(406 days)
The i-STAT CHEM8+ cartridge with the i-STAT 1 System is intended for use in the in vitro quantification of glucose, and creatinine in arterial or venous whole blood in point of care or clinical laboratory settings.
Glucose measurements are used in the diagnosis, monitoring, and treatment of carbohydrate metabolism disorders including, but not limited to, diabetes mellitus, neonatal hypoglycemia, and pancreatic islet cell carcinoma.
Creatinine measurements are used in the diagnosis and treatment of renal diseases, in monitoring renal dialysis, and as a calculation basis for measuring other urine analytes.
The i-STAT CHEM8+ test cartridge contains test reagents to analyze whole blood at the point of care or in the clinical laboratory for glucose and creatinine. 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.
The provided text describes the analytical performance studies for the i-STAT CHEM8+ cartridge with the i-STAT 1 System for measuring glucose and creatinine. While it details numerous performance characteristics, it does not explicitly state "acceptance criteria" for each test. However, the study design and "results met the acceptance criteria" statements imply that certain predefined thresholds were successfully achieved.
Let's break down the information available to address your request:
Acceptance Criteria and Reported Device Performance
The document doesn't provide a consolidated table of explicit acceptance criteria. Instead, it states that results "met the acceptance criteria" for linearity, and it outlines the method for identifying interference (difference between control and test samples outside of the allowed error (Ea)). For precision studies, statistical metrics like Total Standard Deviation (ST) and Coefficient of Variation (CV) are presented, and for method comparison, slope, intercept, and correlation coefficient (r) are given. The implied acceptance is that these values fall within acceptable ranges for a diagnostic device of this type.
Implied Acceptance Criteria and Reported Performance (derived from text):
| Performance Characteristic | Implicit Acceptance Criteria (based on common IVD standards) | Reported Device Performance (Summary) |
|---|---|---|
| Precision (Aqueous Materials) | Low CV values across levels (e.g., <5-15% depending on analyte and concentration) | Creatinine: Total CV L1: 2.1%, L2: 2.4%, L3: 2.1%, L4: 5.7%, L5: 15.6% Glucose: Total CV L1: 1.8%, L2: 1.3%, L3: 0.4%, L4: 0.5%, L5: 0.9% |
| Precision (Whole Blood) | Low CV values across levels (e.g., <5-15% depending on analyte and concentration) | Glucose: Total %CVs ranging from 0.4% to 1.3% Creatinine: Total %CVs ranging from 1.3% to 10.4% |
| Linearity | "Absolute degree of nonlinearity results met the acceptance criteria" | Glucose: Range Tested 17-620 mg/dL, Slope 0.9794, Intercept -1.603, R2 0.9991 Creatinine: Range Tested 0.13-16.2 mg/dL, Slope 1.021, Intercept 0.0763, R2 0.9978 |
| Limit of Quantitation (LoQ) | LoQ should be at or below the lower limit of the reportable range. | Glucose: 12 mg/dL (below reportable range of 20 mg/dL) Creatinine: 0.10 mg/dL (below reportable range of 0.20 mg/dL) |
| Limit of Blank (LoB) / Limit of Detection (LoD) | LoB and LoD values (typically lower than LoQ) | Creatinine: LoB 0.05 mg/dL, LoD 0.10 mg/dL Glucose: LoB 1 mg/dL, LoD 2 mg/dL |
| Hematocrit Sensitivity | Equivalent performance across different hematocrit levels. | "The i-STAT Glucose test performs equivalently at different hematocrit levels." |
| Oxygen Sensitivity | Insensitive to relevant oxygen changes. | "The i-STAT Creatinine and Glucose tests are insensitive to oxygen changes between 20 to >500 mmHg for creatinine and 25 to >500 mmHg for glucose." |
| Altitude | Correlation coefficient and slope results met acceptance criteria. | Creatinine: r 1.00, Slope 1.13 (up to 6367 feet) Glucose: r 1.00, Slope 1.00 (up to 9523 feet) |
| Interference | Absence of significant interference; difference between control/test samples within allowed error (Ea). | Glucose: Lithium Bromide (≥ 11.8 mmol/L) increased results; Hydroxyurea (≥ 0.08 mmol/L) increased results. Creatinine: Lithium Bromide (≥ 18.3 mmol/L) increased results; Hydroxyurea (≥ 0.03 mmol/L) increased results. (Other listed substances showed no interference). |
| Method Comparison (vs. Predicate) | High correlation (r), slope near 1, intercept near 0. | Glucose: N=185, Slope 0.98, Intercept 0.00, r 1.00 Creatinine: N=180, Slope 1.043, Intercept -0.062, r 1.00 |
Study Details:
-
Sample Size used for the Test Set and Data Provenance:
- Precision (Aqueous): N=80 or 81 for each level of Creatinine and Glucose. Data provenance is not specified (e.g., country of origin) but implied to be laboratory-based ("one site"). It is an analytical performance study, not a clinical study on patient samples.
