GEM Premier ChemSTAT

K183555 · Instrumentation Laboratory CO · JFY · Feb 16, 2019 · Clinical Chemistry

Device Facts

• Record ID: K183555
• Device Name: GEM Premier ChemSTAT
• Applicant: Instrumentation Laboratory CO
• Product Code: JFY · Clinical Chemistry
• Decision Date: Feb 16, 2019
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1225
• 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 Creatinine (Crea), Blood Urea Nitrogen (BUN) and Total Carbon Dioxide (tCO2) 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. - Creatinine (Crea) measurements are used in the diagnosis and treatment of renal diseases and in monitoring renal dialysis. - Blood Urea Nitrogen (BUN) or urea measurements are used for the diagnosis, monitoring, and treatment of certain renal and metabolic diseases. - Total carbon dioxide/tCO2 (also referred to as bicarbonate/HCO3-) is used in the diagnosis, monitoring, and treatment of numerous potentially serious disorders associated with changes in body acid-base balance.

Device Story

Portable analyzer for point-of-care or central lab use; processes arterial/venous lithium heparinized whole blood samples. System uses disposable multi-use GEM Premier ChemSTAT Cartridge/PAK containing sensors, solutions, and waste management. Creatinine measured via enzymatic amperometry; BUN via enzymatic potentiometry; tCO2 via potentiometry. Analyzer features touch-screen interface for clinician interaction. Output provides quantitative metabolite concentrations; aids clinicians in diagnosing renal/metabolic disease and acid/base status. Benefits include rapid, on-site diagnostic information for clinical decision-making.

Clinical Evidence

No clinical trials performed. Evidence consists of analytical bench testing: precision (CLSI EP05-A3), linearity (CLSI EP06-A), interference (CLSI EP07), and detection limits (CLSI EP17-A2). Method comparison study (N=405-416) against Roche Cobas analyzers showed high correlation (R=0.986-0.997) across reportable ranges.

Technological Characteristics

Portable analyzer with touch-sensitive screen. Uses disposable, closed-system PAK (cartridge) containing sensors, process control solutions, and waste management. Measurement principles: Enzymatic Amperometry (Creatinine), Enzymatic Potentiometry (BUN), and Potentiometry (tCO2). Calibration via 2-point or 3-point methods. Components traceable to NIST/CLSI standards. Features Intelligent Quality Management (iQM) for continuous monitoring. Connectivity via internal logic/processing.

Indications for Use

Indicated for health care professionals to analyze lithium heparinized whole blood (arterial/venous) for Creatinine, BUN, and tCO2 in clinical/central lab settings. Used for diagnosis/treatment of renal diseases, metabolic diseases, and acid-base balance disorders in patients of all ages.

Regulatory Classification

Identification

A creatinine test system is a device intended to measure creatinine levels in plasma and urine. Creatinine measurements are used in the diagnosis and treatment of renal diseases, in monitoring renal dialysis, and as a calculation basis for measuring other urine analytes.

Predicate Devices

• Cobas Integra Creatinine Plus Ver.2 assay (k024098)
• Cobas Integra Urea/BUN (k954000)
• Cobas Integra Bicarbonate Liquid (k031879)

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: K183555

Trade/Device Name: GEM Premier ChemSTAT Regulation Number: 21 CFR 862.1225 Regulation Name: Creatinine test system Regulatory Class: Class II Product Code: JFY, CDQ, KHS 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.

Please note that if you modify your IVD in the future to exceed any of the limitations to the exemption found in 21 CFR 862.9(c), your device will require a new 510(k) prior to marketing this device in the United States and will not be exempt from the premarket notification requirements so long as it exceeds the limitations to the exemption found in 21 CFR 862.9.

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 (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 medical devices and radiation-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 ([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) k183555

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 Creatinine (Crea), Blood Urea Nitrogen (BUN) and Total Carbon Dioxide (tCO2) 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.

