GEM Premier 5000 (Measured Parameters:Glucose, Lactate and Total Bilirubin)

K160402 · Instrumentation Laboratory CO · CGA · Dec 14, 2016 · Clinical Chemistry

Device Facts

• Record ID: K160402
• Device Name: GEM Premier 5000 (Measured Parameters:Glucose, Lactate and Total Bilirubin)
• Applicant: Instrumentation Laboratory CO
• Product Code: CGA · Clinical Chemistry
• Decision Date: Dec 14, 2016
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1345
• Device Class: Class 2
• Attributes: Pediatric

Intended Use

The GEM Premier 5000 is a portable critical care system for use by health care professionals to rapidly analyze whole blood samples at the point of health care delivery in a clinical setting and in a central laboratory. The instrument provides quantitative measurements of glucose, lactate and total bilirubin from venous, arterial and capillary heparinized whole blood. These parameters aid in the diagnosis of a patient’s metabolite balance. Glucose (Glu) measurement is used in the diagnosis and treatment of carbohydrate metabolism disturbances including diabetes mellitus, neonatal hypoglycemia, and idiopathic hypoglycemia, and of pancreatic islet cell carcinoma. Lactate (Lac) measurement is used: - to evaluate the acid-base status of patients suspected of having lactic acidosis; - to monitor tissue hypoxia and strenuous physical exertion; - in the diagnosis of hyperlactatemia. Total bilirubin measurement is used to aid in assessing the risk of kernicterus and hyperbilirubinemia in neonates.

Device Story

Portable critical care system; analyzes heparinized whole blood (venous, arterial, capillary) for glucose, lactate, and total bilirubin. System comprises GEM Premier 5000 analyzer and GEM Premier 5000 PAK (disposable cartridge). Analyzer features color touch screen; guides operator through sampling. Cartridge contains sensors, CO-Ox/tBili optical cell, process control solutions, pump tubing, and waste bag. Glucose/lactate measured via amperometric biosensors (enzymatic reaction with oxidase, electrochemical oxidation of H2O2). Total bilirubin measured via spectrophotometry (optical absorbance of hemolyzed sample). Used in point-of-care and central laboratory settings by clinicians. Provides quantitative results to aid metabolite balance diagnosis, hypoxia monitoring, and neonatal bilirubin assessment.

Clinical Evidence

Bench testing only. Precision/reproducibility evaluated per CLSI EP05-A3 across multiple sites and operators (N=120 per level for internal studies; 90 per level for external POC sites). Linearity confirmed per CLSI EP06-A (r2 > 0.995). Method comparison per CLSI EP09-A3 against predicate and reference analyzers (Roche Cobas 6000, Ortho Vitros 5600) showed high correlation (r > 0.995). Interference testing performed per CLSI EP-7A; specific biases identified for cyanocobalamin, cyanomethemoglobin, glycolic acid, hydroxocobalamin, hydroxyurea, methylene blue, and turbidity.

Technological Characteristics

Portable analyzer with color touch screen. Disposable multi-use GEM PAK cartridge (sensors, CO-Ox/tBili optical cell, reagents, waste). Amperometric sensing (glucose/lactate); spectrophotometric sensing (tBili). Connectivity: EEPROM on PAK for calibration/test management. Operating temp: 12-32°C. Software: Linux-based. iQM2 statistical process control system for continuous monitoring.

Indications for Use

Indicated for health care professionals to analyze heparinized whole blood (venous, arterial, capillary) for glucose, lactate, and total bilirubin. Glucose: diagnosis/monitoring of carbohydrate metabolism disturbances (diabetes, hypoglycemia, carcinoma). Lactate: evaluation of acid-base status, hypoxia, hyperlactatemia. Total bilirubin: assessment of kernicterus/hyperbilirubinemia risk in neonates.

Regulatory Classification

Identification

A glucose test system is a device intended to measure glucose quantitatively in blood and other body fluids. Glucose measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus, neonatal hypoglycemia, and idiopathic hypoglycemia, and of pancreatic islet cell carcinoma.

Special Controls

*Classification.* Class II (special controls). The device, when it is solely intended for use as a drink to test glucose tolerance, is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.

Predicate Devices

• GEM Premier 4000 (K133407, K142898)

Submission Summary (Full Text)

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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002 December 14, 2016

INSTRUMENTATION LABORATORY CO. CAROL MARBLE REGULATORY AFFAIRS DIRECTOR 180 HARTWELL ROAD BEDFORD MA 01730

Re: K160402

Trade/Device Name: GEM Premier 5000 (Measured Parameters: Glucose, Lactate and Total Bilirubin)

Regulation Number: 21 CFR 862.1345 Regulation Name: Glucose test system Regulatory Class: II Product Code: CGA, MQM, KHP Dated: December 8, 2016 Received: December 9, 2016

Dear Ms. Marble:

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. 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 requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number [phone] or [phone] or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. 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 the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number [phone] or [phone] or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours.

