K Number

Device Name

GEM Premier ChemSTAT

Manufacturer

Instrumentation Laboratory Co.

Date Cleared

2019-02-16

(58 days)

Product Code

JFY CDQ KHS

Regulation Number

862.1225

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 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: Analyzer: The GEM Premier ChemSTAT analyzer has the internal logic and processing power necessary to perform analysis. It employs a unique touch-sensitive color screen and a simple set of menus and buttons for user interaction. The analyzer guides operators through the sampling process with simple, clear messages and prompts. PAK (Cartridge): The disposable, multi-use GEM Premier ChemSTAT PAK is a completely closed cartridge that houses all components necessary to operate the instrument once the GEM PAK is validated. These components include the sensors, Process Control (PC) Solutions, sampler, and waste bag. The values of all PC Solutions are read from the GEM PAK Electronically Erasable Programmable Read Only Memory (EEPROM) chip. The components and processes used to manufacture the PC Solutions in the GEM PAK are traceable to National Institute of Standards and Technology (NIST) standards, Clinical & Laboratory Standards Institute (CLSI) procedures or other internal standards, where available and appropriate. The GEM Premier ChemSTAT PAK has flexible menus to assist facilities in maximizing efficiency. As part of this program, GEM ChemSTAT CVP (Calibration Valuation Products) are external solutions intended to complete the calibration process and final accuracy assessment of the iQM cartridge calibration following warm-up. Intelligent Quality Management (iQM): Intelligent Quality Management (iQM) is used as the quality control and assessment system for the GEM Premier ChemSTAT system. iQM is an active quality process control program designed to provide continuous monitoring of the analytical process before and after sample measurement with real-time, automatic error detection, automatic correction and automatic documentation of all corrective actions. iQM performs 4 types of continuous, quality checks to monitor the performance of the GEM PAK, sensors, and reagents throughout the cartridge use-life. These checks include System, Sensor, Pattern Recognition (PR) and Stability Checks.

More Information

Contact

Type

Center

Panel

Date Received

Product Code

Subsequent Product Codes

Applicant Name (Manufacturer)

Device Name

Decision

Street 1

Street 2

City

State

Country Code

ZIP

Postal Code

Class Advise Committee

SSP Indicator

Third Party Reviewed

Expedited Review

Predicate Devices

K024098, K954000, K031879

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

Unknown
The device description mentions "Pattern Recognition (PR)" as one of the checks performed by the Intelligent Quality Management (iQM) system. While pattern recognition can be a component of AI/ML, the summary does not provide enough detail to confirm if it utilizes AI/ML techniques or is a simpler algorithmic approach. The lack of explicit mentions of AI, ML, or related terms, along with the absence of information on training/test data, makes a definitive determination impossible based solely on this summary.

Therapeutic

No
The device is an in vitro diagnostic (IVD) system used to measure specific blood parameters for diagnostic purposes, not to provide therapy or treatment.

Diagnostic

Yes

The "Intended Use / Indications for Use" section explicitly states that the device provides quantitative measurements of Creatinine, BUN, and tCO2 from whole blood samples, and that "These parameters, along with derived parameters, aid in the diagnosis of a patient's acid/base status and metabolite balance." It then further specifies how each analyte aids in the diagnosis and treatment of various diseases.

SaMD (Software as a Medical Device)

The device description clearly outlines hardware components such as an "Analyzer" with internal logic and a touch-sensitive screen, and a "PAK (Cartridge)" which is a physical, disposable component containing sensors, solutions, and a waste bag. While software is involved in the operation and quality management (iQM), the device is fundamentally a hardware system with integrated software.

IVD (In Vitro Diagnostic)

Based on the provided information, the GEM Premier ChemSTAT is indeed an IVD (In Vitro Diagnostic) device.

Here's why:

Intended Use: The device is intended for the rapid analysis of biological samples (lithium heparinized whole blood) to provide quantitative measurements of specific analytes (Creatinine, BUN, tCO2). These measurements are explicitly stated to "aid in the diagnosis of a patient's acid/base status and metabolite balance" and are used in the "diagnosis and treatment" of various diseases. This aligns directly with the definition of an IVD, which is used to examine specimens derived from the human body to provide information for diagnostic purposes.
Device Description: The device analyzes biological samples using a self-contained cartridge containing sensors and reagents. This is a typical setup for an in vitro diagnostic system.
Performance Studies: The document details various performance studies including precision, linearity, analytical specificity (interference), and clinical testing (method comparison). These are standard studies required for the validation and regulatory approval of IVD devices.
Predicate Devices: The document lists predicate devices which are also IVD systems used for measuring the same analytes. This further supports the classification of the GEM Premier ChemSTAT as an IVD.

In summary, the GEM Premier ChemSTAT meets the criteria of an In Vitro Diagnostic device as it is used to perform tests on biological samples outside of the body to provide information for diagnostic purposes.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

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.