- · Creatinine (Crea) measurements are used in the diagnosis and treatment of renal diseases and in monitoring renal dialysis.
- · Blood Urea Nitrogen (BUN) or urea measurements are used for the diagnosis, monitoring, and treatment of certain renal and metabolic diseases.
- · Total carbon dioxide/tCO2 (also referred to as bicarbonate/HCO3-) is used in the diagnosis, monitoring, and treatment of numerous potentially serious disorders associated with changes in body acid-base balance.

| Type of Use (Select one or both, as applicable) | |
|---------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------|
| <div style="display:inline-flex"><span style="font-size:20px; margin-right:5px;">☒</span>Prescription Use (Part 21 CFR 801 Subpart D)</div> | <div style="display:inline-flex"><span style="font-size:20px; margin-right:5px;">☐</span>Over-The-Counter Use (21 CFR 801 Subpart C)</div> |

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## K183555: GEM Premier ChemSTAT with Creatinine, BUN and tCO2

## 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 11, 2019 |
|-------------------|----------------------|
| Device Trade Name | GEM Premier ChemSTAT |

| | Cobas Integra Creatinine Plus Ver. 2 | K024098 |
|-------------------|--------------------------------------|---------|
| Predicate Devices | Cobas Integra Urea/BUN | K954000 |
| | Cobas Integra Bicarbonate Liquid | K031879 |

| Regulatory Information | | | | | |
|------------------------|-----------------------|-------------------------------------------|----------------|-----------------|-------------------|
| Analyte | Regulation<br>Section | Regulatory Description | Classification | Product<br>Code | Panel |
| Creatinine | 862.1225 | Creatinine test system | Class II | JFY | |
| Blood Urea<br>Nitrogen | 862.1770 | Urea nitrogen test system | Class II | CDQ | Chemistry<br>(75) |
| tCO2 | 862.1160 | Bicarbonate/carbon dioxide<br>test system | Class II | KHS | |

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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 Creatinine, BUN and tCO₂. 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 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.<br>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.<br>The GEM Premier ChemSTAT PAK has flexible menus to assist facilities in maximizing efficiency.<br>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. |

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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 Creatinine (Crea), Blood Urea Nitrogen (BUN) and Total Carbon Dioxide (tCO₂) 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.

- Creatinine (Crea) measurements are used in the diagnosis and treatment of renal diseases and in monitoring renal dialysis.
- Blood Urea Nitrogen (BUN) or urea measurements are used for the diagnosis, monitoring, and ● treatment of certain renal and metabolic diseases.
- Total carbon dioxide/tCO₂ (also referred to as bicarbonate/HCO₃`) is used in the diagnosis, . monitoring, and treatment of numerous potentially serious disorders associated with changes in body acid-base balance.

#### Special Conditions for Use Statement

- For prescription use only.
- For clinical laboratory and point-of-care use

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#### Substantial Equivalency Discussion

The GEM Premier ChemSTAT system is substantially equivalent in function and intended use to the following predicate devices for Creatinine, Urea Nitrogen (BUN) and tCO2:

K954000

K031879

- Creatinine Cobas Integra Creatinine Plus Ver. 2 K024098
- Urea Nitrogen ● Cobas Integra Urea/BUN
- tCO2 Cobas Integra Bicarbonate Liquid .

A comparison to the above predicate devices follow for Creatinine, Urea Nitrogen (BUN) and tCO₂.

