GEM Premier ChemSTAT

K183549 · Instrumentation Laboratory CO · JGS · Feb 16, 2019 · Clinical Chemistry

Device Facts

• Record ID: K183549
• Device Name: GEM Premier ChemSTAT
• Applicant: Instrumentation Laboratory CO
• Product Code: JGS · Clinical Chemistry
• Decision Date: Feb 16, 2019
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1665
• 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 sodium (Na⁺), potassium (K⁺), ionized calcium (Ca²⁺) 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. Ionized calcium (Ca²⁺) 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.

Device Story

Portable critical care analyzer for rapid electrolyte measurement (Na+, K+, Ca++, Cl-) in lithium heparinized whole blood. Operates via aspiration of blood samples into a disposable, self-contained GEM Premier ChemSTAT PAK (cartridge) containing sensors, reagents, and waste management. Used in clinical settings and central labs by healthcare professionals. Employs potentiometry for analyte quantification. Features Intelligent Quality Management (iQM) for continuous, real-time monitoring of sensors and reagents with automatic error detection, correction, and documentation. Results displayed on a touch-sensitive screen to assist clinicians in diagnosing electrolyte/metabolic disorders. Benefits include rapid, point-of-care diagnostic capability, reducing turnaround time for critical care decisions.

Clinical Evidence

Method comparison study conducted at three POC sites (N=435-444 samples per analyte) comparing GEM Premier ChemSTAT to the predicate GEM Premier 4000. Results showed high correlation (R=0.987-0.999) across reportable ranges. Precision studies (internal and external) performed per CLSI EP05-A3 demonstrated total %CVs within specifications (e.g., Na+ 0.4-0.6%, K+ 0.6-2.3%). Linearity and analytical specificity (interference testing) confirmed performance across claimed ranges.

Technological Characteristics

Portable analyzer with touch-sensitive screen. Sensors: PVC-based ion-selective electrodes (ISE). Reference: Ag/Ag+ electrode with open liquid junction. Calibration: 2-point, automated via internal process control solutions. Connectivity: standalone (no wireless/network transmission). Software: Linux-based. Sterilization: N/A (disposable closed cartridge).

Indications for Use

Indicated for healthcare professionals to perform quantitative measurements of sodium, potassium, ionized calcium, and chloride in arterial and venous lithium heparinized whole blood for patients requiring electrolyte balance assessment in clinical or central laboratory settings.

Regulatory Classification

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.

Predicate Devices

• GEM Premier 4000 (k133407)

Submission Summary (Full Text)

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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 ([e-mail]) or phone [phone] 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)

| <div> <span> <span style="font-size: 16px;">☑</span> Prescription Use (Part 21 CFR 801 Subpart D) </span> </div> |
|--------------------------------------------------------------------------------------------------------------------------|
| <div> <span> <span style="font-size: 16px;">☐</span> Over-The-Counter Use (21 CFR 801 Subpart C) </span> </div> |

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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.<br>180 Hartwell Road<br>Bedford, MA 01730, USA |
|-------------------------|-----------------------------------------------------------------------------------------|
| Contact Person | Gabriella Erdosy<br>Phone: [phone]<br>Fax: [phone]<br>Email: [e-mail] |
| Preparation Date | February 15, 2019 |
| Device Trade Name | GEM Premier ChemSTAT |

| Predicate Device | GEM Premier 4000 | K133407 |
|------------------|------------------|---------|
|------------------|------------------|---------|