Product codes (comma separated list FDA assigned to the subject device)

JFY, CDQ, KHS

Device Description

Key Components:
Analyzer: The GEM Premier ChemSTAT analyzer has the internal logic and processing power necessary to perform analysis. It employs a unique touch-sensitive color screen and a simple set of menus and buttons for user interaction. The analyzer guides operators through the sampling process with simple, clear messages and prompts.
PAK (Cartridge): The disposable, multi-use GEM Premier ChemSTAT PAK is a completely closed cartridge that houses all components necessary to operate the instrument once the GEM PAK is validated. These components include the sensors, Process Control (PC) Solutions, sampler, and waste bag.
The values of all PC Solutions are read from the GEM PAK Electronically Erasable Programmable Read Only Memory (EEPROM) chip. The components and processes used to manufacture the PC Solutions in the GEM PAK are traceable to National Institute of Standards and Technology (NIST) standards, Clinical & Laboratory Standards Institute (CLSI) procedures or other internal standards, where available and appropriate.
The GEM Premier ChemSTAT PAK has flexible menus to assist facilities in maximizing efficiency.
As part of this program, GEM ChemSTAT CVP (Calibration Valuation Products) are external solutions intended to complete the calibration process and final accuracy assessment of the iQM cartridge calibration following warm-up.
Intelligent Quality Management (iQM): Intelligent Quality Management (iQM) is used as the quality control and assessment system for the GEM Premier ChemSTAT system. iQM is an active quality process control program designed to provide continuous monitoring of the analytical process before and after sample measurement with real-time, automatic error detection, automatic correction and automatic documentation of all corrective actions. iQM performs 4 types of continuous, quality checks to monitor the performance of the GEM PAK, sensors, and reagents throughout the cartridge use-life. These checks include System, Sensor, Pattern Recognition (PR) and Stability Checks.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Not Found

Indicated Patient Age Range

Not Found

Intended User / Care Setting

health care professionals / clinical setting and in a central laboratory

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

Not Found

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

Internal Precision Study – Whole Blood:

Study Type: Internal Precision Study
Sample Size: N=120 for each level of each analyte
Key Results: All results were within specification.

Reproducibility Study with Aqueous Controls – Point-of-Care (POC) Setting:

Study Type: Reproducibility Study
Sample Size: N=90 pooled across 3 sites for each control level of each analyte. Each control level was run in triplicate, twice a day for 5 days, for a total of 30 replicates per level.
Key Results: All results at all sites were within specification.

External Precision – Whole Blood:

Study Type: External Precision Study
Sample Size: Creatinine (Pooled N=147 for Fixed (SD), Pooled N=54 for Variable (%CV)); BUN (Pooled N=132 for Fixed (SD), Pooled N=66 for Variable (%CV)); tCO2 (Pooled N=81 for Fixed (SD), Pooled N=120 for Variable (%CV)). Less than 10% of samples were contrived.
Key Results: All results at all sites were within specification. Measured data for each analyte were partitioned into zones and identified as Fixed Acceptance Range (Constant SD) or Variable Acceptance Range (Constant %CV).

LoB, LoD and LoQ:

Study Type: Limit of Blank (LoB), Limit of Detection (LoD) and Limit of Quantification (LoQ) establishment.
Sample Size: Not explicitly stated, but established using three (3) lots of GEM Premier ChemSTAT PAKs (cartridges).
Key Results:
- Creatinine (mg/dL): LoB 0.04, LoD 0.07, LoQ 0.10
- BUN (mg/dL): LoB 0.3, LoD 0.3, LoQ 1.2
- tCO2 (mmol/L): LoB 0.0, LoD 0.2, LoQ 2.0

Linearity:

Study Type: Linearity Study
Sample Size: 9 levels per analyte, 18 N per level (total 162 measurements per analyte).
Key Results:
- Creatinine (mg/dL): Slope 1.005, Intercept -0.034, R² 0.9976, Tested Range 0.10 to 16.40, Reportable Range 0.20 to 15.00
- BUN (mg/dL): Slope 1.018, Intercept -0.194, R² 0.9997, Tested Range 2.4 to 122.0, Reportable Range 3.0 to 112.0
- tCO2 (mmol/L): Slope 1.002, Intercept -0.798, R² 0.9986, Tested Range 3.6 to 51.3, Reportable Range 5.0 to 50.0

Analytical Specificity:

Study Type: Interference study
Key Results: Lists numerous substances with no observed interference. Identifies Creatine and Hydroxyurea as interfering substances for Creatinine, with positive bias observed.

Clinical Testing:

Study Type: Method comparison study
Sample Size: 405 for Creatinine and BUN, 416 for tCO2. Less than 10% of samples were contrived.
Key Results: Pooled results from POC sites show:
- Creatinine (mg/dL): N=405, Slope=1.009, Intercept=-0.027, R=0.997, Sample Range=0.20 to 14.18
- BUN (mg/dL): N=405, Slope=0.965, Intercept=0.441, R=0.997, Sample Range=3.0 to 109.7
- tCO2 (mmol/L): N=416, Slope=0.979, Intercept=0.535, R=0.986, Sample Range=5.5 to 47.2
  The analytical and clinical study results demonstrate that the GEM Premier ChemSTAT is safe and effective for its intended purpose and equivalent in performance to the predicate devices.