| Creatinine (Crea) | | |
|--------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Item | Candidate Device:<br>GEM Premier ChemSTAT | Predicate Device:<br>Cobas Integra Creatinine Plus Ver.2 |
| 510(k) No. | K183555 | K024098 |
| Manufacturer | Instrumentation Laboratory Co. | Roche Diagnostics |
| Intended Use | A portable critical care system for use<br>by 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<br>a central laboratory. The instrument<br>provides quantitative measurements<br>of Creatinine (Crea), Blood Urea<br>Nitrogen (BUN) and Total Carbon<br>Dioxide (tCO2) from arterial and<br>venous heparinized whole blood.<br>These parameters, along with derived<br>parameters, aid in the diagnosis of a<br>patient's acid/base status and<br>metabolite balance. | In vitro test for the quantitative<br>determination of creatinine<br>concentration in human serum,<br>plasma and urine on Roche/Hitachi<br>cobas c systems. |
| Intended User | Central Laboratory and Point-of-Care | Central Laboratory Only |
| Measurement Principle | Enzymatic Amperometry | Enzymatic Colorimetry |
| Sample Volume | 150 μL | 2-5 μL |
| Sample Type | Lithium heparinized whole blood<br>(arterial and venous) | Serum, Plasma and Urine |
| Reportable Range | 0.20 to 15.00 mg/dL | 0.06 to 30.5 mg/dL |
| Calibration | 3-point calibration | 2-point calibration |
| Storage Temperature | 15-25°C (PAK) | 2-8°C (Reagents) |
| Substantial Equivalency Discussion (Cont.) | | |
| Blood Urea Nitrogen (BUN) | | |
| Item | Candidate Device:<br>GEM Premier ChemSTAT | Predicate Device:<br>Cobas Integra Urea/BUN |
| 510(k) No. | K183555 | K954000 |
| Manufacturer | Instrumentation Laboratory Co. | Roche Diagnostics |
| Intended Use | A portable critical care system for use<br>by 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<br>a central laboratory. The instrument<br>provides quantitative measurements<br>of Creatinine (Crea), Blood Urea<br>Nitrogen (BUN) and Total Carbon<br>Dioxide (tCO2) from arterial and<br>venous heparinized whole blood.<br>These parameters, along with derived<br>parameters, aid in the diagnosis of a<br>patient's acid/base status and<br>metabolite balance. | In vitro test for the quantitative<br>determination of urea/urea nitrogen<br>concentration in human serum,<br>plasma and urine on Roche/Hitachi<br>cobas c systems. |
| Intended User | Central Laboratory and Point-of-Care | Central Laboratory Only |
| Measurement Principle | Enzymatic Potentiometry | Enzymatic Colorimetry |
| Sample Volume | 150 µL | 2 µL |
| Sample Type | Lithium heparinized whole blood<br>(arterial and venous) | Serum, Plasma and Urine |
| Reportable Range | 3.0 to 112.0 mg/dL | 1.4 to 112 mg/dL |
| Calibration | 2-point calibration | 2-point calibration |
| Storage Temperature | 15-25°C (PAK) | 2-8°C (Reagents) |
| Substantial Equivalency Discussion (Cont.) | | |
| Total Carbon Dioxide (tCO2) | | |
| Item | Candidate Device:<br>GEM Premier ChemSTAT | Predicate Device:<br>Cobas Integra Bicarbonate Liquid |
| 510(k) No. | K183555 | K031879 |
| Manufacturer | Instrumentation Laboratory Co. | Roche Diagnostics |
| Intended Use | A portable critical care system for use<br>by 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<br>a central laboratory. The instrument<br>provides quantitative measurements<br>of Creatinine (Crea), Blood Urea<br>Nitrogen (BUN) and Total Carbon<br>Dioxide (tCO2) from arterial and<br>venous heparinized whole blood.<br>These parameters, along with derived<br>parameters, aid in the diagnosis of a<br>patient's acid/base status and<br>metabolite balance. | In vitro test for the quantitative<br>determination of bicarbonate (HCO3-)<br>concentration in human serum and<br>plasma on Roche/Hitachi cobas c<br>systems. |
| Intended User | Central Laboratory and Point-of-Care | Central Laboratory Only |
| Measurement Principle | Potentiometry | Enzymatic Colorimetry |
| Sample Volume | 150 μL | 2 μL |
| Sample Type | Lithium heparinized whole blood<br>(arterial and venous) | Serum and Plasma |
| Reportable Range | 5.0 to 50.0 mmol/L | 2 to 50 mmol/L |
| Calibration | 2-point calibration | 2-point calibration |
| Storage Temperature | 15-25°C (PAK) | 2-8°C (Reagents) |

