GEM PREMIER 4000 WITH IQM, MODEL 4000; GEM CVP 1 AND 2 WITH CO-OX; GEM CVP 3 AND 4 HEMATOCRIT
Device Facts
| Record ID | K061974 |
|---|---|
| Device Name | GEM PREMIER 4000 WITH IQM, MODEL 4000; GEM CVP 1 AND 2 WITH CO-OX; GEM CVP 3 AND 4 HEMATOCRIT |
| Applicant | Instrumentation Laboratory CO |
| Product Code | CHL · Clinical Chemistry |
| Decision Date | Sep 15, 2006 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 862.1120 |
| Device Class | Class 2 |
Indications for Use
The GEM Premier 4000 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 pH, pCO2, pO2, Na+, K+, Cl-, Ca++, glucose, lactate, hematocrit and CO-Oximetry (tHb, O2Hb, MetHb, HHb) parameters. These parameters, along with derived parameters, aid in the diagnosis of a patient's acid/base status, electrolyte and metabolite balance and oxygen delivery capacity. Intelligent Quality Management (iQM) is used as the quality control and assessment system for the GEM Premier 4000 system. iQM is an active quality process control program designed to provide continuous monitoring of the analytical process with real-time, automatic error detection, automatic correction of the system and automatic documentation of all corrective actions, replacing the use of traditional external quality controls. As part of this program, GEM CVP 1 and 2 (Calibration Valuation Product) with CO-Ox and GEM CVP 3 and 4 Hematocrit are external solutions intended to complete the calibration process and final accuracy assessment of the iQM cartridge calibration after initial warm-up. The reported values for the four levels of GEM CVP (two levels for pH, blood gases, electrolytes, metabolites and CO-Oximetry; two levels for hematocrit) must meet specifications before the iQM cartridge can be used for patient sample measurements. Once the cartridge calibration is verified, the internal iQM program monitors the status of the system during the cartridge use life.
Device Story
Portable critical care system; analyzes whole blood samples at point-of-care or central lab; measures pH, blood gases, electrolytes, glucose, lactate, hematocrit, and CO-Oximetry parameters. Uses potentiometric, amperometric, conductometric, and spectrophotometric sensors. Features Intelligent Quality Management (iQM) system; provides continuous monitoring of analytical process; performs real-time automatic error detection, correction, and documentation; replaces traditional external quality controls. Requires GEM CVP external solutions for initial calibration verification. Healthcare professionals use output to diagnose acid/base status, electrolyte/metabolite balance, and oxygen delivery capacity.
Clinical Evidence
In-house and field site testing performed. No specific clinical trial data provided in summary; substantial equivalence supported by performance testing comparing subject device to predicate devices.
Technological Characteristics
Potentiometric, amperometric, conductivity, and spectrophotometric sensing. Portable form factor. iQM software for automated quality control. Uses external CVP solutions for calibration verification.
Indications for Use
Indicated for use by healthcare professionals to analyze whole blood samples for pH, blood gases, electrolytes, metabolites, hematocrit, and CO-Oximetry parameters to aid in diagnosis of acid/base status, electrolyte/metabolite balance, and oxygen delivery capacity in clinical and laboratory settings.
Regulatory Classification
Identification
A blood gases (PCO2 , PO2 ) and blood pH test system is a device intended to measure certain gases in blood, serum, plasma or pH of blood, serum, and plasma. Measurements of blood gases (PCO2 , PO2 ) and blood pH are used in the diagnosis and treatment of life-threatening acid-base disturbances.
Predicate Devices
Related Devices
- K112995 — GEM PREMIER 4000 · Instrumentation Laboratory CO · May 3, 2012
- K203790 — GEM Premier 5000 · Instrumentation Laboratory CO · Aug 20, 2021
- K133407 — GEM PREMIER 4000 · Instrumentation Laboratory CO · Jan 13, 2014
- K151978 — EDAN i15 Blood Gas and Chemistry Analysis System, EDAN i15 Calibrant Fluid Pack, EDAN i15 Blood Gas and Electrolyte Control, EDAN i15 Hematocrit Control · Edan Instruments, Inc. · Jul 15, 2016
Submission Summary (Full Text)
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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY AND INSTRUMENT COMBINATION TEMPLATE
A. 510(k) Number:
k061974
B. Purpose for Submission:
Clearance of a new device.
C. Measurand:
Blood gases, blood pH, sodium, potassium, calcium, chloride, glucose, lactic acid, hematocrit, carboxyhemoglobin, hemoglobin
D. Type of Test:
Potentiometric for pH, pCO2, Na+, K+, Cl-, Ca++
Amperometric for pO2, Glucose, Lactate
Conductivity for Hematocrit
Spectrophotometry for CO-Oximeter parameters
E. Applicant:
Instrumentation Laboratory Co.
F. Proprietary and Established Names:
GEM® Premier 4000 with iQM® (Intelligent Quality Management)
GEM CVP 1 and 2 (Calibration Valuation Product) with CO-Ox
GEM CVP 3 and 4 (Calibration Valuation Product) Hematocrit
G. Regulatory Information:
1. Regulation section:
GEM Premier 4000 with iQM (Intelligent Quality Management)
| Description | CFR Section |
| --- | --- |
| Blood gases and blood pH | 862.1120 |
| Sodium test system | 862.1665 |
| Potassium test system | 862.1600 |
| Calcium test system | 862.1145 |
| Chloride test system | 862.1170 |
| Glucose test system | 862.1345 |
| Lactic acid test system | 862.1450 |
| Automated hematocrit instrument | 864.5600 |
| Carboxyhemoglobin assay | 864.7425 |
| Automated hemoglobin system | 864.5620 |
| Oximeter to measure hemoglobin | 864.7500 |
| Quality Control Material | 862.1660 |
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GEM CVP 1 and 2 (Calibration Valuation Product) with CO-Ox
| Description | CFR Section |
| --- | --- |
| Quality Control Material | 862.1660 |
GEM CVP 3 and 4 (Calibration Valuation Product) Hematocrit
| Description | CFR Section |
| --- | --- |
| Hematocrit Control | 864.8625 |
2. Classification:
GEM Premier 4000 with iQM (Intelligent Quality Management)
| Description | Class |
| --- | --- |
| Blood gases and blood pH | Class II |
| Sodium test system | Class II |
| Potassium test system | Class II |
| Calcium test system | Class II |
| Chloride test system | Class II |
| Glucose test system | Class II |
| Lactic acid test system | Class I |
| Automated hematocrit instrument | Class II |
| Carboxyhemoglobin assay | Class II |
| Automated hemoglobin system | Class II |
| Oximeter to measure hemoglobin | Class II |
| Quality Control Material | Class I |
GEM CVP 1 and 2 (Calibration Valuation Product) with CO-Ox
| Description | Class |
| --- | --- |
| Quality Control Material | Class I |
GEM CVP 3 and 4 (Calibration Valuation Product) Hematocrit
| Description | Class |
| --- | --- |
| Hematocrit Control | Class II |
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3. Product code:
GEM Premier 4000 with iQM (Intelligent Quality Management)
| Description | Product Code |
| --- | --- |
| Blood gases and blood pH | CHL |
| Sodium test system | JGS |
| Potassium test system | CEM |
| Calcium test system | JFP |
| Chloride test system | CGZ |
| Glucose test system | CGA |
| Lactic acid test system | KHP |
| Automated hematocrit instrument | GKF |
| Carboxyhemoglobin assay | GHS |
| Automated hemoglobin system | GKR |
| Oximeter to measure hemoglobin | GLY |
| Quality Control Material | JJY |
GEM CVP 1 and 2 (Calibration Valuation Product) with CO-Ox
| Description | Product Code |
| --- | --- |
| Quality Control Material | JJY |
GEM CVP 3 and 4 (Calibration Valuation Product) Hematocrit
| Description | Product Code |
| --- | --- |
| Hematocrit Control | GLK |
4. Panel:
75 (Clinical Chemistry), 81 (Hematology)
H. Intended Use:
1. Intended use(s):
See Indications for use.
2. Indication(s) for use:
The GEM Premier 4000 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 pH, pCO2, pO2, Na+, K+, Cl-, Ca++, glucose, lactate, hematocrit and
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CO-Oximetry (tHb, O2Hb, COHb, MetHb, HHb) parameters. These parameters, along with derived parameters, aid in the diagnosis of a patient’s acid/base status, electrolyte and metabolite balance and oxygen delivery capacity.
Intelligent Quality Management (iQM) is used as the quality control and assessment system for the GEM Premier 4000 system. iQM is an active quality process control program designed to provide continuous monitoring of the analytical process with real-time, automatic error detection, automatic correction of the system and automatic documentation of all corrective actions, replacing the use of traditional external quality controls.
As part of this program, GEM CVP 1 and 2 (Calibration Valuation Product) with CO-Ox and GEM CVP 3 and 4 Hematocrit are external solutions intended to complete the calibration process and final accuracy assessment of the iQM cartridge calibration after initial warm-up. The reported values for the four levels of GEM CVP (two levels for pH, blood gases, electrolytes, metabolites and CO-Oximetry; two levels for hematocrit) must meet specifications before the iQM cartridge can be used for patient sample measurements. Once the cartridge calibration is verified, the internal iQM program monitors the status of the system during the cartridge use life.
3. Special conditions for use statement(s):
For prescription use.
4. Special instrument requirements:
GEM Premier 4000 with iQM and GEM CVP
I. Device Description:
The GEM Premier 4000 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 pH, pCO2, pO2, Na+, K+, Cl-, Ca++, glucose, lactate, hematocrit and CO-Oximetry (tHb, O2Hb, COHb, MetHb, HHb) parameters. These parameters, along with derived parameters, aid in the diagnosis of a patient’s acid/base status, electrolyte and metabolite balance and oxygen delivery capacity.
Intelligent Quality Management (iQM) is used as the quality control and assessment system for the GEM Premier 4000 system. iQM is an active quality process control program designed to provide continuous monitoring of the analytical process with real-time, automatic error detection, automatic correction of the system and automatic documentation of all corrective actions, replacing the use of traditional external quality controls.
As part of this program, GEM CVP 1 and 2 (Calibration Valuation Product) with CO-Ox and GEM CVP 3 and 4 Hematocrit are external solutions intended to complete the calibration process and final accuracy assessment of the iQM cartridge calibration after initial warm-up. The reported values for the four levels of GEM CVP (two levels for pH, blood gases, electrolytes, metabolites and CO-Oximetry; two levels for hematocrit) must meet specifications before the iQM cartridge can be used for patient sample measurements. Once
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the cartridge calibration is verified, the internal iQM program monitors the status of the system during the cartridge use life.
J. Substantial Equivalence Information:
1. Predicate device name(s):
IL Synthesis, GEM Premier 3000, and IL 682 CO-Oximeter
2. Predicate 510(k) number(s):
k963800, k052121, and k945677 respectively.