- Precision (Whole Blood): Sample sizes vary per site and level (e.g., N=14 to N=21). The study used "venous whole blood (native or altered) samples." The study was conducted at "3 point of care sites."
- Linearity: Whole blood samples of "varying analyte levels" were prepared. Specific N not provided for this particular section.
- LoQ, LoB/LoD: Whole blood samples were "altered to low glucose" or "blank" concentrations. Specific N not provided for this section.
- Hematocrit Sensitivity: Three hematocrit levels evaluated across four glucose levels. Specific N not provided.
- Oxygen Sensitivity: High and low ranges of oxygen. Specific N not provided.
- Altitude: Not explicitly stated, but results given for "average measured altitude." Specific N not provided.
- Interference: Whole blood samples based on CLSI guidelines. Specific N not provided, but multiple substances tested.
- Method Comparison: N=185 for Glucose, N=180 for Creatinine. Used "Venous and arterial blood specimens" for the i-STAT device and "plasma specimens" for the predicate device. Data provenance is not specified.
Overall Provenance: The studies are "analytical performance" studies, primarily laboratory-based and conducted on various prepared or native samples. There is no indication of geographic origin or whether samples were retrospective or prospective, though for analytical performance, prospective collection for the purpose of the study is common.
-
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- This is an in vitro diagnostic (IVD) device. The "ground truth" for analytical performance studies is established by reference methods or highly accurate laboratory analyzers (the "comparative method"), not by human experts interpreting images or clinical outcomes. In this case, "ground truth" (or comparative method) for the method comparison study was the Beckman DxC, a laboratory analyzer.
-
Adjudication method (e.g., 2+1, 3+1, none) for the test set:
- Not applicable. This is an IVD device measuring analytes, not interpretations of images or clinical assessments requiring human adjudication.
-
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 IVD device for measuring chemical analytes in blood, not an imaging device assisted by AI to be read by human experts.
-
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- The i-STAT device functions as a standalone analyzer that quantifies glucose and creatinine. The performance studies described (precision, linearity, LoQ, LoD, interference, method comparison) are standalone performance studies of the device's ability to measure these analytes. While a human initiates the test and interprets the quantitative result, the measurement process itself is automated (algorithm only).
-
The type of ground truth used (expert concensus, pathology, outcomes data, etc):
- For the method comparison study, the ground truth was essentially the measurements from a legally marketed predicate device (Beckman DxC), which serves as the comparative method in analytical validation. For other analytical performance studies (precision, linearity, LoQ/LoD), the "ground truth" is based on the known concentrations of prepared reference materials or controls, or the statistical evaluation of repeated measurements of samples.
-
The sample size for the training set:
- The documentation does not discuss a "training set" in the context of machine learning or AI models, as this is a traditional IVD device based on electrochemical principles, not an AI/ML device. Therefore, no separate training set is mentioned or applicable in the way it would be for an AI-powered diagnostic.
-
How the ground truth for the training set was established:
- Not applicable, as there is no explicitly mentioned "training set" in the context of an AI/ML model for this traditional IVD device.
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February 7, 2020
Abbott Point of Care Inc. Susan Tibedo Director, Regulatory Affairs 400 College Road East Princeton, NJ 08540
Re: K183678
Trade/Device Name: i-STAT CHEM8+ cartridge with the i-STAT 1 System Regulation Number: 21 CFR 862.1345 Regulation Name: Glucose Test System Regulatory Class: Class II Product Code: CGA, CGL 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 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 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 B. 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) K183678
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 glucose, and creatinine in arterial or venous whole blood in point of care or clinical laboratory settings.
Glucose measurements are used in the diagnosis, monitoring, and treatment of carbohydrate metabolism disorders including, but not limited to, diabetes mellitus, neonatal hypoglycemia, and pancreatic islet cell carcinoma.
