GEM Premier ChemSTAT
Device Facts
| Record ID | K183546 |
|---|---|
| Device Name | GEM Premier ChemSTAT |
| Applicant | Instrumentation Laboratory CO |
| Product Code | CGA · Clinical Chemistry |
| Decision Date | Feb 16, 2019 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 862.1345 |
| Device Class | Class 2 |
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 Glucose (Glu), Lactate (Lac), Hematocrit (Hct), pH and partial pressure of carbon dioxide (pCO2) from arterial and venous heparinized whole blood. These parameters, along with derived parameters, aid in the diagnosis of a patient's acid/base status and metabolite balance. - Glucose (Glu) measurement is used in the diagnosis, monitoring and treatment of carbohydrate metabolism disturbances including diabetes mellitus, neonatal hypoglycemia, idiopathic hypoglycemia, and of pancreatic islet cell carcinoma. - Lactate (Lac) measurement is used to evaluate the acid-base status of patients suspected of having lactic acidosis, to monitor tissue hypoxia and strenuous physical exertion, and in the diagnosis of hyperlactatemia. - Hematocrit (Hct) measurements in whole blood of the packed red cell volume of a blood sample are used to distinguish normal from abnormal states, such as anemia and erythrocytosis (an increase in the number of red cells). - pH and pCO2 measurements in whole blood are used in the diagnosis and treatment of life-threatening acid-base disturbances.
Device Story
Portable critical care system; analyzes lithium heparinized whole blood (arterial/venous) at point-of-care or central lab. Input: whole blood sample via disposable GEM Premier ChemSTAT PAK (cartridge). Operation: cartridge contains sensors, process control solutions, sampler, and waste; analyzer uses internal logic/touchscreen to guide user. Principle: amperometry (Glu, Lac), conductivity (Hct), potentiometry (pH, pCO2). Output: quantitative measurements of Glu, Lac, Hct, pH, pCO2. iQM (Intelligent Quality Management) provides continuous monitoring, automatic error detection, correction, and documentation. Healthcare providers use output to diagnose/monitor acid-base status and metabolite balance; aids clinical decision-making for life-threatening disturbances.
Clinical Evidence
Method comparison study (CLSI EP09c) compared GEM Premier ChemSTAT to GEM Premier 4000 using lithium heparinized whole blood patient samples. Pooled data from 3 POC sites and internal CSL (N=431-559 per analyte) showed high correlation (R=0.995-0.999) across reportable ranges. Precision studies (CLSI EP05-A3) and reproducibility studies (multi-site POC) confirmed performance within specifications. Bench testing included LoB/LoD/LoQ, linearity, and analytical specificity (interference testing).
Technological Characteristics
Portable analyzer with touch-sensitive screen. Disposable multi-use PAK (cartridge) contains sensors, process control solutions, sampler, and waste. Measurement principles: Amperometry (Glu, Lac), Conductivity (Hct), Potentiometry (pH, pCO2). Calibration: 2-point. iQM (Intelligent Quality Management) system for continuous monitoring. Components traceable to NIST/CLSI standards. EEPROM chip in cartridge stores PC solution values.
Indications for Use
Indicated for health care professionals to analyze lithium heparinized whole blood (arterial/venous) for Glu, Lac, Hct, pH, and pCO2. Used for diagnosis, monitoring, and treatment of carbohydrate metabolism disturbances (e.g., diabetes, hypoglycemia), acid-base status (e.g., lactic acidosis, tissue hypoxia), and hematological states (e.g., anemia, erythrocytosis). For prescription use in clinical laboratories and point-of-care settings.
Regulatory Classification
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.
Special Controls
*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.
Predicate Devices
- GEM Premier 4000 (k133407)
Related Devices
- K160412 — GEM Premier 5000 (Measured Parameters: pH, pCO2 and pO2) · Instrumentation Laboratory CO · Dec 14, 2016
- K061974 — GEM PREMIER 4000 WITH IQM, MODEL 4000; GEM CVP 1 AND 2 WITH CO-OX; GEM CVP 3 AND 4 HEMATOCRIT · Instrumentation Laboratory CO · Sep 15, 2006
- K223608 — GEM Premier 7000 with IQM3 · Instrumentation Laboratory Company · Aug 10, 2023
Submission Summary (Full Text)
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February 16, 2019
Instrumentation Laboratory Co. Gabriella Erdosv Regulatory Affairs Manager 180 Hartwell Road Bedford, MA 01730
Re: K183546
Trade/Device Name: GEM Premier ChemSTAT Regulation Number: 21 CFR 862.1345 Regulation Name: Glucose test system Regulatory Class: Class II Product Code: CGA, KHP, GKF, CHL 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.
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Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 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 (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 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, you 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
for Courtney H. Lias, Ph.D. 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) k183546
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 Glucose (Glu), Lactate (Lac), Hematocrit (Hct), pH and partial pressure of carbon dioxide (pCO2) from arterial and venous heparinized whole blood. These parameters, along with derived parameters, aid in the diagnosis of a patient's acid/base status and metabolite balance.
