GEM Premier 5000

K173403 · Instrumentation Laboratory CO · CHL · Dec 29, 2017 · Clinical Chemistry

Device Facts

• Record ID: K173403
• Device Name: GEM Premier 5000
• Applicant: Instrumentation Laboratory CO
• Product Code: CHL · Clinical Chemistry
• Decision Date: Dec 29, 2017
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1120
• Device Class: Class 2

Indications for Use

The GEM Premier 5000 is a portable critical care system for use by health care professionals to rapidly analyze heparinized whole blood samples at the point of health care delivery in a clinical setting and in a central laboratory. The instrument provides quantitative measurements of pH, pCO2, pO2, sodium, potassium, chloride, ionized calcium, glucose, lactate, hematocrit, total bilirubin and CO-Oximetry (tHb, O2Hb, COHb, MetHb, HHb, sO2*) parameters from arterial, venous or capillary heparinized whole blood. 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. *sO2 = ratio between the concentration of oxyhemoglobin and oxyhemoglobin plus deoxyhemoglobin.

Device Story

Portable critical care system; analyzes heparinized whole blood samples (arterial, venous, capillary). System components: GEM Premier 5000 analyzer and GEM Premier 5000 PAK (disposable cartridge containing reagents, sensors, optical cell, sampler, waste bag). Principle of operation: potentiometric sensors (pCO2, K+, Cl-); electrical conductivity (hematocrit); spectrophotometric absorbance (total hemoglobin). Operator: healthcare professional at point-of-care or central lab. Workflow: sample aspiration into cartridge; automated analysis; results displayed on analyzer. Output: quantitative measurements of blood parameters; aids clinical decision-making regarding acid-base status, electrolyte balance, and oxygen delivery. Benefits: rapid diagnostic information for critical care patients.

Clinical Evidence

No clinical trials; performance established via bench and method comparison studies. Precision evaluated internally and at an external POC site using whole blood samples (n=56-120 per study). Method comparison against predicate (GEM Premier 4000) performed with 136-141 samples (native and contrived) spanning reportable ranges. Results showed high correlation (R=0.980-0.995) and acceptable bias at medical decision levels for pCO2, K+, Cl-, Hct, and tHb.

Technological Characteristics

System uses PVC-based ion-selective electrodes (potentiometry) for electrolytes, electrical conductivity for hematocrit, and LED-based spectrophotometry for total hemoglobin. Disposable GEM PAK cartridge contains sensors, optical cell, and reagents. Connectivity: standalone analyzer. Software: embedded firmware. Sterilization: not specified. Materials: PVC, Ag/AgCl electrodes.

Indications for Use

Indicated for health care professionals to analyze heparinized whole blood (arterial, venous, or capillary) for diagnosis of acid-base disturbances, electrolyte/metabolite balance, and oxygen delivery capacity in clinical and central laboratory settings. Used for patients requiring monitoring of pH, blood gases, electrolytes (Na, K, Ca, Cl), glucose, lactate, bilirubin, and CO-Oximetry parameters.

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

• GEM Premier 4000 (k133407)

Submission Summary (Full Text)

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

A. 510(k) Number:
k173403

B. Purpose for Submission:
Addition of capillary heparinized whole blood claims for pCO2, potassium, chloride, hematocrit and total hemoglobin on the GEM Premier 5000.

C. Measurand:
pCO2, potassium, chloride, hematocrit and total hemoglobin.

D. Type of Test:
Quantitative, potentiometric for pCO2, potassium, and chloride
Quantitative, electrical conductivity for hematocrit
Quantitative, spectrophotometric method for total hemoglobin

E. Applicant:
Instrumentation Laboratory Co.

F. Proprietary and Established Names:
GEM Premier 5000

G. Regulatory Information:

| Analyte | Product Code | Classification | Regulation Section | Panel |
| --- | --- | --- | --- | --- |
| pCO2 | CHL | Class II | 862.1120; Blood Gases (pCO2, pO2) and Blood pH system | Chemistry (75) |
| Potassium | CEM | | 862.1600; Potassium test system | |
| Chloride | CGZ | | 862.1170; Chloride test system | |

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| Analyte | Product Code | Classification | Regulation Section | Panel |
| --- | --- | --- | --- | --- |
| Hematocrit | GKF | Class II | 862.5600; Automated hematocrit instrument | Hematology (81) |
| Total Hemoglobin | GKR | | 864.5620; Automated hemoglobin system | |
| | GLY | | 864.7500; Whole blood hemoglobin assays | |