Creatinine measurements are used in the diagnosis and treatment of renal diseases, in monitoring renal dialysis, and as a calculation basis for measuring other urine analytes.
| Type of Use (Select one or both, as applicable) | |
|---|---|
| ------------------------------------------------- | -- |
X 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 | |
|---|---|
| Owner | Abbott Point of Care Inc.400 College Road EastPrinceton, NJ 08540 |
| Contact | Primary: Susan TibedoDirector Regulatory Affairssusan.tibedo@abbott.comPhone: 609-454-9360Secondary: Maria FigueroaManager Regulatory Affairsmaria.l.figueroa@abbott.comPhone: 609-454-9271 |
| Date Prepared | February 5, 2020 |
| 510(k) Number | K183678 |
2. Device Information
Proprietary Name i-STAT CHEM8+ cartridge with i-STAT 1 System
Common Name Chemistry test, analyzer, handheld
| Productcode | Device Classificationname | RegulationNumber | Class | Panel |
|---|---|---|---|---|
| CGA | Glucose Oxidase, Glucose | 862.1345 | II | Clinical Chemistry |
| CGL | Electrode, Ion BasedEnzymatic, Creatinine | 862.1225 | II | Clinical Chemistry |
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3. Predicate Device
| Proprietary | SYNCHRON Systems Glucose Reagent on UniCel DxC |
|---|---|
| Name | 600/800 SYNCHRON Clinical System |
SYNCHRON Systems Creatinine Reagent on UniCel DxC 600/800 SYNCHRON Clinical System
510(k) Number K042291
| Productcode | Device Classificationname | RegulationNumber | Class | Panel |
|---|---|---|---|---|
| CGA | Glucose Oxidase, Glucose | 862.1345 | II | Clinical Chemistry |
| CGX | Alkaline Picrate,Colorimetry, Creatinine | 862.1225 | II | Clinical 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 glucose and creatinine. 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.
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 glucose and creatinine in arterial or venous whole blood in point of care or clinical laboratory settings.
Glucose measurements are used in the diagnosis, monitoring, and treatment of carbohydrate metabolism disorders including, but not limited to, diabetes mellitus, neonatal hypoglycemia, idiopathic hypoglycemia, and pancreatic islet cell carcinoma.
Creatinine measurements are used in the diagnosis and treatment of renal diseases, in monitoring renal dialysis, and as a calculation basis for measuring other urine analytes.
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| Feature orCharacteristic | Predicate | Candidate |
|---|---|---|
| Intended Use | SYNCHRON SystemsGlucose Reagent on UniCelDxC 600/800 SYNCHRONClinical System (K042291)The glucose test system is intendedfor the quantitative determination ofglucose concentration in humanserum, plasma, urine orcerebrospinal fluid (CSF).Glucose measurements are used inthe diagnosis and treatment ofcarbohydrate metabolism disordersincluding diabetes mellitus, neonatalhypoglycemia, idiopathichypoglycemia, and pancreatic isletcell carcinoma. | Glucose Test with i-STAT 1 SystemThe i-STAT CHEM8+ cartridge with thei-STAT 1 System is intended for use inthe in vitro quantification of glucose andcreatinine in arterial or venous wholeblood in point of care or clinicallaboratory settings.Glucose measurements are used in thediagnosis, monitoring, and treatment ofcarbohydrate metabolism disordersincluding, but not limited to, diabetesmellitus, neonatal hypoglycemia,idiopathic hypoglycemia, and pancreaticislet cell carcinoma. |
| Reportable Range | 0.2 – 33.3 mmol/L (Serum, Plasma)0 – 600 mg/dLup to 1200 mg/dL by sampledilution | 1.1 – 38.9 mmol/L (mEq/L)20 – 700 mg/dL0.20 – 7.00 g/L |
| Sample Type | Serum, plasma, urine, CSF | Arterial or venous whole blood |
| Sample Volume | 0.5 mL (500 µL) | 95 µL |
| SamplePreparation | Sample tubes prepared and thenprocessed within analyzer | Ready to Use |
| Traceability | NIST SRM 917 | NIST SRM 965 |
| Calibration | Must be conducted every 24 hoursand with each new reagent | 1-point on-board contained within thecartridge |
| Time to Test(Sample Stability) | Serum or plasma: Within 8 hours atroom temperature, or up to 48 hoursif stored at +2°C to +8°CUrine: Within 2 hours of collection | Heparinized samples: within 30 minutes ofcollection |
| Principle ofMeasurement | O2 depletion by glucose oxidaseactivity | Amperometric measurement of oxidizedhydrogen peroxide produced by glucoseoxidase activity |