- · Glucose (Glu) measurement is used in the diagnosis, monitoring and treatment of carbohydrate metabolism disturbances including diabetes mellitus, neonatal hypoglycemia, idiopathic hypoglycemia, and of pancreatic islet cell carcinoma.
- · Lactate (Lac) measurement is used to evaluate the acid-base status of patients suspected of having lacidosis, to monitor tissue hypoxia and strenuous physical exertion, and in the diagnosis of hyperlactatemia.
- Hematocrit (Hct) measurements in whole blood of the packed red cell volume of a blood sample are used to distinguish normal from abnormal states, such as anemia and erythrocytosis (an increase in the number of ed cells).
- · DH and pCO2 measurements in whole blood are used in the diagnosis and treatment of life-threatening acid-base disturbances.
| Type of Use (Select one or both, as applicable) | |
|------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------|
| <div style="display:flex; align-items:center;"><span style="font-size:16px;">☑</span> Prescription Use (Part 21 CFR 801 Subpart D)</div> | <div style="display:flex; align-items:center;"><span style="font-size:16px;">☐</span> Over-The-Counter Use (21 CFR 801 Subpart C)</div> |
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## K183546: GEM Premier ChemSTAT
## 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.<br>180 Hartwell Road<br>Bedford, MA 01730, USA |
|-------------------------|------------------------------------------------------------------------------------|
|-------------------------|------------------------------------------------------------------------------------|
| Contact Person | Gabriella Erdosy |
|----------------|-------------------------|
| | Phone: 781-861-4571 |
| | Fax: 781-861-4207 |
| | Email: gerdosy@ilww.com |
| Preparation Date | February 11, 2019 |
|------------------|-------------------|
|------------------|-------------------|
| Device Trade Name | GEM Premier ChemSTAT |
|-------------------|----------------------|
|-------------------|----------------------|
| Predicate Device | GEM Premier 4000 | K133407 |
|------------------|------------------|---------|
|------------------|------------------|---------|
| Regulatory Information | | | | | |
|------------------------|-----------------------|-------------------------------------------|----------------|-----------------|--------------------|
| Analyte | Regulation<br>Section | Regulatory Description | Classification | Product<br>Code | Panel |
| Glucose | 862.1345 | Glucose test system | Class II | CGA | Chemistry<br>(75) |
| Lactate | 862.1450 | Lactic acid test system | Class I | KHP | Chemistry<br>(75) |
| Hematocrit | 864.5600 | Automated hematocrit<br>instrument | Class II | GKF | Hematology<br>(81) |
| pH and pCO2 | 862.1120 | Blood Gases (pCO2) and<br>Blood pH system | Class II | CHL | Chemistry<br>(75) |
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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 Glu, Lac, Hct, pH, and pCO2. 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 and<br>processing power necessary to perform analysis. It employs a<br>unique touch-sensitive color screen and a simple set of menus and<br>buttons for user interaction. The analyzer guides operators through<br>the sampling process with simple, clear messages and prompts. |
| PAK (Cartridge) | The disposable, multi-use GEM Premier ChemSTAT PAK is a<br>completely closed cartridge that houses all components necessary<br>to operate the instrument once the GEM PAK is validated. These<br>components include the sensors, Process Control (PC) Solutions,<br>sampler, and waste bag.<br><br>The values of all PC Solutions are read from the GEM PAK<br>Electronically Erasable Programmable Read Only Memory<br>(EEPROM) chip. The components and processes used to<br>manufacture the PC Solutions in the GEM PAK are traceable to<br>National Institute of Standards and Technology (NIST) standards,<br>Clinical & Laboratory Standards Institute (CLSI) procedures or other<br>internal standards, where available and appropriate.<br><br>The GEM Premier ChemSTAT PAK has flexible menus to assist<br>facilities in maximizing efficiency.<br><br>As part of this program, GEM ChemSTAT CVP (Calibration Valuation<br>Products) are external solutions intended to complete the<br>calibration process and final accuracy assessment of the iQM<br>cartridge calibration following warm-up. |
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| Device Description (Cont.) | |
|-----------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intelligent Quality Management<br>(iQM) | Intelligent Quality Management (iQM) is used as the quality<br>control and assessment system for the GEM Premier ChemSTAT<br>system. iQM is an active quality process control program designed<br>to provide continuous monitoring of the analytical process before<br>and after sample measurement with real-time, automatic error<br>detection, automatic correction and automatic documentation of<br>all corrective actions.<br>iQM performs 4 types of continuous, quality checks to monitor<br>the performance of the GEM PAK, sensors, and reagents<br>throughout the cartridge use-life. These checks include System,<br>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 Glucose (Glu), Lactate (Lac), Hematocrit (Hct), pH, and partial pressure of carbon dioxide (pCQ₂) from arterial and venous heparinized whole blood. These parameters, along with derived parameters, aid in the diagnosis of a patient's acid/base status and metabolite balance.