H. Intended Use:

1. Intended use(s):

See Indications for use below

2. Indication(s) for use:

The GEM Premier 5000 is a portable critical care system for use by health care professionals to rapidly analyze heparinized whole blood samples at the point of health care delivery in a clinical setting and in a central laboratory. The instrument provides quantitative measurements of pH, $p\mathrm{CO}_2$, $p\mathrm{O}_2$, sodium, potassium, chloride, ionized calcium, glucose, lactate, hematocrit, total bilirubin and CO-Oximetry (tHb, $\mathrm{O}_2\mathrm{Hb}$, COHb, MetHb, HHb, $\mathrm{sO}_2^*$) parameters from arterial, venous or capillary heparinized whole blood. 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.

*sO₂ = ratio between the concentration of oxyhemoglobin and oxyhemoglobin plus deoxyhemoglobin.

- pH, $p\mathrm{CO}_2$, and $p\mathrm{O}_2$ measurements in whole blood are used in the diagnosis and treatment of life-threatening acid-base disturbances.
- Electrolytes in the human body have multiple roles. Nearly all metabolic processes depend on or vary with electrolytes:
- Sodium (Na⁺) measurements are used in the diagnosis and treatment of aldosteronism, diabetes insipidus, adrenal hypertension, Addison’s disease, dehydration, inappropriate antidiuretic secretion, or other diseases involving electrolyte imbalance.
- Potassium (K⁺) measurements are used to monitor electrolyte balance in the diagnosis and treatment of disease conditions characterized by low or high blood potassium levels.
- Ionized calcium (Ca²⁺) measurements are used in the diagnosis and treatment of parathyroid disease, a variety of bone diseases, chronic renal disease and tetany.
- Chloride (Cl⁻) measurements are used in the diagnosis and treatment of electrolyte and metabolic disorders, such as cystic fibrosis and diabetic acidosis.
- Hematocrit (Hct) measurements in whole blood of the packed red cell volume of a

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blood sample are used to distinguish normal from abnormal states, such as anemia and erythrocytosis (an increase in the number of red cells).

- Glucose (Glu) measurement is used in the diagnosis, monitoring and treatment of carbohydrate metabolism disturbances including diabetes mellitus, neonatal hypoglycemia, idiopathic hypoglycemia, and pancreatic islet cell carcinoma.
- Lactate (Lac) measurement is used:
- to evaluate the acid-base status of patients suspected of having lactic acidosis;
- to monitor tissue hypoxia and strenuous physical exertion;
- in the diagnosis of hyperlactatemia.
- Total Bilirubin (tBili) measurement is used to aid in assessing the risk of kernicterus and hyperbilirubinemia in neonates.
- CO-Oximetry (tHb, COHb, MetHb, O₂Hb, HHb, and sO₂) evaluates the ability of the blood to carry oxygen by measuring total hemoglobin and determining the percentage of functional and dysfunctional hemoglobin species.
- Total Hemoglobin (tHb): Total hemoglobin measurements are used to measure the hemoglobin content of whole blood for the detection of anemia.
- COHb: Carboxyhemoglobin measurements are used to determine the carboxyhemoglobin content of human blood as an aid in the diagnosis of carbon monoxide poisoning.
- MetHb: Methemoglobin measurements are used to determine different conditions of methemoglobinemia.
- HHb: Deoxyhemoglobin, as a fraction of total hemoglobin, is used in combination with oxyhemoglobin to measure oxygen status.
- O₂Hb: Oxyhemoglobin, as a fraction of total hemoglobin, is used in combination with deoxyhemoglobin to measure oxygen status.
- sO₂: Oxygen saturation, more specifically the ratio between the concentration of oxyhemoglobin and oxyhemoglobin plus deoxyhemoglobin, is used to measure oxygen status.

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 2 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. There are 5 process control solutions (A, B, C, D and E), 1 reference electrode solution and 1 lysing solution in each GEM Premier 5000 PAK. The 5 process control solutions are utilized each day at different frequencies to confirm sensor, CO-Ox and PAK performance.