# Courtney

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

Enclosure

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# Indications for Use

510(k) Number (if known) K160402

Device Name

GEM Premier 5000 (Measured Parameters: Glucose, Lactate, Total Bilirubin)

#### Indications for Use (Describe)

The GEM Premier 5000 is a portable critical care system for use by health care professionals to rapidly analyze heparinized whole blood samples at the point of health care delivery in a clinical setting and in a central laboratory. The instrument provides quantitative measurements of glucose, lactate and total bilirubin from venous, arterial and capillary heparinized whole blood. These parameters aid in the diagnosis of a patient's metabolite balance.

Glucose (Clu) measurement is used in the diagnosis, monitoring and treatment of carbohydrate metabolism disturbances including diabetes mellitus, neonatal hypoglycemia, idiopathic hypoglycemia, and pancreatic islet cell carcinoma.

Lactate (Lac) measurement is used:

- · to evaluate the acid-base status of patients suspected of having lactic acidosis;
- · to monitor tissue hypoxia and strenuous physical exertion;
- · in the diagnosis of hyperlactatemia.

Total bilirubin measurement is used to aid in assessing the risk of kernicterus and hyperbilirubinemia in neonates.

| 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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# 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 | Carol Marble, Regulatory Affairs Director<br>Phone: [phone]<br>Fax: [phone]<br>Email: [e-mail] |
|----------------|------------------------------------------------------------------------------------------------------------------|
|----------------|------------------------------------------------------------------------------------------------------------------|

| Preparation Date | December 8, 2016 |
|------------------|------------------|
|------------------|------------------|

| Device Trade Name | GEM Premier 5000<br>(Measured Parameters: Glucose, Lactate, Total Bilirubin) |
|-------------------|------------------------------------------------------------------------------|
|-------------------|------------------------------------------------------------------------------|

| Predicate Devices | GEM Premier 4000 | K133407 | Glucose and Lactate |
|-------------------|------------------|---------|---------------------|
| | ABL 837 | K142898 | Total Bilirubin |

| Regulatory Information | | | | | |
|------------------------|-----------------------|-------------------------------------------------------------|-----------------|-----------------|-------|
| GEM Premier 5000 | | | | | |
| Analyte | Regulation<br>Section | Regulatory Description | Class | Product<br>Code | Panel |
| Glucose | 862.1345 | Glucose test system | II | CGA | |
| Lactate | 862.1450 | Lactic acid test system | I* | KHP | 75 |
| Total Bilirubin | 862.1113 | Bilirubin (total and unbound)<br>in the neonate test system | I<br>(Reserved) | MQM | |

* Meets limitations of exemptions per 21 CFR 862.9(c)(9)

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# Device Description

The GEM Premier 5000 system provides health care professionals in central laboratory or point-of-care clinical settings with fast, accurate, quantitative measurements of glucose, lactate and total bilirubin from venous, arterial and capillary heparinized whole blood.

| Key Components | Description |
|---------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Analyzer | Employs a unique color touch screen and a simple set of menus and<br>buttons for user interaction. The analyzer guides operators through the<br>sampling process with simple, clear messages and prompts. |
| GEM Premier 5000 PAK<br>(disposable, multi-use GEM PAK) | Houses all required components necessary to operate the instrument<br>once the cartridge is validated. These components include the sensors,<br>CO-Ox/tBili optical cell, Process Control (PC) Solutions, sampler, pump<br>tubing, distribution valve and waste bag. The GEM PAK has flexible<br>menus and test volume options to assist facilities in maximizing<br>efficiency.<br>NOTE: The EEPROM on the GEM PAK includes all solution values and<br>controls the analyte menu and number of tests.<br>Step 1: After inserting the GEM PAK, the instrument will perform an<br>automated PAK warm-up during which the sensors are<br>hydrated and a variety of checks occur, all of which take<br>about 40 minutes. During warm-up, the instrument requires<br>no user intervention.<br>Step 2: After GEM PAK warmup, Auto PAK Validation (APV) process is<br>automatically completed: two completely independent<br>solutions (PC Solution D and E) that are traceable to NIST<br>standards, CLSI procedures or internal standards, containing<br>two levels of concentration for each analyte, are run by the<br>analyzer to validate the integrity of the PC Solutions and the<br>overall performance of the analytical system.<br>NOTE: For total bilirubin, CVP 5 tBili (Calibration Valuation Product)<br>must be run prior to performing tBili samples.<br>Step 3: After successful performance of APV, iQM2 manages the<br>quality control process, replacing external quality controls. |
| Intelligent Quality Management 2<br>(iQM2) | iQM2 is an active quality process control program designed to provide<br>continuous monitoring of the analytical process before, during and<br>after sample measurement with real-time, automatic error detection,<br>automatic correction of the system and automatic documentation of all<br>corrective actions.<br>iQM2 is a statistical process control system that performs 5 types of<br>continuous, quality checks to monitor the performance of the GEM<br>PAK, sensors, CO-Ox, and reagents. These checks include System,<br>Sensor, IntraSpect, Pattern Recognition and Stability Checks. |

