(58 days)
The GEM Premier ChemSTAT is a portable critical care system for use by health care professionals to rapidly analyze lithium heparinized whole blood samples at the point of health care delivery in a clinical setting and in a central laboratory. The instrument provides quantitative measurements of Sodium (Na+), Ionized Calcium (Ca++) and Chloride (C1-) from arterial and venous heparinized whole blood. These parameters. along with derived parameters, aid in the diagnosis of a patient's electrolyte balance.
Electrolytes in the human body have multiple roles. Nearly all metabolic processes depend on or vary with electrolytes:
- · Sodium (Na+) measurements are used in the diagnosis and treatment of aldosteronism, diabetes insipidus, adrenal hypertension, Addison's disease, dehydration, inappropriate antidiuretic secretion, or other diseases involving electrolyte imbalance.
- · Potassium (K+) measurements are used to monitor electrolyte balance in the diagnosis and treatment of disease conditions characterized by low or high blood potassium levels.
- Ionized calcium (Ca++) measurements are used in the diagnosis and treatment of parathyroid disease, a variety of bone diseases, chronic renal disease and tetany.
- · Chloride (Cl-) measurements are used in the diagnosis and metabolic and metabolic disorders, such as, cystic fibrosis and diabetic acidosis.
The GEM Premier ChemSTAT is a portable system that analyzes arterial and venous lithium heparinized whole blood at the point of health care delivery in a clinical setting and in a central laboratory for Na*, K*, Ca** and Cl . All tests are included in a single self-contained, disposable GEM Premier ChemSTAT PAK (cartridge).
Key Components:
Analyzer: The GEM Premier ChemSTAT analyzer has the internal logic and processing power necessary to perform analysis. It employs a unique touch-sensitive color screen and a simple set of menus and buttons for user interaction. The analyzer guides operators through the sampling process with simple, clear messages and prompts.
PAK (Cartridge): The disposable, multi-use GEM Premier ChemSTAT PAK is a completely closed cartridge that houses all components necessary to operate the instrument once the GEM PAK is validated. These components include the sensors, Process Control (PC) Solutions, sampler, and waste bag. The values of all PC Solutions are read from the GEM PAK Electronically Erasable Programmable Read Only Memory (EEPROM) chip. The components and processes used to manufacture the PC Solutions in the GEM PAK are traceable to National Institute of Standards and Technology (NIST) standards, Clinical & Laboratory Standards Institute (CLSI) procedures or other internal standards, where available and appropriate. The GEM Premier ChemSTAT PAK has flexible menus to assist facilities in maximizing efficiency. As part of this program, GEM ChemSTAT CVP (Calibration Valuation Products) are external solutions intended to complete the calibration process and final accuracy assessment of the iQM cartridge calibration following warm-up.
Intelligent Quality Management (iQM): Intelligent Quality Management (iQM) is used as the quality control and assessment system for the GEM Premier ChemSTAT system. iQM is an active quality process control program designed to provide continuous monitoring of the analytical process before and after sample measurement with real-time, automatic error detection, automatic correction and automatic documentation of all corrective actions. iQM performs 4 types of continuous, quality checks to monitor the performance of the GEM PAK, sensors, and reagents throughout the cartridge use-life. These checks include System, Sensor, Pattern Recognition (PR) and Stability Checks.
The provided FDA 510(k) summary for the GEM Premier ChemSTAT describes the device's analytical performance, which is a type of acceptance criteria study. This document is not for an AI/ML device, but rather for an in-vitro diagnostic device that measures specific analytes. Therefore, many of the requested elements pertaining to AI/MRMC studies, expert ground truth, and training sets are not applicable or not provided in this type of submission. However, I can extract information related to the device's analytical performance and the studies conducted to demonstrate its performance against predefined criteria.
Here's a breakdown of the acceptance criteria and performance study details, focusing on what is available in the provided document:
Acceptance Criteria and Reported Device Performance
The acceptance criteria are implicitly defined by the analytical performance specifications and the comparison to the predicate device. The performance studies aim to demonstrate that the device meets these standards.