| Reagent Format | Reagent handling system, storedwithin analyzer | Cartridge |
| Reagent Storageand Stability | Room temperature | 2°C to 8°C (35-46°F) |
| Analyzer Type | Floor Model | Handheld |
6. Summary Comparison of Technological Characteristics
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| Similarities and Differences: System (Test and Instrument): Creatinine (CREA) | ||
|---|---|---|
| Feature orCharacteristic | PredicateSYNCHRON SystemsCreatinine Reagent on UniCelDxC 600/800 SYNCHRONClinical System (K042291) | CandidateCREA Test with i-STAT 1 System |
| Intended Use | The creatinine test system is intendedfor the quantitative determination ofcreatinine in human serum and urine.Measurements of creatinine are usedin the diagnosis and treatment ofrenal disease. Serum creatininemeasurements prove useful inevaluation of kidney glomerularfunction and in monitoring renaldialysis. | The i-STAT CHEM8+ cartridge with thein vitro quantification of glucose andcreatinine in arterial or venous wholeblood in point of care or clinicallaboratory settings.Creatinine measurements are used in thediagnosis and treatment of renal diseases,in monitoring renal dialysis, and as acalculation basis for measuring otherurine analytes. |
| Reportable Range | 0.1 – 25.0 mg/dL (Serum) | 0.2-20.0 mg/dL |
| Sample Type | Serum, urine | Arterial or venous whole blood |
| Sample Volume | 0.5 mL (500 $\mu$ L) | 95 $\mu$ L |
| SamplePreparation | Sample tubes prepared and thenprocessed within analyzer | Ready to Use |
| Traceability | Isotope Dilution Mass Spectroscopy | NIST SRM 967 |
| Calibration | Must be conducted every 24 hoursand with each new reagent | 1-point on-board contained within thecartridge |
| Time to Test(Sample Stability) | Serum or plasma: Within 8 hours atroom temperature, or up to 48 hoursif stored at +2°C to +8°CUrine: Within 2 hours of collection | Heparinized samples: within 30 minutesof collection |
| Principle ofMeasurement | Colorimetric (520 nm) measurementof creatinine-alkaline picratecomplex formation | Amperometric measurement of oxidizedhydrogen peroxide produced bycreatinine amidinohydrolase activity |
| Reagent Format | Reagent handling system, storedwithin analyzer | Cartridge |
| Reagent Storageand Stability | Room temperature | 2°C to 8°C (35-46°F) |
| Analyzer Type | Floor Model | Handheld |
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7. Performance Characteristics
Analytical Performance
- a. Precision
Precision 20 days (aqueous materials)
The precision of the i-STAT Glucose and Creatinine tests on the i-STAT 1 Wireless Analyzer 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', Sr), within-run, (Sr), between-run, (Sr) 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 of i-STAT Glucose and Creatinine tests on the i-STAT 1Analyzer | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| i-STATTest | FluidLevel | N | Mean | Total | Within-run | Between-run | Between-day | ||||
| ST | CVT(%) | Sr | CVr(%) | Srr | CVrr(%) | Sdd | CVdd(%) | ||||
| Creatinine(mg/dL) | CV L1 | 81 | 15.90 | 0.337 | 2.1 | 0.321 | 2.0 | 0.096 | 0.6 | 0.030 | 0.2 |
| CV L2 | 81 | 4.23 | 0.101 | 2.4 | 0.093 | 2.2 | 0.029 | 0.7 | 0.027 | 0.6 | |
| CV L3 | 81 | 1.69 | 0.035 | 2.1 | 0.033 | 2.0 | 0.008 | 0.5 | 0.007 | 0.4 | |
| CV L4 | 80 | 0.51 | 0.029 | 5.7 | 0.027 | 5.3 | 0.008 | 1.6 | 0.006 | 1.2 | |
| CV L5 | 80 | 0.18 | 0.028 | 15.6 | 0.026 | 14.4 | 0.007 | 3.9 | 0.007 | 3.9 | |
| Glucose(mg/dL) | CV L1 | 80 | 26.7 | 0.49 | 1.8 | 0.47 | 1.8 | 0.13 | 0.5 | 0.10 | 0.4 |
| CV L2 | 81 | 40.9 | 0.52 | 1.3 | 0.46 | 1.1 | 0.16 | 0.4 | 0.18 | 0.4 | |
| CV L3 | 81 | 123.0 | 0.47 | 0.4 | 0.43 | 0.3 | 0.13 | 0.1 | 0.12 | 0.1 | |
| CV L4 | 80 | 286.5 | 1.40 | 0.5 | 1.25 | 0.4 | 0.55 | 0.2 | 0.33 | 0.1 | |
| CV L5 | 80 | 608.1 | 5.56 | 0.9 | 5.21 | 0.9 | 1.46 | 0.2 | 1.31 | 0.2 |
Precision (Whole Blood)
The whole blood precision of the i-STAT Glucose and Creatinine Tests on the i-STAT 1 Analyzer were evaluated using venous whole blood (native or altered) samples targeted to four 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 Wireless Analyzers (total of 21 test results per sample per instrument). The results of the whole blood precision using the i-STAT 1 Wireless Analyzer are shown in Table 2.