- . Glucose (Glu) measurement is used in the diagnosis, monitoring and treatment of carbohydrate metabolism disturbances including diabetes mellitus, neonatal hypoglycemia, idiopathic hypoglycemia, and of pancreatic islet cell carcinoma.
- Lactate (Lac) measurement is used to evaluate the acid-base status of patients suspected of ● having lactic acidosis, to monitor tissue hypoxia and strenuous physical exertion, and in the diagnosis of hyperlactatemia.
- Hematocrit (Hct) measurements in whole blood of the packed red cell volume of a blood sample are used to distinguish normal from abnormal states, such as anemia and erythrocytosis (an increase in the number of red cells).
- pH and pCO2 measurements in whole blood are used in the diagnosis and treatment of life-● threatening acid-base disturbances.
### 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:<br>GEM Premier ChemSTAT | Predicate Device:<br>GEM Premier 4000 | |
| 510(k) No. | K183546 | K133407 | |
| Manufacturer | Instrumentation Laboratory Co. | Same | |
| Intended Use | 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 Glucose (Glu), Lactate (Lac), Hematocrit (Hct), pH and partial pressure of carbon dioxide (pCO2) from arterial and venous heparinized whole blood. These parameters, along with derived parameters, aid in the diagnosis of a patient's acid/base status and metabolite balance. | Same | |
| Intended User | Central Laboratory and Point-of-Care | Same | |
| Measurement Principle | Glu<br><br>Lac<br><br>Hct<br><br>pH<br><br>pCO2 | Amperometry<br><br>Amperometry<br><br>Conductivity<br><br>Potentiometry<br><br>Potentiometry | Same<br><br>Same<br><br>Same<br><br>Same<br><br>Same |
| | Sample Volume | 150 μL | 65 to 150 μL<br>(dependent on sample mode) |
| | Sample Type | Lithium heparinized whole blood<br>(arterial and venous) | Same<br>(arterial, venous and capillary) |
| | Substantial Equivalency (Cont.) | | |
| | Item | Candidate Device:<br>GEM Premier ChemSTAT | Predicate Device:<br>GEM Premier 4000 |
| Reportable Range | Glu | 4 to 685 mg/dL | Same |
| | Lac | 0.3 to 17.0 mmol/L | Same |
| | Hct | 15 to 72% | Same |
| | pH | 7.00 to 8.00 | Same |
| | pCO2 | 6 to 125 mmHg | Same |
| PAK Storage Temperature | 15-25°C | Same | |
| Calibration | 2-point calibration | Same | |
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### Performance Summary
### Internal Precision Study – Whole Blood
In accordance with CLSI EP05-A3, an internal precision study was performed using five (5) different concentrations of whole blood per analyte, each run 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 | Whole<br>Blood<br>Level | N | Mean | Within Run<br>SD | Within Run<br>%CV | Total<br>SD | Total<br>%CV |
|---------------------|-------------------------|-----|------|------------------|-------------------|-------------|--------------|
| Glucose<br>(mg/dL) | Level 1 | 120 | 24 | 0.5 | 2.3% | 0.5 | 2.3% |
| | Level 2 | 120 | 48 | 0.9 | 1.9% | 0.9 | 1.9% |
| | Level 3 | 120 | 122 | 1.3 | 1.1% | 1.7 | 1.4% |
| | Level 4 | 120 | 356 | 2.7 | 0.8% | 3.2 | 0.9% |
| | Level 5 | 120 | 620 | 3.2 | 0.5% | 5.4 | 0.9% |
| Lactate<br>(mmol/L) | Level 1 | 120 | 0.7 | 0.06 | 8.9% | 0.06 | 8.9% |
| | Level 2 | 120 | 2.0 | 0.06 | 2.8% | 0.07 | 3.3% |
| | Level 3 | 120 | 4.9 | 0.05 | 1.1% | 0.11 | 2.3% |
| | Level 4 | 120 | 7.8 | 0.13 | 1.7% | 0.18 | 2.3% |
| | Level 5 | 120 | 14.2 | 0.23 | 1.6% | 0.34 | 2.4% |
| Hct<br>(%) | Level 1 | 120 | 18 | 0.3 | 1.6% | 0.3 | 1.6% |
| | Level 2 | 120 | 33 | 0.3 | 0.9% | 0.4 | 1.1% |
| | Level 3 | 120 | 44 | 0.3 | 0.7% | 0.4 | 0.9% |
| | Level 4 | 120 | 57 | 0.3 | 0.5% | 0.4 | 0.7% |
| | Level 5 | 120 | 65 | 0.4 | 0.7% | 0.5 | 0.8% |
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| Analyte | Whole<br>Blood<br>Level | N | Mean | Within Run<br>SD | Within Run<br>%CV | Total<br>SD | Total<br>%CV |
|----------------|-------------------------|-----|------|------------------|-------------------|-------------|--------------|
