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

Indications for 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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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE

A. 510(k) Number:
k160402

B. Purpose for Submission:
New device

C. Measurand:
Glucose, lactate, and total bilirubin (tBili)

D. Type of Test:
Quantitative, enzymatic for glucose and lactate, spectrophotometric for total bilirubin

E. Applicant:
Instrumentation Laboratory Inc.

F. Proprietary and Established Names:
GEM Premier 5000 (Measured Parameters: Glucose, Lactate, Total Bilirubin)

G. Regulatory Information:

| Product Code | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| CGA | Class II | 21 CFR 862.1345 Glucose Test System | Clinical Chemistry (75) |
| KHP | Class I* | 21 CFR 862.1450 Lactic Acid Test System | |
| MQM | Class I, reserved | 21 CFR 862.1113 Bilirubin (total and unbound) in the neonate test system | |

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

H. Intended Use:

1. Intended use(s):
See Indications for use below

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2. Indication(s) for 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.

3. Special conditions for use statement(s):

For prescription use only at point-of-care and central laboratory settings

4. Special instrument requirements:

GEM Premier 5000 analyzer

I. Device Description:

The GEM Premier 5000 system contains two key components: the GEM Premier 5000 analyzer and the GEM Premier 5000 PAK (cartridge). The GEM Premier 5000 PAK contains reagents, sensors, optical cell for Co-Ox and total bilirubin, sampler and waste bag. It enables analysis of 75 to 600 samples per cartridge. Analyzer: Employs a unique color touch 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.

GEM Premier 5000 PAK: Houses all required components necessary to operate the instrument once the cartridge is validated. These components include the sensors, CO-Ox/tBili optical cell, Process Control (PC) Solutions, sampler, pump tubing, distribution valve and waste bag. The GEM PAK has flexible menus and test volume options to assist facilities in maximizing efficiency.

J. Substantial Equivalence Information:

1. Predicate device name(s):

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GEM Premier 4000

2. Predicate 510(k) number(s):

K133407 for glucose and lactate
K142898 for total bilirubin

3. Comparison with predicate:

| Item | GEM Premier 5000 for measurement of glucose, lactate, and total bilirubin (Candidate Device k160402) | GEM Premier 4000 for measurement of glucose, lactate, and total bilirubin (Predicate Device K133407, K112995) |
| --- | --- | --- |
| Similarities and differences | | |
| 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. | Same. |
| Intended User | Central Laboratory and Point-of-Care | Same. |
| Types of Measurements | Amperometry: Glucose and Lactate Spectrophotometry: Total Bilirubin | Same. |
| Sampling Modes and Sample Volumes | Normal Mode 150 μL
Micro Mode 65 μL
tBili/CO-Ox Mode 100 μL | Same. |
| Sample Type | Glucose: Heparinized whole blood (arterial, venous, capillary)
Lactate: Heparinized whole blood (arterial, venous, capillary)
Total Bilirubin: Heparinized whole blood (arterial, venous, capillary) | Glucose: Heparinized whole blood
Lactate: Heparinized whole blood
Total Bilirubin: Heparinized whole blood and Heparinized plasma |
| Measuring Range | Glucose: 4 to 685 mg/dL
Lactate: 0.3 to 17.0 mmol/L
tBili: 2.0 to 40.0 mg/dL | Glucose 4 to 685 mg/dL
Lactate 0.3 to 17.0 mmol/L
tBili 0.0 to 58.5 mg/dL |

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| Item | GEM Premier 5000 for measurement of glucose, lactate, and total bilirubin (Candidate Device k160402) | GEM Premier 4000 for measurement of glucose, lactate, and total bilirubin (Predicate Device K133407, K112995) |
| --- | --- | --- |
| Instrument Dimensions | GEM Premier 5000 Instrument: • Height: 18.6 inches • Width: 13.0 inches • Depth: 16.4 inches • Weight: 45.4 pounds | GEM Premier 4000 Instrument: • Height: 18 inches • Width: 12 inches • Depth: 15 inches • Weight: 44 pounds |
| Calibration | 2-point calibration | Same |