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| | Indications for Use / Intended Use |
|------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| GEM Premier 5000 | The GEM Premier 5000 is a portable critical care system for use by<br>health care professionals to rapidly analyze heparinized whole<br>blood samples at the point of health care delivery in a clinical<br>setting and in a central laboratory. The instrument provides<br>quantitative measurements of glucose, lactate and total bilirubin<br>from venous, arterial and capillary heparinized whole blood. These<br>parameters aid in the diagnosis of a patient's metabolite balance.<br>Glucose (Glu) measurement is used in the diagnosis, monitoring<br>and treatment of carbohydrate metabolism disturbances including<br>diabetes mellitus, neonatal hypoglycemia, idiopathic hypoglycemia,<br>and pancreatic islet cell carcinoma. |
| | Lactate (Lac) measurement is used:<br>• to evaluate the acid-base status of patients suspected of<br>having lactic acidosis;<br>• to monitor tissue hypoxia and strenuous physical exertion;<br>• in the diagnosis of hyperlactatemia. |
| | Total bilirubin measurement is used to aid in assessing the risk of<br>kernicterus and hyperbilirubinemia in neonates. |

# Special Conditions for Use Statement

- For prescription use only.
·

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

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| Substantial Equivalency | | | | |
|--------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------|
| The GEM Premier 5000 system is substantially equivalent in function and intended use to the following predicate devices: | | | | |
| • Predicate Device No. 1: | GEM Premier 4000 for glucose and lactate. | | | |
| • Predicate Device No. 2: | ABL 837 for total bilirubin. | | | |
| Item | Predicate Devices | New Device | | |
| Trade Names | GEM Premier 4000<br>ABL 837 | K133407<br>K142898 | GEM Premier 5000 | K160402 |
| Manufacturers | GEM Premier 4000<br>ABL 837 | Instrumentation Laboratory Co.<br>Radiometer Medical ApS | Instrumentation Laboratory Co. | |
| Indications<br>for Use | The GEM Premier 4000 is a portable critical care system for use by<br>health care professionals to rapidly analyze whole blood samples<br>at the point of health care delivery in a clinical setting and in a<br>central laboratory. The instrument provides quantitative<br>measurements of pH, pCO2, pO2, sodium, potassium, chloride,<br>ionized calcium, glucose, lactate, hematocrit, total bilirubin and<br>CO-Oximetry (tHb, O₂Hb, COHb, MetHb, HHb) parameters. Total<br>bilirubin can also be quantitated from heparinized plasma samples<br>when analyzed in the tBili/CO-Ox mode. These parameters, along<br>with derived parameters, aid in the diagnosis of a patient's<br>acid/base status, electrolyte and metabolite balance and oxygen<br>delivery capacity. Total bilirubin measurements are used in the<br>diagnosis and management of biliary tract obstructions, liver<br>disease and various hemolytic diseases and disorders involving the<br>metabolism of bilirubin. In neonates, the level of total bilirubin is<br>used to aid in assessing the risk of kernicterus. | | The GEM Premier 5000 is a portable critical care system for use<br>by health care professionals to rapidly analyze heparinized whole<br>blood samples at the point of health care delivery in a clinical<br>setting and in a central laboratory. The instrument provides<br>quantitative measurements of glucose, lactate and total bilirubin<br>from venous, arterial and capillary heparinized whole blood.<br>These parameters aid in the diagnosis of a patient's metabolite<br>balance.<br>Glucose (Glu) measurement is used in the diagnosis, monitoring<br>and treatment of carbohydrate metabolism disturbances<br>including diabetes mellitus, neonatal hypoglycemia, idiopathic<br>hypoglycemia, and pancreatic islet cell carcinoma.<br>Lactate (Lac) measurement is used:<br>• to evaluate the acid-base status of patients suspected of<br>having lactic acidosis;<br>• to monitor tissue hypoxia and strenuous physical exertion;<br>• in the diagnosis of hyperlactatemia.<br>Total bilirubin measurement is used to aid in assessing the risk<br>of kernicterus and hyperbilirubinemia in neonates. | |