| pH | Level 1 | 120 | 7.07 | 0.008 | 0.1% | 0.008 | 0.1% |
| | Level 2 | 120 | 7.25 | 0.007 | 0.1% | 0.007 | 0.1% |
| | Level 3 | 120 | 7.34 | 0.008 | 0.1% | 0.008 | 0.1% |
| | Level 4 | 120 | 7.49 | 0.009 | 0.1% | 0.010 | 0.1% |
| | Level 5 | 120 | 7.69 | 0.010 | 0.1% | 0.013 | 0.2% |
| pCO2<br>(mmHg) | Level 1 | 120 | 110 | 1.4 | 1.3% | 1.4 | 1.3% |
| | Level 2 | 120 | 71 | 0.9 | 1.2% | 0.9 | 1.2% |
| | Level 3 | 120 | 51 | 0.7 | 1.4% | 0.7 | 1.4% |
| | Level 4 | 120 | 29 | 0.4 | 1.5% | 0.5 | 1.6% |
| | Level 5 | 120 | 12 | 0.6 | 4.8% | 0.6 | 4.8% |
## Internal Precision Study – Whole Blood (Cont.)
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#### Reproducibility Study with Aqueous Controls – Point-of-Care (POC) Setting
In accordance with CLSI EPOS-A3, a reproducibith controls at three (3) external clinical point-of-care (POC) sites. The studies were run by a total of nine (9) different operators on six (6) different GEM Premier ChemSTAT instruments, usingle lot of GEM Premier ChemSTAT PAKs (cartridges). Each site used seven (7) levels of quality control material for Glu and S (2 levels of GEM ChemSTAT PVP) , six (6) levels for Hct (2 levels of GEM ChemSTAT CVP and 4 levels of GEM Cherels of (6) levels for pH and pCO2 (2 levels of GEM ChemSTAT CVP and 4 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).
All results at all sites were within specification.
| Pooled Multi-Site POC Data | | | | | | | | | | | | | |
|----------------------------|------------------|----|------|---------------|------|-------------|------|-------------|------|--------------|------|-----------------|-------|
| Analyte | Control<br>Level | N | Mean | Repeatability | | Between-Run | | Between-Day | | Between-Site | | Reproducibility | |
| | | | | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| Glucose<br>(mg/dL) | CVP Level 1 | 90 | 392 | 1.0 | 0.2% | 3.9 | 1.0% | 0.7 | 0.2% | 4.3 | 1.1% | 5.9 | 1.5% |
| | CVP Level 2 | 90 | 78 | 1.5 | 1.9% | 0.0 | 0.0% | 0.6 | 0.8% | 0.0 | 0.0% | 1.6 | 2.1% |
| | PVP Level 1 | 90 | 642 | 1.3 | 0.2% | 1.4 | 0.2% | 1.1 | 0.2% | 6.5 | 1.0% | 6.8 | 1.1% |
| | PVP Level 2 | 90 | 393 | 1.6 | 0.4% | 1.3 | 0.3% | 1.3 | 0.3% | 3.3 | 0.8% | 4.2 | 1.1% |
| | PVP Level 3 | 90 | 115 | 1.4 | 1.2% | 0.6 | 0.5% | 0.0 | 0.0% | 0.0 | 0.0% | 1.5 | 1.3% |
| | PVP Level 4 | 90 | 80 | 0.6 | 0.7% | 0.3 | 0.4% | 0.5 | 0.6% | 0.3 | 0.3% | 0.9 | 1.1% |
| | PVP Level 5 | 90 | 14 | 0.5 | 3.6% | 0.0 | 0.0% | 0.2 | 1.6% | 1.4 | 9.7% | 1.5 | 10.5% |
| Pooled Multi-Site POC Data | | | | | | | | | | | | | |
| Analyte | Control Level | | | Repeatability | | Between-Run | | Between-Day | | Between-Site | | Reproducibility | |
| | | N | Mean | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| Lactate<br>(mmol/L) | CVP Level 1 | 90 | 8.2 | 0.04 | 0.5% | 0.04 | 0.5% | 0.02 | 0.3% | 0.03 | 0.3% | 0.07 | 0.8% |
| | CVP Level 2 | 90 | 1.7 | 0.03 | 1.8% | 0.00 | 0.0% | 0.01 | 0.7% | 0.04 | 2.4% | 0.05 | 3.1% |
| | PVP Level 1 | 90 | 15.7 | 0.07 | 0.4% | 0.07 | 0.4% | 0.07 | 0.5% | 0.09 | 0.6% | 0.15 | 0.9% |
| | PVP Level 2 | 90 | 8.1 | 0.06 | 0.7% | 0.04 | 0.5% | 0.04 | 0.4% | 0.07 | 0.9% | 0.11 | 1.3% |
| | PVP Level 3 | 90 | 5.0 | 0.03 | 0.6% | 0.00 | 0.0% | 0.04 | 0.8% | 0.03 | 0.6% | 0.06 | 1.2% |