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| Table 2: Whole Blood Precision Results – i-STAT 1 System | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Within-Analyzer | Total | |||||||||
| i-STAT Test | Level | Site | N | Mean | SD | %CV | SD | SD 95% CI | %CV | %CV 95% CI |
| 01 | 21 | 95.3 | 0.98 | 1.0 | 0.98 | 0.81 to 1.39 | 1.0 | 0.8 to 1.5 | ||
| 01 | 21 | 72.3 | 1.23 | 1.7 | 1.23 | 1.03 to 1.75 | 1.7 | 1.4 to 2.4 | ||
| 02 | 21 | 95.1 | 0.90 | 0.9 | 0.90 | 0.75 to 1.27 | 0.9 | 0.8 to 1.3 | ||
| 30-110 | 02 | 21 | 95.5 | 0.69 | 0.7 | 0.69 | 0.57 to 0.98 | 0.7 | 0.6 to 1.0 | |
| 02 | 21 | 80.0 | 0.38 | 0.5 | 0.38 | 0.31 to 0.63 | 0.5 | 0.4 to 0.8 | ||
| 03 | 21 | 101.3 | 0.76 | 0.8 | 0.76 | 0.61 to 1.17 | 0.8 | 0.6 to 1.2 | ||
| 03 | 21 | 87.8 | 0.58 | 0.7 | 0.58 | 0.47 to 0.86 | 0.7 | 0.5 to 1.0 | ||
| 03 | 21 | 98.9 | 0.58 | 0.6 | 0.63 | 0.50 to 1.07 | 0.6 | 0.5 to 1.1 | ||
| Glucose(mg/dL) | 01 | 21 | 148.2 | 0.62 | 0.4 | 0.62 | 0.51 to 0.88 | 0.4 | 0.3 to 0.6 | |
| 111-150 | 02 | 20 | 143.0 | 0.85 | 0.6 | 0.85 | 0.70 to 1.22 | 0.6 | 0.5 to 0.9 | |
| 02 | 14 | 143.3 | 1.25 | 0.9 | 1.25 | 1.06 to 2.03 | 0.9 | 0.7 to 1.4 | ||
| 03 | 21 | 142.2 | 0.79 | 0.6 | 0.79 | 0.65 to 1.12 | 0.6 | 0.5 to 0.8 | ||
| 01 | 21 | 385.7 | 2.38 | 0.6 | 2.98 | 2.33 to 5.40 | 0.8 | 0.6 to 1.4 | ||
| 151-400 | 02 | 21 | 318.0 | 3.25 | 1.0 | 3.25 | 2.70 to 4.62 | 1.0 | 0.8 to 1.5 | |
| 03 | 21 | 151.8 | 1.02 | 0.7 | 1.02 | 0.83 to 1.57 | 0.7 | 0.5 to 1.0 | ||
| 01 | 21 | 618.4 | 7.95 | 1.3 | 7.95 | 6.54 to 11.67 | 1.3 | 1.1 to 1.9 | ||
| 401-700 | 02 | 21 | 444.2 | 2.23 | 0.5 | 2.23 | 1.85 to 3.14 | 0.5 | 0.4 to 0.7 | |
| 03 | 21 | 582.0 | 2.82 | 0.5 | 2.93 | 2.33 to 4.84 | 0.5 | 0.4 to 0.8 | ||
| 01 | 21 | 0.82 | 0.038 | 4.6 | 0.044 | 0.035 to 0.078 | 5.4 | 4.3 to 9.5 | ||
| 01 | 21 | 0.60 | 0.038 | 6.3 | 0.038 | 0.031 to 0.053 | 6.3 | 5.2 to 8.8 | ||
| <1 | 01 | 21 | 0.52 | 0.049 | 9.4 | 0.049 | 0.040 to 0.070 | 9.4 | 7.7 to 13.5 | |
| 02 | 20 | 0.96 | 0.049 | 5.1 | 0.051 | 0.041 to 0.086 | 5.3 | 4.3 to 9.0 | ||
| 02 | 21 | 0.96 | 0.053 | 5.5 | 0.053 | 0.044 to 0.080 | 5.5 | 4.6 to 8.3 | ||
| 02 | 21 | 0.56 | 0.058 | 10.4 | 0.058 | 0.048 to 0.082 | 10.4 | 8.6 to 14.6 | ||
| 02 | 21 | 0.87 | 0.044 | 5.1 | 0.049 | 0.039 to 0.084 | 5.6 | 4.5 to 9.7 | ||
| 03 | 21 | 0.81 | 0.031 | 3.8 | 0.031 | 0.025 to 0.048 | 3.8 | 3.1 to 5.9 | ||
| 03 | 21 | 0.70 | 0.031 | 4.4 | 0.032 | 0.025 to 0.052 | 4.6 | 3.6 to 7.4 | ||
| 03 | 21 | 0.59 | 0.031 | 5.3 | 0.031 | 0.025 to 0.048 | 5.3 | 4.2 to 8.1 | ||
| Creatinine(mg/dL) | 1-15 | 03 | 21 | 1.23 | 0.049 | 4.0 | 0.049 | 0.039 to 0.078 | 4.0 | 3.2 to 6.3 |