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| Substantial Equivalency (Cont.) | | |
|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------|
| <b>NOTE:</b> The comparison on this page is to the predicate device, the GEM Premier 4000, <i>except</i> where noted<br>to the predicate device for Total Bilirubin (tBili), ABL 837. | | |
| Item | Predicate Devices | New Device |
| Trade Names | GEM Premier 4000<br>(All Analytes <i>except</i> tBili)<br>K133407<br>ABL 837<br>Total Bilirubin (tBili)<br>K142898 | GEM Premier 5000<br>K160402 |
| Intended User | Central Laboratory and Point-of-Care | Same |
| Sample Type<br>(Glucose and Lactate) | Heparinized whole blood | Venous, arterial and capillary<br>heparinized whole blood |
| Sample Type<br>(tBili on ABL 837) | Heparinized whole blood<br>Heparinized plasma | Venous, arterial and capillary<br>heparinized whole blood |
| Intended Population<br>(tBili on ABL 837) | Total Bilirubin for adults and neonates | Total Bilirubin for neonates only. |
| Metabolite Measurement | Amperometry: Glucose and Lactate | Same |
| Total Bilirubin ( <i>vs.</i> ABL 837) | Spectrophotometry | Same |
| Sample Introduction | Aspiration | Same |
| PAK Shelf-Life Stability | Up to 180 days | Same |
| PAK Storage Temperature | 15-25°C | Same |
| System Operating Temperature | 12-32°C | Same |
| Operating System Software | Linux-based | Same |
| Calibration | 2-point calibration | Same |
| External QC Material | CVP 1 and 2 | PC Solution D and E (PAK Internal) |
| | CVP 3 and 4 | PC Solution D and E (PAK Internal) |
| | CVP 5 tBili<br>GEM System Evaluator | Same; No Formulation Change<br>GEM Premier 5000 claims added |
| Substantial Equivalency (Cont.) | | |
| <b>NOTE:</b> The comparison on this page is to the predicate device, the GEM Premier 4000, <i>except</i> where<br>noted to the predicate device for Total Bilirubin (tBili), ABL 837. | | |
| Item | Predicate Devices | New Device |
| Trade Names | GEM Premier 4000<br>(All Analytes <i>except</i> tBili)<br>K133407<br><br>ABL 837<br>Total Bilirubin (tBili)<br>K142898 | GEM Premier 5000<br>K160402 |
| Instrument Dimensions | GEM Premier 4000 Instrument:<br>• Height: 18 inches<br>• Width: 12 inches<br>• Depth: 15 inches<br>• Weight: 44 pounds | GEM Premier 5000 Instrument:<br>• Height: 18.6 inches<br>• Width: 13.0 inches<br>• Depth: 16.4 inches<br>• Weight: 45.4 pounds |
| Cartridge (PAK) Dimensions | GEM Premier 4000 Cartridge (PAK):<br>• Height: 6.75 inches<br>• Width: 10 inches<br>• Depth: 8 inches<br>• Weight: 8 pounds | GEM Premier 5000 Cartridge (PAK):<br>• Height: 6.75 inches<br>• Width: 10 inches<br>• Depth: 8 inches<br>• Weight: 8.1 pounds |
| Reportable Range | Analyte | GEM Premier 5000 |
| | Glucose<br>4 to 685 mg/dL | 4 to 685 mg/dL |
| | Lactate<br>0.3 to 17.0 mmol/L | 0.3 to 17.0 mmol/L |
| | tBili<br>0.0 to 58.5 mg/dL | 2.0 to 40.0 mg/dL |

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### Performance Summary

#### Internal Precision Study - Aqueous Controls

In accordance with CLSI EP05-A3, an internal 20-day precision study was performed on the GEM Premier 5000, with GEM System Evaluator and CVP 5 tBili. Each of the control levels was run on three (3) GEM Premier 5000 analyzers for twenty (20) days, with two (2) runs per day and one (1) replicate measured per run per level (n=120). All results were within specification.