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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 |
|-----------------------|-------------------------|-----|-------|------------------|-------------------|-------------|--------------|
| Creatinine<br>(mg/dL) | Level 1 | 120 | 0.48 | 0.014 | 2.9% | 0.017 | 3.6% |
| | Level 2 | 120 | 1.53 | 0.016 | 1.0% | 0.032 | 2.1% |
| | Level 3 | 120 | 2.83 | 0.019 | 0.7% | 0.067 | 2.4% |
| | Level 4 | 120 | 5.67 | 0.028 | 0.5% | 0.121 | 2.1% |
| | Level 5 | 120 | 9.36 | 0.056 | 0.6% | 0.235 | 2.5% |
| BUN<br>(mg/dL) | Level 1 | 120 | 6.5 | 0.06 | 1.0% | 0.08 | 1.1% |
| | Level 2 | 120 | 25.7 | 0.24 | 0.9% | 0.27 | 1.1% |
| | Level 3 | 120 | 50.0 | 0.88 | 1.8% | 0.88 | 1.8% |
| | Level 4 | 120 | 81.9 | 1.37 | 1.7% | 1.37 | 1.7% |
| | Level 5 | 120 | 102.4 | 1.44 | 1.4% | 1.57 | 1.5% |
| tCO2<br>(mmol/L) | Level 1 | 120 | 8.0 | 0.11 | 1.3% | 0.12 | 1.5% |
| | Level 2 | 120 | 14.8 | 0.22 | 1.5% | 0.22 | 1.5% |
| | Level 3 | 120 | 21.2 | 0.23 | 1.1% | 0.30 | 1.4% |
| | Level 4 | 120 | 32.8 | 0.23 | 0.7% | 0.54 | 1.7% |
| | Level 5 | 120 | 43.5 | 0.30 | 0.7% | 0.88 | 2.0% |

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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 control 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 nine (9) levels of quality control mor Creatinine (4 levels of GEM ChemSTAT PVP) and seven (7) levels for BUN and tCO2 (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).

All results at all sites were within specification.