| 03 | 21 | 1.17 | 0.049 | 4.2 | 0.049 | 0.040 to 0.074 | 4.2 | 3.4 to 6.3 | ||
| 1.5-2.0 | 01 | 21 | 1.53 | 0.049 | 3.2 | 0.049 | 0.040 to 0.074 | 3.2 | 2.6 to 4.8 | |
| 02 | 14 | 1.83 | 0.053 | 2.9 | 0.053 | 0.044 to 0.090 | 2.9 | 2.4 to 4.9 | ||
| 02 | 21 | 1.97 | 0.062 | 3.1 | 0.062 | 0.051 to 0.092 | 3.1 | 2.6 to 4.7 | ||
| 03 | 21 | 1.70 | 0.058 | 3.4 | 0.058 | 0.047 to 0.088 | 3.4 | 2.8 to 5.2 | ||
| 5.0-7.0 | 01 | 21 | 5.62 | 0.172 | 3.1 | 0.172 | 0.142 to 0.246 | 3.1 | 2.5 to 4.4 | |
| 02 | 21 | 6.31 | 0.246 | 3.9 | 0.246 | 0.202 to 0.366 | 3.9 | 3.2 to 5.8 | ||
| 03 | 21 | 5.30 | 0.072 | 1.4 | 0.072 | 0.059 to 0.107 | 1.4 | 1.1 to 2.0 | ||
| 7.0-12 | 02 | 21 | 9.47 | 0.127 | 1.3 | 0.155 | 0.121 to 0.277 | 1.6 | 1.3 to 2.9 | |
| 01 | 21 | 14.37 | 0.388 | 2.7 | 0.388 | 0.321 to 0.561 | 2.7 | 2.2 to 3.9 | ||
| >12 | 02 | 21 | 14.90 | 0.515 | 3.5 | 0.515 | 0.427 to 0.732 | 3.5 | 2.9 to 4.9 | |
| 03 | 21 | 14.30 | 0.558 | 3.9 | 0.558 | 0.462 to 0.795 | 3.9 | 3.2 to 5.6 |
{9}------------------------------------------------
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 Glucose and Creatinine tests on the i-STAT 1 Analyzer were evaluated by preparing whole blood samples of varying analyte levels that spanned the reportable range of the test. The best fitting regression model was the third order model. The absolute degree of nonlinearity results met the acceptance criteria for each of the levels tested for each analyte. Therefore, the i-STAT Glucose and Creatinine test demonstrated linearity over the reportable range as shown in Table 3. Regression summary of the Glucose and Creatinine response versus the concentration of the whole blood samples of varying analyte levels is also provided in Table 3.
| Table 3: Regression Summary for the i-STAT tests on the i-STAT 1 Analyzer | |||||
|---|---|---|---|---|---|
| i-STAT Test | Reportable Range | Range Tested | Slope | Intercept | R2 |
| Glucose (mg/dL) | 20-700 | 17 - 620 | 0.9794 | -1.603 | 0.9991 |
| Creatinine (mg/dL) | 0.20 – 20.0 | 0.13 - 16.2 | 1.021 | 0.0763 | 0.9978 |
c. Limit of Quantitation (LoO)
The study was based on the CLSI EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline-Second Edition.
The LoO of the i-STAT Glucose and Creatinine tests were evaluated on the i-STAT 1 Analyzer using whole blood that was altered to low glucose (< 20 mg/dL) and low creatinine (< 0.2 mg/dL) concentrations and two test cartridge lots. The LoQs for the i-STAT Glucose and Creatinine tests were determined to be 12 mg/dL and 0.10 mg/dL respectively, which is below the lower limit of the reportable range for each of the i-STAT Glucose and Creatinine tests as shown in Table 3.