# K. Standard/Guidance Document Referenced (if applicable):

CLSI - EP05-A3 Evaluation of Precision of Quantitative Measurement Procedures

CLSI - EP06-A Evaluation of Linearity of Quantitative Measurement Procedures

CLSI - EP07-A2. Interference Testing in Clinical Chemistry

CLSI - EP09-A3 Measurement Procedure Comparison and Bias Estimation Using Patient Samples

CLSI - EP17-A2 Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures

CLSI - EP25-A Evaluation of Stability of In Vitro Diagnostic Reagents

# L. Test Principle:

The glucose and lactate sensors are amperometric biosensors consisting of a platinum electrode poised at a positive potential with respect to the card reference electrode. Glucose or lactate determination is accomplished by enzymatic reaction of glucose or lactate with oxygen in the presence of glucose oxidase or lactate oxidase and the electrochemical oxidation of the resulting hydrogen peroxide at the platinum electrode. The current flow between the platinum electrode and the ground electrode is proportional to the rate at which hydrogen peroxide molecules diffuse to the platinum and are oxidized, which in turn is directly proportional to the metabolite (glucose or lactate) concentration $\mathrm{I} = (\mathrm{S} \times \mathrm{metabolite}) + \mathrm{IZ}$ , where "I" is the electrode current, "S" is the sensitivity, and IZ is the zero current. The value of S and IZ can be calculated from the Process Control Solution data for the sensor. The equation can then be solved for the metabolite concentration, where "I" becomes the electrode current produced by the blood sample.

Total bilirubin measurement is based on an optical absorbance measurement of the sample. An in-line optical assay is integrated in to the GEM PAK flow path where the hemolyzed whole blood sample provides a measure of total bilirubin and CO-Oximetry. The optical cell is a flow through channel with two parallel plate optical windows separated by a well-defined path length. The chemical lysing of the sample is implemented to minimize the scattering effect of the blood and to make the spectral measurement more reliable. The optical measurement hardware consisting of a white light-emitting diode (LED) light source, a neon

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reference and a high resolution spectrometer with a holographic diffraction grating and a charge-coupled device (CCD) array are all contained in the analyzer. Only the optical cell is located in the disposable cartridge (GEM PAK) and is aligned with the analyzer optics for spectral measurements following installation of the GEM PAK.

## M. Performance Characteristics (if/when applicable):

### 1. Analytical performance:

#### a. Precision/Reproducibility:

Both Internal and External Precision studies were performed in accordance with CLSI EP05-A3 guidance.

#### Internal Precision Studies:

1) An internal 20-day precision study was performed on the GEM Premier 5000 with GEM System Evaluator 1, 2 and 3. Each of the control levels was run on 3 GEM Premier 5000 analyzers for 20 days, with 2 runs per day and 1 replicate measured per run per level. Results are summarized below:

| Material | Analyte | Level | Mean | N | Within Run SD | Within Run %CV | Total SD | Total %CV |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| GEM System Evaluator 1, 2, and 3 | Glucose (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% |
| | Lactate (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% |
| | tBili (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 (mg/dL) | NA | 4.8 | 120 | 0.13 | 2.6% | 0.18 | 3.7% |

2) An addition internal precision study was performed using five levels of whole blood samples under normal mode (150 μL), micro capillary (65 μL) mode and tBili /CO-Ox Mode (100 μL). Due to the instability of whole blood, fresh whole blood samples were prepared each day. Testing was completed in 8 replicates per run for each level and 1 run per day for 5 days on 3 GEM Premier 5000 instruments. Results are summarized below:

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| Analyte | Mode | Level | Mean | N | Within Run SD | Within Run %CV | Total SD* | Total %CV* |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Glucose (mg/dL) | Normal 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% |
| | Micro 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 (mmol/L) | Normal 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% |
| | Micro 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% |
| | | 5 | 18.2 | 120 | 0.31 | 1.7% | 0.37 | 2.0% |
| tBili (mg/dL) | Normal 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 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% |

* The day-to-day contribution was excluded in total precision evaluation for whole blood samples since different whole blood samples were prepared each day.