3. Comparison with predicate:
| Similarities | | |
| --- | --- | --- |
| Item | GEM Premier 4000 with iQM and GEM CVP | Predicate Devices |
| Indications for Use | The GEM Premier 4000 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 pH, blood gases, Na+, K+, Cl-, Ca++, glucose, lactate, hematocrit and CO-Oximetry (tHb, O2Hb, COHb, MetHb, HHb) parameters. These parameters, along with derived parameters, aid in the diagnosis of a patient's acid/base status, electrolyte and metabolite balance and oxygen delivery capacity. | The GEM Premier 3000 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. The instrument provides quantitative measurements of pH, pCO2, pO2, Na+, K+, Ca++, glucose, lactate and hematocrit. These parameters, along with derived parameters, aid in the diagnosis of a patient's acid/base status, oxygen delivery capacity, and electrolyte and metabolite balance. NOTE: The GEM Premier 4000 introduces additional measured parameters for chloride and CO-Oximetry. |
| Operating Principle | • Electrochemical: potentiometric ion-selective electrode
• Electrochemical: amperometric enzyme biosensor
• Electrochemical: Conductometric measurement of red cell volume
• Optical measurement of hemoglobin and fractional derivatives of hemoglobin in lysed blood | Same |
| Sample Type | Whole blood samples | Same |
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| Differences | | |
| --- | --- | --- |
| Item | GEM Premier 4000 with iQM and GEM CVP | Predicate Devices |
| Quality Control Principle | Active quality process control program using external Calibration Valuation Product (CVP), four internal Process Control Solutions (PCSs) and Failure Pattern Recognition (FPR) software designed to provide immediate error detection and automatic remedial action, replacing the use of traditional external quality controls. | GEM Premier 3000 with iQM:
• Same as GEM Premier 4000
IL Synthesis (Chloride) and IL CO-Oximeter 682:
• Use of multi-level external quality control solutions on a regular basis for error detection. |
| Detection Frequency | GEM Premier 4000 Internal Process Control Solutions (PCSs):
• PC Solution B is the primary Process Control Solution measured at a minimum of every half hour or after every sample. Furthermore, Solution B is monitored every 30 seconds while residing in the sensor card between measurements. Further, PC Solution B is used as a reference blank for CO-Oximetry.
• PC Solution A is measured at a minimum of every 4 hours. All sensor slope values are also measured and checked. Slope, which is an indicator of sensor sensitivity and drift, must be within allowable limits. PC Solution A also contains dyes that are used for checking functionality of the optical cell and the co-oximetry.
• PC Solution C is measured at a minimum of once every 24 hours. PC Solution C is primarily used for measuring low-level oxygen; however, PC Solution C is also used to provide an additional measurement of pH, pCO_{2} and K^{+} sensor functionality.
• PC Solution D is measured every 12 hours. Solution D provides additional | GEM Premier 3000 Internal Process Control Solutions (PCSs):
• PC Solution B is the primary Process Control Solution measured at a minimum of every half hour or after every sample. Furthermore, Solution B is monitored every 30 seconds while residing in the sensor card between measurements.
• PC Solution A is measured at a minimum of every 4 hours. All sensor slope values are also measured and checked. Slope, which is an indicator of sensor sensitivity and drift, must be within allowable limits.
• PC Solution C is measured at a minimum of once every 24 hours. PC Solution C is primarily used for measuring low-level oxygen; however, PC Solution C is also used to provide an additional measurement of pH and pCO_{2} sensor functionality.
IL Synthesis (Chloride) and IL CO-Oximeter 682:
• Use of external quality control |
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| Differences | | |
| --- | --- | --- |
| Item | GEM Premier 4000 with iQM and GEM CVP | Predicate Devices |
| | measurement for all analytes including co-oximetry. Reference values for analytes in solution D are established within the first 3 days after cartridge insertion by averaging multiple measurements of the D solution. The D sensor check starts once the reference values are established. | solutions on a regular basis for error detection.
• Traditional controls may not detect the error for 8 or more hours, based on the frequency of running the control solutions. |
K. Standard/Guidance Document Referenced (if applicable):
None identified.
L. Test Principle:
The GEM Premier 4000 analyzer uses potentiometric sensors to measure $p\mathrm{CO}_2$, pH, $\mathrm{Na}^+$, $\mathrm{K}^+$, $\mathrm{Cl}^-$ and $\mathrm{Ca}^{++}$, amperometric electrodes to measure $p\mathrm{O}_2$, glucose and lactate concentrations and blood conductivity to measure hematocrit. CO-Oximetry measurements involve chemically lysing the whole blood sample and then utilizing a broad spectrum spectrometer to evaluate the sample at a variety of wavelengths.
M. Performance Characteristics (if/when applicable):
1. Analytical performance:
a. Precision/Reproducibility:
To verify the performance of the GEM Premier 4000, whole blood precision testing was performed in-house on 6 to 12 different GEM Premier 4000 instruments, depending on the analyte. Six levels for pH, blood gases, potassium, glucose and lactate, 7 levels for sodium, calcium and chloride, 8 levels for hematocrit and 5 to 9 levels for CO-Oximetry were evaluated using whole blood from healthy adult volunteers.
Samples were altered with various levels of analytes (salts, gases, or plasma) to span the claimed measuring range and tested in 3 replicates per run on each instrument. All parameters were tested once in week two of the cartridge use life. The data was used to show within run standard deviations and %CV pooled. Results are summarized below.
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| pH | | | |
| --- | --- | --- | --- |
| N per Level | Mean | SD | % CV |
| 35 | 7.030 | 0.008 | 0.12 |
| 36 | 7.086 | 0.007 | 0.10 |
| 35 | 7.235 | 0.009 | 0.12 |
| 35 | 7.350 | 0.010 | 0.13 |
| 36 | 7.483 | 0.011 | 0.14 |
| 33 | 7.675 | 0.024 | 0.31 |
| pCO2 | | | |
| N per Level | Mean (mmHg) | SD | % CV |
| 34 | 11.3 | 0.60 | 5.33 |
| 36 | 24.5 | 0.07 | 0.29 |
| 35 | 39.9 | 0.89 | 2.24 |
| 35 | 59.6 | 0.72 | 1.21 |
| 36 | 105.8 | 0.92 | 0.87 |
| 35 | 125.2 | 1.26 | 1.01 |
| pO2 | | | |
| N per Level | Mean (mmHg) | SD | % CV |
| 36 | 28.5 | 0.94 | 3.31 |
| 35 | 49.0 | 0.81 | 1.66 |
| 35 | 105.7 | 4.35 | 4.12 |
| 35 | 203.9 | 4.48 | 2.20 |
| 36 | 420.5 | 8.75 | 2.08 |
| 30 | 714.5 | 36.80 | 5.15 |
| | | | |
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| Na+ | | | |
| --- | --- | --- | --- |
| N per Level | Mean (mmol/L) | SD | % CV |
| 30 | 108.9 | 0.63 | 0.58 |
| 30 | 121.0 | 0.55 | 0.45 |
| 29 | 130.1 | 1.51 | 1.16 |
| 29 | 139.2 | 1.99 | 1.43 |
| 30 | 156.2 | 0.89 | 0.57 |
| 30 | 170.0 | 0.91 | 0.54 |
| 30 | 177.2 | 1.99 | 1.12 |
| K+ | | | |
| N per Level | Mean (mmol/L) | SD | % CV |
| 30 | 1.98 | 0.10 | 4.79 |
| 30 | 4.11 | 0.11 | 2.61 |
| 27 | 5.02 | 0.06 | 1.24 |
| 30 | 7.50 | 0.08 | 1.03 |
| 30 | 10.20 | 0.07 | 0.68 |
| 30 | 18.99 | 0.20 | 1.05 |
| Ca++ | | | |
| N per Level | Mean (mmol/L) | SD | % CV |
| 33 | 0.422 | 0.005 | 1.27 |
| 33 | 1.223 | 0.010 | 0.78 |
| 33 | 1.509 | 0.017 | 1.11 |
| 30 | 1.929 | 0.015 | 0.77 |
| 33 | 2.524 | 0.011 | 0.43 |
| 33 | 3.747 | 0.018 | 0.48 |
| 33 | 4.319 | 0.039 | 0.90 |
| | | | |
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| Cl- | | | |
| --- | --- | --- | --- |
| N per Level | Mean (mmol/L) | SD | % CV |
| 33 | 61.7 | 0.43 | 0.69 |
| 33 | 78.5 | 0.25 | 0.31 |
| 30 | 100.3 | 0.41 | 0.41 |
| 33 | 124.3 | 0.88 | 0.71 |
| 33 | 132.0 | 0.97 | 0.74 |
| 33 | 143.8 | 0.66 | 0.46 |
| 33 | 161.4 | 0.31 | 0.19 |
| Glucose | | | |
| N per Level | Mean (mg/dL) | SD | % CV |
| 29 | 46.3 | 0.69 | 1.48 |
| 30 | 105.8 | 2.02 | 1.91 |
| 30 | 202.2 | 1.92 | 0.95 |
| 30 | 340.1 | 1.51 | 0.44 |
| 29 | 464.0 | 4.68 | 1.01 |
| 27 | 708.3 | 9.73 | 1.37 |
| Lactate | | | |
| N per Level | Mean (mmol/L) | SD | % CV |
| 33 | 1.11 | 0.07 | 6.49 |
| 33 | 2.38 | 0.17 | 7.23 |
| 33 | 4.23 | 0.11 | 2.64 |
| 33 | 7.86 | 0.11 | 1.37 |
| 33 | 13.75 | 0.11 | 0.83 |
| 33 | 17.21 | 0.36 | 2.11 |
| | | | |
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| Hematocrit | | | |
| --- | --- | --- | --- |
| N per Level | Mean (%) | SD | % CV |
| 36 | 19.4 | 0.37 | 1.92 |
| 36 | 22.1 | 0.29 | 1.30 |
| 36 | 25.1 | 0.17 | 0.67 |
| 36 | 34.1 | 0.37 | 1.09 |
| 36 | 46.4 | 0.29 | 0.62 |
| 36 | 65.0 | 0.65 | 0.99 |
| 36 | 69.8 | 0.37 | 0.53 |
| 35 | 73.0 | 0.55 | 0.76 |
| tHb | | | |
| N per Level | Mean (g/dL) | SD | % CV |
| 18 | 6.1 | 0.1 | 0.9 |
| 18 | 6.8 | 0.1 | 1.1 |
| 17 | 7.7 | 0.1 | 1.2 |
| 18 | 10.3 | 0.2 | 1.5 |
| 107 | 15.4 | 0.2 | 1.2 |
| 144 | 16.8 | 0.2 | 1.2 |
| 36 | 17.7 | 0.3 | 1.5 |
| 18 | 18.9 | 0.1 | 0.7 |
| 17 | 21.6 | 0.5 | 2.4 |
| | | | |
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| O2Hb | | | |
| --- | --- | --- | --- |
| N per Level | Mean (%) | SD | % CV |
| 18 | 0.4 | 0.3 | * |
| 18 | 2.9 | 0.2 | * |
| 18 | 26.9 | 0.1 | 0.4 |
| 18 | 35.0 | 0.3 | 1.0 |
| 18 | 50.2 | 0.1 | 0.3 |
| 18 | 66.5 | 0.4 | 0.6 |
| 35 | 73.5 | 0.2 | 0.2 |
| 54 | 88.8 | 0.2 | 0.2 |
| 197 | 95.4 | 0.7 | 0.8 |
* SD calculations were used for the CO-Oximeter fractions with Mean values ≤ 3.0.
| COHb | | | |
| --- | --- | --- | --- |
| N per Level | Mean (%) | SD | % CV |
| 124 | 1.0 | 0.4 | * |
| 160 | 1.7 | 0.4 | * |
| 18 | 5.3 | 0.1 | 1.0 |
| 18 | 10.4 | 0.1 | 0.8 |
| 18 | 24.5 | 0.1 | 0.5 |
| 18 | 49.6 | 0.2 | 0.3 |
| 18 | 73.2 | 0.2 | 0.2 |
| 18 | 99.2 | 0.6 | 0.6 |
| | | | |
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| MetHb | | | |
| --- | --- | --- | --- |
| N per Level | Mean (%) | SD | % CV |
| 321 | 0.5 | 0.4 | * |
| 18 | 3.9 | 0.2 | 4.6 |
| 18 | 6.8 | 0.1 | 2.0 |
| 18 | 12.3 | 0.2 | 2.0 |
| 17 | 27.3 | 0.2 | 0.8 |
| HHb | | | |
| N per Level | Mean (%) | SD | % CV |
| 225 | 0.1 | 0.2 | * |
| 77 | 1.2 | 0.6 | * |
| 36 | 3.0 | 0.4 | * |
| 18 | 32.1 | 0.5 | 1.4 |
| 18 | 64.0 | 0.3 | 0.5 |
| 18 | 96.4 | 0.2 | 0.2 |
* Only SD calculations were used for the CO-Oximeter fractions with Mean values ≤ 3.0.