| Regulatory Information | | | | | |
|------------------------|-----------------------|---------------------------------------------------------------------|---------------------|-----------------|-------------------|
| Device | Regulation<br>Section | Regulatory Description | Classification | Product<br>Code | Panel |
| Analyzer | 862.2160 | Analyzer, chemistry<br>(photometric, discrete), for<br>clinical use | Class I<br>(Exempt) | JJE | |
| Sodium | 862.1665 | Sodium test system | Class II | JGS | Chemistry<br>(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 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. |
| | The values of all PC Solutions are read from the GEM PAK<br>Electronically Erasable Programmable Read Only<br>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. |
| | The GEM Premier ChemSTAT PAK has flexible menus to assist<br>facilities in maximizing efficiency. |
| | 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<br>designed to provide continuous monitoring of the analytical<br>process before and after sample measurement with real-time,<br>automatic error detection, automatic correction and automatic<br>documentation of all corrective actions.<br><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 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:<br>GEM Premier ChemSTAT | Predicate Device:<br>GEM Premier 4000 | |
| 510(k) No. | Pending | K133407 | |
| Manufacturer | Instrumentation Laboratory Co. | Same | |
| Intended Use | A portable critical care system for use by<br>health care professionals to rapidly<br>analyze lithium heparinized whole<br>blood samples at the point of health<br>care delivery in a clinical setting and in a<br>central laboratory. The instrument<br>provides quantitative measurements of<br>Sodium (Na+), Potassium (K+), Ionized<br>Calcium (Ca++) and Chloride (Cl-) from<br>arterial and venous heparinized whole<br>blood. These parameters, along with<br>derived parameters, aid in the diagnosis<br>of 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<br>(dependent on sample mode) | |
| Sample Type | Lithium heparinized whole blood<br>(arterial and venous) | Same<br>(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:<br>GEM Premier ChemSTAT | Predicate Device:<br>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 | Whole<br>Blood<br>Level | N | Mean | Within Run<br>SD | Within Run<br>%CV | Analyzer-<br>to-<br>Analyzer<br>SD | Analyzer-<br>to-<br>Analyzer<br>%CV | Total<br>SD | Total<br>%CV |
|-----------------|-------------------------|-----|------|------------------|-------------------|------------------------------------|-------------------------------------|-------------|--------------|
| Na+<br>(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+<br>(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 | Whole<br>Blood<br>Level | N | Mean | Within Run<br>SD | Within Run<br>%CV | Analyzer-<br>to-<br>Analyzer<br>SD | Analyzer-<br>to-<br>Analyzer<br>%CV | Total<br>SD | Total<br>%CV |
|------------------|-------------------------|-----|------|------------------|-------------------|------------------------------------|-------------------------------------|-------------|--------------|
| Ca++<br>(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-<br>(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 | Control<br>Level | N | Mean | Repeatability | | Between-Run | | Between-Day | | Between-Site | | Reproducibility | |
| | | | | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| Na+<br>(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 | Control<br>Level | N | Mean | Repeatability | | Between-Run | | Between-Day | | Between-Site | | Reproducibility | |
| | | | | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| K+<br>(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+<br>(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++<br>(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++<br>(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 | Control<br>Level | N | Mean | Repeatability | | Between-Run | | Between-Day | | Between-Site | | Reproducibility | |
| | | | | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| Cl-<br>(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.

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#### Reproducibility Study with Aqueous Controls – Point-of-Care (POC) Setting (Cont.)

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## Reproducibility Study with Aqueous Controls – Point-of-Care (POC) Setting (Cont.)

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#### 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 |
|-----------------|---------------------------------------|--------|-----|------|----------------------------|
| Na+<br>(mmol/L) | Fixed<br>(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+<br>(mmol/L) | Fixed<br>(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+<br>(mmol/L) | Fixed<br>(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+<br>(mmol/L) | Variable<br>(%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 Variable<br>Acceptance Range | Site | N | Mean | Within Sample<br>SD of %CV |
|------------------|---------------------------------------|--------|-----|------|----------------------------|
| Ca++<br>(mmol/L) | Fixed<br>(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++<br>(mmol/L) | Variable<br>(%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-<br>(mmol/L) | Fixed<br>(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-<br>(mmol/L) | Variable<br>(%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 | # of<br>Levels | N per<br>Level | Slope | Intercept | R2 | Tested<br>Range | Reportable<br>Range |
|------------------|----------------|----------------|-------|-----------|--------|-----------------|---------------------|
| Na+<br>(mmol/L) | 9 | 18 | 1.023 | -1.189 | 0.9997 | 92 to 200 | 100 to 180 |
| K+<br>(mmol/L) | 9 | 18 | 0.995 | 0.057 | 0.9998 | 0.2 to 19.6 | 0.3 to 19.0 |
| Ca++<br>(mmol/L) | 9 | 18 | 0.986 | 0.019 | 0.9984 | 0.04 to 4.27 | 0.10 to 4.25 |
| Cl-<br>(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<br>(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):

| 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 |
|------------------------------|----------------------|--------------------------|----------------------------------------|----------------------------|------------------------------------------------------------------|-------------------------------------------------|
| Hemoglobin<br>(Hemolysis) | Potassium | 3.5 mmol/L | 1000 mg/dL | +16 % | 155 mg/dL | +7% |
| Hemoglobin<br>(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<br>(Intralipid) | Potassium | 3.5 mmol/L | 2000 mg/dL<br>(1 % Intralipid) | +11 % | 689 mg/dL<br>(0.34 %) | +7% |
| Triglyceride<br>(Intralipid) | Potassium | 5.0 mmol/L | 2000 mg/dL<br>(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 GEM<br>Premier ChemSTAT as described above are substantially equivalent to<br>that of the predicate device (GEM Premier 4000) for Sodium,<br>Potassium, Ionized Calcium and Chloride. |
|------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | 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). |