221163.20.490.30.490.40 to 0.700.30.2 to 0.4
0321150.10.380.30.380.31 to 0.570.30.2 to 0.4
Potassium(mmol/L)2.75-3.251212.800.0220.80.0220.017 to 0.0350.80.6 to 1.3
2212.800.0000.00.0000.000 to 0.0000.00.0 to 0.0
3213.050.0581.90.0580.048 to 0.0831.91.6 to 2.7
1214.300.0000.00.0000.000 to 0.0000.00.0 to 0.0
1214.000.0220.60.0220.017 to 0.0350.60.4 to 0.9
1213.980.0491.20.0490.040 0.0701.21.0 to 1.8
2204.950.0591.20.0590.049 to 0.0851.21.0 to 1.7
2144.200.0000.00.0000.000 to 0.0000.00.0 to 0.0
2214.130.0531.30.0530.044 to 0.0761.31.1 to 1.8
>3.25 -<5.552214.240.0581.40.0580.048 to 0.0821.41.1 to 1.9
2214.290.0380.90.0380.031 to 0.0570.90.7 to 1.3
2214.100.0000.00.0000.000 to 0.0000.00.0 to 0.0
3214.800.0310.60.0320.025 to 0.0520.70.5 to 1.1
3213.970.0531.30.0530.044 to 0.0781.31.1 to 2.0
3214.000.0000.00.0000.000 to 0.0000.00.0 to 0.0
3213.400.0000.00.0000.000 to 0.0000.00.0 to 0.0
1215.800.0220.40.0220.017 to 0.0350.40.3 to 0.6
5.55 -6.052215.850.0581.00.0580.048 to 0.0831.00.8 to 1.4
3215.710.0380.70.0380.031 to 0.0570.70.5 to 1.0
1217.600.0000.00.0000.000 to 0.0000.00.0 to 0.0
7.25 -7.752217.640.0530.70.0530.044 to 0.0810.70.6 to 1.1
3217.730.0530.70.0530.044 to 0.0780.70.6 to 1.0
Table 2: Whole Blood Precision Results - i-STAT 1 Wireless Analyzer
i-STATTestLevelSiteNMeanWithin-AnalyzerTotal
SD%CVSDSD 95% CI%CV%CV 95% CI
<80012177.00.530.70.530.44 to 0.800.70.6 to 1.0
022177.40.951.20.950.78 to 1.401.21.0 to 1.8
032176.90.620.80.660.53 to 1.110.90.7 to 1.4
0121102.00.620.60.620.51 to 0.890.60.5 to 0.9
012197.00.310.30.320.25 to 0.520.30.3 to 0.5
0121102.30.530.50.530.44 to 0.780.50.4 to 0.8
0221100.20.320.30.370.29 to 0.660.40.3 to 0.7
0221101.30.530.50.530.44 to 0.900.50.4 to 0.9
0221103.50.380.40.520.40 to 0.990.50.4 to 1.0
Chloride(mmol/L)90-1120221102.10.310.30.310.25 to 0.480.30.2 to 0.5
0221101.40.440.40.510.41 to 0.910.50.4 to 0.9
0221101.00.220.20.220.17 to 0.350.20.2 to 0.3
0321104.00.490.50.500.40 to 0.820.50.4 to 0.8
0321104.00.620.60.620.50 to 0.950.60.5 to 0.9
0321103.10.490.50.540.43 to 0.940.50.4 to 0.9
0321101.00.310.30.320.25 to 0.520.30.2 to 0.5
032199.80.440.40.440.36 to 0.640.40.4 to 0.6
0121126.10.580.50.580.47 to 0.860.50.4 to 0.7
>1200221123.80.690.60.690.57 to 0.980.60.5 to 0.8
0321123.20.440.40.550.43 to 1.000.40.3 to 0.8
01215.00.000.00.000.00 to 0.000.00.0 to 0.0
< 1001215.50.498.90.510.41 to 0.869.47.5 to 15.6
02217.00.000.00.000.00 to 0.000.00.0 to 0.0
03216.90.314.50.360.29 to 0.645.34.2 to 9.3
BUN(mg/dL)012114.00.000.00.000.00 to 0.000.00.0 to 0.0
022018.00.231.30.230.18 to 0.371.31.0 to 2.1
10-25021423.50.602.50.600.50 to 1.002.52.1 to 4.3
022120.90.381.80.380.31 to 0.571.81.5 to 2.7
022110.00.000.00.000.00 to 0.000.00.0 to 0.0
032111.00.222.00.220.17 to 0.352.01.5 to 3.2
032114.00.000.00.000.00 to 0.000.00.0 to 0.0
032113.90.312.20.310.25 to 0.482.21.8 to 3.5
012138.00.441.10.500.40 to 0.881.31.1 to 2.3
25-50022146.01.112.41.120.89 to 1.812.41.9 to 3.9
032127.80.622.20.710.56 to 1.242.62.0 to 4.5
0121111.82.822.52.822.31 to 4.202.52.1 to 3.8
> 1100221125.01.721.41.971.56 to 3.441.61.2 to 2.8
0321118.61.831.51.831.50 to 2.711.51.3 to 2.3