To verify the performance of the GEM CVP, precision data were generated using GEM CVP 1 and 2 (Calibration Valuation Product) with CO-Ox (two levels for pH, blood gases, electrolytes, metabolites and CO-Oximetry) and GEM CVP 3 and 4 Hematocrit (two levels). The control levels were assayed twice a day in duplicate over 10 days for a total of 20 runs on 3 different GEM Premier 4000 instruments $(N = 120)$ . The day-to-day and total $\% \mathrm{CV}$ (or SD) were calculated across all 3 instruments. SD is used for pH and the CO-Oximeter fractions. Results are summarized below.
| GEM CVP with CO-Ox | Parameter | Mean | Day-to-Day % CV (or SD) | Total % CV (or SD) | Total Spec. % CV (or SD) |
| --- | --- | --- | --- | --- | --- |
| | pH | 7.156 | 0.0021 (SD) | 0.0060 (SD) | 0.020 (SD) |
| | pCO2(mmHg) | 68.9 | 0.87 | 2.31 | 4.0 |
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| GEM CVP with CO-Ox | Parameter | Mean | Day-to-Day % CV (or SD) | Total % CV (or SD) | Total Spec. % CV (or SD) |
| --- | --- | --- | --- | --- | --- |
| Level 1 | pO2(mmHg) | 36.0 | 3.76 | 10.0 | 12.5 |
| | Na+(mmol/L) | 124.9 | 0.23 | 0.59 | 1.60 |
| | K+(mmol/L) | 2.27 | 0.72 | 1.95 | 11.0 |
| | Ca++(mmol/L) | 1.59 | 0.20 | 0.71 | 5.0 |
| | Cl-(mmol/L) | 91.1 | 0.30 | 0.53 | 2.5 |
| | Glucose (mg/dL) | 362.3 | 0.72 | 2.99 | 6.0 |
| | Lactate (mmol/L) | 7.03 | 0.81 | 3.61 | 7.5 |
| | tHb (g/dL) | 16.84 | 0.95 | 1.44 | 2.1 |
| | O2Hb (%) | 86.9 | 0.00 (SD) | 0.00 (SD) | 1.0 (SD) |
| | COHb (%) | 3.59 | 0.01 (SD) | 0.03 (SD) | 1.0 (SD) |
| | MetHb (%) | 3.90 | 0.00 (SD) | 0.00 (SD) | 1.0 (SD) |
| | HHb (%) | 5.69 | 0.00 (SD) | 0.03 (SD) | 3.0 (SD) |
| GEM CVP with CO-Ox | Parameter | Mean | Day-to-Day % CV (or SD) | Total % CV (or SD) | Total Spec. % CV (or SD) |
| --- | --- | --- | --- | --- | --- |
| Level 2 | pH | 7.580 | 0.0006 (SD) | 0.0024 (SD) | 0.020 (SD) |
| | pCO2(mmHg) | 13.8 | 0.34 | 4.40 | 18.12 |
| | pO2(mmHg) | 123.8 | 0.83 | 3.16 | 5.0 |
| | Na+(mmol/L) | 154 | 0.00 | 0.54 | 1.3 |
| | K+(mmol/L) | 7.64 | 0.35 | 0.78 | 3.5 |
| | Ca++(mmol/L) | 0.82 | 0.75 | 1.10 | 6.1 |
| | Cl-(mmol/L) | 133.2 | 0.36 | 0.58 | 2.5 |
| | Glucose (mg/dL) | 74.9 | 0.28 | 2.37 | 8.0 |
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| GEM CVP with CO-Ox | Parameter | Mean | Day-to-Day % CV (or SD) | Total % CV (or SD) | Total Spec. % CV (or SD) |
| --- | --- | --- | --- | --- | --- |
| | Lactate (mmol/L) | 1.60 | 0.72 | 4.81 | 12.5 |
| | tHb (g/dL) | 7.63 | 1.42 | 2.20 | 4.59 |
| | O2Hb (%) | 39.20 | 0.03 (SD) | 0.05 (SD) | 1.0 (SD) |
| | COHb (%) | 30.70 | 0.00 (SD) | 0.00 (SD) | 1.0 (SD) |
| | MetHb (%) | 8.98 | 0.02 (SD) | 0.04 (SD) | 1.0 (SD) |
| | HHb (%) | 21.10 | 0.00 (SD) | 0.00 (SD) | 3.0 (SD) |
| GEM CVP Hematocrit | Parameter | Mean | Day-to-Day % CV | Total % CV | Total Spec. % CV |
| --- | --- | --- | --- | --- | --- |
| Level 3 | Hematocrit (%) | 22.4 | 0.23 | 0.47 | 2.0 |
| Level 4 | Hematocrit (%) | 43.0 | 0.00 | 0.16 | 2.0 |
# b. Linearity/assay reportable range:
The data from the whole blood precision study above were used in the linearity calculations provided below. The following reference analyzers were used:
| Description | 510(k) | Analyte(s) |
| --- | --- | --- |
| GEM 3000 with iQM and GEM CVP | k052121 | pH, electrolytes (except chloride), glucose, lactate and hematocrit [except for Glu levels > 500 mg/dL and Lac levels > 15 mmol/L, which used the ABL 735 analyzer (K991417) and Hct levels > 65%, which used spun crit] |
| Tonometry | NA | Blood gases |
| IL Synthesis | K963800 | Chloride |
| IL 682 CO-Oximeter | K945677 | CO-Oximeter parameters [except for tHb levels > 20 g/dL, which used the ABL 735 analyzer (K991417)] |
{15}
Results are summarized below:
| Parameter | N per Level | Slope | Intercept | R2 | Range |
| --- | --- | --- | --- | --- | --- |
| pH | 33 to 36 | 0.9576 | 0.3189 | 0.9971 | 7.01 to 7.70 |
| pCO2(mmHg) | 34 to 36 | 0.9888 | 0.1274 | 0.9967 | 10.5 to 124.9 |
| pO2(mmHg) | 30 to 36 | 1.0412 | -3.388 | 0.9938 | 30.2 to 689.4 |
| Na+(mmol/L) | 29 to 30 | 0.9586 | 6.1116 | 0.9952 | 107.3 to 179.7 |
| K+(mmol/L) | 27 to 30 | 1.0366 | -0.2831 | 0.9981 | 2.1 to 19.0 |
| Ca++ (mmol/L) | 30 to 33 | 1.0098 | -0.0038 | 0.9953 | 0.44 to 4.25 |
| Cl-(mmol/L) | 30 to 33 | 1.0465 | -5.3123 | 0.9984 | 63 to 158 |
| Glucose (mg/dL) | 27 to 30 | 1.0318 | -6.5867 | 0.9960 | 44 to 685 |
| Lactate (mmol/L) | 33 | 1.0164 | -0.1171 | 0.9969 | 1.0 to 17.0 |
| Hct (%) | 35 to 36 | 1.0273 | -0.3038 | 0.9989 | 19 to 72 |
| tHb (g/dL) | 17 to 144 | 1.0036 | -0.1839 | 0.9956 | 6.0 to 22.5 |
| O2Hb (%) | 18 to 197 | 0.9905 | 0.5235 | 0.9996 | 0.0 to 98.0 |
| COHb (%) | 18 to 160 | 0.9943 | 0.0507 | 0.9997 | 0.0 to 99.3 |
| MetHb (%) | 17 to 321 | 0.9944 | 0.0174 | 0.9945 | 0.0 to 27.8 |
| HHb (%) | 18 to 225 | 1.003 | 0.1054 | 0.9997 | 0.0 to 96.2 |
A separate study was performed to show that the instrument is linear with regards to the lowest detectable limit of glucose indicated in the functional sensitivity study (below). Five levels of glucose (1.3, 6, 18, 54, and $94\mathrm{mg / dL}$ ) were used with 3 replicates per level. Samples were tested on 9 GEM 4000 instruments and were compared to tests run on 3 GEM 3000 instruments resulting in 27 samples per level of glucose. The linearity was summarized as Observed $= 1.0552$ (Expected) $+1.2853$ ; $\mathbf{r}^2 = 0.9998$ .
c. Traceability, Stability, Expected values (controls, calibrators, or methods):
Traceability:
| Analytes | Traceability Methods and Materials |
| --- | --- |
| pH & Ca++ | Per NIST pub. no. 260-53 (Dec.'75) and CLSI no. C46-A for pH and IFCC no. 1994-03-30 and CLSI no. C39-A for Ca++, i.e., direct |
| | for pH and IFCC, i.e., direct |
| Na+(mmol/L) | 29 to 30 |
| K+(mmol/L) | 27 to 30 |
| Ca++ (mmol/L) | 30 to 33 |
| Cl-(mmol/L) | 30 to 33 |
| Glucose (mg/dL) | 27 to 30 |
| Lactate (mmol/L) | 33 |
| Hct (%) | 35 to 36 |
| tHb (g/dL) | 17 to 144 |
| O2Hb (%) | 18 to 197 |
| COHb (%) | 18 to 160 |
| MetHb (%) | 17 to 321 |
| HHb (%) | 18 to 225 |
{16}
| Analytes | Traceability Methods and Materials |
| --- | --- |
| | potentiometry vs. secondary standards prepared from: ·phosphate salts for pH, #186I & 186II ·calcium carbonate for Ca++, #915, all from NIST |
| pCO2& pO2 | Per CLSI nos. C21-A & C46-A, i.e., tonometry at 37°C using gas mixtures assured to ±0.01% vs. NIST. |
| Na+ & K+ | Per CLSI No. C29-A and NIST pub. no. 260-60 (Aug.'78) and 260-63 (May'79), i.e., flame photometry vs. secondary standards prepared from NaCl & KCl, #919 & #918, NIST. |
| Cl- | Per NIST pub. No. 260-67 (Nov.'79) and CLSI no. RS10-P, i.e., coulometric-amperometric titration with silver ion vs. secondary standards prepared from NaCl, #919, NIST. |
| Glucose and Lactate | Automated spectrophotometry: ·Glucose: hexokinase method per CDC no. 77-8330 and CLSI no. RS1-A using secondary standard prepared from NIST #917. ·Lactate: no ref. method established for lactate. Lactate oxidase is used with secondary std. prep'd from Fluka cat. no. 71718 (99%). |
| Hct | Correlation to blood using centrifugation per CLSI H7-A3. Maintained conductivity from lot to lot by controlling sodium concentration. |
| tHb | Correlation to blood per CLSI H15-A3 (2000) using hemoglobincyanide colorimetry and cyanMetHb standards. |
# Stability:
Testing supports the stability claims in the product insert. Stability claims are listed below.
GEM CVP 1 and 2 with CO-Ox: Unopened ampules are stable until the expiration date shown on the label when stored at $2 - 80^{\circ}\mathrm{C}$ , or up to 9 months at room temperature $(15 - 25^{\circ}\mathrm{C})$ , providing storage does not exceed the expiration date.
GEM CVP 3 and 4 Hematocrit: Unopened ampules are stable until the expiration date shown on the label when stored at room temperature $15 - 25^{\circ}\mathrm{C}$ . DO NOT FREEZE.
GEM Premier 4000 cartridge: Data support a shelf-life claim of 3 months.