Table 1: Acceptance Criteria (Implicit from Study Outcomes) and Reported Device Performance for GEM Premier ChemSTAT
| Performance Metric | Analyte | Acceptance Criteria (Stated Goal / Implied Target) | Reported Device Performance |
|---|---|---|---|
| Precision (Internal) | Na+ | All results within specification (implied acceptable SD/CV based on clinical utility and state of the art) | Ranges from 0.4% to 0.6% Total %CV (Na+); 0.2% to 2.3% Total %CV (K+); 0.8% to 2.8% Total %CV (Ca++); 0.9% to 1.5% Total %CV (Cl-) |
| K+ | See above | ||
| Ca++ | See above | ||
| Cl- | See above | ||
| Reproducibility (Aqueous Controls - POC) | Na+ | All results at all sites within specification (implied acceptable Reproducibility SD/CV) | Reproducibility %CV ranges from 0.5% to 0.8% (Na+); 0.0% to 1.2% (K+); 0.7% to 1.7% (Ca++); 0.8% to 3.3% (Cl-) |
| K+ | See above | ||
| Ca++ | See above | ||
| Cl- | See above | ||
| External Precision (Whole Blood - POC) | Na+ | All results at all sites within specification; Measured data partitioned into Fixed Acceptance Range (Constant SD) or Variable Acceptance Range (Constant %CV). | Pooled "Within Sample SD of %CV" of 1.1% (Na+); 0.08% (K+); 0.006 (Ca++); 0.6% (Cl-) |
| K+ | See above | ||
| Ca++ | See above | ||
| Cl- | See above | ||
| LoB, LoD, LoQ | All Analytes | Established values for each analyte | Na+: LoB 69, LoD 70, LoQ 88; K+: LoB 0.0, LoD 0.1, LoQ 0.3; Ca++: LoB 0.00, LoD 0.01, LoQ 0.05; Cl-: LoB 4, LoD 4, LoQ 36 |
| Linearity | All Analytes | R2 close to 1.0, slope close to 1.0, intercept close to 0; Claimed reportable range supported. | Na+: Slope 1.023, Intercept -1.189, R2 0.9997; K+: Slope 0.995, Intercept 0.057, R2 0.9998; Ca++: Slope 0.986, Intercept 0.019, R2 0.9984; Cl-: Slope 1.011, Intercept -1.909, R2 0.9998. Claimed ranges are 100-180 mmol/L (Na+), 0.3-19.0 mmol/L (K+), 0.10-4.25 mmol/L (Ca++), 40-158 mmol/L (Cl-). |
| Analytical Specificity (Interference) | All Analytes | No significant interference with listed substances at specific concentrations (implied bias < acceptable threshold) and identification of concentrations for observed interference. | Many substances showed no interference. Specific interferences identified for Hemoglobin (Potassium), Perchlorate (Chloride), and Triglyceride (Potassium) with quantified bias at lowest impact concentrations. |
| Clinical Testing (Method Comparison) | All Analytes | Substantially equivalent performance to predicate device (GEM Premier 4000) for R value, slope, and intercept. | Na+: R 0.987, Slope 1.021, Intercept -2.157; K+: R 0.999, Slope 1.000, Intercept 0.100; Ca++: R 0.999, Slope 1.000, Intercept 0.015; Cl-: R 0.994, Slope 1.000, Intercept 1.000. |
Details of the Study
-
Sample sizes used for the test set and the data provenance:
- Internal Precision Study – Whole Blood: 120 replicates per level for each of 5 levels (N=600 total samples analyzed for each analyte). Data provenance is internal (Instrumentation Laboratory Co.). The study simulates an internal lab environment.
- Reproducibility Study with Aqueous Controls – POC Setting: 90 pooled replicates per level for each of 7 levels (N=630 samples analyzed for each analyte). The study was performed at three (3) external clinical point-of-care (POC) sites.
- External Precision – Whole Blood: Variable N per site. For the Na+, K+, Ca++, Cl- main ranges, N=~63-69 samples per site for 3 sites, pooled N=195. For specific lower/higher ranges, N=3 samples per site for 3 sites, pooled N=9. The study was performed at three (3) external clinical point-of-care (POC) sites. Less than 10% of samples were "contrived" (meaning artificially prepared or modified) and the rest were patient samples from the intended use population. Data provenance is implied to be mixed: patient samples are real-world, while contrived samples are laboratory-sourced. The locations are referred to as "external clinical point-of-care (POC) sites", implying real-world clinical settings, likely within the US given FDA submission. It is a prospective study as samples were "run" during the study.
- LoB, LoD, LoQ: No specific N mentioned, but involved testing with three (3) lots of GEM Premier ChemSTAT PAKs.
- Linearity: 18 replicates per level (9 levels, total of 162 samples) for each analyte. Whole blood samples, prepared by spiking or diluting, were used.
- Analytical Specificity (Interference): Not explicitly stated, but various substances were screened at different concentrations. Implied to be laboratory-based evaluation.
- Clinical Testing (Method Comparison):
- Na+: N=436 patient samples.
- K+: N=442 patient samples.
- Ca++: N=444 patient samples.
- Cl-: N=435 patient samples.
- Data provenance: Patient samples from the intended use population, collected at three (3) point-of-care (POC) sites. Less than 10% of samples were contrived. Implied to be prospective as a method comparison study involving running samples.
-
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- For this type of in-vitro diagnostic device, "ground truth" for clinical samples is typically established by comparative measurement against a predicate device or a reference method, rather than by expert consensus (as would be the case for image interpretation, for example).
- The "ground truth" in the Clinical Testing (Method Comparison) was established by comparing the GEM Premier ChemSTAT's measurements to those of the GEM Premier 4000 (K133407), which is the legally marketed predicate device. Operator qualifications involved "health care professionals" for point-of-care use, and "internal precision studies" would be performed by qualified lab personnel. Specific expert qualifications are not detailed beyond "health care professionals."
-
Adjudication method (e.g. 2+1, 3+1, none) for the test set:
- Not applicable/Not mentioned. This is a quantitative measurement device, not an interpretation task requiring adjudication. The performance is assessed statistically (SD, CV, R, slope, intercept).
-
If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:
- Not applicable. This is not an AI/ML device or an imaging device requiring human reader interpretation. It is an IVD device providing quantitative measurements.
-
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- This is an in-vitro diagnostic instrument. Its primary function is "standalone" measurement of analytes. The performance studies (precision, linearity, interference, method comparison) assess the instrument's inherent analytical capabilities. There is no "human-in-the-loop performance" in the sense of an AI assisting human interpretation; direct measurement is the output.
-
The type of ground truth used (expert consensus, pathology, outcomes data, etc):
- For LoB, LoD, LoQ, Linearity, Analytical Specificity, and Internal Precision: Ground truth is against known concentrations in prepared samples (standards, calibrators, controls, spiked/diluted samples). This is a metrological approach.
- For Clinical Testing (Method Comparison) and External Precision (Whole Blood): Ground truth is established by the measurements from the predicate device (GEM Premier 4000) for patient samples. The assumption is that the predicate device provides clinically acceptable and accurate measurements for comparison.