| Pooled Multi-Site POC Data | | | | | | | | | | | | | |
|----------------------------|------------------|----|------|---------------|------|-------------|------|-------------|------|--------------|------|-----------------|-------|
| Analyte | Control<br>Level | | Mean | Repeatability | | Between-Run | | Between-Day | | Between-Site | | Reproducibility | |
| | | N | | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| Creatinine<br>(mg/dL) | CVP Level 1 | 90 | 0.96 | 0.016 | 1.6% | 0.025 | 2.7% | 0.020 | 2.1% | 0.054 | 5.7% | 0.065 | 6.8% |
| | CVP Level 2 | 90 | 5.17 | 0.105 | 2.0% | 0.116 | 2.2% | 0.000 | 0.0% | 0.048 | 0.9% | 0.164 | 3.2% |
| | CVP Level 3 | 90 | 0.98 | 0.015 | 1.6% | 0.023 | 2.3% | 0.000 | 0.0% | 0.014 | 1.4% | 0.031 | 3.1% |
| | CVP Level 4 | 90 | 0.62 | 0.011 | 1.8% | 0.032 | 5.2% | 0.000 | 0.0% | 0.052 | 8.4% | 0.063 | 10.1% |
| | PVP Level 1 | 90 | 0.46 | 0.011 | 2.3% | 0.011 | 2.3% | 0.010 | 2.1% | 0.037 | 7.9% | 0.041 | 8.8% |
| | PVP Level 2 | 90 | 1.03 | 0.017 | 1.7% | 0.015 | 1.5% | 0.029 | 2.8% | 0.068 | 6.6% | 0.077 | 7.5% |
| | PVP Level 3 | 90 | 3.02 | 0.036 | 1.2% | 0.041 | 1.4% | 0.000 | 0.0% | 0.102 | 3.4% | 0.116 | 3.8% |
| | PVP Level 4 | 90 | 5.37 | 0.093 | 1.7% | 0.054 | 1.0% | 0.000 | 0.0% | 0.073 | 1.4% | 0.130 | 2.4% |
| | PVP Level 5 | 90 | 8.31 | 0.083 | 1.0% | 0.094 | 1.1% | 0.039 | 0.5% | 0.045 | 0.5% | 0.139 | 1.7% |
| Pooled Multi-Site POC Data | | | | | | | | | | | | | |
| Analyte | Control Level | N | Mean | Repeatability | | Between-Run | | Between-Day | | Between-Site | | Reproducibility | |
| | | | | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| BUN<br>(mg/dL) | CVP Level 1 | 90 | 15.5 | 0.26 | 1.7% | 0.14 | 0.9% | 0.00 | 0.0% | 0.08 | 0.5% | 0.31 | 2.0% |
| | CVP Level 2 | 90 | 57.2 | 0.44 | 0.8% | 0.18 | 0.3% | 1.14 | 2.0% | 1.31 | 2.3% | 1.80 | 3.1% |
| BUN<br>(mg/dL) | PVP Level 1 | 90 | 5.7 | 0.10 | 1.9% | 0.00 | 0.0% | 0.01 | 0.1% | 0.08 | 1.5% | 0.13 | 2.4% |
| | PVP Level 2 | 90 | 15.5 | 0.24 | 1.6% | 0.05 | 0.3% | 0.00 | 0.0% | 0.09 | 0.6% | 0.26 | 1.7% |
| | PVP Level 3 | 90 | 38.2 | 0.33 | 0.9% | 0.19 | 0.5% | 0.67 | 1.8% | 0.68 | 1.8% | 1.03 | 2.7% |
| | PVP Level 4 | 90 | 56.5 | 0.61 | 1.1% | 0.00 | 0.0% | 1.08 | 1.9% | 1.21 | 2.1% | 1.73 | 3.1% |
| | PVP Level 5 | 90 | 96.2 | 1.26 | 1.3% | 0.00 | 0.0% | 1.78 | 1.9% | 1.93 | 2.0% | 2.91 | 3.0% |
| tCO2<br>(mmol/L) | CVP Level 1 | 90 | 25.4 | 0.15 | 0.6% | 0.10 | 0.4% | 0.25 | 1.0% | 0.55 | 2.2% | 0.63 | 2.5% |
| | CVP Level 2 | 90 | 13.0 | 0.13 | 1.0% | 0.00 | 0.0% | 0.21 | 1.6% | 0.53 | 4.0% | 0.58 | 4.5% |
| tCO2<br>(mmol/L) | PVP Level 1 | 90 | 41.1 | 0.42 | 1.0% | 0.00 | 0.0% | 0.50 | 1.2% | 1.05 | 2.6% | 1.23 | 3.0% |
| | PVP Level 2 | 90 | 25.7 | 0.25 | 1.0% | 0.00 | 0.0% | 0.14 | 0.5% | 0.52 | 2.0% | 0.60 | 2.3% |
| | PVP Level 3 | 90 | 18.7 | 0.18 | 1.0% | 0.00 | 0.0% | 0.04 | 0.2% | 0.08 | 0.4% | 0.20 | 1.1% |
| | PVP Level 4 | 90 | 13.0 | 0.12 | 0.9% | 0.00 | 0.0% | 0.18 | 1.4% | 0.53 | 4.1% | 0.57 | 4.4% |
| | PVP Level 5 | 90 | 8.0 | 0.10 | 1.2% | 0.00 | 0.0% | 0.15 | 1.9% | 0.40 | 5.0% | 0.44 | 5.5% |