| Material | Analyte | Level | Mean | N | Within<br>Analyzer<br>SD | Within<br>Analyzer<br>%CV | Total SD | Total<br>%CV |
|----------------------------|---------------------|---------|------|-----|--------------------------|---------------------------|----------|--------------|
| GEM<br>System<br>Evaluator | Glucose<br>(mg/dL) | Level 1 | 378 | 120 | 10.9 | 2.9% | 11.2 | 3.0% |
| | | Level 2 | 104 | 120 | 1.6 | 1.6% | 1.6 | 1.6% |
| | | Level 3 | 46 | 120 | 1.3 | 2.7% | 1.3 | 2.7% |
| GEM<br>System<br>Evaluator | Lactate<br>(mmol/L) | Level 1 | 7.3 | 120 | 0.06 | 0.9% | 0.07 | 0.9% |
| | | Level 2 | 0.8 | 120 | 0.03 | 3.7% | 0.03 | 3.7% |
| | | Level 3 | 2.5 | 120 | 0.04 | 1.8% | 0.04 | 1.8% |
| GEM<br>System<br>Evaluator | tBili<br>(mg/dL) | Level 1 | 33.8 | 120 | 0.14 | 0.4% | 0.16 | 0.5% |
| | | Level 2 | 17.7 | 120 | 0.13 | 0.8% | 0.18 | 1.0% |
| | | Level 3 | 3.3 | 120 | 0.13 | 4.0% | 0.16 | 4.9% |
| CVP 5 tBili | tBili<br>(mg/dL) | NA | 4.8 | 120 | 0.13 | 2.6% | 0.18 | 3.7% |

# Internal Precision Study – GEM PAK (Cartridge) Process Control Solutions D and E

In accordance with CLSI EP05-A3, an internal 20-day precision study was performed with the GEM PAK (cartridge) Process Control Solutions (PCS) D and E run on three (3) GEM Premier 5000 analyzers for twenty (20) days, with two (2) runs per day and one (1) replicate measured per run per level (N=120 per analyte/per level). All results were within specification.

| Material | Analyte | Mean | N | Within Analyzer<br>SD | Within Analyzer<br>%CV |
|----------|---------------------|------|-----|-----------------------|------------------------|
| PCS D | Glucose<br>(mg/dL) | 347 | 120 | 1.7 | 0.5% |
| PCS E | Glucose<br>(mg/dL) | 71 | 120 | 0.6 | 0.8% |
| PCS D | Lactate<br>(mmol/L) | 8.0 | 120 | 0.11 | 1.3% |
| PCS E | Lactate<br>(mmol/L) | 1.6 | 120 | 0.02 | 1.3% |
| PCS D | tBili<br>(mg/dL) | 10.4 | 120 | 0.05 | 0.4% |
| PCS E | tBili<br>(mg/dL) | 20.0 | 120 | 0.04 | 0.2% |

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#### 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 5000 analyzers per sample mode for five (5) days, with one (1) run per day and eight (8) replicates measured per run per level (N=120 per analyte/per sample mode). All results were within specification.

Sample Modes and Volumes:

- . Normal Mode 150 µL
- Micro Mode 65 µL
- . tBili / CO-Ox Mode 100 µL

| Analyte | Mode | Level | Mean | N | Within<br>Run<br>SD | Within<br>Run<br>%CV | Total SD | Total<br>%CV |
|---------------------|----------------|-------|------|-----|---------------------|----------------------|----------|--------------|
| Glucose<br>(mg/dL) | Normal<br>Mode | 1 | 24 | 120 | 0.8 | 3.3% | 0.8 | 3.5% |
| | | 2 | 42 | 120 | 0.8 | 2.0% | 1.1 | 2.7% |
| | | 3 | 120 | 120 | 1.7 | 1.4% | 2.5 | 2.1% |
| | | 4 | 179 | 120 | 3.1 | 1.7% | 4.0 | 2.2% |
| | | 5 | 729 | 120 | 13.1 | 1.8% | 13.4 | 1.8% |
| Glucose<br>(mg/dL) | Micro<br>Mode | 1 | 26 | 120 | 0.7 | 2.8% | 0.8 | 3.0% |
| | | 2 | 44 | 120 | 0.8 | 1.8% | 1.2 | 2.7% |
| | | 3 | 118 | 120 | 2.5 | 2.1% | 3.0 | 2.6% |
| | | 4 | 176 | 120 | 2.9 | 1.7% | 4.1 | 2.3% |
| | | 5 | 761 | 120 | 11.6 | 1.5% | 24.9 | 3.3% |
| Lactate<br>(mmol/L) | Normal<br>Mode | 1 | 0.5 | 120 | 0.05 | 9.4% | 0.05 | 9.4% |
| | | 2 | 1.8 | 120 | 0.06 | 3.3% | 0.07 | 3.7% |
| | | 3 | 4.9 | 120 | 0.09 | 1.7% | 0.10 | 2.0% |
| | | 4 | 7.8 | 120 | 0.17 | 2.1% | 0.18 | 2.3% |
| | | 5 | 17.9 | 120 | 0.40 | 2.2% | 0.45 | 2.5% |
| Lactate<br>(mmol/L) | Micro<br>Mode | 1 | 0.5 | 120 | 0.04 | 7.5% | 0.04 | 7.6% |
| | | 2 | 1.9 | 120 | 0.05 | 2.9% | 0.06 | 3.1% |
| | | 3 | 4.9 | 120 | 0.14 | 2.9% | 0.15 | 3.1% |
| | | 4 | 7.8 | 120 | 0.13 | 1.6% | 0.16 | 2.0% |
| Analyte | Mode | Level | Mean | N | Within<br>Run<br>SD | Within<br>Run<br>%CV | Total SD | Total<br>%CV |
| | | 5 | 18.2 | 120 | 0.31 | 1.7% | 0.37 | 2.0% |