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

See performance summary for SD, %CV, Slope, Intercept, R, LoB, LoD, LoQ, and bias.

Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.

K024098, K954000, K031879

Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).

Not Found

Regulation Number and Section

§ 862.1225 Creatinine test system.

(a)
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.(b)
Classification. Class II.

Summary

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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.

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 (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Kellie B. Kelm -S

Courtney H. Lias, Ph.D. for Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

Indications for Use

510(k) Number (if known) K183555

Device Name GEM Premier ChemSTAT

Indications for Use (Describe)

· 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)
☒Prescription Use (Part 21 CFR 801 Subpart D)	☐Over-The-Counter Use (21 CFR 801 Subpart C)

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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.
180 Hartwell Road
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

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

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

Device Description

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.
The values of all PC Solutions are read from the GEM PAK Electronically Erasable Programmable Read Only Memory (EEPROM) chip. The components and processes used to manufacture the PC Solutions in the GEM PAK are traceable to National Institute of Standards and Technology (NIST) standards, Clinical & Laboratory Standards Institute (CLSI) procedures or other internal standards, where available and appropriate.
The GEM Premier ChemSTAT PAK has flexible menus to assist facilities in maximizing efficiency.
As part of this program, GEM ChemSTAT CVP (Calibration Valuation Products) are external solutions intended to complete the calibration process and final accuracy assessment of the iQM cartridge calibration following warm-up.

Device Description (Cont.)
Intelligent Quality Management
(iQM)	Intelligent Quality Management (iQM) is used as the quality
control and assessment system for the GEM Premier ChemSTAT
system. iQM is an active quality process control program
designed to provide continuous monitoring of the analytical
process before and after sample measurement with real-time,
automatic error detection, automatic correction and automatic
documentation of all corrective actions.

iQM performs 4 types of continuous, quality checks to monitor
the performance of the GEM PAK, sensors, and reagents
throughout the cartridge use-life. These checks include System,
Sensor, Pattern Recognition (PR) and Stability Checks. |

Indications for Use / Intended Use

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

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:
GEM Premier ChemSTAT	Predicate Device:
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
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.	In vitro test for the quantitative
determination of creatinine
concentration in human serum,
plasma and urine on Roche/Hitachi
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
(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:
GEM Premier ChemSTAT	Predicate Device:
Cobas Integra Urea/BUN
510(k) No.	K183555	K954000
Manufacturer	Instrumentation Laboratory Co.	Roche Diagnostics
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 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.	In vitro test for the quantitative
determination of urea/urea nitrogen
concentration in human serum,
plasma and urine on Roche/Hitachi
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
(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:
GEM Premier ChemSTAT	Predicate Device:
Cobas Integra Bicarbonate Liquid
510(k) No.	K183555	K031879
Manufacturer	Instrumentation Laboratory Co.	Roche Diagnostics
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 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.	In vitro test for the quantitative
determination of bicarbonate (HCO3-)
concentration in human serum and
plasma on Roche/Hitachi cobas c
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
(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)

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
Blood
Level | N | Mean | Within Run
SD | Within Run
%CV | Total
SD | Total
%CV |
|-----------------------|-------------------------|-----|-------|------------------|-------------------|-------------|--------------|
| Creatinine
(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
(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
(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% |

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
Level		Mean	Repeatability		Between-Run		Between-Day		Between-Site		Reproducibility
		N		SD	%CV	SD	%CV	SD	%CV	SD	%CV	SD	%CV
Creatinine
(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
(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
(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
(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
(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%

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

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

All results at all sites were within specification.

| Analyte | Fixed or Variable
Acceptance Range | Site | N | Mean | Within Sample
SD of %CV |
|------------------|---------------------------------------|--------|-----|------|----------------------------|
| tCO2
(mmol/L) | Fixed
(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
(mmol/L) | Variable
(%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.)

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

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
(1% Intralipid)	Creatinine, BUN, tCO2
Uric acid	1.4 mmol/L	Creatinine
Vancomycin	82.8 µmol/L	Creatinine, BUN, tCO2

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
Substance | Affected
Analytes | Analyte
Concentration | Interfering
Concentration
Tested | Bias
Observed
(Mean) | Lowest
Interfering
Concentration
with Analyte
Impact | Bias Observed
at the Lowest
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 |

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 ( 90 yr)	mg/dL
Urea*	1.1-8.9 (1 wk)	mmol/L
	1.4-6.8 ( 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.

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
Premier ChemSTAT as described above are substantially equivalent to
that of the predicate devices: Cobas Integra Creatinine Plus Ver. 2
(K024098), Cobas Integra Urea/BUN (K954000) and Cobas Integra
Bicarbonate Liquid (K031879).

The analytical and clinical study results demonstrate that the GEM
Premier ChemSTAT is safe and effective for its intended purpose and
equivalent in performance to the predicate devices: Cobas Integra
Creatinine Plus Ver. 2 (K024098), Cobas Integra Urea/BUN (K954000)
and Cobas Integra Bicarbonate Liquid (K031879). |

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