# Expected values:
Expected values for the GEM CVP 1, 2, 3, and 4 as well as the cartridge are listed below.
| Parameters | GEM CVP with CO-Ox | |
| --- | --- | --- |
| | Level 1 | Level 2 |
| pH | 7.15 | 7.57 |
{17}
| Parameters | GEM CVP with CO-Ox | |
| --- | --- | --- |
| | Level 1 | Level 2 |
| pCO2(mmHg) | 76 | 14 |
| pO2(mmHg) | 38 | 127 |
| Na+(mmol/L) | 126 | 155 |
| K+(mmol/L) | 3.5 | 7.8 |
| Ca++ (mmol/L) | 1.61 | 0.81 |
| Cl-(mmol/L) | 105 | 132 |
| Glucose (mg/dL) | 380 | 77 |
| Lactate (mmol/L) | 7.3 | 1.7 |
| tHb (g/dL) | 17.0 | 7.8 |
| O2Hb (%) | 87 | 39 |
| COHb (%) | 3 | 31 |
| MetHb (%) | 4 | 9 |
| HHb (%) | 6 | 21 |
| Parameters | GEM CVP Hematocrit | | |
| --- | --- | --- | --- |
| | Level 3 | Level 4 | |
| Hct (%) | 23 | 43 | |
| Parameters | Internal GEM Premier 4000 Process Control Solutions | | | |
| --- | --- | --- | --- | --- |
| | A | B | C | D |
| pH | 6.90 | 7.40 | 8.00 | 7.30 |
| pCO2(mmHg) | 64 | 34 | 34 | 22 |
| pO2(mmHg) | 115 | 175 | 3 | 80 |
| Na+(mmol/L) | 105 | 153 | | 165 |
| K+(mmol/L) | 7.1 | 2.0 | 4.2 | 14.0 |
| Ca++ (mmol/L) | 1.6 | 0.8 | 1.7 | 0.8 |
| Cl-(mmol/L) | 1.0 | 0.3 | 0.3 | 0.3 |
| Glucose (mg/dL) | 38 | 7 | 7 | 7 |
| Lactate (mmol/L) | 7.3 | 1.7 | 4.2 | 14.0 |
| tHb (g/dL) | 17.0 | 7.8 | 1.7 | 4.2 |
| O2Hb (%) | 87 | 39 | 39 | 39 |
| COHb (%) | 3 | 31 | 31 | 31 |
| MetHb (%) | 4 | 9 | 9 | 9 |
| HHb (%) | 6 | 21 | 21 | 21 |
{18}
| Parameters | Internal GEM Premier 4000 Process Control Solutions | | | |
| --- | --- | --- | --- | --- |
| | A | B | C | D |
| Ca++ (mmol/L) | 1.80 | 0.76 | | 1.25 |
| Cl- (mmol/L) | 48 | 91 | | 135 |
| Glucose (mg/dL) | 144 | 0 | | 350 |
| Lactate (mmol/L) | 3.3 | 0 | | 8.0 |
| tHb (g/dL) | 14.5 | 0 | | 7.5 |
| O2Hb (%) | 89.5 | | | 69.5 |
| COHb (%) | 2.5 | | | 4.5 |
| MetHb (%) | 1.5 | | | 4.0 |
| HHb (%) | 6.5 | | | 22.0 |
| Hct (%) | 28 | 16 | | |
# d. Detection limit:
Functional sensitivity was determined for all measured analytes on the GEM Premier 4000. Functional sensitivity was defined by the sponsor as the lowest concentration of an analyte at which quantitative information is available and where a coefficient of variation (CV) of $\leq 20\%$ (within run) is obtained. In this test, a run was performed consisting of 10 replicates of the same whole blood sample on at least 4 different GEM Premier 4000 instruments. Pooled within run SD and $\%$ CV were calculated.
Functional sensitivity was used to determine the low limit of the reportable range for all measured analytes on the GEM Premier 4000. The proposed low limit of the reportable range is above the observed functional sensitivity requirement for all analytes.
| % CV (Spec. ≤ 20%) | NA | 4.0 | 18.1 | 3.2 | 15.6 | 3.8 | 0.5 | 9.2 | 12.0 | 3.1 | 0.9 |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Low limit (or high for pH) | pH | pCO2mmHg | pO2mmHg | Na+mmol/L | K+mmol/L | Ca++mmol/L | Cl- mmol/L | Glucose mg/dL | Lactate mmol/L | Hct % | tHb g/dL |
| of reportable range | 8.00 | 6 | 5 | 100 | 0.2 | 0.10 | 40 | 4 | 0.3 | 15 | 5.0 |
| N | 50 | 50 | 40 | 50 | 50 | 50 | 50 | 40 | 60 | 50 | 50 |
| | | | | | | | | | | | |
| Grand Mean | 8.000 | 5.6 | 4.6 | 86.6 | 0.19 | 0.099 | 40.0 | 3.9 | 0.23 | 14.7 | 4.30 |
| Pooled SD | 0.020 | 0.2 | 0.8 | 2.8 | 0.03 | 0.004 | 0.2 | 0.4 | 0.03 | 0.5 | 0.04 |
{19}
Below are the measuring and tested ranges for the GEM Premier 4000 analyzer as indicated in the product labeling. The measuring ranges are the ranges that the system will support in terms of actual numeric values that the system can report. The tested ranges are supported by the linearity study (above), in conjunction with the functional sensitivity data in this section (above).
| Parameter | Units | GEM Premier 4000 Measuring Range | GEM Premier 4000 Tested Range |
| --- | --- | --- | --- |
| pH | pH Scale | 6.8 to 8.0 | 7.0 to 8.0 |
| pCO2 | mmHg | 0 to 150 | 6 to 125 |
| pO2 | mmHg | 0 to 800 | 5 to 690 |
| Na+ | mmol/L | 70 to 200 | 100 to 180 |
| K+ | mmol/L | 0 to 20 | 0.2 to 19 |
| Ca++ | mmol/L | 0.10 to 5.00 | 0.10 to 4.25 |
| Cl- | mmol/L | 40 to 170 | 40 to 158 |
| Glu | mg/dL | 0 to 750 | 4 to 685 |
| Lac | mmol/L | 0 to 20 | 0.3 to 17 |
| Hct | % | 15 to 75 | 15 to 72 |
| tHb | g/dL | 5 to 23 | 5 to 23 |
| O2Hb | % | -10 to 110 | 0 to 98 |
| COHb | % | -10 to 110 | 0 to 99 |
| MetHb | % | -10 to 110 | 0 to 28 |
| HHb | % | -10 to 110 | 0 to 96 |
# e. Analytical specificity:
The following substances did not show noticeable interference with the indicated analytes on the GEM Premier 4000 when tested at the concentrations listed. Interference testing was performed in duplicate on a minimum of three GEM Premier 4000 instruments, with the number of instruments indicated in parentheses in the column entitled "Mean Interference".
{20}
| Substance | Possible Affected Analytes | Analyte Conc. | Interferant Concentrations Tested | Mean Interference (N instruments) | SD | ± Bias Spec. |
| --- | --- | --- | --- | --- | --- | --- |
| Acetaminophen | glucose | 80 mg/dL | 20 mg/dL | +2 mg/dL (6) | 1.4 | 6 mg/dL |
| | lactate | 1.3 mmol/L | | +0.03 mmol/L (6) | 0.04 | 0.2 mmol/L |
| Acetoacetate | glucose | 100 mg/dL | 2 mmol/L | -2.1 mg/dL (4) | 1.3 | 6 mg/dL |
| | lactate | 2.5 mmol/L | | -0.05 mmol/L (5) | 0.01 | 0.2 mmol/L |
| Ammonium | Na+ | 140 mmol/L | 80 μmol/L | +0.6 mmol/L (5) | 1.6 | 2 mmol/L |
| | | | 3000 μmol/L | +1.2 mmol/L (5) | 1.4 | |
| | K+ | 4.0 mmol/L | 80 μmol/L | +0.03 mmol/L (5) | 0.01 | 0.25 mmol/L |
| | | | 3000 μmol/L | +0.08 mmol/L (5) | 0.01 | |
| Ascorbic acid | glucose | 80 mg/dL | 3 mg/dL | +1.5 mg/dL (5) | 0.8 | 6 mg/dL |
| | lactate | 1.3 mmol/L | | +0.05 mmol/L (5) | 0.05 | 0.2 mmol/L |
| Benzalkonium | Na+ | 140 mmol/L | 5 mg/L | 1.4 mmol/L (8) | 0.7 | 2 mmol/L |
| | | | 10 mg/L | 1.7 mmol/L (8) | 0.5 | |
| Bilirubin | tHb | 13.7 g/dL | 20 mg/dL | 0.2 g/dL (5) | 0.1 | 0.35 g/dL |
| | O2Hb | 97.2% | | 0.5% (5) | 0.1 | 1% |
| | COHb | 1.5% | | -0.6% (5) | 0.1 | 1% |
| | MetHb | 0.5% | | -0.8% (5) | 0.2 | 1% |
| | HHb | 0.8% | | 0.9% (5) | 0.2 | 3% |
| Chlorpromazine | glucose | 100 mg/dL | 0.2 mmol/L | -0.9 mg/dL (4) | 2.2 | 6 mg/dL |
| | lactate | 2.5 mmol/L | | -0.03 mmol/L (5) | 0.02 | 0.2 mmol/L |
| Citrate | Cl- | 109 mmol/L | 12 mmol/L | 2.7 mmol/L (7) | 0.4 | 2.7 mmol/L |
| | glucose | 85 mg/dL | | 1.4 mg/dL (6) | 3.6 | 6 mg/dL |
| | lactate | 1.8 mmol/L | | 0.2 mmol/L (6) | 0.1 | 0.2 mmol/L |
$^{1}$ Correction for fetal hemoglobin is applied by the instrument and therefore, the reported result would not exhibit any interference.