# External Precision Studies:

3) A reproducibility study was performed at 3 external clinical point-of-care (POC) sites in hospital settings. The studies were run by a total of 9 different operators (perfusionists and respiratory therapists) on 3 different GEM Premier 5000 instruments using a single lot of GEM Premier 5000 PAK (cartridge). Each site

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used the same lots of GEM System Evaluator (GSE) 1, 2 and 3, running each control level in triplicate, twice a day for 5 days, for a total of 30 replicates per level per site. The pooled repeatability and reproducibility results for these 3 POC sites are summarized below:

| Analyte | Level | N | Mean | Repeatability | | Reproducibility | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | | | SD | %CV | SD | %CV |
| Gluc (mg/dL) | 1 | 90 | 381 | 2.1 | 0.5% | 4.1 | 1.2% |
| | 2 | 90 | 102 | 0.5 | 0.5% | 0.8 | 0.8% |
| | 3 | 90 | 45 | 0.5 | 1.2% | 0.6 | 1.4% |
| Lac (mmol/L) | 1 | 90 | 7.2 | 0.06 | 0.8% | 0.109 | 1.3% |
| | 2 | 90 | 0.8 | 0.02 | 2.3% | 0.02 | 2.5% |
| | 3 | 90 | 2.4 | 0.02 | 0.7% | 0.06 | 2.3% |
| tBili (mg/dL) | 1 | 90 | 33.7 | 0.14 | 0.4% | 0.16 | 0.5% |
| | 2 | 90 | 17.6 | 0.10 | 0.5% | 0.13 | 0.7% |
| | 3 | 90 | 3.2 | 0.10 | 3.0% | 0.10 | 3.3% |
| | CVP 5 tBili | 90 | 4.9 | 0.11 | 2.2% | 0.17 | 3.5% |

4) To evaluate whole blood imprecision on the new GEM Premier 5000 system in the central laboratory and point-of-care (POC) settings, whole blood patient samples were tested at 2 external central laboratories and 1 internal Customer Simulation Laboratory, 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 under both normal mode $(150~\mu \mathrm{L})$ and micro capillary $(65~\mu \mathrm{L})$ mode. Due to the use of unique whole blood samples at each clinical site, only repeatability can be evaluated. Reproducibility was not assessed for the whole blood samples. At the internal Customer Simulation Laboratory, 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.

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Individual and Multisite Results for Glucose in Normal Mode

| Analyte | Sample Mode | Site | N | Mean | Min | Max | Within sample %CV |
| --- | --- | --- | --- | --- | --- | --- | --- |
| Glu (mg/dl) | Normal Mode | POC1 | 51 | 140 | 76 | 337 | 1.1% |
| | | POC2 | 39 | 142 | 80 | 201 | 1.0% |
| | | POC3 | 27 | 137 | 105 | 182 | 1.2% |
| | | POC-All | 117 | 140 | 76 | 337 | 1.1% |
| | | CSL | 33 | 113 | 79 | 365 | 1.7% |
| | | Lab1 | 30 | 163 | 100 | 230 | 1.0% |
| | | Lab2 | 30 | 132 | 76 | 261 | 1.0% |
| | | Lab-All | 93 | 135 | 76 | 365 | 1.2% |

Individual and Multisite Results for Glucose in Micro Mode

| Analyte | Sample Mode | Site | N | Mean | Min | Max | Within sample %CV |
| --- | --- | --- | --- | --- | --- | --- | --- |
| Glu (mg/dl) | Micro Mode | POC1 | 30 | 155 | 79 | 378 | 1.0% |
| | | POC2 | 36 | 146 | 100 | 294 | 1.0% |
| | | POC3 | 30 | 122 | 70 | 206 | 0.8% |
| | | POC-All | 96 | 141 | 70 | 378 | 0.9% |
| | | CSL | 33 | 110 | 74 | 371 | 0.8% |
| | | Lab1 | 30 | 166 | 101 | 231 | 1.2% |
| | | Lab2 | 30 | 136 | 75 | 298 | 1.4% |
| | | Lab-All | 93 | 136 | 74 | 371 | 1.1% |