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K160402

Performance Summary (Cont.)

# Internal Precision Study – Whole Blood (Cont.)

| Analyte | Mode | Level | Mean | N | Within<br>Run<br>SD | Within<br>Run<br>%CV | Total SD | Total<br>%CV |
|---------------------|----------------|-------|------|------|---------------------|----------------------|----------|--------------|
| tBili<br>(mg/dL) | Normal<br>Mode | 1 | 3.3 | 120 | 0.12 | 3.5% | 0.24 | 7.3% |
| | | 2 | 6.2 | 120 | 0.12 | 1.8% | 0.29 | 4.6% |
| | | 3 | 14.1 | 120 | 0.13 | 0.9% | 0.41 | 2.9% |
| | | 4 | 19.7 | 120 | 0.17 | 0.9% | 0.50 | 2.5% |
| | | 5 | 29.6 | 120 | 0.18 | 0.6% | 0.75 | 2.5% |
| tBili/CO-Ox<br>Mode | 1 | 3.3 | 120 | 0.10 | 2.9% | 0.12 | 3.7% | |
| | 2 | 6.3 | 120 | 0.13 | 2.0% | 0.19 | 3.0% | |
| | 3 | 14.0 | 120 | 0.14 | 1.0% | 0.27 | 1.9% | |
| | 4 | 19.6 | 120 | 0.17 | 0.9% | 0.36 | 1.8% | |
| | 5 | 29.4 | 120 | 0.16 | 0.5% | 0.51 | 1.7% | |

{12}------------------------------------------------

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

In accordance with CLSI EP05-A3, a reproducibility study was performed at three (3) external clinical point-of-care (PCC) sites The studies were run by a total of nine (9) different operators on three (3) different GEM Premier 5000 instruments, using a single bot of GEM Premier 5000 PAK (cartidges). Each site used the same lots of GEM System Evaluator (GSE) and CVP 5 tBili, runing each control level in triplicate, twice a day for 5 days, for a total of 30 replicates per level (N=90 pooled). All results at all sites were within specification.

| Pooled Multi-Site POC Data (Cont.) | | | | | | | | | | | | | | | | |
|------------------------------------|--------------------|----|-----------------|--------|---------------|------|---------------|------|-------------|------|-------------|------|--------------|------|-----------------|------|
| | Material/<br>Level | | Insert<br>Range | Target | SD/CV<br>Spec | Mean | Repeatability | | Between-Run | | Between-Day | | Between-Site | | Reproducibility | |
| Analyte | | N | | | | | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| Glu<br>(mg/dL) | GSE 1 | 90 | 347-411 | 379 | 5% | 381 | 2.1 | 0.5% | 1.1 | 0.3% | 2.8 | 0.7% | 2.9 | 0.8% | 4.7 | 1.2% |
| | GSE 2 | 90 | 93-117 | 105 | 5% | 102 | 0.5 | 0.5% | 0.3 | 0.3% | 0.5 | 0.5% | 0.2 | 0.2% | 0.8 | 0.8% |
| | GSE 3 | 90 | 38-56 | 47 | 3 | 45 | 0.5 | 1.2% | 0.0 | 0.0% | 0.3 | 0.7% | 0.1 | 0.2% | 0.6 | 1.4% |
| Lac<br>(mmol/L) | GSE 1 | 90 | 6.5-8.1 | 7.3 | 7.5% | 7.2 | 0.06 | 0.8% | 0.06 | 0.8% | 0.05 | 0.7% | 0.00 | 0.0% | 0.09 | 1.3% |
| | GSE 2 | 90 | 0.5-1.1 | 0.8 | 0.2 | 0.8 | 0.02 | 2.3% | 0.00 | 0.0% | 0.01 | 1.1% | 0.00 | 0.0% | 0.02 | 2.5% |
| | GSE 3 | 90 | 2.0-3.0 | 2.5 | 0.2 | 2.4 | 0.02 | 0.7% | 0.03 | 1.2% | 0.04 | 1.8% | 0.00 | 0.0% | 0.06 | 2.3% |
| tBili<br>(mg/dL) | GSE 1 | 90 | 32.5-34.9 | 33.7 | 10% | 33.7 | 0.14 | 0.4% | 0.00 | 0.0% | 0.05 | 0.1% | 0.07 | 0.2% | 0.16 | 0.5% |
| | GSE 2 | 90 | 16.9-18.5 | 17.7 | 10% | 17.6 | 0.10 | 0.5% | 0.00 | 0.0% | 0.05 | 0.3% | 0.07 | 0.4% | 0.13 | 0.7% |
| | GSE 3 | 90 | 2.5-3.9 | 3.2 | 0.4 | 3.2 | 0.10 | 3.0% | 0.02 | 0.8% | 0.03 | 0.8% | 0.01 | 0.3% | 0.10 | 3.3% |
| | CVP-5 | 90 | 4.0-6.0 | 5.0 | 10% | 4.9 | 0.11 | 2.2% | 0.00 | 0.0% | 0.05 | 1.0% | 0.12 | 2.5% | 0.17 | 3.5% |