| Substance | Possible Affected Analytes | Analyte Conc. | Interferant Concentrations Tested | Mean Interference (N instruments) | SD | ± Bias Spec. |
| --- | --- | --- | --- | --- | --- | --- |
| Ethanol | glucose | 90 mg/dL | 100 mg/dL | 2.5 mg/dL (3) | 1.5 | 6 mg/dL |
| | | | 350 mg/dL | 5.7 mg/dL (3) | 1.1 | |
| | lactate | 2.2 mmol/L | 100 mg/dL | 0.15 mmol/L (3) | 0.10 | 0.2 mmol/L |
| | | | 350 mg/dL | 0.19 mmol/L (3) | 0.07 | |
{21}
| Substance | Possible Affected Analytes | Analyte Conc. | Interferant Concentrations Tested | Mean Interference (N instruments) | SD | ± Bias Spec. |
| --- | --- | --- | --- | --- | --- | --- |
| Evans Blue | tHb | 15.7 g/dL | 10 mg/L | -0.1 g/dL (5) | 0.3 | 0.35 g/dL |
| O2Hb | 97.0% | | 0.8% (5) | 0.3 | 1% |
| COHb | 1.3% | | 0.1% (5) | 0.3 | 1% |
| MetHb | 0.7% | | -0.2% (5) | 0.1 | 1% |
| HHb | 1.1% | | -0.7% (5) | 0.1 | 3% |
| Fetal hemoglobin1 | tHb | 5.9 g/dL | 50% | -0.1g/dL(5) | 0.0 | 0.35 g/dL |
| O2Hb | 95.7% | | 1.1 % (5) | 0.3 | 1% |
| COHb | 0.4% | | 1.8 % (5) | 0.2 | 1% |
| MetHb | 3.3% | | -0.3 % (5) | 0.2 | 1% |
| HHb | 0.7% | | -2.6 % (5) | 0.2 | 3% |
| tHb | 6.8 g/dL | 76% | -0.1 g/dL (5) | 0.0 | 0.35 g/dL |
| O2Hb | 95.2% | | 0.8 % (5) | 0.2 | 1% |
| COHb | 1.0% | | 2.0 % (5) | 0.1 | 1% |
| MetHb | 4.2% | | 0.0 % (5) | 0.1 | 1% |
| HHb | -0.3% | | -2.9 % (5) | 0.1 | 3% |
| Flaxedil | glucose | 90 mg/dL | 2 mg/dL | 1.2 mg/dL (4) | 0.4 | 6 mg/dL |
| | | 5 mg/dL | 0.6 mg/dL (4) | 0.8 | |
| lactate | 1.5 mmol/L | 2 mg/dL | 0.01 mmol/L (4) | 0.04 | 0.2 mmol/L |
| | | 5 mg/dL | 0.06 mmol/L (4) | 0.03 | |
| Halothane | pO2 | 92 mmHg | 74 μg/mL | 3.1 mmHg (4) | 3.0 | 10 mmHg |
| | | 374 μg/mL | 3.1 mmHg (4) | 2.7 | |
| Substance | Possible Affected Analytes | Analyte Conc. | Interferant Concentrations Tested | Mean Interference (N instruments) | SD | ± Bias Spec. |
| --- | --- | --- | --- | --- | --- | --- |
| Hemoglobin Based Oxygen Carriers (Hemopure®) | tHb | 13.5 g/dL | 1.0 g/dL | N/A | N/A | 0.35 g/dL |
| | O2Hb | 97.9% | | N/A | N/A | 1% |
| | COHb | 1.3% | | 0.3% (5) | 0.1 | 1% |
| | MetHb | 0.0% | | 0.0% (5) | 0.0 | 1% |
| | HHb | 0.8% | | N/A | N/A | 3% |
{22}
| Substance | Possible Affected Analytes | Analyte Conc. | Interferant Concentrations Tested | Mean Interference (N instruments) | SD | ± Bias Spec. |
| --- | --- | --- | --- | --- | --- | --- |
| | tHb | 13.5 g/dL | 1.5 g/dL | N/A | N/A | 0.35 g/dL |
| | O2Hb | 97.9% | | N/A | N/A | 1% |
| | COHb | 1.3% | | 0.5% (5) | 0.1 | 1% |
| | MetHb | 0.0% | | 0.0% (5) | 0.0 | 1% |
| | HHb | 0.8% | | N/A | N/A | 3% |
| | tHb | 13.5 g/dL | 3.2 g/dL | N/A | N/A | 0.35 g/dL |
| | O2Hb | 97.9% | | N/A | N/A | 1% |
| | COHb | 1.3% | | 0.6% (5) | 0.1 | 1% |
| | MetHb | 0.0% | | -0.3% (5) | 0.0 | 1% |
| | HHb | 0.8% | | N/A | N/A | 3% |
| | tHb | 13.5 g/dL | 6.4 g/dL | N/A | N/A | 0.35 g/dL |
| | O2Hb | 97.9% | | N/A | N/A | 1% |
| | COHb | 1.3% | | 0.8% (5) | 0.1 | 1% |
| | MetHb | 0.0% | | -0.8% (5) | 0.2 | 1% |
| | HHb | 0.8% | | N/A | N/A | 3% |
| Heparin | Cl- | 109 mmol/L | 100 IU/mL | 0.7 mmol/L (7) | 0.6 | 2.7 mmol/L |
| β-hydroxybutyrate | glucose | 100 mg/dL | 2 mmol/L | 1.0 mg/dL (4) | 4.8 | 6 mg/dL |
| | lactate | 2.5 mmol/L | | -0.02 mmol/L (5) | 0.01 | 0.2 mmol/L |
| Ibuprofen | glucose | 100 mg/dL | 2 mmol/L | -0.3 mg/dL (4) | 2.1 | 6 mg/dL |
| | lactate | 2.5 mmol/L | | -0.01 mmol/L (5) | 0.01 | 0.2 mmol/L |
| Indocyanine green | tHb | 13.7 g/dL | 10 mg/L | 0.1 g/dL (5) | 0.1 | 0.35 g/dL |
| | O2Hb | 97.2% | | 0.0% (5) | 0.2 | 1% |
| | COHb | 1.5% | | 0.0% (5) | 0.2 | 1% |
| | MetHb | 0.5% | | 0.0% (5) | 0.3 | 1% |
| | HHb | 0.8% | | -0.1% (5) | 0.3 | 3% |
| Maltose | glucose | 100 mg/dL | 0.2 mg/mL | -1.8 mg/dL (4) | 0.6 | 6 mg/dL |
| | lactate | 2.5 mmol/L | | -0.03 mmol/L (5) | 0.01 | 0.2 mmol/L |
| Methylene blue | tHb | 13.6 g/dL | 40 mg/L | -0.4 g/dL (5) | 0.0 | 0.35 g/dL |
| | O2Hb | 97.4% | | -0.5% (5) | 0.1 | 1% |
| | COHb | 1.3% | | 0.0% (5) | 0.2 | 1% |
| | MetHb | 0.0% | | 0.0% (5) | 0.0 | 1% |
| | HHb | 0.8% | | N/A | N/A | 3% |
{23}
The following substances showed noticeable interference with certain analytes on the GEM Premier 4000, causing falsely elevated results as indicated below:
| Substance | Affected Analyte | Analyte Conc. | Interferant Concentration Producing Interference | Mean Interference (N instruments) | SD | ± Bias Spec. |
| --- | --- | --- | --- | --- | --- | --- |
| Benzalkonium2 | Ca++ | 1.20 mmol/L | 5 mg/L | 0.11 mmol/L (8) | 0.01 | 0.06 mmol/L |
| Bromide | Cl- | 109 mmol/L | 10 mmol/L | 151.3 mmol/L (6) | 6.4 | 2.7 mmol/L |
| Cyanomethemoglobin3 | tHb | 17.5 g/dL | >4% | 1.0 g/dL (5) | 0.1 | 0.35 g/dL |
| O2Hb | 97.1% | -0.4 % (5) | 0.3 | 1% |
| COHb | 2.0% | -0.2 % (5) | 0.0 | 1% |
| MetHb | 0.5% | 0.4 % (5) | 0.2 | 1% |
| HHb | 0.4% | 0.2 % (5) | 0.1 | 3% |
| Dopamine | glucose | 60 mg/dL | 5 mg/dL | 6.4 mg/dL (7) | 8.4 | 6 mg/dL |
| lactate | 2.7 mmol/L | -0.06 mmol/L (7) | 0.29 | 0.2 mmol/L |
| Diphenol | Na+ | 1.20 mmol/L | 5 mg/L | 0.11 mmol/L (8) | 0.01 | 0.06 mmol/L |
| Diphenol | Cl- | 109 mmol/L | 10 mmol/L | 151.3 mmol/L (6) | 6.4 | 2.7 mmol/L |
| Diphenol | Na+ | 1.20 mmol/L | 5 mg/L | 0.11 mmol/L (8) | 0.01 | 0.06 mmol/L |
{24}
| Substance | Affected Analyte | Analyte Conc. | Interferant Concentration Producing Interference | Mean Interference (N instruments) | SD | ± Bias Spec. |
| --- | --- | --- | --- | --- | --- | --- |
| Dobutamine | glucose | 80 mg/dL | 2 mg/dL | 6.0 mg/dL (5) | 7.4 | 6 mg/dL |
| | lactate | 2.0 mmol/L | | 0.17 mmol/L (6) | 0.20 | 0.2 mmol/L |
| Fluoride | Cl- | 109 mmol/L | 500 mg/dL | 13.0 mmol/L (4) | 0.9 | 2.7 mmol/L |
| | lactate | 2.0 mmol/L | | 0.18 mmol/L (4) | 0.13 | 0.2 mmol/L |
| Glycolic acid | lactate | 2.5 mmol/L | 1 mmol/L | 12.6 mmol/L (4) | 0.72 | 0.2 mmol/L |
| Hemoglobin Based Oxygen Carriers (Hemopure®) | hematocrit | 20% | 3.2 g/dL | 4 % (4) | 0.2 | 2% |
| Hydroxyurea | glucose | 90 mg/dL | 0.8 mg/dL | 25.3 mg/dL (4) | 2.3 | 6 mg/dL |
| | lactate | 1.4 mmol/L | | 0.97 mmol/L (4) | 0.13 | 0.2 mmol/L |
| Iodide | Cl- | 109 mmol/L | 3 mmol/L | 8.6 mmol/L (7) | 0.7 | 2.7 mmol/L |
| Isoniazide | glucose | 80 mg/dL | 5 mg/dL | 3.6 mg/dL (3) | 4.7 | 6 mg/dL |
| | lactate | 1.3 mmol/L | | 0.21 mmol/L (3) | 0.04 | 0.2 mmol/L |
| Oxalate | Cl- | 110 mmol/L | 500 mg/dL | 4.8 mmol/L (7) | 0.4 | 2.7 mmol/L |
| | lactate | 2.0 mmol/L | | 0.33 mmol/L (7) | 0.06 | 0.2 mmol/L |
| Salicylate | Cl- | 110 mmol/L | 4 mmol/L | 4.6 mmol/L (4) | 0.6 | 2.7 mmol/L |
| Sulfhemoglobin3 | tHb | 13.6 g/dL | >3% | 1.2 g/dL(5) | 0.1 | 0.35 g/dL |
| | O2Hb | 97.7% | | -1.0 % (5) | 0.3 | 1% |
| | COHb | 2.0% | | -0.1 % (5) | 0.0 | 1% |
| | MetHb | 0.5% | | 0.9 % (5) | 0.1 | 1% |
| | HHb | -0.2% | | 0.2 % (5) | 0.2 | 3% |
| Thiopental2 | pCO2 | 30 mmHg | 30 mg/L | 96.5 mmHg (3) | 74.8 | 4.5 mmHg |
| | Ca++ | 1.05 mmol/L | 50 mg/L | 0.08 mmol/L (3) | 0.04 | 0.05 mmol/L |
| Turbidity3 | tHb | 13.6 g/dL | 5% based on turbidity created by Intralipid® fat emulsion | 0.0 g/dL (5) | 0.0 | 0.35 g/dL |
| | O2Hb | 97.4% | | 0.5 % (5) | 0.1 | 1% |
| | COHb | 2.3% | | -0.5 % (5) | 0.1 | 1% |
| | MetHb | 0.1% | | -0.6 % (5) | 0.2 | 1% |
| | HHb | 0.2% | | 0.6 % (5) | 0.1 | 3% |
| Uric acid | glucose | 80 mg/dL | 20 mg/dL | 10.7 mg/dL (3) | 2.1 | 6 mg/dL |
| | lactate | 1.4 mmol/L | | 0.17 mmol/L (3) | 0.04 | 0.2 mmol/L |
| Vitamin D3 | glucose | 80 mg/dL | 20 mg/dL | 10.7 mg/dL (3) | 2.1 | 6 mg/dL |
| | lactate | 1.4 mmol/L | | 0.17 mmol/L (3) | 0.04 | 0.2 mmol/L |
| Vitamin E | glucose | 80 mg/dL | 20 mg/dL | 10.7 mg/dL (3) | 2.1 | 6 mg/dL |
| | lactate | 1.4 mmol/L | | 0.17 mmol/L (3) | 0.04 | 0.2 mmol/L |
{25}
26
2 The GEM Premier 4000 with iQM (Intelligent Quality Management) employs failure pattern recognition checks. These checks include the presence of positively charged lipophilic compounds (e.g., benzalkonium) and negatively charged lipophilic compounds (e.g., thiopental).
$^3$ CO-Oximetry interference is detected and flagged by failure pattern recognition checks.
The following substances showed noticeable interference with the glucose channel on the GEM Premier 4000, causing falsely lowered results.
| Substance | Affected Analyte | Analyte Conc. | Interferant Concentration Producing Interference | Mean Interference (N instruments) | SD | ± Bias Spec. |
| --- | --- | --- | --- | --- | --- | --- |
| Oxalate | glucose | 85 mg/dL | 1000 mg/dL | -16.6 mg/dL (7) | 16.6 | 6 mg/dL |
| Fluoride | glucose | 80 mg/dL | 500 mg/dL | -2.2 mg/dL (4) | 5.0 | 6 mg/dL |
f. Assay cut-off:
Not Applicable.