Individual and Multisite Results for Lactate in Normal Mode

| Analyte | Sample Mode | Site | N | Mean | Min | Max | Within sample SD |
| --- | --- | --- | --- | --- | --- | --- | --- |
| Lactate (mmol/L) | Normal Mode | POC1 | 33 | 1.7 | 1.1 | 2.3 | 0.07 |
| | | POC2 | 12 | 1.8 | 1.4 | 2.6 | 0.03 |
| | | POC3 | 21 | 2.0 | 1.3 | 2.6 | 0.06 |
| | | POC-All | 66 | 1.9 | 1.1 | 2.6 | 0.06 |
| | | CSL | 30 | 1.7 | 0.7 | 2.2 | 0.03 |
| | | Lab 1 | 21 | 2.0 | 1.5 | 2.6 | 0.07 |
| | | Lab 2 | 15 | 2.0 | 1.7 | 2.5 | 0.06 |
| | | Lab-All | 66 | 1.9 | 0.7 | 2.6 | 0.06 |

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Individual and Multisite Results for Lactate in Micro Mode

| Analyte | Sample Mode | Site | N | Mean | Min | Max | Within sample SD |
| --- | --- | --- | --- | --- | --- | --- | --- |
| Lactate (mmol/L) | Micro Mode | POC1 | 27 | 1.9 | 1.3 | 2.4 | 0.06 |
| | | POC2 | 33 | 1.6 | 0.8 | 2.5 | 0.05 |
| | | POC3 | 18 | 1.6 | 0.6 | 2.5 | 0.06 |
| | | POC-All | 78 | 1.7 | 0.6 | 2.5 | 0.05 |
| | | CSL | 30 | 1.9 | 0.9 | 2.5 | 0.04 |
| | | Lab 1 | 30 | 1.8 | 1.1 | 2.6 | 0.08 |
| | | Lab 2 | 12 | 1.9 | 1.5 | 2.7 | 0.06 |
| | | Lab-All | 72 | 1.8 | 0.9 | 2.7 | 0.06 |

Individual and Multisite Results for Total Bilirubin in Normal Mode

| Analyte | Sample Mode | Site | N | Mean | Min | Max | Within sample SD |
| --- | --- | --- | --- | --- | --- | --- | --- |
| tBili (mg/dL) | Normal Mode | POC1 | 24 | 18.7 | 5.5 | 37.2 | 0.8% |
| | | POC2 | 24 | 16.8 | 3.6 | 36.0 | 2.0% |
| | | POC3 | 27 | 11.5 | 4.7 | 21.8 | 1.9% |
| | | POC-All | 75 | 15.5 | 3.6 | 37.2 | 1.6% |
| | | CSL | 15 | 18.5 | 18.0 | 19.1 | 0.6% |
| | | Lab1 | 6 | 4.9 | 4.0 | 5.2 | 7.5% |
| | | Lab-All | 21 | 14.6 | 4.0 | 19.1 | 2.5% |

Individual and Multisite Results for Total Bilirubin in tBili/CO-Ox Mode

| Analyte | Sample Mode | Site | N | Mean | Min | Max | Within sample SD |
| --- | --- | --- | --- | --- | --- | --- | --- |
| tBili (mg/dL) | tBili/ CO-Ox Mode | POC1 | 33 | 22.1 | 4.0 | 39.3 | 1.2% |
| | | POC2 | 27 | 11.6 | 4.0 | 36.6 | 1.6% |
| | | POC3 | 30 | 11.8 | 5.1 | 20.0 | 1.3% |
| | | POC-All | 90 | 15.5 | 4.0 | 39.3 | 1.4% |
| | | CSL | 15 | 18.3 | 17.9 | 18.9 | 0.7% |
| | | Lab1 | 3 | 8.3 | 8.1 | 8.5 | 2.5% |
| | | Lab-All | 18 | 16.7 | 8.1 | 18.9 | 1.0% |

b. Linearity/assay reportable range:

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.