{13}------------------------------------------------

#### External Precision - Whole Blood

To evaluate whole blood precision on the GEM Premier 5000 system in the central laboratory and point-ofcare (POC) settings, whole blood patient samples were tested at 2 external central laboratories and 1 internal Customer Simulation Laboratory (CSL), as well as at 3 external POC locations. For the central laboratory setting, the studies were performed by 3 operators on 3 GEM Premier 5000 instruments using a single lot of GEM Premier 5000 PAK (cartridge). For the POC setting, the studies were performed by 11 operators on 3 GEM Premier 5000 instruments, using a single lot of GEM Premier 5000 PAK (cartridge). At least two whole blood specimens were analyzed in triplicate daily for 5 days in both normal mode (150 µL) and micro capillary (65 µL) mode. At the internal Customer Simulation Laboratory (CSL), contrived whole blood specimens were analyzed in addition to native specimens in order to cover the low and high medical decision levels of each analyte.

The precision results are summarized below:

| Analyte | Mode | Site | N | Mean | Within Sample<br>%CV or SD |
|----------------|----------------|---------|-----|------|----------------------------|
| Glu<br>(mg/dL) | Normal<br>Mode | POC1 | 51 | 140 | 1.1% |
| | | POC2 | 39 | 142 | 1.0% |
| | | POC3 | 27 | 137 | 1.2% |
| | | POC-All | 117 | 140 | 1.1% |
| | Normal<br>Mode | CSL | 33 | 113 | 1.7% |
| | | Lab1 | 30 | 163 | 1.0% |
| | | Lab2 | 30 | 132 | 1.0% |
| | | Lab-All | 93 | 135 | 1.2% |
| | Micro<br>Mode | POC1 | 30 | 155 | 1.0% |
| | | POC2 | 36 | 146 | 1.0% |
| | | POC3 | 30 | 122 | 0.8% |
| | | POC-All | 96 | 141 | 0.9% |
| | Micro<br>Mode | CSL | 33 | 110 | 0.8% |
| | | Lab1 | 30 | 166 | 1.2% |
| | | Lab2 | 30 | 136 | 1.4% |
| | | Lab-All | 93 | 136 | 1.1% |

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

# External Precision – Whole Blood (Cont.)

| Analyte | Mode | Site | N | Mean | Within Sample<br>%CV or SD |
|---------------------|----------------|---------|----|------|----------------------------|
| Lactate<br>(mmol/L) | Normal<br>Mode | POC1 | 33 | 1.7 | 0.07 |
| | | POC2 | 12 | 1.8 | 0.03 |
| | | POC3 | 21 | 2.0 | 0.06 |
| | | POC-All | 66 | 1.9 | 0.06 |
| | | CSL | 30 | 1.7 | 0.03 |
| | | Lab1 | 21 | 2.0 | 0.07 |
| | | Lab2 | 15 | 2.0 | 0.06 |
| | | Lab-All | 66 | 1.9 | 0.06 |
| | Micro<br>Mode | POC1 | 27 | 1.9 | 0.06 |
| | | POC2 | 33 | 1.6 | 0.05 |
| | | POC3 | 18 | 1.6 | 0.06 |
| | | POC-All | 78 | 1.7 | 0.05 |
| | | CSL | 30 | 1.9 | 0.04 |
| | | Lab1 | 30 | 1.8 | 0.08 |
| | | Lab2 | 12 | 1.9 | 0.06 |
| | | Lab-All | 72 | 1.8 | 0.06 |