2. Comparison studies:
a. Method comparison with predicate device:
The sponsor had method comparison studies performed at 3 point of care sites and 3 laboratory sites. Results of these studies are summarized below.
Point-of-Care Testing Site No. 1:
At the point-of-care setting, a GEM Premier 3000 was used as the reference for pH, blood gases, electrolytes (except chloride), glucose, lactate, hematocrit, and an IL CO-Oximeter 682 was used for CO-Oximetry. Samples were tested for chloride at the central laboratory using a Beckman Synchron CX7 (K910185).
Testing included 70 whole blood samples obtained from patients in a critical care unit submitted for stat analysis over a one-week period. Each sample was assayed in duplicate on the GEM Premier 4000 and the reference devices for a total of N=140 individual results per instrument, with the exceptions noted below.
{26}
# Summary Statistics
| Analyte | N | Slope | Intercept | r | Sample Range |
| --- | --- | --- | --- | --- | --- |
| pH | 134 | 1.076 | -0.572 | 0.991 | 7.19-7.76 |
| pCO2(mmHg) | 134 | 0.919 | 2.16 | 0.997 | 25-98 |
| pO2(mmHg) | 133 | 1.024 | -1.078 | 0.998 | 19-491 |
| Na+(mmol/L) | 134 | 0.942 | 8.65 | 0.958 | 128-153 |
| K+(mmol/L) | 134 | 0.975 | 0.043 | 0.992 | 3.0-5.5 |
| Ca++ (mmol/L) | 134 | 0.904 | 0.118 | 0.979 | 0.72-1.38 |
| Cl-(mmol/L) | 42 | 0.982 | 3.280 | 0.901 | 88-116 |
| Glucose (mg/dL) | 43 | 1.044 | 0.199 | 0.992 | 55-321 |
| Lactate (mmol/L) | 134 | 1.004 | 0.223 | 0.996 | 0.4-5.4 |
| Hct (%) | 134 | 1.003 | 0.782 | 0.986 | 17-51 |
| tHb (g/dL) | 133 | 1.009 | -0.356 | 0.989 | 6.7-16.0 |
| O2Hb (%) | 133 | 0.974 | 2.678 | 0.998 | 30.1-98.4 |
| HHb (%) | 133 | 0.979 | 0.147 | 0.999 | 0-67.9 |
NOTE: For carboxyhemoglobin and methemoglobin results, due to the narrow range of blood samples used in the study, partitioned difference analysis method was used to assess the $95\%$ confidence interval of the bias.
| Parameter | N | Range | 95% CI of Bias | Bias Spec. |
| --- | --- | --- | --- | --- |
| COHb (%) | 133 | 0.8 – 6.9 | -0.7 to -0.6 | ± 1.0 |
| MetHb (%) | 133 | 0 – 2.2 | 0.0 - 0.1 | ± 1.0 |
{27}
# Point-of-Care Testing Site No. 2:
At the point-of-care setting, a GEM Premier 3000 was used as the reference for pH, blood gases, electrolytes (except chloride), glucose, lactate, hematocrit, and an IL CO-Oximeter 682 was used for CO-Oximetry. Samples were tested for chloride at the central laboratory using a Beckman Synchron CX7 (K910185).
Testing included 72 whole blood samples obtained from patients in a critical care unit submitted for stat analysis over a one-week period. Each sample was assayed in duplicate on the GEM Premier 4000 and the reference devices, except for three samples that were only tested in singlet, for a total of $N = 141$ individual results per instrument, with the exceptions noted below.
Summary Statistics
| Analyte | N | Slope | Intercept | r | Sample Range |
| --- | --- | --- | --- | --- | --- |
| pH | 120 | 1.132 | -0.984 | 0.985 | 7.19-7.56 |
| pCO2(mmHg) | 120 | 0.970 | 1.276 | 0.991 | 27-71 |
| pO2(mmHg) | 120 | 1.064 | -5.139 | 0.997 | 31-440 |
| Na+(mmol/L) | 37 | 1.090 | -11.38 | 0.979 | 127-152 |
| K+(mmol/L) | 110 | 0.995 | -0.034 | 0.985 | 3.5-8.3 |
| Ca++(mmol/L) | 120 | 0.867 | 0.178 | 0.859 | 0.92-1.41 |
| Cl-(mmol/L) | 17 | 0.892 | 14.729 | 0.805 | 91-117 |
| Glucose (mg/dL) | 120 | 0.983 | 8.632 | 0.993 | 69-354 |
| Lactate (mmol/L) | 120 | 0.984 | 0.178 | 0.989 | 0.4-3.4 |
| Hct (%) | 118 | 0.959 | 2.551 | 0.967 | 19-51 |
| tHb (g/dL) | 112 | 1.037 | -0.485 | 0.990 | 7.6-16.0 |
| O2Hb (%) | 112 | 1.004 | -0.512 | 0.997 | 60-99 |
| HHb (%) | 112 | 0.997 | -0.018 | 0.999 | 0-39 |
NOTE: For carboxyhemoglobin and methemoglobin results, due to the narrow range of blood samples used in the study, partitioned difference analysis method was used to assess the $95\%$ confidence interval of the bias.
{28}
| Parameter | N | Range | 95% CI of Bias | Bias Spec. |
| --- | --- | --- | --- | --- |
| COHb (%) | 112 | 0.3 – 6.2 | 0.0 to 0.3 | ± 1.0 |
| MetHb (%) | 112 | -0.3 – 1.8 | -0.2 to -0.03 | ± 1.0 |
# Point-of-Care Testing Site No. 3:
At the point-of-care setting, a GEM Premier 3000 was used as the reference for pH, blood gases, electrolytes (except chloride), glucose, lactate, hematocrit, and an IL CO-Oximeter 682 was used for CO-Oximetry. Samples were tested for chloride at the central laboratory using a J&J Vitros 950 (K946090).
Testing included 65 whole blood samples obtained from patients in an intensive care unit submitted for stat analysis over a one-week period. Each sample was assayed in duplicate on the GEM Premier 4000 and the reference devices for a total of $N = 130$ individual results per instrument, with the exceptions noted below.
Summary Statistics
| Analyte | N | Slope | Intercept | r | Sample Range |
| --- | --- | --- | --- | --- | --- |
| pH | 98 | 1.089 | -0.657 | 0.988 | 7.27-7.57 |
| pCO2(mmHg) | 98 | 0.989 | -0.929 | 0.994 | 26-74 |
| pO2(mmHg) | 98 | 0.939 | 6.313 | 0.997 | 57-280 |
| Na+(mmol/L) | 98 | 0.958 | 7.274 | 0.964 | 124-150 |
| K+(mmol/L) | 98 | 0.984 | 0.031 | 0.995 | 2.1-5.8 |
| Ca++ (mmol/L) | 98 | 0.902 | 0.141 | 0.980 | 0.78-1.28 |
| Cl-(mmol/L) | 98 | 0.999 | -1.700 | 0.918 | 91 - 129 |
| Glucose (mg/dL) | 98 | 1.009 | 0.480 | 0.996 | 87-361 |
| Lactate (mmol/L) | 89 | 0.972 | 0.171 | 0.991 | 0.5-3.2 |
| Hct (%) | 98 | 0.957 | 1.403 | 0.989 | 19-54 |
| tHb (g/dL) | 97 | 0.996 | -0.074 | 0.996 | 6.2 - 16.6 |
{29}
| Analyte | N | Slope | Intercept | r | Sample Range |
| --- | --- | --- | --- | --- | --- |
| O2Hb (%) | 97 | 0.953 | 4.254 | 0.971 | 86.7 – 98.7 |
| HHb (%) | 97 | 0.988 | -0.074 | 0.999 | 0.1 – 12.6 |
NOTE: For carboxyhemoglobin and methemoglobin results, due to the narrow range of blood samples used in the study, partitioned difference analysis method was used to assess the $95\%$ confidence interval of the bias.
| Parameter | N | Range | 95% CI of Bias | Bias Spec. |
| --- | --- | --- | --- | --- |
| COHb (%) | 97 | 0 – 1.9 | 0.6 - 0.7 | ± 1.0 |
| MetHb (%) | 97 | 0 – 1.8 | -0.5 to -0.3 | ± 1.0 |
# Laboratory Testing Site No. 1:
A GEM Premier 3000 was used as the reference for pH, blood gases, electrolytes (except chloride), glucose, lactate, hematocrit, a J&J Vitros 950 (K946090) was used for chloride, and an IL CO-Oximeter 682 was used for CO-Oximetry.
Testing included 165 whole blood samples obtained from patients in the hospital submitted for stat analysis over a three-week period. Each sample was assayed in duplicate on the GEM Premier 4000 and the reference devices. However, 22 samples were missing values on the reference device and 7 samples were not measured on the GEM Premier 4000, bringing the final total to $\mathrm{N} = 301$ .
Summary Statistics
| Analyte | N | Slope | Intercept | r | Sample Range |
| --- | --- | --- | --- | --- | --- |
| pH | 297 | 0.989 | 0.080 | 0.992 | 7.06-7.57 |
| pCO2(mmHg) | 297 | 0.922 | 2.178 | 0.996 | 26-105 |
| pO2(mmHg) | 286 | 0.992 | -1.271 | 0.993 | 48-470 |
| Na+(mmol/L) | 297 | 0.849 | 22.248 | 0.887 | 123-154 |
| K+(mmol/L) | 297 | 1.022 | -0.147 | 0.990 | 2.7-6.1 |
{30}
| Analyte | N | Slope | Intercept | r | Sample Range |
| --- | --- | --- | --- | --- | --- |
| Ca++ (mmol/L) | 297 | 0.920 | 0.088 | 0.958 | 0.88-1.79 |
| Cl- (mmol/L) | 140 | 1.275 | -30.081 | 0.949 | 93-120 |
| Glucose (mg/dL) | 157 | 0.954 | 7.039 | 0.989 | 67-269 |
| Lactate (mmol/L) | 297 | 1.162 | -0.105 | 0.989 | 0.4-13.0 |
| Hct (%) | 277 | 1.002 | 0.430 | 0.987 | 17-53 |
| tHb (g/dL) | 273 | 0.994 | -0.200 | 0.995 | 6.4 – 16.7 |
| O2Hb (%) | 273 | 0.977 | 3.322 | 0.968 | 82.7 – 99.2 |
| HHb (%) | 273 | 0.983 | -0.456 | 0.981 | 0 – 14.7 |
NOTE: For carboxyhemoglobin and methemoglobin results, due to the narrow range of blood samples used in the study, partitioned difference analysis method was used to assess the $95\%$ confidence interval of the bias.
| Parameter | N | Range | 95% CI of Bias | Bias Spec. |
| --- | --- | --- | --- | --- |
| COHb (%) | 273 | 0.3 – 6.5 | -0.3 to -0.2 | ± 1.0 |
| MetHb (%) | 273 | 0 – 2.5 | -0.5 to -0.4 | ± 1.0 |
# Laboratory Testing Site No. 2:
A GEM Premier 3000 was used as the reference for pH, blood gases, electrolytes (except chloride), glucose, lactate, hematocrit, a Beckman Synchron LX20 (K965240) was used for chloride, and an IL CO-Oximeter 682 was used for CO-Oximetry.
Testing included 159 whole blood samples obtained from hospital patients submitted for routine and stat analysis over a three-week period. Each sample was assayed in duplicate on the GEM Premier 4000 and the reference devices for a total of $N = 318$ individual results per instrument, with the exceptions noted below.