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| Analyte | Claimed Measuring Range | Sample Range Tested (mmol/L) | Slope | Intercept | γ2 |
| --- | --- | --- | --- | --- | --- |
| Glucose (mg/dL) | 4 to 685 | 1 – 777 | 0.982 | -12.489 | 0.995 |
| Lactate (mmol/L) | 0.3 to 17.0 | 0.2 – 25.5 | 1.037 | -0.131 | 0.998 |
| Total Bilirubin (mg/dL) | 2.0 to 40.0 | 1.4 – 43.7 | 1.040 | 0.227 | 0.998 |

The presented data demonstrates linearity across the claimed measuring range of the device for the 3 analytes (glucose, lactate, and total bilirubin).

c. Traceability, Stability, Expected values (controls, calibrators, or methods):

Traceability

The GEM Premier 5000 Glucose is traceable by automated spectrophotometry using hexokinase method per CDC no. 77-8330 using secondary standard prepared from NIST #917.

No reference method is established for lactate. By automated spectrophotometry using lactate oxidase with secondary standard prepared from USP #1614308.

The GEM Premier 5000 bilirubin measurement is traceable to modified Jendrassik-Grof method using NIST #916a standard reference material.

d. Detection limit:

In accordance with CLSI EP17-A2, LoB, LoD and LoQ were established for glucose, lactate and total bilirubin, using three (3) lots of GEM Premier 5000 PAKs (cartridges). Samples tested were all lithium heparin whole blood samples. LoB was determined by running three blank samples in 60 replicates per day over 3 days using 3 lots of GEM Premier 5000 PAKs (cartridges) on 3 different GEM Premier 5000 instruments.

LoD and LoQ were determined by running low level samples in 60 replicates per day over 3 days using 3 lots of GEM Premier 5000 PAKs (cartridges) on 3 different GEM Premier 5000 instruments. LoD is calculated based on LoB (mean) + 1.65 SD (low sample). LoQ was defined as the lowest concentration at which measured total error is less than the pre-defined total error. The results are summarized in the table below:

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The claimed measuring range of the assays is summarized in the tables below:

| Analyte | Claimed measuring range |
| --- | --- |
| Glucose | 4 to 685 mg/dL |
| Lactate | 0.3 to 17.0 mmol/L |
| Total Bilirubin | 2.0 to 40.0 mg/dL |

# e. Analytical specificity:

Interference studies were performed according to CLSI EP-7A guidance to determine the effects from potential interferents on the electrolyte assays. Various concentrations of interferents were spiked into two levels (low and high) of each analyte. Testing was performed in singlet per level using 3 GEM Premier 5000 analyzers. The sponsor's definition of non-significant interference for each analyte was as follows: $10\%$ for glucose, $\pm 10\%$ for tBili, and $\pm 0.4$ mmol/L for lactate.

The highest concentration tested that shows non-significant interference are summarized below:

| 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 |
| Ciprofloxin | 30.2 μmol/L | tBili |

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| Substance | Concentration | Tested analytes with no observed interference |
| --- | --- | --- |
| (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 triethiodide) | 5 mg/dL | Glucose, Lactate |
| (Sodium) Fluoride | 105 μmol/L | Glucose, Lactate |
| Fructose | 1 mmol/L | Glucose, Lactate |
| Galactose | 0.84 mmol/L | Glucose, Lactate |
| Gentamycin | 21 μmol/L | tBili |
| Glucose | 1000 mg/dL | Lactate |
| Glycolic acid | 1 mmol/L | Glucose |
| Hematocrit | 25% | Glucose |
| | 75% | Glucose |
| Hemoglobin | 20 g/dL | tBili |
| Heparin | 100,000 U/L | Glucose, Lactate |
| β-hydroxybutyrate | 2 mmol/L | Glucose, Lactate |
| Ibuprofen | 2425 μmol/L | Glucose, Lactate |
| Icodextrin | 20 mg/dL | Glucose, Lactate |
| Indocyanine Green | 10 mg/L | tBili |
| Isoniazide | 292 μmol/L | Glucose, Lactate |
| Lactate | 6.6 mmol/L | Glucose |
| Lithium (Chloride) | 3.2 mmol/L | tBili |
| Maltose | 200 mg/dL | Glucose, Lactate |
| Mannose | 20 mg/dL | Glucose, Lactate |
| Nitric oxide | 100 mg/dL | Glucose |
| Oxidized chloride | 100 mg/dL | Glucose |
| Oxidized phosphine | 100 mg/dL | Glucose |
| Oxidized phosphine | 100 mg/dL | Glucose |
| Oxidized phosphine | 100 mg/dL | Glucose |
| Oxidized phosphine | 100 mg | Glucose |