| | PVP Level 4 | 90 | 1.7 | 0.03 | 1.5% | 0.01 | 0.4% | 0.01 | 0.6% | 0.01 | 0.9% | 0.03 | 1.9% |
| | PVP Level 5 | 90 | 0.5 | 0.02 | 4.1% | 0.00 | 0.0% | 0.03 | 5.1% | 0.03 | 5.6% | 0.04 | 8.6% |
| Hematocrit<br>(%) | CVP Level 1 | 90 | 42 | 0.0 | 0.0% | 0.0 | 0.0% | 0.0 | 0.0% | 0.0 | 0.0% | 0.0 | 0.0% |
| | CVP Level 2 | 90 | 22 | 0.0 | 0.0% | 0.0 | 0.0% | 0.0 | 0.0% | 0.0 | 0.0% | 0.0 | 0.0% |
| | critPVP Level 1 | 90 | 18 | 0.0 | 0.0% | 0.0 | 0.0% | 0.0 | 0.0% | 0.0 | 0.0% | 0.0 | 0.0% |
| | critPVP Level 2 | 90 | 23 | 0.0 | 0.0% | 0.0 | 0.0% | 0.0 | 0.0% | 0.0 | 0.0% | 0.0 | 0.0% |
| | critPVP Level 3 | 90 | 43 | 0.1 | 0.2% | 0.0 | 0.0% | 0.0 | 0.0% | 0.0 | 0.0% | 0.1 | 0.2% |
| | critPVP Level 4 | 90 | 68 | 0.0 | 0.0% | 0.0 | 0.0% | 0.0 | 0.0% | 0.0 | 0.0% | 0.0 | 0.0% |
| Pooled Multi-Site POC Data | | | | | | | | | | | | | |
| Analyte | Control<br>Level | N | Mean | Repeatability | | Between-Run | | Between-Day | | Between-Site | | Reproducibility | |
| | | | | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| pH | CVP Level 1 | 90 | 7.11 | 0.005 | 0.1% | 0.002 | 0.0% | 0.002 | 0.0% | 0.000 | 0.0% | 0.006 | 0.1% |
| | CVP Level 2 | 90 | 7.54 | 0.003 | 0.0% | 0.001 | 0.0% | 0.001 | 0.0% | 0.001 | 0.0% | 0.003 | 0.0% |
| | PVP Level 1 | 90 | 7.59 | 0.004 | 0.1% | 0.001 | 0.0% | 0.002 | 0.0% | 0.002 | 0.0% | 0.005 | 0.1% |
| | PVP Level 2 | 90 | 7.11 | 0.007 | 0.1% | 0.000 | 0.0% | 0.003 | 0.0% | 0.000 | 0.0% | 0.008 | 0.1% |
| | PVP Level 3 | 90 | 7.36 | 0.003 | 0.0% | 0.004 | 0.1% | 0.000 | 0.0% | 0.001 | 0.0% | 0.005 | 0.1% |
| | PVP Level 4 | 90 | 7.55 | 0.004 | 0.1% | 0.001 | 0.0% | 0.002 | 0.0% | 0.002 | 0.0% | 0.005 | 0.1% |
| pCO2<br>(mmHg) | CVP Level 1 | 90 | 92 | 1.2 | 1.4% | 1.6 | 1.7% | 0.0 | 0.0% | 0.2 | 0.2% | 2.0 | 2.2% |
| | CVP Level 2 | 90 | 16 | 0.3 | 2.0% | 0.0 | 0.0% | 0.1 | 0.6% | 0.3 | 1.9% | 0.4 | 2.8% |
| | PVP Level 1 | 90 | 60 | 1.1 | 1.9% | 0.0 | 0.0% | 0.2 | 0.3% | 0.5 | 0.9% | 1.3 | 2.1% |
| | PVP Level 2 | 90 | 92 | 2.1 | 2.3% | 0.6 | 0.6% | 0.8 | 0.9% | 0.8 | 0.8% | 2.5 | 2.7% |
| | PVP Level 3 | 90 | 38 | 0.6 | 1.6% | 0.2 | 0.5% | 0.0 | 0.0% | 0.3 | 0.9% | 0.7 | 1.9% |
| | PVP Level 4 | 90 | 16 | 0.4 | 2.4% | 0.1 | 0.8% | 0.1 | 0.5% | 0.2 | 1.2% | 0.4 | 2.8% |
{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 Variable<br>Acceptance Range | Site | N | Mean | Within Sample<br>SD of %CV |
|---------------------|---------------------------------------|--------|-----|------|----------------------------|
| Glucose<br>(mg/dL) | Fixed<br>(SD) | POC 1 | 12 | 38 | 1.7 |
| | | POC 2 | 3 | 23 | 0.6 |
| | Variable<br>(%CV) | POC 3 | 15 | 49 | 1.7 |
| | | Pooled | 30 | 42 | 1.6 |
| | Variable<br>(%CV) | POC 1 | 54 | 122 | 1.0% |
| | | POC 2 | 63 | 112 | 0.8% |
| | | POC 3 | 51 | 115 | 1.0% |
| | | Pooled | 168 | 116 | 0.9% |
| Lactate<br>(mmol/L) | Fixed<br>(SD) | POC 1 | 9 | 1.9 | 0.07 |
| | | POC 2 | 27 | 1.8 | 0.08 |
| | Variable<br>(%CV) | POC 3 | 9 | 2.2 | 0.07 |
| | | Pooled | 45 | 1.9 | 0.08 |
| | Variable<br>(%CV) | POC 1 | 57 | 5.7 | 1.7% |
| | | POC 2 | 39 | 3.7 | 2.5% |
| | | POC 3 | 54 | 3.8 | 1.8% |
| | | Pooled | 150 | 4.5 | 1.9% |
All results at all sites were within specification.