-
The sample size for the training set:
- Not applicable. This is not an AI/ML device, so there is no "training set" in the machine learning sense. The device is based on established electrochemical principles (potentiometry).
-
How the ground truth for the training set was established:
- Not applicable, as there is no "training set" for an AI/ML model. The device's calibration and internal quality control use known standards and calibrated reference materials.
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February 16, 2019
Instrumentation Laboratory Co. Gabriella Erdosy Regulatory Affairs Manager 180 Hartwell Road Bedford. MA 01730
Re: K183549
Trade/Device Name: GEM Premier ChemSTAT Regulation Number: 21 CFR 862.1665 Regulation Name: Sodium test system Regulatory Class: Class II Product Code: JGS, CEM, JFP, CGZ, JJE Dated: December 19, 2018 Received: December 20, 2018
Dear Gabriella Erdosy:
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/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.html; 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 http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, vou may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/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 -S
Courtney H. Lias, Ph.D. for Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K183549
Device Name GEM Premier ChemSTAT
Indications for Use (Describe)
The GEM Premier ChemSTAT is a portable critical care system for use by health care professionals to rapidly analyze lithium heparinized whole blood samples at the point of health care delivery in a clinical setting and in a central laboratory. The instrument provides quantitative measurements of Sodium (Na+), Ionized Calcium (Ca++) and Chloride (C1-) from arterial and venous heparinized whole blood. These parameters. along with derived parameters, aid in the diagnosis of a patient's electrolyte balance.
Electrolytes in the human body have multiple roles. Nearly all metabolic processes depend on or vary with electrolytes:
- · Sodium (Na+) measurements are used in the diagnosis and treatment of aldosteronism, diabetes insipidus, adrenal hypertension, Addison's disease, dehydration, inappropriate antidiuretic secretion, or other diseases involving electrolyte imbalance.
- · Potassium (K+) measurements are used to monitor electrolyte balance in the diagnosis and treatment of disease conditions characterized by low or high blood potassium levels.
- Ionized calcium (Ca++) measurements are used in the diagnosis and treatment of parathyroid disease, a variety of bone diseases, chronic renal disease and tetany.
- · Chloride (Cl-) measurements are used in the diagnosis and metabolic and metabolic disorders, such as, cystic fibrosis and diabetic acidosis.
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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K183549: GEM Premier ChemSTAT with Na*, K*, Ca** and Cl
510(k) Summary
This 510(k) Summary of Safety and Effectiveness is being submitted in accordance with the requirements of the Safe Medical Device Act of 1990 and 21 CFR 807.92.
| Submitter's Information | Instrumentation Laboratory (IL) Co.180 Hartwell RoadBedford, MA 01730, USA |
|---|---|
| Contact Person | Gabriella ErdosyPhone: 781-861-4571Fax: 781-861-4207Email: gerdosy@ilww.com |
| Preparation Date | February 15, 2019 |
| Device Trade Name | GEM Premier ChemSTAT |
| Predicate Device | GEM Premier 4000 | K133407 |
|---|---|---|
| ------------------ | ------------------ | --------- |
| Regulatory Information | |||||
|---|---|---|---|---|---|
| Device | RegulationSection | Regulatory Description | Classification | ProductCode | Panel |
| Analyzer | 862.2160 | Analyzer, chemistry(photometric, discrete), forclinical use | Class I(Exempt) | JJE | |
| Sodium | 862.1665 | Sodium test system | Class II | JGS | Chemistry(75) |
| Potassium | 862.1600 | Potassium test system | Class II | CEM | |
| Ionized Calcium | 862.1145 | Calcium test system | Class II | JFP | |
| Chloride | 862.1170 | Chloride test system | Class II | CGZ |
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Device Description
The GEM Premier ChemSTAT is a portable system that analyzes arterial and venous lithium heparinized whole blood at the point of health care delivery in a clinical setting and in a central laboratory for Na*, K*, Ca** and Cl . All tests are included in a single self-contained, disposable GEM Premier ChemSTAT PAK (cartridge).
| Key Components | Description |
|---|---|
| Analyzer | The GEM Premier ChemSTAT analyzer has the internal logic andprocessing power necessary to perform analysis. It employs aunique touch-sensitive color screen and a simple set of menus andbuttons for user interaction. The analyzer guides operators throughthe sampling process with simple, clear messages and prompts. |
| PAK (Cartridge) | The disposable, multi-use GEM Premier ChemSTAT PAK is acompletely closed cartridge that houses all components necessaryto operate the instrument once the GEM PAK is validated. Thesecomponents include the sensors, Process Control (PC) Solutions,sampler, and waste bag. |
| The values of all PC Solutions are read from the GEM PAKElectronically Erasable Programmable Read OnlyMemory(EEPROM) chip. The components and processes used tomanufacture the PC Solutions in the GEM PAK are traceable toNational Institute of Standards and Technology (NIST) standards,Clinical & Laboratory Standards Institute (CLSI) procedures or otherinternal standards, where available and appropriate. | |
| The GEM Premier ChemSTAT PAK has flexible menus to assistfacilities in maximizing efficiency. | |
| As part of this program, GEM ChemSTAT CVP (Calibration ValuationProducts) are external solutions intended to complete thecalibration process and final accuracy assessment of the iQMcartridge calibration following warm-up. |
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| Device Description (Cont.) | |
|---|---|
| Intelligent Quality Management(iQM) | Intelligent Quality Management (iQM) is used as the qualitycontrol and assessment system for the GEM Premier ChemSTATsystem. iQM is an active quality process control programdesigned to provide continuous monitoring of the analyticalprocess before and after sample measurement with real-time,automatic error detection, automatic correction and automaticdocumentation of all corrective actions.iQM performs 4 types of continuous, quality checks to monitorthe performance of the GEM PAK, sensors, and reagentsthroughout the cartridge use-life. These checks include System,Sensor, Pattern Recognition (PR) and Stability Checks. |
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Indications for Use / Intended Use
The GEM Premier ChemSTAT is a portable critical care system for use by health care professionals to rapidly analyze lithium heparinized whole blood samples at the point of health care delivery in a clinical setting and in a central laboratory. The instrument provides quantitative measurements of Sodium (Na*), Potassium (K*), Ionized Calcium (Ca*) and Chloride (Cl) from arterial and venous heparinized whole blood. These parameters, along with derived parameters, aid in the diagnosis of a patient's electrolyte balance.