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| Substance | Concentration | Tested analytes with no observed interference |
| --- | --- | --- |
| Methadone | 6.46 μmol/L | tBili |
| Morphine | 1.75 μmol/L | tBili |
| Omeprazole | 17.4 μmol/L | tBili |
| (Sodium) Oxalate | 500 mg/dL | Glucose, Lactate |
| pO2 | 30 mmHg | Glucose, Lactate |
| Pralidoxime iodide | 40 μg/mL | Glucose, Lactate |
| Propofol | 0.05 mg/mL | tBili |
| Pyruvate | 309 μmol/L | Glucose, Lactate |
| Sulfhemoglobin | 10% | tBili |
| Suxamethonium | 68 μmol/L | tBili |
| (Sodium) Thiocyanate | 6880 μmol/L | Glucose, Lactate |
| Thiopental | 248 μmol/L | tBili |
| Thyroxine | 1.29 μmol/L | tBili |
| Urea | 42.9 mmol/L | Glucose, Lactate |
| Uric acid | 1.4 mmol/L | Glucose, Lactate |
| Xylose | 20 mg/dL | Glucose, Lactate |

The table below lists substances that demonstrated interference with glucose, lactate or total bilirubin (tBili) results and the concentration of the interfering substance, as well as the bias and its direction (positive / negative):

| Interfering Substance | Affected Analyte | Analyte Concentration | Interfering Concentration Tested | Bias Observed (Mean) | Lowest Interfering Concentration with Analyte Impact | Bias Observed at the Lowest Concentration |
| --- | --- | --- | --- | --- | --- | --- |
| Cyanocobalamin | tBili | 4.8 mg/dL | 0.18 g/L | -11% | 0.16 g/L | -10% |
| | | 13.3 mg/dL | 0.53 g/L | -10% | 0.47 g/L | -10% |
| Cyanomethemo globin | tBili | 5.2 mg/dL | 1.0% | +18% | 0.5% | +10% |
| | | 15.1 mg/dL | 3.0% | +15% | 2.1% | +10% |
| Cyanocobalamin | tBili | 1.0 mg/dL | 0.025 mg/dL | +10% | 0.025 mg/dL | +10% |
| | | 2.0 mg/dL | 0.025 mg/dL | +10% | 0.025 mg/dL | +10% |