{15}------------------------------------------------
| Analyte | Fixed or Variable<br>Acceptance Range | Site | N | Mean | Within Sample<br>SD of %CV |
|-------------------|---------------------------------------|--------|-----|------|----------------------------|
| Hematocrit<br>(%) | Fixed<br>(SD) | POC 1 | 69 | 32 | 0.5 |
| | | POC 2 | 66 | 40 | 0.4 |
| | | POC 3 | 63 | 31 | 0.6 |
| | | Pooled | 198 | 35 | 0.5 |
| pH | Fixed<br>(SD) | POC 1 | 63 | 7.26 | 0.008 |
| | | POC 2 | 66 | 7.36 | 0.009 |
| | | POC 3 | 66 | 7.31 | 0.007 |
| | | Pooled | 195 | 7.31 | 0.008 |
| pCO2<br>(mmHg) | Fixed<br>(SD) | POC 1 | 54 | 49 | 1.2 |
| | | POC 2 | 60 | 40 | 0.7 |
| | | POC 3 | 60 | 50 | 0.9 |
| | | Pooled | 174 | 46 | 0.9 |
| pCO2<br>(mmHg) | Variable<br>(%CV) | POC 1 | 18 | 74 | 1.4% |
| | | POC 2 | 6 | 66 | 1.6% |
| | | POC 3 | 3 | 78 | 1.5% |
| | | Pooled | 27 | 73 | 1.5% |
## 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 Glu, Lac, Hct, pH, and pCO2, using three (3) lots of GEM Premier ChemSTAT PAKs (cartridges).
| Analyte | LoB | LoD | LoQ |
|------------------|------|------|------|
| Glucose (mg/dL) | 0 | 1 | 1 |
| Lactate (mmol/L) | 0.0 | 0.0 | 0.1 |
| Hematocrit (%) | 2 | 3 | 10 |
| pH | 8.69 | 8.62 | 8.06 |
| pCO2 (mmHg) | 1 | 3 | 3 |
Following are the combined data results for LoB, LoD and LoQ:
#### Linearity
In accordance with CLSI EP06-A, a minimum of nine (9) levels per analyte were prepared by spiking or diluting whole blood to challenge the claimed reportable range for Glu, Lac, Hct, pH, and pCO₂. Each blood level was analyzed in triplicate on six (6) GEM Premier ChemSTAT test analyzers (except pH and pCO2, which were tested on 3 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 | # of<br>Levels | N per<br>Level | Slope | Intercept | R² | Tested<br>Range | Reportable<br>Range |
|------------------------|----------------|----------------|-------|-----------|--------|-----------------|---------------------|
| Glucose<br>(mg/dL) | 9 | 18 | 1.023 | -0.502 | 1.0000 | 3 to 749 | 4 to 685 |
| Lactate<br>(mmol/L) | 9 | 18 | 1.004 | 0.000 | 0.9998 | 0.2 to 17.8 | 0.3 to 17.0 |
| Hematocrit<br>(%) | 9 | 18 | 0.984 | 1.909 | 0.9975 | 13 to 74 | 15 to 72 |
| pH | 10 | 9 | 1.006 | -0.042 | 0.9996 | 6.76 to 8.10 | 7.00 to 8.00 |
| <i>p</i> CO2<br>(mmHg) | 9 | 9 | 1.030 | -0.843 | 0.9994 | 2 to 137 | 6 to 125 |
{17}------------------------------------------------
## Analytical Specificity
In accordance with EP07 3d Edition, an interference study was conducted on the GEM Premier ChemSTAT for Glu, Lac, Hct, pH, and pCO2.