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

# External Precision – Whole Blood (Cont.)

| Analyte | Mode | Site | N | Mean | Within Sample<br>%CV or SD |
|-------------------------|----------------|---------|------|------|----------------------------|
| tBili<br>(mg/dL) | Normal<br>Mode | POC1 | 24 | 18.7 | 0.8% |
| | | POC2 | 24 | 16.8 | 2.0% |
| | | POC3 | 27 | 11.5 | 1.9% |
| | | POC-All | 75 | 15.5 | 1.6% |
| | | CSL | 15 | 18.5 | 0.6% |
| | | Lab1 | 6 | 4.9 | 7.5% |
| | | Lab-All | 21 | 14.6 | 2.5% |
| tBili/<br>CO-Ox<br>Mode | POC1 | 33 | 22.1 | 1.2% | |
| | POC2 | 27 | 11.6 | 1.6% | |
| | POC3 | 30 | 11.8 | 1.3% | |
| | POC-All | 90 | 15.5 | 1.4% | |
| | CSL | 15 | 18.3 | 0.7% | |
| | Lab1 | 3 | 8.3 | 2.5% | |
| | Lab-All | 18 | 16.7 | 1.0% | |

Note: No Lab 2 results presented for Total Bilirubin.

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

#### LoB, LoD and LoQ

In accordance with CLSI EP17-A2, LoB, LoQ and LoQ were established for glucose, lactate and total bilirubin, using three (3) lots of GEM Premier 5000 PAKs (cartridges).

| Analyte | LoB | LoD | LoQ |
|-------------------------|-----|-----|-----|
| Glucose (mg/dL) | 0 | 2 | 2 |
| Lactose (mmol/L) | 0.0 | 0.0 | 0.2 |
| Total Bilirubin (mg/dL) | 0.1 | 0.3 | 1.4 |

Following are the combined data results for LoB, LoD and LoQ:

#### 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 each parameter. Each blood level was analyzed in triplicate on three (3) GEM Premier 5000 test analyzers and results compared to 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 | R² | Tested<br>Range | Reportable<br>Range |
|---------------------|----------------|----------------|-------|-----------|-------|-----------------|---------------------|
| Glucose<br>(mg/dL) | 9 | 9 | 0.982 | -12.489 | 0.995 | 1 to 777 | 4 to 685 |
| Lactate<br>(mmol/L) | 9 | 9 | 1.037 | -0.131 | 0.998 | 0.2 to 25.5 | 0.3 to 17.0 |
| tBili<br>(mg/dL) | 9 | 9 | 1.040 | 0.227 | 0.998 | 1.4 to 43.7 | 2.0 to 40.0 |

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

# Analytical Specificity

In accordance with EP07-A2, an interference study was conducted on the GEM Premier 5000.

The table below and on the next page lists substances that were screen tested with no observed interference on glucose, lactate and/or total bilirubin (tBili) results:

| Substance | Concentration | Tested analytes with no observed interference |
|--------------------------------------|---------------|-----------------------------------------------|
| Acetaminophen | 1324 µmol/L | Glucose, Lactate, tBili |
| Acetoacetate | 2 mmol/L | Glucose, Lactate |
| N-acetylcysteine | 10.2 mmol/L | Glucose, Lactate |
| Amoxicillin | 206 µmol/L | tBili |
| Ascorbic acid | 342 µmol/L | Glucose, Lactate, tBili |
| Benzalkonium (Chloride) | 5 mg/L | tBili |
| Bilirubin | 20 mg/dL | tBili |
| Biliverdin | 4 mg/dL | tBili |
| Ceftriaxone | 1460 µmol/L | tBili |
| Chlorpromazine | 6.3 µmol/L | Glucose, Lactate |
| Ciprofloxacin | 30.2 µmol/L | tBili |
| (Sodium) Citrate | 12 mmol/L | Glucose, Lactate |
| Creatinine | 5 mg/dL | Glucose, Lactate |
| Diazepam | 18 µmol/L | tBili |
| Dobutamine | 2 mg/dL | Glucose, Lactate |
| Dopamine | 5.87 µmol/L | Glucose, Lactate |
| Epinephrine | 0.5 µmol/L | tBili |
| Ethanol | 86.8 mmol/L | Glucose, Lactate |
| Evans Blue | 10 mg/L | tBili |
| Fetal Hemoglobin | 75% | tBili |
| Flaxedil (Gallamine<br>triethi…