Electrolytes in the human body have multiple roles. Nearly all metabolic processes depend on or vary with electrolytes:
- . Sodium (Na*) measurements are used in the diagnosis and treatment of aldosteronism, diabetes insipidus, adrenal hypertension, Addison's disease, dehydration, inappropriate antidiuretic secretion, or other diseases involving electrolyte imbalance.
- . Potassium (K*) measurements are used to monitor electrolyte balance in the diagnosis and treatment of disease conditions characterized by low or high blood potassium levels.
- lonized calcium (Ca*) measurements are used in the diagnosis and treatment of parathyroid . disease, a variety of bone diseases, chronic renal disease and tetany.
- . Chloride (Cl) measurements are used in the diagnosis and treatment of electrolyte and metabolic disorders, such as, cystic fibrosis and diabetic acidosis.
Special Conditions for Use Statement
- For prescription use only.
- . For clinical laboratory and point-of-care use
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| Substantial Equivalency | |||
|---|---|---|---|
| Item | Candidate Device:GEM Premier ChemSTAT | Predicate Device:GEM Premier 4000 | |
| 510(k) No. | Pending | K133407 | |
| Manufacturer | Instrumentation Laboratory Co. | Same | |
| Intended Use | A portable critical care system for use byhealth care professionals to rapidlyanalyze lithium heparinized wholeblood samples at the point of healthcare delivery in a clinical setting and in acentral laboratory. The instrumentprovides quantitative measurements ofSodium (Na+), Potassium (K+), IonizedCalcium (Ca++) and Chloride (Cl-) fromarterial and venous heparinized wholeblood. These parameters, along withderived parameters, aid in the diagnosisof a patient's electrolyte balance. | Same | |
| Intended User | Central Laboratory and Point-of-Care | Same | |
| Measurement Principle | Na+ | Potentiometry | Same |
| K+ | Potentiometry | Same | |
| Ca++ | Potentiometry | Same | |
| Cl- | Potentiometry | Same | |
| Sample Volume | 150 μL | 65 to 150 μL(dependent on sample mode) | |
| Sample Type | Lithium heparinized whole blood(arterial and venous) | Same(arterial, venous and capillary) | |
| Reportable Range | Na+ | 100 to 180 mmol/L | Same |
| K+ | 0.3 to 19.0 mmol/L | 0.2 to 19.0 mmol/L | |
| Ca++ | 0.10 to 4.25 mmol/L | Same | |
| Cl- | 40 to 158 mmol/L | Same | |
| Substantial Equivalency (Cont.) | |||
| Item | Candidate Device:GEM Premier ChemSTAT | Predicate Device:GEM Premier 4000 | |
| PAK Storage Temperature | 15-25°C | Same | |
| Calibration | 2-point calibration | Same | |
| Instrument Sample Introduction | Aspiration | Same | |
| Instrument Operating Temperature | 12-32°C | Same | |
| Software Operating System | Linux-based | Same | |
| Instrument User Interface | Menu Driven Touch Screen | Same |
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Performance Summary
Internal Precision Study – Whole Blood
In accordance with CLS EPO5-A3, an internal precisions of ve (5) different concentrations of whole blood per analyte, each un on three (3) GEM Premier ChemSTAT analyzers for five (5) days, with one (1) run per day and eight (8) replicates measured per run per level (N=120).
All results were within specification.
| Analyte | WholeBloodLevel | N | Mean | Within RunSD | Within Run%CV | Analyzer-to-AnalyzerSD | Analyzer-to-Analyzer%CV | TotalSD | Total%CV |
|---|---|---|---|---|---|---|---|---|---|
| Na+(mmol/L) | Level 1 | 120 | 106 | 0.5 | 0.5% | 0.4 | 0.3% | 0.6 | 0.6% |
| Level 2 | 120 | 118 | 0.4 | 0.4% | 0.4 | 0.4% | 0.6 | 0.5% | |
| Level 3 | 120 | 132 | 0.5 | 0.4% | 0.0 | 0.0% | 0.5 | 0.4% | |
| Level 4 | 120 | 152 | 0.7 | 0.4% | 0.3 | 0.2% | 0.8 | 0.5% | |
| Level 5 | 120 | 175 | 0.6 | 0.3% | 0.6 | 0.3% | 0.8 | 0.5% | |
| K+(mmol/L) | Level 1 | 120 | 1.5 | 0.03 | 2.2% | 0.01 | 0.8% | 0.04 | 2.3% |
| Level 2 | 120 | 3.4 | 0.03 | 0.9% | 0.01 | 0.4% | 0.03 | 0.9% | |
| Level 3 | 120 | 5.8 | 0.04 | 0.7% | 0.02 | 0.4% | 0.04 | 0.7% | |
| Level 4 | 120 | 7.9 | 0.04 | 0.5% | 0.02 | 0.3% | 0.05 | 0.6% | |
| Level 5 | 120 | 18.1 | 0.04 | 0.2% | 0.11 | 0.6% | 0.12 | 0.6% |
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Internal Precision Study – Whole Blood (Cont.)