The table below and on the next two pages lists the substances that were screened with no observed interference on Glu, Lac, Hct, pH, and/or pCO₂:
| Test Substance | Test Concentration | Tested analytes where interference was not observed |
|-------------------------------|------------------------------------------------|-----------------------------------------------------|
| Acetaminophen | 1030 µmol/L | Glucose, Lactate |
| Acetoacetate | 2 mmol/L | Glucose, Lactate |
| Albumin (Human) | 60 g/L | Hct |
| Ascorbic acid | 298 µmol/L | Glucose, Lactate |
| Atracurium | 50 mg/L | Glucose, Lactate, Hct, pH, pCO2 |
| Bilirubin | 40 mg/dL | Glucose, Lactate, Hct, pH, pCO2 |
| Ceftriaxone | 1510 µmol/L | Glucose, Lactate, Hct, pH, pCO2 |
| Chlorpromazine | 10.3 µmol/L | Glucose, Lactate |
| Dobutamine | 0.121 mg/dL | Glucose, Lactate |
| Dopamine | 4.06 µmol/L | Glucose, Lactate |
| Epinephrine | 0.5 µmol/L | Glucose, Lactate, Hct, pH, pCO2 |
| Ethanol | 130 mmol/L | Glucose, Lactate |
| Ethylene glycol | 8.8 mmol/L | Glucose, Lactate |
| Etomidate | 50 mg/L | Glucose, Lactate, Hct, pH, pCO2 |
| Fentanyl | 0.03 µg/mL | Glucose, Lactate, Hct, pH, pCO2 |
| Fructose | 1 mmol/L | Glucose |
| Furosemide | 48.1 µmol/L | Glucose, Lactate, Hct, pH, pCO2 |
| Gadodiamide | 1.4 mmol/L | Glucose, Lactate, Hct, pH, pCO2 |
| Glycolic acid | 1.0 mmol/L | Glucose |
| Test Substance | Test Concentration | Tested analytes where interference was not observed |
| Hematocrit | 25% | pH, pCO₂, Glucose, Lactate |
| Hematocrit | 60% | pH, pCO₂, Glucose, Lactate |
| Hemoglobin (Hemolysis) | 1000 mg/dL | Glucose, Lactate, Hct, pH, pCO₂ |
| Heparin | 100,000 U/L | Glucose, Lactate |
| β-hydroxybutyrate | 2 mmol/L | Glucose, Lactate, pH |
| Ibuprofen | 1060 µmol/L | Glucose, Lactate, Hct, pH, pCO₂ |
| Icodextrin | 20 mg/dL | Glucose, Lactate |
| Isoniazid | 438 µmol/L | Glucose, Lactate |
| Leukocytes / Platelets | 24.81 / 452 (x10³/µl)<br>27.60 / 564 (x10³/µl) | Hct 30%<br>Hct 60% |
| Maltose | 360 mg/dL | Glucose, Lactate |
| Methadone | 10.3 µmol/L | Glucose, Lactate, Hct, pH, pCO₂ |
| Midazolam | 0.376 mg/dL | Glucose, Lactate, Hct, pH, pCO₂ |
| Morphine | 27.3 µmol/L | Glucose, Lactate, Hct, pH, pCO₂ |
| N-Acetyl-L-cysteine | 920 µmol/L | Glucose, Lactate, Hct, pH, pCO₂ |
| Phenobarbital | 2970 µmol/L | Glucose, Lactate, Hct, pH, pCO₂ |
| Piperacillin | 110 mg/dL | Glucose, Lactate, Hct, pH, pCO₂ |
| pO2 | 30 mmHg | Glucose, Lactate |
| Pralidoxime iodide | 4 mg/dL | Glucose, Lactate |
| Propofol | 4.8 mg/dL | Glucose, Lactate, Hct, pH, pCO₂ |
| Suxamethonium | 68 µmol/L | Glucose, Lactate, Hct, pH, pCO₂ |
| Tazobactam | 3.05 mg/dL | Glucose, Lactate, Hct, pH, pCO₂ |
| Thiocyanate | 898 µmol/L | Glucose, Lactate |
| Test Substance | Test Concentration | Tested analytes where interference was not observed |
| Thiopental | 1660 µmol/L | pCO2 |
| Triglycerides<br>(Intralipid) | 2000 mg/dL<br>(1% Intralipid) | Glucose, Lactate, Hct, pH, pCO2 |