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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 |
|-----------------------|---------------------------------------|--------|-----|------|----------------------------|
| Creatinine<br>(mg/dL) | Fixed<br>(SD) | POC 1 | 33 | 0.91 | 0.011 |
| | | POC 2 | 60 | 0.88 | 0.014 |
| | Fixed<br>(SD) | POC 3 | 54 | 0.72 | 0.013 |
| | Fixed<br>(SD) | Pooled | 147 | 0.83 | 0.013 |
| Creatinine<br>(mg/dL) | Variable<br>(%CV) | POC 1 | 36 | 3.50 | 1.4% |
| | | POC 2 | 6 | 5.13 | 1.4% |
| | Variable<br>(%CV) | POC 3 | 12 | 3.52 | 0.6% |
| | Variable<br>(%CV) | Pooled | 54 | 3.69 | 1.2% |
| BUN<br>(mg/dL) | Fixed<br>(SD) | POC 1 | 36 | 15.2 | 0.18 |
| | | POC 2 | 54 | 12.4 | 0.18 |
| | Fixed<br>(SD) | POC 3 | 42 | 11.8 | 0.12 |
| | Fixed<br>(SD) | Pooled | 132 | 13.0 | 0.16 |
| BUN<br>(mg/dL) | Variable<br>(%CV) | POC 1 | 33 | 45.6 | 2.8% |
| | | POC 2 | 12 | 36.4 | 0.7% |
| | Variable<br>(%CV) | POC 3 | 21 | 52.1 | 0.9% |
| | Variable<br>(%CV) | Pooled | 66 | 46.0 | 1.9% |

All results at all sites were within specification.

{14}------------------------------------------------

| Analyte | Fixed or Variable<br>Acceptance Range | Site | N | Mean | Within Sample<br>SD of %CV |
|------------------|---------------------------------------|--------|-----|------|----------------------------|
| tCO2<br>(mmol/L) | Fixed<br>(SD) | POC 1 | 33 | 14.8 | 0.11 |
| | | POC 2 | 30 | 17.4 | 0.12 |
| | | POC 3 | 18 | 15.4 | 0.12 |
| | | Pooled | 81 | 15.9 | 0.12 |
| tCO2<br>(mmol/L) | Variable<br>(%CV) | POC 1 | 39 | 24.6 | 1.1% |
| | | POC 2 | 36 | 22.9 | 0.9% |
| | | POC 3 | 45 | 23.2 | 0.5% |
| | | Pooled | 120 | 23.6 | 0.9% |

## External Precision – Whole Blood (Cont.)

{15}------------------------------------------------

### 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 Creatinine, BUN and tCO₂, 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 |
|--------------------|------|------|------|
| Creatinine (mg/dL) | 0.04 | 0.07 | 0.10 |
| BUN (mg/dL) | 0.3 | 0.3 | 1.2 |
| tCO2 (mmol/L) | 0.0 | 0.2 | 2.0 |

#### 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 Creatinine, BUN and tCQ₂. Each blood level was analyzed in triplicate on six (6) GEM Premier ChemSTAT test analyzers and results compared to the reference analyzers.

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 | R 2 | Tested<br>Range | Reportable<br>Range |
|-----------------------|----------------|----------------|-------|-----------|--------|-----------------|---------------------|
| Creatinine<br>(mg/dL) | 9 | 18 | 1.005 | -0.034 | 0.9976 | 0.10 to 16.40 | 0.20 to 15.00 |
| BUN<br>(mg/dL) | 9 | 18 | 1.018 | -0.194 | 0.9997 | 2.4 to 122.0 | 3.0 to 112.0 |
| tCO2<br>(mmol/L) | 9 | 18 | 1.002 | -0.798 | 0.9986 | 3.6 to 51.3 | 5.0 to 50.0 |

{16}------------------------------------------------

### Analytical Specificity

In accordance with EP07 3d Edition, an interference study was conducted on the GEM Premier ChemSTAT for Creatinine, BUN and tCO2.