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/LoD of the i-STAT glucose and creatinine tests were evaluated on the i-STAT 1 Analyzer using whole blood that was altered to "blank" analyte (glucose or creatinine) concentration for LoB testing and two "low" analyte (glucose or creatinine) concentrations for LoD testing. The LoB and LoD were determined based on the maximal LoB or LoD value obtained for each lot tested. The LoB and LoD for i-STAT Creatinine and Glucose tests on the i-STAT 1 Analyzer were determined as shown in the Table 4 below.
| Table 4: Summary of LoB and LoD Results Per Test (mg/dL) | ||
|---|---|---|
| i-STAT Test | LoB | LoD |
| Creatinine | 0.05 | 0.10 |
| Glucose | 1 | 2 |
{10}------------------------------------------------
Hematocrit Sensitivity to the i-STAT Glucose Test e.
A hematocrit sensitivity study was performed for the i-STAT Glucose test to assess the effect of hematocrit. Three hematocrit levels (low, mid and high) were evaluated across four (4) glucose levels across the reportable range of the test.
The results of the study demonstrated that the i-STAT Glucose test performs equivalently at different hematocrit levels when tested on the i-STAT 1 analyzer.
f. Oxygen Sensitivity
The effect on oxygen on the i-STAT Creatinine and Glucose tests 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 Creatinine and Glucose tests are insensitive to oxygen changes between 20 to >500 mmHg for creatinine and 25 to >500 mmHg for glucose.
g. Altitude
The results of the study show equivalent creatinine results at elevations up to 6367 feet and for glucose up to 9523 feet. The correlation coefficient and slope results from the Passing-Bablok regression analysis met the acceptance criteria as summarized as shown in Table below.
| Test | Average MeasuredAltitude | Results |
|---|---|---|
| Creatinine | 6367 feet | r 1.00Slope 1.13 |
| Glucose | 9523 feet | r 1.00Slope 1.00 |
{11}------------------------------------------------
h. Interference
The interference performance of the i-STAT Glucose and Creatinine tests 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 Glucose and Creatinine tests and the interference results.
| Table 6: Summary of Substance Tested and Interference Results for the i-STAT Glucosetest | ||||
|---|---|---|---|---|
| Substance | Test Concentration | Interference | Interference | |
| mmol/L | mg/dL | (Yes/No) | Results | |
| Acetaldehyde | 0.045a | 0.2 | No | |
| Acetaminophen | 1.03 | 15.6 | No | |
| Lithium Acetoacetate | 2.0 | 20 | No | |
| N-Acetyl-L-Cysteine | 0.92 | 15.0 | No | |
| Ammonium Chloride | 2.0a | 10.70 | No | |
| L-Ascorbic Acid | 0.298 | 5.25 | No | |
| Bilirubin | 0.684 | 40 | No | |
| Lithium Bromide | 37.5a | 325.69 | Yes | Decreased results≥ 11.8 mmol/L |
| Cholesterol | 10.3 | 400 | No | |
| Creatinine | 1.326 | 15 | No | |
| Dopamine Hydrochloride | 4.06 µmol/L | 0.0621 | No | |
| Ethanol | 130 | 600 | No | |
| Lithium Fluoride | 0.0632 | 0.12 | No | |
| Formaldehyde | 0.133a | 0.399 | No | |
| Fructose | 1 | 18 | No | |
| Galactose | 3.33 | 60 | No | |
| Gentamicin Sulfate | 0.0628 | 3 | No | |
| Glucosamine Hydrochloride | 0.030a | 0.647 | No | |
| Glutathione, reduced | 3 | 3 mEq/L | No | |
| Glycolic Acid | 10.0a | 76.05 | No |
i-STAT Glucose Test
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.