| Uric acid | 1.4 mmol/L | Glucose, Lactate |
| Vancomycin | 82.8 µmol/L | Glucose, Lactate, Hct, pH, pCO2 |
| Xylose | 20 mg/dL | Glucose |
{18}------------------------------------------------
# Analytical Specificity (Cont.)
{19}------------------------------------------------
## Analytical Specificity (Cont.)
The table below lists substances that demonstrated interference with Glu, Lac, Hct, pH and/or pCO2 and the concentration of the interfering substance, as well as the bias observed and its direction (positive / negative):
| Interfering<br>Substance | Affected<br>Analytes | Analyte<br>Concentration | Interfering<br>Concentration<br>Tested | Bias<br>Observed<br>(Mean) | Lowest<br>Interfering<br>Concentration<br>with Analyte<br>Impact | Bias Observed<br>at the Lowest<br>Concentration |
|--------------------------|----------------------|--------------------------|----------------------------------------|----------------------------|------------------------------------------------------------------|-------------------------------------------------|
| Galactose | Glucose | 40 mg/dL | 3.33 mmol/L | +13 % | 2.77 mmol/L | +10 % |
| | | 220 mg/dL | | No Interference Observed | | |
| Glycolic acid | Lactate | 1.0 mmol/L | 1.0 mmol/L | +1.5<br>mmol/L | 0.3 mmol/L | +0.4 mmol/L |
| | | 1.7 mmol/L | | +1.6<br>mmol/L | 0.3 mmol/L | +0.4 mmol/L |
| Hydroxyurea | Glucose | 40 mg/dL | 3.08 mg/dL | +207 % | 0.15 mg/dL | +10 % |
| | | 220 mg/dL | | +34 % | 0.90 mg/dL | +10 % |
| Hydroxyurea | Lactate | 1.0 mmol/L | 3.08 mg/dL | +3.8<br>mmol/L | 0.30 mg/dL | +0.4 mmol/L |
| | | 1.7 mmol/L | | +3.5<br>mmol/L | 0.33 mg/dL | +0.4 mmol/L |
| Mannose | Glucose | 40 mg/dL | 20 mg/dL | +12 % | 19 mg/dL | +10 % |
| | | 220 mg/dL | | No Interference Observed | | |
| Thiopental | pH | 7.40 | 1660 μmol/L | +0.04 | 789 µmol/L | +0.02 |
| | | 7.25 | | +0.03 | 1175 µmol/L | +0.02 |
{20}------------------------------------------------
| Analyte | Reference Range | Unit |
|---------|------------------------------------------------------------------------------------------|--------|
| Glu* | 65 to 95 | mg/dL |
| | 3.6 to 5.3 | mmol/L |
| Lac* | 0.36 to 0.75 (arterial at rest) | mmol/L |
| | 2.24 to 6.76 (arterial at rest) | mg/dL |
| | 0.56 to 1.39 (venous at rest) | mmol/L |
| | 5.0 to 12.5 (venous at rest) | mg/dL |
| Hct* | 39-51 (male) and 35-47 (female) | % |
| pH* | 7.35 to 7.45 | pH |
| cH* | 44.7 to 35.5 | nmol/L |
| cH* | 44.7 to 35.5 | nEq/L |
| pH* | 7.32 to 7.43 (venous) | pH |
| cH* | 47.9 to 37.2 (venous) | nmol/L |
| cH* | 47.9 to 37.2 (venous) | nEq/L |
| pCO2** | 35 to 48 (male) and 32 to 45 (female) | mmHg |
| | 4.6 to 6.4 (male) and 4.3 to 6.0 (female) | kPa |
| | 6 to 7 mmHg (0.80 to 0.93 kPa) higher than arterial pCO2<br>(venous blood, right atrium) | |
#### Reference Ranges
* Burtis, Carl and David Bruns, Tietz Textbook of Clinical Chemistry and Molecular Diagnostics, Elsevier Saunders, 7th Edition, 2015, pages 952-982.
** Wu, A., Tietz Clinical Guide to Laboratory Tests, W.B. Saunders Co., St. Louis MO, 4th Edition, 2006, pages 216.
{21}------------------------------------------------
#### Clinical Testing
In accordance with EP09c, a method comparison study was conducted 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.
- Study Design: ●
- Three (3) external point-of-care (POC) sites
- For pH and pCO2 only, internal Customer Simulation Laboratory (CSL) at IL, where multiple intended ● POC users were brought on site to run spiked samples to cover the reportable ranges.
The pooled results from the POC sites and the IL internal Customer Simulation Laboratory (CSL) are presented below.
| Pooled Point-of-Care Sites and CSL Data | | | | | |
|-----------------------------------------|-----|-------|-----------|-------|--------------|
| Analyte | N | Slope | Intercept | R | Sample Range |
| Glucose (mg/dL) | 432 | 1.019 | -0.558 | 0.999 | 35 to 684 |
| Lactate (mmol/L) | 432 | 1.000 | -0.100 | 0.997 | 0.6 to 16.0 |
| Hematocrit (%) | 431 | 1.032 | -0.626 | 0.997 | 16 to 71 |
| pH | 552 | 1.006 | -0.038 | 0.995 | 7.03 to 7.87 |
| pCO2 (mmHg) | 559 | 1.000 | 0.000 | 0.996 | 7 to 120 |
| Conclusion | The technological and functional characteristics of the new GEM<br>Premier ChemSTAT as described above are substantially equivalent to<br>that of the predicate device (GEM Premier 4000) for Glucose, Lactate,<br>Hematocrit, pH and pCO2. |
|------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | The analytical and clinical study results demonstrate that the GEM<br>Premier ChemSTAT is safe and effective for its intended purpose and<br>equivalent in performance to the predicate device (K133407). |