The table below and on the next two pages lists the substances that were screened with no observed interference on Creatinine, BUN and/or tCO₂:

| Test Substance | Test Concentration | Tested analytes where interference was not observed |
|---------------------------|-------------------------------|-----------------------------------------------------|
| Acetaminophen | 1030 µmol/L | Creatinine |
| Acetoacetate | 2 mmol/L | Creatinine |
| Ammonium (Chloride) | 151 µmol/L | BUN |
| Ascorbic acid | 298 µmol/L | Creatinine |
| Atracurium | 50 mg/L | Creatinine, BUN, tCO2 |
| Benzalkonium (Chloride) | 5 mg/L | BUN |
| Bilirubin | 40 mg/dL | Creatinine, BUN, tCO2 |
| Ceftriaxone | 1510 µmol/L | Creatinine, BUN, tCO2 |
| Chlorpromazine | 10.3 µmol/L | Creatinine |
| Diatrizoate Sodium | 301 µmol/L | Creatinine, BUN |
| Dobutamine | 0.121 mg/dL | Creatinine |
| Dopamine | 4.06 µmol/L | Creatinine |
| Epinephrine | 0.5 µmol/L | Creatinine, BUN, tCO2 |
| Ethanol | 130 mmol/L | Creatinine |
| Ethylene glycol | 8.8 mmol/L | Creatinine |
| Etomidate | 50 mg/L | Creatinine, BUN, tCO2 |
| Fentanyl | 0.03 µg/mL | Creatinine, BUN, tCO2 |
| Furosemide | 48.1 µmol/L | Creatinine, BUN, tCO2 |
| Gadodiamide | 1.4 mmol/L | Creatinine, BUN, tCO2 |
| Test Substance | Test Concentration | Tested analytes where interference was not observed |
| Glycolic acid | 1.0 mmol/L | Creatinine |
| Hematocrit | 25% | Creatinine |
| Hematocrit | 60% | Creatinine |
| Hemoglobin (Hemolysis) | 1000 mg/dL | Creatinine, BUN, tCO2 |
| Heparin | 100,000 U/L | Creatinine, BUN |
| β-hydroxybutyrate | 2 mmol/L | Creatinine |
| Hydroxyurea | 3.08 mg/dL | BUN |
| Ibuprofen | 1060 µmol/L | Creatinine, BUN, tCO2 |
| Icodextrin | 20 mg/dL | Creatinine |
| Isoniazid | 438 µmol/L | Creatinine |
| Leflunomide | 100 µg/mL | BUN |
| Methadone | 10.3 µmol/L | Creatinine, BUN, tCO2 |
| Midazolam | 0.376 mg/dL | Creatinine, BUN, tCO2 |
| Morphine | 27.3 µmol/L | Creatinine, BUN, tCO2 |
| N-Acetyl-L-cysteine | 920µmol/L | Creatinine, BUN, tCO2 |
| Perchlorate | 20 mg/dL | BUN |
| Phenobarbital | 2970 µmol/L | Creatinine, BUN, tCO2 |
| Piperacillin | 110 mg/dL | Creatinine, BUN, tCO2 |
| pO2 | 30 mmHg | Creatinine |
| Pralidoxime iodide | 4 mg/dL | Creatinine |
| Propofol | 4.8 mg/dL | Creatinine, BUN, tCO2 |
| Salicylic acid | 0.207 mmol/L | BUN |
| Suxamethonium | 68 µmol/L | Creatinine, BUN, tCO2 |
| Tazobactam | 3.05 mg/dL | Creatinine, BUN, tCO2 |
| Test Substance | Test Concentration | Tested analytes where interference was not observed |
| Teriflunomide | 100 µg/mL | BUN |
| Thiocyanate | 898 µmol/L | BUN, Creatinine |
| Thiopental | 1660 µmol/L | BUN, tCO2 |
| Triglyceride (Intralipid) | 2000 mg/dL<br>(1% Intralipid) | Creatinine, BUN, tCO2 |
| Uric acid | 1.4 mmol/L | Creatinine |
| Vancomycin | 82.8 µmol/L | Creatinine, BUN, tCO2 |