| Analyte | WholeBloodLevel | N | Mean | Within RunSD | Within Run%CV | Analyzer-to-AnalyzerSD | Analyzer-to-Analyzer%CV | TotalSD | Total%CV |
|---|---|---|---|---|---|---|---|---|---|
| Ca++(mmol/L) | Level 1 | 120 | 0.19 | 0.003 | 1.7% | 0.004 | 2.3% | 0.005 | 2.8% |
| Level 2 | 120 | 0.38 | 0.004 | 1.1% | 0.003 | 0.7% | 0.005 | 1.3% | |
| Level 3 | 120 | 0.82 | 0.007 | 0.8% | 0.3% | 0.3% | 0.007 | 0.8% | |
| Level 4 | 120 | 1.60 | 0.012 | 0.7% | 0.010 | 0.7% | 0.016 | 1.0% | |
| Level 5 | 120 | 3.79 | 0.029 | 0.8% | 0.039 | 1.0% | 0.048 | 1.3% | |
| Cl-(mmol/L) | Level 1 | 120 | 54 | 0.4 | 0.7% | 0.5 | 0.9% | 0.6 | 1.1% |
| Level 2 | 120 | 75 | 0.3 | 0.4% | 0.6 | 0.8% | 0.7 | 0.9% | |
| Level 3 | 120 | 90 | 0.5 | 0.5% | 0.8 | 0.9% | 0.9 | 1.0% | |
| Level 4 | 120 | 118 | 0.6 | 0.5% | 1.4 | 1.2% | 1.5 | 1.3% | |
| Level 5 | 120 | 142 | 0.5 | 0.3% | 2.0 | 1.4% | 2.1 | 1.5% |
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Reproducibility Study with Aqueous Controls – Point-of-Care (POC) Setting
In accordance with CLSI EP05-A3, a reproducibility study was performed with controls at three (POC) sites. The studies were run by a total of nine (9) different operators on six (6) different GEM Premier ChemSTAT instruments, using a single Intern PAKs (cartridges). Each site used seven (7) levels of quality control material for each analyte (2 levels of GEM ChemSTAT PVP), running each control level in triplicate, twice a day for 5 days, for a total of 30 replicates per level (N=90 pooled across 3 sites).
| Pooled Multi-Site POC Data | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Analyte | ControlLevel | N | Mean | Repeatability | Between-Run | Between-Day | Between-Site | Reproducibility | |||||
| SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | ||||
| Na+(mmol/L) | CVP Level 1 | 90 | 124 | 0.8 | 0.7% | 0.4 | 0.3% | 0.0 | 0.0% | 0.5 | 0.4% | 1.0 | 0.8% |
| CVP Level 2 | 90 | 156 | 0.7 | 0.4% | 0.4 | 0.2% | 0.2 | 0.1% | 0.0 | 0.0% | 0.8 | 0.5% | |
| PVP Level 1 | 90 | 106 | 0.5 | 0.4% | 0.0 | 0.0% | 0.2 | 0.2% | 0.3 | 0.3% | 0.6 | 0.6% | |
| PVP Level 2 | 90 | 125 | 0.4 | 0.3% | 0.3 | 0.2% | 0.0 | 0.0% | 0.4 | 0.3% | 0.6 | 0.5% | |
| PVP Level 3 | 90 | 140 | 0.6 | 0.4% | 0.6 | 0.4% | 0.0 | 0.0% | 0.1 | 0.1% | 0.8 | 0.6% | |
| PVP Level 4 | 90 | 155 | 0.6 | 0.4% | 0.3 | 0.2% | 0.2 | 0.1% | 0.2 | 0.1% | 0.7 | 0.5% | |
| PVP Level 5 | 90 | 177 | 0.9 | 0.5% | 0.1 | 0.0% | 0.5 | 0.3% | 0.7 | 0.4% | 1.2 | 0.7% | |
| Pooled Multi-Site POC Data | |||||||||||||
| Analyte | ControlLevel | N | Mean | Repeatability | Between-Run | Between-Day | Between-Site | Reproducibility | |||||
| SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | ||||
| K+(mmol/L) | CVP Level 1 | 90 | 2.5 | 0.00 | 0.0% | 0.02 | 0.7% | 0.00 | 0.0% | 0.00 | 0.0% | 0.02 | 0.7% |
| CVP Level 2 | 90 | 7.4 | 0.03 | 0.4% | 0.05 | 0.7% | 0.00 | 0.0% | 0.01 | 0.1% | 0.06 | 0.8% | |
| K+(mmol/L) | PVP Level 1 | 90 | 1.2 | 0.00 | 0.0% | 0.00 | 0.0% | 0.00 | 0.0% | 0.00 | 0.0% | 0.00 | 0.0% |
| PVP Level 2 | 90 | 2.5 | 0.00 | 0.0% | 0.00 | 0.0% | 0.00 | 0.0% | 0.00 | 0.0% | 0.00 | 0.0% | |
| PVP Level 3 | 90 | 4.6 | 0.03 | 0.6% | 0.04 | 0.9% | 0.00 | 0.0% | 0.02 | 0.5% | 0.05 | 1.2% | |
| PVP Level 4 | 90 | 7.3 | 0.03 | 0.4% | 0.02 | 0.3% | 0.00 | 0.0% | 0.02 | 0.2% | 0.04 | 0.5% | |
| PVP Level 5 | 90 | 9.6 | 0.04 | 0.5% | 0.01 | 0.1% | 0.02 | 0.2% | 0.06 | 0.6% | 0.08 | 0.8% | |