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| Interfering Substance | Affected Analyte | Analyte Concentration | Interfering Concentration Tested | Bias Observed (Mean) | Lowest Interfering Concentration with Analyte Impact | Bias Observed at the Lowest Concentration |
| --- | --- | --- | --- | --- | --- | --- |
| Glycolic Acid | Lactate | 1.0 mmol/L | 0.250 mmol/L | +0.4 mmol/L | 0.237 mmol/L | +0.4 mmol/L |
| | | 2.9 mmol/L | 0.250 mmol/L | +0.4 mmol/L | 0.241 mmol/L | +0.4 mmol/L |
| Hydroxocobalamin | tBili | 5.0 mg/dL | 0.18 g/L | -14% | 0.12 g/L | -10% |
| | | 14.7 mg/dL | 0.35 g/L | -13% | 0.27 g/L | -10% |
| Hydroxyurea | Glucose | 86 mg/dL | 0.60 mg/dL | +15% | 0.41 mg/dL | +10% |
| | | 115 mg/dL | 0.60 mg/dL | +11% | 0.57 mg/dL | +10% |
| Hydroxyurea | Lactate | 1.0 mmol/L | 0.40 mg/dL | 0.4 mmol/L | 0.37 mg/dL | +0.4 mmol/L |
| | | 2.8 mmol/L | 0.40 mg/dL | 0.5 mmol/L | 0.35 mg/dL | +0.4 mmol/L |
| Methylene Blue | tBili | 5.0 mg/dL | 10 mg/L | -25% | 4.6 mg/L | -10% |
| | | 14.2 mg/dL | 15 mg/L | -11% | 12.9 mg/L | -10% |
| Turbidity (Intralipid) | tBili | 4.8 mg/dL | 1505 mg/dL | -11% | 1143 mg/dL | -10% |
| | | 14.0 mg/dL | 2006 mg/dL | No Interference Observed | | |

f. Assay cut-off:

Not Applicable

## 2. Comparison studies:

a. Method comparison with predicate device:

In accordance with EP09-A3, a method comparison study was conducted on the GEM Premier 5000 in the point-of-care (POC) setting using heparinized whole blood patient samples from the intended use population.

In each setting, the performance of the GEM Premier 5000 was compared to the GEM Premier 4000, except tBili, which used the commercially available whole blood or chemistry analyzer in use at each facility.

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For glucose and lactate, the pooled results from the POC sites and the IL internal Customer Simulation Laboratory (CSL) for the Normal Mode (with samples collected in syringes) are presented below:

| Syringe Samples | | | | | |
| --- | --- | --- | --- | --- | --- |
| Analyte | N | Slope | Intercept | r | Sample Range |
| Glucose (mg/dL) | 489 | 0.973 | 3.622 | 0.998 | 12 to 619 |
| Lactate (mmol/L) | 488 | 1.000 | 0.000 | 0.996 | 0.5 to 15.0 |

Another method comparison study for capillary whole blood for glucose and lactate was performed at an external POC site in a hospital and an internal laboratory. Capillary whole blood specimens were collected via capillary puncture into 2 capillary tubes containing lithium heparin, and tested immediately on GEM4000 (predicate) and GEM5000 (new device). In addition, $<20\%$ of altered capillary samples were tested internally to cover the claimed measuring ranges. The study results are summarized below:

| Capillary Samples | | | | | |
| --- | --- | --- | --- | --- | --- |
| Analyte | N | Slope | Intercept | r | Sample Range |
| Glucose (mg/dL) | 197 | 0.966 | 4.775 | 0.997 | 12 to 637 |
| Lactate (mmol/L) | 201 | 1.000 | 0.000 | 0.995 | 0.4 to 16.4 |

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Results based on native capillary samples at Medical Decision Level (MDL) are shown below:

| Native Capillary Samples | | | | | | |
| --- | --- | --- | --- | --- | --- | --- |
| Analyte | N | Range Min | Range Max | MDL | Bias at MDL | 95% CI of Bias at MDL |
| Glu (mg/dL) | 171 | 68 | 280 | 45 | 3.9 | 1.0 to 6.2 |
| | | | | 120 | 1.8% | -0.1% to 2.9% |
| | | | | 180 | -0.5% | -2.0% to 2.1% |
| | | | | 350 | -0.9% | -4.0% to 1.1% |
| Lac (mg/dL) | 171 | 0.4 | 3.7 | 2.0 | 0.00 | 0.00 to 0.11 |
| | | | | 5.0 | 0.0% | 0.00% to 10.3% |

For Total Bilirubin (tBili), the pooled results*** from the POC sites, with a combination of heel-stick samples (capillary Blood) and syringe (arterial/venous), are presented below for the different instrument modes:

| Normal Mode | | | | | |
| --- | --- | --- | --- | --- | --- |
| Predicate | N | Slope | Intercept | r | Sample Range |
| tBili (mg/dL) vs. Roche Cobas 6000* | 53 | 1.062 | 0.630 | 0.996 | 3.1 to 39.7 |
| tBili (mg/dL) vs. Ortho Clinical Diagnostics Vitros 5600** | 76 | 1.076 | -0.099 | 0.996 | 2.0 to 39.7 |