{17}------------------------------------------------

## Analytical Specificity (Cont.)

{18}------------------------------------------------

### Analytical Specificity (Cont.)

The table below lists substance that demonstrated interference with Creatinine, BUN and/or tCO₂ 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 |
|--------------------------|----------------------|--------------------------|----------------------------------------|----------------------------|------------------------------------------------------------------|-------------------------------------------------|
| Creatine | Creatinine | 0.60 mg/dL | 0.382 mmol/L | +0.23 mg/dL | 0.33 mmol/L | +0.20 mg/dL |
| | | 2.00 mg/dL | | No Interference Observed | | |
| Hydroxyurea | Creatinine | 0.60 mg/dL | 0.77 mg/dL | +1.06 mg/dL | 0.15 mg/dL | 0.20 mg/dL |
| | | 2.00 mg/dL | | +1.08 mg/dL | 0.12 mg/dL | 0.20 mg/dL |

{19}------------------------------------------------

| Analyte | Reference Range | Unit |
|---------|--------------------------|--------|
| Crea* | 0.04-0.33 (0-1 yr) | mg/dL |
| | 0.04-0.45 (2-5 yr) | mg/dL |
| | 0.20-0.52 (6-9 yr) | mg/dL |
| | 0.22-0.59 (10 yr) | mg/dL |
| | 0.62-1.10 (male adult) | mg/dL |
| | 0.45-0.75 (female adult) | mg/dL |
| Crea* | 4-29 (0-1 yr) | μmol/L |
| | 4-40 (2-5 yr) | μmol/L |
| | 18-46 (6-9 yr) | μmol/L |
| | 19-52 (10 yr) | μmol/L |
| | 55-96 (male adult) | μmol/L |
| | 40-66 (female adult) | μmol/L |
| BUN* | 3-25 (1 wk) | mg/dL |
| | 4-19 (< 1 yr) | mg/dL |
| | 5-18 (infant/child) | mg/dL |
| | 6-20 (18-60 yr) | mg/dL |
| | 8-23 (60-90 yr) | mg/dL |
| | 10-31 (> 90 yr) | mg/dL |
| Urea* | 1.1-8.9 (1 wk) | mmol/L |
| | 1.4-6.8 (< 1 yr) | mmol/L |
| | 1.8-6.4 (infant/child) | mmol/L |
| | 2.1-7.1 (18-60 yr) | mmol/L |
| | 2.9-8.2 (60-90 yr) | mmol/L |
| | 3.6-11.1 (> 90 yr) | mmol/L |
| tCO2** | 19.0-24.0 | mmol/L |
| | 22.0-26.0 (venous) | mmol/L |

#### 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 316 and 1096.

{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 respective predicate devices, 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 |
| Creatinine (mg/dL) | 405 | 1.009 | -0.027 | 0.997 | 0.20 to 14.18 |
| BUN (mg/dL) | 405 | 0.965 | 0.441 | 0.997 | 3.0 to 109.7 |
| tCO2 (mmol/L) | 416 | 0.979 | 0.535 | 0.986 | 5.5 to 47.2 |

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 devices: Cobas Integra Creatinine Plus Ver. 2<br>(K024098), Cobas Integra Urea/BUN (K954000) and Cobas Integra<br>Bicarbonate Liquid (K031879).<br><br>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 devices: Cobas Integra<br>Creatinine Plus Ver. 2 (K024098), Cobas Integra Urea/BUN (K954000)<br>and Cobas Integra Bicarbonate Liquid (K031879). |
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