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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 Sodium, Potassium, Chloride, and BUN tests on the i-STAT 1 Analyzer was evaluated by preparing whole blood samples of varying analyte levels that spanned the reportable range of the tests. The i-STAT Sodium, Potassium, Chloride, and BUN tests demonstrated linearity over the reportable range as shown in Table 3. Regression summary of the Sodium, Potassium, Chloride, and BUN response

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Table 3: Regression Summary for the i-STAT tests on the i-STAT 1 Analyzer
i-STAT TestReportableRangeRange TestedSlopeInterceptR2
Sodium (mmol/L)100 - 18089 – 2051.077-5.2440.9994
Potassium (mmol/L)2.0 - 9.01.7 – 10.41.109-0.1360.9999
Chloride (mmol/L)65 - 14076 – 158 WB54 – 157 Plasma0.8670.9697.3532.1300.99830.9987
BUN (mg/dL)3 - 1402 - 1430.9460.2090.9950

versus the concentration of the whole blood samples of varying analyte levels is also provided in Table 3.

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 LoQs of the i-STAT Sodium, Potassium and BUN tests were evaluated on the i-STAT 1 Analyzer using whole blood that was altered to low sodium (<100 mmol/L), potassium (< 2.0 mmol/L), or BUN (<3 mg/dL) concentrations and two test cartridge lots. For Chloride, plasma samples that were altered to <65 mmol/L were evaluated as whole blood samples altered to achieve a chloride concentration <65 mmol/L have been found to hemolyze. The LoQs for the i-STAT Sodium Potassium, Chloride, and BUN tests on the i-STAT 1 Analyzer were determined to be 91 mmol/L, 1.5 mmol/L, 56 mmol/L, and 1 mg/dL, respectively.

d. Interference

The interference performance of the i-STAT Sodium, Potassium, Chloride, and BUN tests on 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 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.

Tables 4, 5, 6 and 7 contain the list of potentially interfering substances tested for the i-STAT Sodium, Potassium, Chloride, and BUN tests and the interference results.

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i-STAT Sodium Test

Table 4: Summary of Substance Tested and Interference Results for the i-STATSodium test
SubstanceTest ConcentrationInterferenceInterference
mmol/Lmg/dL(Yes/No)Results
Acetaminophen1.0315.6No
N-Acetyl-L-Cysteine0.9215.0No
Acetylsalicylic Acid0.1673.0No
Ammonium Chloride2.0a10.7No
Ascorbic Acid0.2985.25No
Bilirubin0.68440No
Lithium Bromide37.5a325.69No
β-Hydroxybutyric Acid6.0a62.47No
Calcium Chloride520No
Hemoglobin10 g/L1000No
Sodium Heparin3.30 U/mL330 U/dLNo
Ibuprofen1.0621.9No
Lithium Lactate1090No
Lithium Chloride3.2a13.6No
Lithium Salicylate0.2072.86No
Magnesium Chloride4.110No
Sodium Thiosulfate16.7a264.04YesIncreased results≥ 3.1 mmol/L
Triglyceride16.941500No
Uric Acid1.423.5No
Cholesterol10.3400No

i-STAT Potassium Test

Table 5: Summary of Substance Tested and Interference Results for the i-STATPotassium test
SubstanceTest ConcentrationInterferenceInterference
mmol/Lmg/dL(Yes/No)Results
Acetaminophen1.0315.6No
N-Acetyl-L-Cysteine0.9215.0No
Ammonium Chloride2.0a10.7No
Ascorbic Acid0.2985.25No
Benzalkonium Chloride0.031.13No
β-Hydroxybutyric Acid6.0a62.47No
Bilirubin0.68440No
Lithium Bromide37.5a325.69No
Calcium Chloride5.020No
Hemoglobin10 g/L1000No
Lithium Lactate1090No
Lithium Chloride3.2a13.6No
Magnesium Chloride4.110No
Lithium Salicylate0.2072.86No