| Ca++(mmol/L) | CVP Level 1 | 90 | 0.89 | 0.009 | 1.0% | 0.001 | 0.1% | 0.000 | 0.0% | 0.002 | 0.3% | 0.010 | 1.1% |
| CVP Level 2 | 90 | 1.54 | 0.009 | 0.6% | 0.007 | 0.4% | 0.000 | 0.0% | 0.002 | 0.1% | 0.011 | 0.7% | |
| PVP Level 1 | 90 | 0.37 | 0.004 | 1.1% | 0.003 | 0.9% | 0.000 | 0.0% | 0.003 | 0.9% | 0.006 | 1.7% | |
| PVP Level 2 | 90 | 0.90 | 0.006 | 0.6% | 0.005 | 0.5% | 0.000 | 0.0% | 0.003 | 0.4% | 0.008 | 0.9% | |
| PVP Level 3 | 90 | 1.10 | 0.007 | 0.7% | 0.008 | 0.7% | 0.000 | 0.0% | 0.000 | 0.0% | 0.011 | 1.0% | |
| Ca++(mmol/L) | PVP Level 4 | 90 | 1.56 | 0.009 | 0.6% | 0.006 | 0.4% | 0.000 | 0.0% | 0.002 | 0.2% | 0.011 | 0.7% |
| PVP Level 5 | 90 | 2.23 | 0.015 | 0.7% | 0.011 | 0.5% | 0.003 | 0.1% | 0.000 | 0.0% | 0.019 | 0.9% | |
| Pooled Multi-Site POC Data | |||||||||||||
| Analyte | ControlLevel | N | Mean | Repeatability | Between-Run | Between-Day | Between-Site | Reproducibility | |||||
| SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | ||||
| Cl-(mmol/L) | CVP Level 1 | 90 | 91 | 0.6 | 0.6% | 0.3 | 0.3% | 0.2 | 0.2% | 0.3 | 0.3% | 0.7 | 0.8% |
| CVP Level 2 | 90 | 135 | 0.4 | 0.3% | 0.1 | 0.1% | 0.1 | 0.1% | 2.1 | 1.5% | 2.1 | 1.6% | |
| PVP Level 1 | 90 | 72 | 0.3 | 0.5% | 0.0 | 0.0% | 0.3 | 0.4% | 2.3 | 3.2% | 2.3 | 3.3% | |
| PVP Level 2 | 90 | 92 | 0.5 | 0.6% | 0.2 | 0.2% | 0.2 | 0.2% | 0.3 | 0.3% | 0.7 | 0.8% | |
| PVP Level 3 | 90 | 106 | 0.5 | 0.4% | 0.3 | 0.3% | 0.0 | 0.0% | 0.7 | 0.7% | 0.9 | 0.9% | |
| PVP Level 4 | 90 | 135 | 0.6 | 0.4% | 0.4 | 0.3% | 0.1 | 0.1% | 2.1 | 1.5% | 2.2 | 1.6% | |
| PVP Level 5 | 90 | 152 | 0.8 | 0.5% | 0.0 | 0.0% | 0.4 | 0.3% | 2.7 | 1.8% | 2.9 | 1.9% |
All results at all sites were within specification.
{12}------------------------------------------------
Reproducibility Study with Aqueous Controls – Point-of-Care (POC) Setting (Cont.)
{13}------------------------------------------------
Reproducibility Study with Aqueous Controls – Point-of-Care (POC) Setting (Cont.)
{14}------------------------------------------------
External Precision – Whole Blood
A precision study was performed with whole blood patient samples at three (3) external clinical point-ofcare (POC) sites. The studies were run by six (6) different operators on three (3) different GEM Premier ChemSTAT instruments, using a single lot of GEM Premier ChemSTAT PAKs (cartridges). Less than 10% of samples included in the study were contrived.
For data analysis and acceptance criteria application, measured data for each analyte were partitioned into zones and identified as Fixed Acceptance Range (Constant SD) or Variable Acceptance Range (Constant %CV).
| Analyte | Fixed or VariableAcceptance Range | Site | N | Mean | Within SampleSD of %CV |
|---|---|---|---|---|---|
| Na+(mmol/L) | Fixed(SD) | POC 1 | 69 | 139 | 1.0 |
| POC 2 | 63 | 140 | 1.0 | ||
| POC 3 | 63 | 140 | 1.3 | ||
| Pooled | 195 | 140 | 1.1 | ||
| Na+(mmol/L) | Fixed(SD) | POC 1 | 3 | 106 | 0.6 |
| POC 2 | 3 | 106 | 0.0 | ||
| POC 3 | 3 | 103 | 0.6 | ||
| Pooled | 9 | 105 | 0.5 | ||
| K+(mmol/L) | Fixed(SD) | POC 1 | 69 | 4.1 | 0.12 |
| POC 2 | 63 | 4.0 | 0.03 | ||
| POC 3 | 63 | 3.6 | 0.04 | ||
| Pooled | 195 | 3.9 | 0.08 | ||
| K+(mmol/L) | Variable(%CV) | POC 1 | 3 | 8.2 | 0.7% |
| POC 2 | 3 | 7.3 | 0.0% | ||
| POC 3 | 3 | 7.9 | 0.7% | ||
| Pooled | 9 | 7.8 | 0.5% |
All results at all sites were within specification.