{31}
32
Summary Statistics
| Analyte | N | Slope | Intercept | r | Sample Range |
| --- | --- | --- | --- | --- | --- |
| pH | 290 | 1.094 | -0.702 | 0.990 | 7.12 – 7.55 |
| pCO_{2} (mmHg) | 291 | 0.978 | 0.161 | 0.989 | 22 – 98 |
| pO_{2} (mmHg) | 291 | 0.951 | 7.919 | 0.995 | 27 – 538 |
| Na^{+} (mmol/L) | 291 | 0.876 | 16.185 | 0.953 | 124 – 152 |
| K^{+} (mmol/L) | 291 | 1.039 | -0.200 | 0.991 | 2.6 – 6.9 |
| Ca^{++} (mmol/L) | 291 | 0.950 | 0.062 | 0.979 | 0.82 – 1.89 |
| Cl^{-} (mmol/L) | 116 | 0.984 | 2.333 | 0.912 | 82-125 |
| Lactate (mmol/L) | 289 | 0.983 | 0.189 | 0.995 | 0.4 – 13.0 |
| tHb (g/dL) | 280 | 1.061 | -0.274 | 0.994 | 7.1 – 16.7 |
| O_{2}Hb (%) | 280 | 0.980 | 2.031 | 0.995 | 47 – 98.9 |
| HHb (%) | 280 | 0.999 | -0.398 | 0.997 | 0 – 50.7 |
NOTE: For carboxyhemoglobin and methemoglobin results, due to the narrow range of blood samples used in the study, partitioned difference analysis method was used to assess the 95% confidence interval of the bias.
| Parameter | N | Range | 95% CI of Bias | Bias Spec. |
| --- | --- | --- | --- | --- |
| COHb (%) | 280 | -0.1 – 3.3 | 0.17 – 0.24 | ±1.0 |
| MetHb (%) | 280 | 0.3 – 2.3 | 0.0 to 0.1 | ±1.0 |
Laboratory Testing Site No. 3:
A GEM Premier 3000 was used as the reference for pH, blood gases, electrolytes (except chloride), glucose, lactate, hematocrit, and an IL CO-Oximeter 682 was used for CO-Oximetry. Chloride was not run at this site.
Testing included 97 whole blood samples obtained from patients in the hospital submitted for stat analysis over a one-week period. Each sample was assayed in
{32}
duplicate on the GEM Premier 4000 and the reference devices. However, two sample results were unavailable (one on the reference device and one on the GEM Premier 4000), bringing the total to $N = 192$ individual results per instrument, with the exceptions noted below.
Summary Statistics
| Analyte | N | Slope | Intercept | r | Sample Range |
| --- | --- | --- | --- | --- | --- |
| pH | 184 | 1.076 | -0.574 | 0.995 | 7.01-7.57 |
| pCO2(mmHg) | 184 | 0.962 | 0.325 | 0.994 | 27-79 |
| pO2(mmHg) | 184 | 0.954 | 1.028 | 0.993 | 28-321 |
| Na+(mmol/L) | 184 | 0.924 | 11.372 | 0.975 | 130-150 |
| K+(mmol/L) | 184 | 1.018 | -0.103 | 0.995 | 2.6-6.0 |
| Ca++ (mmol/L) | 184 | 0.985 | 0.048 | 0.988 | 0.91-1.49 |
| Glucose (mg/dL) | 98 | 0.977 | 2.190 | 0.995 | 57-237 |
| Lactate (mmol/L) | 184 | 0.946 | 0.057 | 0.999 | 0.7-12.3 |
| Hct (%) | 184 | 1.002 | 1.243 | 0.981 | 21-51 |
| tHb (g/dL) | 175 | 0.989 | -0.153 | 0.987 | 7.5 - 17.2 |
| O2Hb (%) | 175 | 1.002 | 0.316 | 0.996 | 52.1 - 98.2 |
| HHb (%) | 175 | 1.010 | -0.433 | 0.999 | 0 - 46.3 |
NOTE: For carboxyhemoglobin and methemoglobin results, due to the narrow range of blood samples used in the study, partitioned difference analysis method was used to assess the $95\%$ confidence interval of the bias.
| Parameter | N | Range | 95% CI of Bias | Bias Spec. |
| --- | --- | --- | --- | --- |
| COHb (%) | 175 | 0 – 6.7 | 0.1 - 0.3 | ± 1.0 |
| MetHb (%) | 175 | 0.2 – 1.4 | -0.3 to -0.2 | ± 1.0 |
{33}
# b. Matrix comparison:
A study was performed to demonstrate equivalence between the normal, capillary and micro sampling modes on the GEM Premier 4000. Each day, two whole blood sample preparations (Level 1 and Level 2) were tested in duplicate twice per day for 10 days on each of three different GEM Premier 4000 for a total of 40 samples per instrument and a pooled total of $N = 120$ per level.
To compensate for day-to-day sample preparation variation, the evaluation utilized normalization techniques. The following reference instruments were run to monitor any sample degradation thus allowing for these normalization techniques:
| Description | 510(k) | Analyte(s) |
| --- | --- | --- |
| GEM 3000 with iQM and GEM CVP | K022158 | pH, blood gases, electrolytes (except chloride), glucose, lactate and hematocrit |
| IL Synthesis | K963800 | Chloride |
| IL 682 CO-Oximeter | K945677 | CO-Oximeter parameters |
The micro mode is not applicable to the CO-Oximetry parameters.
The table below and on the following pages contain the pooled SD for each analyte on the three different GEM Premier 4000 instruments, for each sampling mode, for two concentration levels. The specifications for within run and total SD are provided in each table for each level.
| Level 1 | pH | | | | |
| --- | --- | --- | --- | --- | --- |
| Sampling Mode | N | Mean | Within Run SD | Day-to-Day SD | Total SD |
| Normal | 120 | 7.05 | 0.009 | 0.005 | 0.011 |
| Capillary | 120 | 7.05 | 0.008 | 0.005 | 0.010 |
| Micro | 120 | 7.07 | 0.011 | 0.007 | 0.015 |
| Spec. (SD) | | | 0.015 | | 0.020 |
| Level 2 | pH | | | | |
| --- | --- | --- | --- | --- | --- |
| Sampling Mode | N | Mean | Within Run SD | Day-to-Day SD | Total SD |
| Normal | 120 | 7.36 | 0.007 | 0.007 | 0.010 |
| Capillary | 120 | 7.36 | 0.007 | 0.007 | 0.013 |
| Micro | 120 | 7.35 | 0.009 | 0.007 | 0.012 |
| Spec. (SD) | | | 0.015 | | 0.020 |
{34}
| Level 1 | pCO2 | | | | |
| --- | --- | --- | --- | --- | --- |
| Sampling Mode | N | Mean mmHg | Within Run SD | Day-to-Day SD | Total SD |
| Normal | 120 | 58.6 | 1.2 | 0.4 | 1.7 |
| Capillary | 120 | 57.7 | 1.0 | 1.0 | 1.6 |
| Micro | 120 | 61.3 | 1.7 | 1.0 | 2.5 |
| Spec. (SD) | | | 1.88 (2.3 Micro) | | 2.5 (3.0 Micro) |
| Level 2 | pCO2 | | | | |
| --- | --- | --- | --- | --- | --- |
| Sampling Mode | N | Mean mmHg | Within Run SD | Day-to-Day SD | Total SD |
| Normal | 120 | 40.9 | 0.7 | 0.4 | 1.0 |
| Capillary | 120 | 40.2 | 0.9 | 0.0 | 1.3 |
| Micro | 120 | 40.6 | 1.3 | 0.2 | 1.7 |
| Spec. (SD) | | | 1.88 (2.3 Micro) | | 2.5 (3.0 Micro) |
| Level 1 | pO2 | | | | |
| --- | --- | --- | --- | --- | --- |
| Sampling Mode | N | Mean mmHg | Within Run SD | Day-to-Day SD | Total SD |
| Normal | 108 | 30 | 1.9 | 1.1 | 2.6 |
| Capillary | 108 | 29 | 0.8 | 0.5 | 1.7 |
| Micro | 108 | 29 | 1.1 | 0.9 | 2.4 |
| Spec. (SD) | | | 3.4 | | 4.5 |
| Level 2 | pO2 | | | | |
| --- | --- | --- | --- | --- | --- |
| Sampling Mode | N | Mean mmHg | Within Run SD | Day-to-Day SD | Total SD |
| Normal | 108 | 53 | 2.2 | 1.0 | 2.5 |
| Capillary | 108 | 51 | 1.6 | 0.7 | 2.0 |
| Micro | 108 | 55 | 1.2 | 0.1 | 2.1 |
| Spec. (SD) | | | 3.4 | | 4.5 |
| Level 1 | Sodium | | | | |
| --- | --- | --- | --- | --- | --- |
| Sampling Mode | N | Mean mmol/L | Within Run SD | Day-to-Day SD | Total SD |
| Normal | 120 | 123 | 0.8 | 0.1 | 1.0 |
| Capillary | 120 | 124 | 0.7 | 0.8 | 1.2 |
| Micro | 120 | 120 | 0.7 | 1.0 | 1.4 |
| Spec. (SD) | | | 1.5 | | 2.0 |
| Level 2 | Sodium | | | | |
| --- | --- | --- | --- | --- | --- |
| Sampling Mode | N | Mean mmol/L | Within Run SD | Day-to-Day SD | Total SD |
| Normal | 120 | 148 | 0.9 | 0.0 | 2.0 |
| Capillary | 120 | 150 | 1.1 | 0.5 | 1.8 |
| Micro | 120 | 147 | 1.0 | 1.2 | 2.0 |
| Spec. (SD) | | | 1.5 | | 2.0 |
| Level 1 | Potassium | | | | |
| --- | --- | --- | --- | --- | --- |
| Sampling Mode | N | Mean mmol/L | Within Run SD | Day-to-Day SD | Total SD |
| Normal | 120 | 2.0 | 0.15 | 0.00 | 0.18 |
| Capillary | 120 | 1.9 | 0.04 | 0.06 | 0.08 |
| Micro | 120 | 2.2 | 0.03 | 0.03 | 0.12 |
| Spec. (SD) | | | 0.17 | | 0.25 |
| Level 2 | Potassium | | | | |
| --- | --- | --- | --- | --- | --- |
| Sampling Mode | N | Mean mmol/L | Within Run SD | Day-to-Day SD | Total SD |
| Normal | 120 | 6.8 | 0.14 | 0.04 | 0.17 |
| Capillary | 120 | 6.6 | 0.13 | 0.00 | 0.18 |
| Micro | 120 | 6.9 | 0.08 | 0.07 | 0.16 |
| Spec. (SD) | | | 0.26 | | 0.34 |
{35}
| Level 1 | Ionized Calcium | | | | |
| --- | --- | --- | --- | --- | --- |
| Sampling Mode | N | Mean mmol/L | Within Run SD | Day-to-Day SD | Total SD |
| Normal | 120 | 0.52 | 0.01 | 0.01 | 0.01 |
| Capillary | 120 | 0.52 | 0.01 | 0.01 | 0.01 |
| Micro | 120 | 0.46 | 0.01 | 0.01 | 0.01 |
| Spec. (SD) | | | 0.04 | | 0.05 |
| Level 2 | Ionized Calcium | | | | |
| --- | --- | --- | --- | --- | --- |
| Sampling Mode | N | Mean mmol/L | Within Run SD | Day-to-Day SD | Total SD |
| Normal | 120 | 0.5 | 0.01 | 0.01 | 0.02 |
| Capillary | 120 | 0.5 | 0.02 | 0.01 | 0.02 |
| Micro | 120 | 0.46 | 0.02 | 0.01 | 0.02 |
| Spec. (SD) | | | 0.04 | | 0.05 |
| Level 1 | Chloride | | | | |
| --- | --- | --- | --- | --- | --- |
| Sampling Mode | N | Mean mmol/L | Within Run SD | Day-to-Day SD | Total SD |
| Normal | 120 | 62 | 0.5 | 0.2 | 0.7 |
| Capillary | 120 | 62 | 0.5 | 0.3 | 0.7 |
| Micro | 120 | 62 | 0.4 | 0.5 | 0.8 |
| Spec. (SD) | | | 1.1 | | 1.5 |
| Level 2 | Chloride | | | | |
| --- | --- | --- | --- | --- | --- |
| Sampling Mode | N | Mean mmol/L | Within Run SD | Day-to-Day SD | Total SD |
| Normal | 120 | 0.5 | 0.01 | 0.01 | 0.02 |
| Capillary | 120 | 0.5 | 0.02 | 0.01 | 0.02 |
| Micro | 120 | 0.46 | 0.02 | 0.01 | 0.02 |
| Spec. (SD) | | | 0.04 | | 0.05 |
| Level 1 | Glucose | | | | |
| --- | --- | --- | --- | --- | --- |