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| Capillary Mode | | | | | |
| --- | --- | --- | --- | --- | --- |
| Predicate | N | Slope | Intercept | r | Sample Range |
| tBili (mg/dL) vs. Roche Cobas 6000* | 58 | 1.051 | 0.533 | 0.996 | 3.9 to 39.9 |
| tBili (mg/dL) vs. Ortho Clinical Diagnostics Vitros 5600** | 77 | 1.072 | -0.255 | 0.996 | 2.1 to 39.4 |
| tBili/CO-Ox Mode | | | | | |
| Predicate | N | Slope | Intercept | r | Sample Range |
| tBili (mg/dL) vs. Roche Cobas 6000* | 53 | 1.068 | 0.404 | 0.996 | 2.0 to 39.7 |
| tBili (mg/dL) vs. Ortho Clinical Diagnostics Vitros 5600** | 77 | 1.076 | -0.163 | 0.995 | 2.0 to 39.2 |

*tBili data against Roche Cobas 6000 were from one (1) POC site.
**tBili data against Ortho Clinical Diagnostics Vitros 5600 were from two (2) POC sites.
***8% of the total samples are spiked samples

b. Matrix comparison:

Not applicable. Sponsor stated that only lithium heparin anticoagulant whole blood is the acceptable sample type to be used for their device.

3. Clinical studies:

a. Clinical Sensitivity:

Not Applicable

b. Clinical specificity:

Not Applicable

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c. Other clinical supportive data (when a. and b. are not applicable):

Not Applicable

# 4. Clinical cut-off:

Not Applicable

5. Expected values/Reference range:

| Analyte | Reference Range | Unit |
| --- | --- | --- |
| Glu1,2 | 65 to 95 | mg/dL |
| Glu1,2 | 3.6 to 5.3 | mmol/L |
| Lac1 | 0.36 to 0.75 (at rest) | mmol/L |
| Lac1 | 2.24 to 6.76 (at rest) | mg/dL |
| Lac1 | 0.56 to 1.39 (venous) | mmol/L |
| Lac1 | 2.0 to 12.5 (venous) | mg/dL |
| Analyte | Age | Reference Range | Unit |
| --- | --- | --- | --- |
| tBili2 | Premature Infant 0 – 1 day | <8.0 | mg/dL |
| | Premature Infant 0 – 1 day | <137 | μmol/L |
| | Premature Infant 1 – 2 days | <12.0 | mg/dL |
| | Premature Infant 1 – 2 days | <205 | μmol/L |
| | Premature Infant 3 – 5 days | <16.0 | mg/dL |
| | Premature Infant 3 – 5 days | <274 | μmol/L |
| | Full-term Infant 0 – 1 day | 1.4 – 8.7 | mg/dL |
| | Full-term Infant 0 – 1 day | 24 – 149 | μmol/L |
| | Full-term Infant 1 – 2 days | 3.4 – 11.5 | mg/dL |
| | Full-term Infant 1 – 2 days | 58 – 197 | μmol/L |
| | Full-term Infant 3 – 5 days | 1.5 – 12.0 | mg/dL |
| | Full-term Infant 3 – 5 days | 26 – 105 | μmol/L |
| | >5 days to < 60 years | 0.3 – 1.2 | mg/dL |
| | >5 days to < 60 years | 5 – 21 | μmol/L |

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1. Burtis, Carl and David Bruns, Tietz Textbook of Clinical Chemistry and Molecular Diagnostics, Elsevier Saunders, 7th edition, 2015.
2. Wu, A., Tietz Clinical Guide to Laboratory Tests, W.B. Saunders Co., St. Louis MO, 4th Edition, 2006.

N. Proposed Labeling:

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

O. Conclusion:

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

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