{15}------------------------------------------------
| Analyte | Fixed or VariableAcceptance Range | Site | N | Mean | Within SampleSD of %CV |
|---|---|---|---|---|---|
| Ca++(mmol/L) | Fixed(SD) | POC 1 | 3 | 0.34 | 0.006 |
| POC 2 | 3 | 0.38 | 0.006 | ||
| POC 3 | 3 | 0.41 | 0.006 | ||
| Pooled | 9 | 0.38 | 0.006 | ||
| Ca++(mmol/L) | Variable(%CV) | POC 1 | 69 | 1.20 | 1.1% |
| POC 2 | 63 | 1.22 | 1.4% | ||
| POC 3 | 63 | 1.22 | 1.8% | ||
| Pooled | 195 | 1.21 | 1.4% | ||
| Cl-(mmol/L) | Fixed(SD) | POC 1 | 3 | 73 | 0.0 |
| POC 2 | 3 | 40 | 0.0 | ||
| POC 3 | 3 | 44 | 0.0 | ||
| Pooled | 9 | 52 | 0.0 | ||
| Cl-(mmol/L) | Variable(%CV) | POC 1 | 69 | 102 | 0.5% |
| POC 2 | 63 | 105 | 0.7% | ||
| POC 3 | 63 | 105 | 0.5% | ||
| Pooled | 195 | 104 | 0.6% |
External Precision – Whole Blood (Cont.)
{16}------------------------------------------------
LoB, LoD and LoQ
In accordance with CLSI EP17-A2, Limit of Blank (LoB), Limit of Detection (LoD) and Limit of Quantification (LoQ) were established for Na*, K*, Ca** and Cl*, using three (3) lots of GEM Premier ChemSTAT PAKs (cartridges).
Following are the combined data results for LoB, LoD and LoQ:
| Analyte | LoB | LoD | LoQ |
|---|---|---|---|
| Na+ (mmol/L) | 69 | 70 | 88 |
| K+ (mmol/L) | 0.0 | 0.1 | 0.3 |
| Ca++ (mmol/L) | 0.00 | 0.01 | 0.05 |
| Cl- (mmol/L) | 4 | 4 | 36 |
Linearity
In accordance with CLSI EP06-A, nine (9) levels per analyte were prepared by spiking or diluting whole blood to challenge the claimed reportable range for Nat, K*, Ca** and Cl*. Each blood level was analyzed in triplicate on six (6) GEM Premier ChemSTAT test analyzers and results compared to the reference analyzer.
Combined data from limit of quantitation (LoQ) and linearity were used to support the lower limits of the claimed reportable ranges.
| Analyte | # ofLevels | N perLevel | Slope | Intercept | R2 | TestedRange | ReportableRange |
|---|---|---|---|---|---|---|---|
| Na+(mmol/L) | 9 | 18 | 1.023 | -1.189 | 0.9997 | 92 to 200 | 100 to 180 |
| K+(mmol/L) | 9 | 18 | 0.995 | 0.057 | 0.9998 | 0.2 to 19.6 | 0.3 to 19.0 |
| Ca++(mmol/L) | 9 | 18 | 0.986 | 0.019 | 0.9984 | 0.04 to 4.27 | 0.10 to 4.25 |
| Cl-(mmol/L) | 9 | 18 | 1.011 | -1.909 | 0.9998 | 34 to 177 | 40 to 158 |
{17}------------------------------------------------
Analytical Specificity
In accordance with EP07 3d Edition, an interference study was conducted on the GEM Premier ChemSTAT for Na*, K*, Ca** and Cl¯.
The table below and on the next page lists the substances that were screened with no observed interference on Na*, K*, Ca** and/or Cl¯:
| Test Substance | Test Concentration | Tested analytes where interference was not observed |
|---|---|---|
| Atracurium | 50 mg/L | Sodium, Potassium, Ionized Calcium, Chloride |
| Benzalkonium (Chloride) | 5 mg/L | Sodium, Potassium, Ionized Calcium, Chloride |
| Bilirubin | 40 mg/dL | Sodium, Potassium, Ionized Calcium, Chloride |
| Ceftriaxone | 1510 µmol/L | Sodium, Potassium, Ionized Calcium, Chloride |
| Epinephrine | 0.5 µmol/L | Sodium, Potassium, Ionized Calcium, Chloride |
| Etomidate | 50 mg/L | Sodium, Potassium, Ionized Calcium, Chloride |
| Fentanyl | 0.03 µg/mL | Sodium, Potassium, Ionized Calcium, Chloride |
| Furosemide | 48.1 µmol/L | Sodium, Potassium, Ionized Calcium, Chloride |
| Gadodiamide | 1.4 mmol/L | Sodium, Potassium, Ionized Calcium, Chloride |
| Hemoglobin (Hemolysis) | 1000 mg/dL | Sodium, Ionized Calcium, Chloride |
| Heparin | 100,000 U/L | Sodium, Potassium, Ionized Calcium, Chloride |
| Ibuprofen | 1060 µmol/L | Sodium, Potassium, Ionized Calcium, Chloride |
| Leflunomide | 100 µg/mL | Sodium, Potassium, Ionized Calcium, Chloride |
| Lithium | 3.2 mmol/L | Sodium, Potassium |
| Methadone | 10.3 µmol/L | Sodium, Potassium, Ionized Calcium, Chloride |
| Midazolam | 0.376 mg/dL | Sodium, Potassium, Ionized Calcium, Chloride |
| Morphine | 27.3 µmol/L | Sodium, Potassium, Ionized Calcium, Chloride |
| N-Acetyl-L-cysteine | 920µmol/L | Sodium, Potassium, Ionized Calcium, Chloride |
| Perchlorate | 20 mg/dL | Sodium, Potassium, Ionized Calcium |