{12}------------------------------------------------
| test | ||||
|---|---|---|---|---|
| Substance | Test Concentration | Interference | Interference | |
| mmol/L | mg/dL | (Yes/No) | Results | |
| Guaifenesin | 0.0227 | 0.45 | No | |
| Hemoglobin | 10 g/L | 1000 | No | |
| Sodium Heparin | 3.30 U/mL | 330 U/dL | No | |
| β-Hydroxybutyric Acid | 6.0aa | 62.47 | No | |
| Hydroxyurea | 0.405 | 3.08 | Yes | Increased results≥ 0.08 mmol/L |
| Ibuprofen | 1.06 | 21.9 | No | |
| Isoniazid | 0.438 | 6 | No | |
| Lithium Lactate | 10 | 90 | No | |
| Mannose | 1.0a | 18.02 | No | |
| Maltose | 10.5 | 360 | No | |
| pH | 8.0 pH units | N/A | No | |
| Lithium Pyruvate | 0.570 | 5 | No | |
| Lithium Salicylate | 0.207 | 2.86 | No | |
| Lithium Thiocyanate | 0.898 | 5.22 | No | |
| Sodium Thiosulfate | 16.7a | 264.04 | No | |
| Triglyceride | 16.94 | 1500 | No | |
| Uric Acid | 1.4 | 23.5 | No | |
| Xylose | 3a | 45.04 | No | |
| Gentisic Acid | 0.0973 | 1.50 | No |
| Table 6: Summary of Substance Tested and Interference Results for the i-STAT Glucose
i-STAT Creatinine Test
| Table 7: Summary of Substance Tested and Interference Results for the i-STATCreatinine test | |||||
|---|---|---|---|---|---|
| Substance | Test Concentration | Interference | Interference | ||
| mmol/L | mg/dL | (Yes/No) | Results | ||
| Acetaldehyde | 0.045a | 0.2 | No | ||
| Acetaminophen | 1.03 | 15.6 | No | ||
| N-Acetyl-L-Cysteine | 0.92 | 15.0 | No | ||
| L-Ascorbic Acid | 0.298 | 5.25 | No | ||
| β-Hydroxybutyric Acid | 6.0a | 62.47 | No | ||
| Bicarbonate | 35.0 | 294.0 | No | ||
| Bilirubin | 0.684 | 40 | No | ||
| Lithium Bromide | 37.5a | 325.69 | Yes | Increased results≥ 18.3 mmol/L | |
| Calcium Chloride | 5.0 | 20 | No | ||
| Creatine | 0.382a | 5.01 | No | ||
| Dopamine Hydrochloride | 4.06 umol/L | 0.0621 | No | ||
| Formaldehyde | 0.133a | 0.399 | No |
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.
{13}------------------------------------------------
| Table 7: Summary of Substance Tested and Interference Results for the I-STAT Creatinine test | ||||
|---|---|---|---|---|
| Substance | Test Concentration | Interference (Yes/No) | Interference Results | |
| mmol/L | mg/dL | |||
| Glycolic Acid | 10.0a | 76.05 | No | |
| Hemoglobin | 10 g/L | 1000 | No | |
| Hydroxyurea | 0.405 | 3.08 | Yes | Increased results≥ 0.03 mmol/L |
| Lithium Lactate | 10 | 90 | No | |
| Methyldopa | 107 $ μ $ mol/L | 2.25 | No | |
| pH | 8.0 pH units | N/A | No | |
| Lithium Pyruvate | 0.570 | 5 | No | |
| Lithium Salicylate | 0.207 | 2.86 | No | |
| Sodium Thiosulfate | 16.7a | 264.04 | No | |
| Triglyceride | 16.94 | 1500 | No | |
| Uric Acid | 1.4 | 23.5 | No |
| Table 7: Summary of Substance Tested and Interference Results for the i-STAT
Comparison Study
Method Comparison with Predicate Device i.
Method comparison was demonstrated in a study comparing the i-STAT Glucose and Creatinine test performance on the i-STAT 1 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 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 versus the singlicate result of the comparative method.
The i-STAT System automatically runs a comprehensive set of quality checks of both the analyzer and cartridge performance each time a sample is tested. This internal quality system will suppress results by generating a Quality Check Code (OCC) if the analyzer, cartridge or sample does not meet certain internal specifications. When a QCC occurs, a single code number, the type of problem and the next step to be taken will be displayed on the i-STAT Analyzer. The failure rate for a single cartridge due to OCCs may be as high as 4%. The rate of failure for two consecutive cartridges due to QCCs may be as high as 1.7%.
| Table 5: Method Comparison Results | |||||
|---|---|---|---|---|---|
| i-STAT Test | N | Slope | Intercept | r | |
| Glucose | 185 | 0.98 | 0.00 | 1.00 | |
| Creatinine | 180 | 1.043 | -0.062 | 1.00 |
8. Conclusion
The results of these studies demonstrate that performance of the i-STAT CHEM8+ Glucose and Creatinine tests with the i-STAT 1 System are substantially equivalent to the comparative method.
§ 862.1345 Glucose test system.
(a)
Identification. A glucose test system is a device intended to measure glucose quantitatively in blood and other body fluids. Glucose measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus, neonatal hypoglycemia, and idiopathic hypoglycemia, and of pancreatic islet cell carcinoma.(b)
Classification. Class II (special controls). The device, when it is solely intended for use as a drink to test glucose tolerance, is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.