| Sampling Mode | N | Mean mg/dL | Within Run SD | Day-to-Day SD | Total SD |
| Normal | 80 | 34 | 1.3 | 1.1 | 1.8 |
| Capillary | 80 | 34 | 1.2 | 0.8 | 2.3 |
| Micro | 80 | 32 | 0.8 | 0.5 | 1.8 |
| Spec. (SD) | | | 2.25 | | 3.00 |
| Level 2 | Glucose | | | | |
| --- | --- | --- | --- | --- | --- |
| Sampling Mode | N | Mean mg/dL | Within Run SD | Day-to-Day SD | Total SD |
| Normal | 80 | 180 | 2.0 | 4.2 | 7.9 |
| Capillary | 80 | 178 | 2.0 | 3.7 | 7.9 |
| Micro | 80 | 181 | 2.4 | 4.0 | 7.4 |
| Spec. (SD) | | | 6.56 | | 8.75 |
| Level 1 | Lactate | | | | |
| --- | --- | --- | --- | --- | --- |
| Sampling Mode | N | Mean mmol/L | Within Run SD | Day-to-Day SD | Total SD |
| Normal | 120 | 1.7 | 0.07 | 0.02 | 0.08 |
| Capillary | 120 | 1.7 | 0.08 | 0.03 | 0.10 |
| Micro | 120 | 1.6 | 0.06 | 0.05 | 0.10 |
| Spec. (SD) | | | 0.15 | | 0.20 |
| Level 2 | Lactate | | | | |
| --- | --- | --- | --- | --- | --- |
| Sampling Mode | N | Mean mmol/L | Within Run SD | Day-to-Day SD | Total SD |
| Normal | 120 | 5.4 | 0.12 | 0.11 | 0.16 |
| Capillary | 120 | 5.4 | 0.14 | 0.09 | 0.17 |
| Micro | 120 | 5.3 | 0.11 | 0.05 | 0.18 |
| Spec. (SD) | | | 0.32 | | 0.42 |
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| Level 1 | Hematocrit | | | | |
| --- | --- | --- | --- | --- | --- |
| Sampling Mode | N | Mean % | Within Run SD | Day-to-Day SD | Total SD |
| Normal | 120 | 26.33 | 0.51 | 0.42 | 0.80 |
| Capillary | 120 | 26.30 | 0.44 | 0.55 | 0.87 |
| Micro | 120 | 26.67 | 0.75 | 0.62 | 1.10 |
| Spec. (SD) | | | 1.50 | | 2.00 |
| Level 2 | Hematocrit | | | | |
| --- | --- | --- | --- | --- | --- |
| Sampling Mode | N | Mean % | Within Run SD | Day-to-Day SD | Total SD |
| Normal | 120 | 45.50 | 0.64 | 0.17 | 0.88 |
| Capillary | 120 | 45.37 | 0.65 | 0.29 | 0.88 |
| Micro | 120 | 46.23 | 0.80 | 0.54 | 1.21 |
| Spec. (SD) | | | 1.50 | | 2.00 |
| Level 1 | Total Hemoglobin | | | | |
| --- | --- | --- | --- | --- | --- |
| Sampling Mode | N | Mean g/dL | Within Run SD | Day-to-Day SD | Total SD |
| Normal | 120 | 10.43 | 0.065 | 0.098 | 0.141 |
| Capillary | 120 | 10.58 | 0.078 | 0.108 | 0.157 |
| Spec. (SD) | | | 0.260 | | 0.350 |
| Level 2 | Total Hemoglobin | | | | |
| --- | --- | --- | --- | --- | --- |
| Sampling Mode | N | Mean g/dL | Within Run SD | Day-to-Day SD | Total SD |
| Normal | 120 | 14.82 | 0.145 | 0.070 | 0.251 |
| Capillary | 120 | 14.89 | 0.188 | 0.083 | 0.225 |
| Spec. (SD) | | | 0.260 | | 0.350 |
| Level 1 | O2Hb | | | | |
| --- | --- | --- | --- | --- | --- |
| Sampling Mode | N | Mean % | Within Run SD | Day-to-Day SD | Total SD |
| Normal | 120 | 88.9 | 0.19 | 0.47 | 0.56 |
| Capillary | 120 | 88.8 | 0.17 | 0.47 | 0.54 |
| Spec. (SD) | | | 0.75 | | 1.00 |
| Level 1 | COHb | | | | |
| Sampling Mode | N | Mean % | Within Run SD | Day-to-Day SD | Total SD |
| Normal | 120 | 10.66 | 0.11 | 0.20 | 0.32 |
| Capillary | 120 | 10.71 | 0.20 | 0.28 | 0.42 |
| Spec. (SD) | | | 0.75 | | 1.00 |
| Level 1 | MetHb | | | | |
| Sampling Mode | N | Mean % | Within Run SD | Day-to-Day SD | Total SD |
| Normal | 120 | 3.30 | 0.14 | 0.15 | 0.26 |
| Level 2 | O2Hb | | | | |
| --- | --- | --- | --- | --- | --- |
| Sampling Mode | N | Mean % | Within Run SD | Day-to-Day SD | Total SD |
| Normal | 120 | 36.0 | 0.50 | 0.21 | 0.63 |
| Capillary | 120 | 36.1 | 0.37 | 0.02 | 0.41 |
| Spec. (SD) | | | 0.75 | | 1.00 |
| Level 2 | COHb | | | | |
| Sampling Mode | N | Mean % | Within Run SD | Day-to-Day SD | Total SD |
| Normal | 120 | 0.84 | 0.14 | 0.13 | 0.20 |
| Capillary | 120 | 0.84 | 0.15 | 0.11 | 0.20 |
| Spec. (SD) | | | 0.75 | | 1.00 |
| Level 2 | MetHb | | | | |
| Sampling Mode | N | Mean % | Within Run SD | Day-to-Day SD | Total SD |
| Normal | 120 | 6.20 | 0.16 | 0.22 | 0.30 |
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| Capillary | 120 | 3.29 | 0.15 | 0.20 | 0.28 |
| --- | --- | --- | --- | --- | --- |
| Spec. (SD) | | | 0.75 | | 1.00 |
| Level 1 | HHb | | | | |
| Sampling Mode | N | Mean % | Within Run SD | Day-to-Day SD | Total SD |
| Normal | 120 | 0.00 | 0.15 | 0.32 | 0.37 |
| Capillary | 120 | 0.00 | 0.27 | 0.34 | 0.43 |
| Spec. (SD) | | | 2.25 | | 3.00 |
| Capillary | 120 | 6.12 | 0.17 | 0.28 | 0.37 |
| --- | --- | --- | --- | --- | --- |
| Spec. (SD) | | | 0.75 | | 1.00 |
| Level 2 | HHb | | | | |
| Sampling Mode | N | Mean % | Within Run SD | Day-to-Day SD | Total SD |
| Normal | 120 | 63.0 | 0.47 | 0.40 | 0.72 |
| Capillary | 120 | 62.9 | 0.37 | 0.13 | 0.43 |
| Spec. (SD) | | | 2.25 | | 3.00 |
# 3. Clinical studies:
a. Clinical Sensitivity: Not Applicable.
b. Clinical specificity: Not Applicable.
c. Other clinical supportive data (when a. and b. are not applicable): See the Method Comparison section above.
# 4. Clinical cut-off:
Not Applicable.
# 5. Expected values/Reference range:
The following table provides general reference ranges from published literature. The sponsor recommends that each laboratory should establish its own reference ranges.
| Measured Analyte | Units | Arterial Reference Range (Adult) |
| --- | --- | --- |
| pH | n/a | 7.35 to 7.45 |
| pCO2 | mmHg | 35 to 48 |
| pO2 | mmHg | 83 to 108 |
| Na+ | mmol/L | 136 to 145 (1,2) |
| K+ | mmol/L | 3.4 to 4.5 (1) |
| Ca++ | mmol/L | 1.15 to 1.35 |
| Cl- | mmol/L | 98 to 107 (1,2) |
| Glu | mg/dL | 60 to 95 |
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| Measured Analyte | Units | Arterial Reference Range (Adult) |
| --- | --- | --- |
| Lac | mmol/L | 0.5 to 2.2 |
| Hct | % | 35 to 51 |
| tHb | g/dL | 11.7 to 17.4 |
| O_{2}Hb | % | 94 to 97 |
| COHb | % | 0.5 to 1.5 (non-smoking) |
| MetHb | % | < 1.0 |
| HHb | % | 0 to 5 |
¹ Plasma (Hep)² Serum
References:
- Henry, JB, Clinical Diagnosis & Management by Laboratory Methods, WB Saunders Co., Philadelphia, 18th Edition, 1991.
- Tietz, NW, Fundamentals of Clinical Chemistry, WB Saunders Co., Philadelphia, 4th Edition, 1996.
- Bishop, ML, Duben-Engelkirk, JL, Fody, EP, Clinical Chemistry – Principles Procedures Correlations, JB Lippincott Co., 2nd Edition, 1992.
N. Instrument Name:
GEM® Premier 4000 with iQM® (Intelligent Quality Management)
GEM CVP 1 and 2 (Calibration Valuation Product) with CO-Ox
GEM CVP 3 and 4 (Calibration Valuation Product) Hematocrit
O. System Descriptions:
1. Modes of Operation:
The instrument has three modes of operation: normal, capillary, and micro mode. The system's core operation module (the PAK cartridge) can also be purchased in different configurations of analyte measuring capabilities (e.g. with or without electrolyte testing).
2. Software:
FDA has reviewed applicant's Hazard Analysis and software development processes for this line of product types:
Yes ☐ X ☐ or No ☐
3. Specimen Identification:
Sample identification is performed through an interface which instructs the device which sample types are to be detected.
4. Specimen Sampling and Handling:
The sponsor indicates in the operator's manual that it is recommended that the samples be well mixed prior to introduction into the analyzer. In the operator's manual, topics
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covered by training videos on the system are identified with icons. The videos cover topics such as sample handling, patient sampling, and inserting and removing the cartridge. The sponsor also cautions the user that only sodium or lithium anticoagulant be used with samples.
5. Calibration:
As part of this program, GEM CVP (Calibration Valuation Product) with CO-Ox and GEM CVP Hematocrit are external solutions intended to complete the calibration process and final accuracy assessment of the iQM cartridge calibration after initial warm-up. The reported values for the four levels of GEM CVP (two levels for pH, blood gases, electrolytes, metabolites and CO-Oximetry; two levels for hematocrit) must meet specifications before the iQM cartridge can be used for patient sample measurements. Once the cartridge calibration is verified, the internal iQM program monitors the status of the system during the cartridge use life. The GEM CVP solutions are pre-tonometered and contain known quantities of the analytes and dyes tested using CLSI and NIST traceable reference standards.
6. Quality Control:
The sensors of the instrument are calibrated and monitored with four Process Control Solutions A, B, C and D. These solutions are pre-tonometered and contain known quantities of the analytes and dyes tested using NIST traceable reference standards. The solutions are sealed in gas impermeable bags with no headspace.
P. Other Supportive Instrument Performance Characteristics Data Not Covered In The "Performance Characteristics" Section above:
Q. Proposed Labeling:
The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.
R. Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.
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