| Phenobarbital | 2970 µmol/L | Sodium, Potassium, Ionized Calcium, Chloride |
| Test Substance | Test Concentration | Tested analytes where interference was not observed |
| Piperacillin | 110 mg/dL | Sodium, Potassium, Ionized Calcium, Chloride |
| Propofol | 4.8 mg/dL | Sodium, Potassium, Ionized Calcium, Chloride |
| Salicylic acid | 0.207 mmol/L | Sodium, Potassium, Ionized Calcium, Chloride |
| Suxamethonium | 68 µmol/L | Sodium, Potassium, Ionized Calcium, Chloride |
| Tazobactam | 3.05 mg/dL | Sodium, Potassium, Ionized Calcium, Chloride |
| Teriflunomide | 100 µg/mL | Sodium, Potassium, Ionized Calcium, Chloride |
| Thiocyanate | 898 µmol/L | Sodium, Potassium, Ionized Calcium, Chloride |
| Thiopental | 1660 µmol/L | Sodium, Potassium, Ionized Calcium, Chloride |
| Triglycerides (Intralipid) | 2000 mg/dL(1% Intralipid) | Sodium, Chloride, Ionized Calcium |
| Vancomycin | 82.8 µmol/L | Sodium, Potassium, Ionized Calcium, Chloride |
{18}------------------------------------------------
Analytical Specificity (Cont.)
The table below lists substances that demonstrated interference with Na*, K*, Ca** and the concentration of the interfering substance, as well as the bias observed and its direction (positive / negative):
| InterferingSubstance | AffectedAnalytes | AnalyteConcentration | InterferingConcentrationTested | BiasObserved(Mean) | LowestInterferingConcentrationwith AnalyteImpact | Bias Observedat the LowestConcentration |
|---|---|---|---|---|---|---|
| Hemoglobin(Hemolysis) | Potassium | 3.5 mmol/L | 1000 mg/dL | +16 % | 155 mg/dL | +7% |
| Hemoglobin(Hemolysis) | Potassium | 5.0 mmol/L | 1000 mg/dL | +15 % | 228 mg/dL | +7% |
| Perchlorate | Chloride | 100 mmol/L | 20 mg/dL | +6 % | 18 mg/dL | +5% |
| Perchlorate | Chloride | 110 mmol/L | 20 mg/dL | +5 % | 17 mg/dL | +5% |
| Triglyceride(Intralipid) | Potassium | 3.5 mmol/L | 2000 mg/dL(1 % Intralipid) | +11 % | 689 mg/dL(0.34 %) | +7% |
| Triglyceride(Intralipid) | Potassium | 5.0 mmol/L | 2000 mg/dL(1 % Intralipid) | No Interference Observed |
{19}------------------------------------------------
| Analyte | Reference Range | Unit |
|---|---|---|
| $Na^+$ | 136 to 145 | mmol/L |
| 136 to 145 | mEq/L | |
| $K^+$ | 3.5 to 5.1 | mmol/L |
| 3.5 to 5.1 | mEq/L | |
| $Ca^{++}$ | 1.15 to 1.33 | mmol/L |
| 2.30 to 2.66 | mEq/L | |
| 4.60 to 5.32 | mg/dL | |
| 1.16 to 1.32 (venous) | mmol/L | |
| 2.32 to 2.64 (venous) | mEq/L | |
| 4.64 to 5.28 (venous) | mg/dL | |
| $Cl^-$ | 98 to 107 | mmol/L |
| 98 to 107 | mEq/L |
Reference Ranges
Source: Burtis, Carl and David Bruns, Tietz Textbook of Clinical Chemistry and Molecular Diagnostics, Elsevier Saunders, 7th Edition, 2015, pages 952-982.
{20}------------------------------------------------
Clinical Testing
In accordance with EP09c, a method comparison study was conducted at three (3) point-of-care (POC) sites on the GEM Premier ChemSTAT compared to the predicate device, the GEM Premier 4000 (K133407), using lithium heparinized whole blood patient samples from the intended use population. Less than 10% of samples included in the study were contrived.
| Pooled Point-of-Care Sites | |||||
|---|---|---|---|---|---|
| Analyte | N | Slope | Intercept | R | Sample Range |
| Na+ (mmol/L) | 436 | 1.021 | -2.157 | 0.987 | 100 to 170 |
| K+ (mmol/L) | 442 | 1.000 | 0.100 | 0.999 | 0.5 to 18.2 |
| Ca++ (mmol/L) | 444 | 1.000 | 0.015 | 0.999 | 0.26 to 4.08 |
| Cl- (mmol/L) | 435 | 1.000 | 1.000 | 0.994 | 45 to 154 |
The pooled results from the POC sites are presented below.
| Conclusion | The technological and functional characteristics of the new GEMPremier ChemSTAT as described above are substantially equivalent tothat of the predicate device (GEM Premier 4000) for Sodium,Potassium, Ionized Calcium and Chloride. |
|---|---|
| The analytical and clinical study results demonstrate that the GEMPremier ChemSTAT is safe and effective for its intended purpose andequivalent in performance to the predicate device (K133407). |
§ 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.