ª No CLSI EP37 test concentration available. The molecular weight of the substance tested was used to convert the test concentration from mmol/L to mg/dL. The molecular weight of each substance could vary depending on the form chosen.

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Table 5: Summary of Substance Tested and Interference Results for the i-STATPotassium test
SubstanceTest ConcentrationInterferenceInterference
mmol/Lmg/dL(Yes/No)Results
Sodium Thiosulfate16.7aa264.04No
Triglyceride16.941500No
Cholesterol10.3400No

i-STAT Chloride Test

Table 6: Summary of Substance Tested and Interference Results for the i-STATChloride test
SubstanceTest ConcentrationInterference(Yes/No)InterferenceResults
Acetaminophen1.0315.6No
N-Acetyl-L-Cysteine0.9215.0No
L-Ascorbic Acid0.2985.25No
Bicarbonate35.0a294No
Bilirubin0.68440No
Lithium Bromide37.5325.69YesIncreased results≥ 2.4 mmol/L
β-Hydroxybutyric Acid6.0a62.47No
Hemoglobin10 g/L1000No
Sodium lodide2.99a44.82No
Lithium Lactate1090No
Sodium Oxalate0.091.206No
Lithium Salicylate0.2072.86No
Lithium Thiocyanate0.8985.22No
Sodium Thiosulfate16.7a264.04YesIncreased results≥ 4.19 mmol/L
Triglyceride16.941500No
Cholesterol10.3400No

i-STAT BUN Test

Table 7: Summary of Substance Tested and Interference Results for i-STAT BUNtest
SubstanceTest ConcentrationInterferenceInterference
mmol/Lmg/dL(Yes/No)Results
Acetaminophen1.0315.6No
N-Acetyl-L-Cysteine0.9215.0No
L-Ascorbic Acid0.2985.25No
β-Hydroxybutyric Acid6.0a62.47No
Bilirubin0.68440No
Lithium Bromide37.5a325.69No
Hemoglobin10 g/L1000No
Hydroxyurea0.4053.08No
Lithium Lactate1090No

ª No CLSI EP37 test concentration available. The molecular weight of the substance tested was used to convert the test concentration from mmol/L to mg/dL. The molecular weight of each substance could vary depending on the form chosen.

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Table 7: Summary of Substance Tested and Interference Results for i-STAT BUNtest
SubstanceTest ConcentrationInterference(Yes/No)InterferenceResults
pH8.0 pHunitsN/ANo
Lithium Salicylate0.2072.86No
Lithium Thiocyanate0.8985.22No
Sodium Thiosulfate16.7a264.04No
Triglyceride16.941500YesIncreased results≥ 10.2 mmol/L
Cholesterol10.3400No

Table 7: Summary of Substance Tested and Interference Results for i-STAT BUN
test

Comparison Study

e. Method Comparison with Predicate Device

Method comparison was demonstrated in a study comparing the i-STAT Sodium Potassium, Chloride, and BUN tests performance on the i-STAT 1 System to the Beckman DxC. The study was based on CLSI guideline EP09c-ED3. Venous and arterial blood specimens were evaluated and analyzed on the i-STAT 1 Analyzer against plasma specimens on the Beckman DxC. A Passing-Bablok linear regression analysis was performed using the first replicate result from the i-STAT 1 Analyzer versus the singlicate result of the comparative method.

Table 8: Method Comparison Results
i-STAT TestNSlopeInterceptr
Sodium1871.002.000.96
Potassium1891.000.000.99
Chloride1761.0000.0000.96
Bun1840.9401.6750.99

8. Conclusion

The results of these studies demonstrate that performance of the i-STAT CHEM8+ Sodium, Potassium, Chloride and BUN test with the i-STAT 1 System are substantially equivalent to the comparative method.

§ 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.