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The target values of the Process Control Solutions are stated in the following table:

| Analyte | Units | A | B | C | D | E |
| --- | --- | --- | --- | --- | --- | --- |
| K+ | mmol/L | 7.1 | 1.9 | N/A | 7.2 | 4.5 |
| Cl- | mmol/L | 49 | 88 | N/A | 141 | 101 |
| pCO2 | mmHg | 65 | 33 | 33 | 25 | 67 |
| Hct | (%) | 28 | 19 | N/A | 26 | 38 |
| tHb | (g/dL) | 14.2 | 0 | N/A | 7.3 | 16.5 |

# J. Substantial Equivalence Information:

1. Predicate device name(s):

GEM Premier 4000

2. Predicate $510(\mathbf{k})$ number(s):

k133407

3. Comparison with predicate:

| Similarities | | |
| --- | --- | --- |
| Item | Candidate Device GEM Premier 5000 k173403 | Predicate Device GEM Premier 4000 k133407 |
| Intended Use | 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. | Same |
| Intended User | Central Laboratory and Point-of-Care sites | Same |
| Sample Introduction | Aspiration | Same |
| PAK Shelf-Life Stability | Up to 180 days | Same |
| PAK Storage Temperature | 15-25°C | Same |
| System Operating Temperature | 12-32°C | Same |
| Calibration | 2-point | Same |
| Reportable range pCO2 | 6 to 125 mmHg | Same |
| Reportable range Cl- | 40 to 158 mmol/L | Same |
| Reportable range Hct | 15 to 72% | Same |
| Reportable range tHb | 3.0 to 23.0 g/dL | Same |

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| Differences | | |
| --- | --- | --- |
| Item | Candidate Device GEM Premier 5000 | Predicate Device GEM Premier 4000 |
| Reportable range K+ | 1.0 to 19.0 mmol/L | 0.2 to 19.0 mmol/L |

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

- CLSI EP5-A3, Evaluation of Precision Performance of Quantitative Measurement Methods; Third Edition, 2014.
- CLSI EP9-A3; Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline – Third Edition, 2013

# L. Test Principle:

The electrolyte sensors $(\mathrm{K}+,$ and Cl-) are polyvinyl chloride (PVC) based ion selective electrodes consisting of an internal $\mathrm{Ag / AgCl}$ reference electrode and an internal electrolyte layer. Their potentials are measured against the card reference electrode $(\mathrm{Ag / Ag + })$ . The electrolyte sensors are based on the principle of ion selective electrodes; in which electrical potential can be established across a membrane resulting from chemical selectivity of the membrane to a specific ion. The electrical potential is proportional to the logarithm of the analyte activity in the sample, and the concentration of the desired ions is calculated using Nernst equation.

pCO2 is measured by potentiometry using a sensor on the GEM Premier 5000 PAK. The result may be corrected for actual patient temperature if different than $37^{\circ}\mathrm{C}$ .

Hematocrit is measured by an electrical conductivity technique. The conductivity technique is based on the principle that because plasma is more conductive than blood cells due to the high resistance of the cell membranes, the resistivity of blood will increase as the concentration of cells increases. This relationship is expressed by the Maxwell-Fricke equation: $r = Rp \times (1 + Hct / 100) / (1 - Hct / 100)$ , where "r" is the blood resistivity, $Rp$ is a constant based on the plasma resistivity, and $Hct$ is hematocrit. The electrode chamber contains a miniature conductivity cell. By applying an alternating potential through the cell, the resistance of the fluid in the cell can be determined by means of Ohm's Law.

Total hemoglobin measurement is based on an optical absorbance measurement of the sample. An in-line optical cell is integrated in the flow path of the hemolyzed sample to provide a measure of hemoglobin and its derivatives. 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 reference and a high resolution spectrometer with a holographic diffraction grating and a charge-coupled device

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(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:

Three separate studies were conducted to evaluate the precision of the GEM Premier 5000 system for $\mathrm{pCO_2}$ , $\mathrm{K}^+$ , Cl, - Hct and tHb.

Internal Precision Studies

i. An internal precision study was performed using 5 whole blood samples with different concentrations of analytes, each run on 3 GEM Premier 5000 analyzers (a different cartridge lot was used with each instrument) for 5 days, with 1 run per day and 8 replicates measured per run per level. Samples were transferred from syringe to a capillary device prior testing. The results are summarized below:

| Analyte | System Evaluator Level | N | Mean | Within Run | | Between Instrument/Lot | | Total | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | | | SD | %CV | SD | %CV | SD | %CV |
| pCO2 (mmHg) | 1 | 120 | 9.9 | 0.5 | 5.1 | 0.7 | 7.6% | 0.9 | 9.1 |
| | 2 | 120 | 34.5 | 0.6 | 1.9 | 0.4 | 1.2% | 0.8 | 2.2 |
| | 3 | 120 | 49.0 | 0.5 | 1.1 | 0.7 | 1.4% | 0.9 | 1.8 |
| | 4 | 120 | 68.9 | 1.6 | 2.3 | 1.4 | 2.1% | 2.1 | 3.1 |
| | 5 | 120 | 108.9 | 2.4 | 2.2 | 2.3 | 2.1% | 3.3 | 3.0 |
| K+ (mmol/L) | 1 | 120 | 1.46 | 0.05 | 3.2 | 0.02 | 1.4% | 0.05 | 3.5 |
| | 2 | 120 | 2.70 | 0.06 | 2.1 | 0.01 | 0.3% | 0.06 | 2.1 |
| | 3 | 120 | 5.43 | 0.04 | 0.8 | 0.02 | 0.4% | 0.05 | 0.9 |
| | 4 | 120 | 7.16 | 0.07 | 1.0 | 0.04 | 0.5% | 0.08 | 1.1 |
| | 5 | 120 | 17.29 | 0.15 | 0.9 | 0.12 | 0.7% | 0.20 | 1.1 |
| Cl- (mmol/L) | 1 | 120 | 53.4 | 0.4 | 1.0 | 0.1 | 0.2% | 0.4 | 0.8 |
| | 2 | 120 | 75.8 | 0.4 | 0.9 | 0.2 | 0.2% | 0.4 | 0.5 |
| | 3 | 120 | 89.8 | 0.4 | 0.8 | 0.1 | 0.1% | 0.4 | 0.4 |
| | 4 | 120 | 110.7 | 0.4 | 0.5 | 0.3 | 0.3% | 0.5 | 0.5 |
| | 5 | 120 | 152.8 | 0.7 | 0.4 | 0.6 | 0.4% | 0.9 | 0.6 |
| Hct (%) | 1 | 120 | 19.3 | 0.6 | 2.9 | 0.2 | 1.0% | 0.6 | 3.0 |
| | 2 | 120 | 32.8 | 0.6 | 1.9 | 0.2 | 0.5% | 0.6 | 2.0 |
| | 3 | 120 | 44.7 | 0.6 | 1.3 | 0.3 | 0.6% | 0.6 | 1.4 |
| | 4 | 120 | 55.0 | 0.8 | 1.5 | 0.4 | 0.8% | 0.9 | 1.6 |
| | 5 | 120 | 63.7 | 1.3 | 2.0 | 0.9 | 1.4% | 1.6 | 2.5 |

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| Analyte | System Evaluator Level | N | Mean | Within Run | | Between Instrument/Lot | | Total | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | | | SD | %CV | SD | %CV | SD | %CV |
| tHb (g/dL) | 1 | 120 | 7.02 | 0.16 | 2.3 | 0.00 | 0.0% | 0.16 | 2.3 |
| | 2 | 120 | 11.06 | 0.09 | 0.8 | 0.03 | 0.3% | 0.09 | 0.9 |
| | 3 | 120 | 14.47 | 0.10 | 0.7 | 0.05 | 0.3% | 0.11 | 0.8 |
| | 4 | 120 | 17.34 | 0.09 | 0.5 | 0.02 | 0.1% | 0.09 | 0.5 |
| | 5 | 120 | 19.92 | 0.25 | 1.3 | 0.00 | 0.0% | 0.25 | 1.3 |

# ii. Capillary Finger-stick Samples

An internal study was conducted in a Customer Simulation Laboratory (CSL) using native capillary whole blood samples. POC operators collected 2 capillary tubes per donor via finger stick puncture and tested each capillary tube in singlicate. Each sample pair was analyzed on the same GEM Premier 5000 analyzer. The results are summarized below:

| Analyte | n | Mean | Within Sample Precision | |
| --- | --- | --- | --- | --- |
| | | | SD | %CV |
| pCO2 (mmHg) | 56 | 39 | 1.3 | 3.3 |
| K+(mmol/L) | 56 | 4.1 | 0.11 | 2.6 |
| Cl-(mmol/L) | 56 | 106 | 0.3 | 0.3 |
| Hct (%) | 56 | 43 | 0.7 | 1.7 |
| tHb (g/dL) | 56 | 14.2 | 0.14 | 1.0 |

# External precision study

iii. A precision study was performed on a GEM Premier 5000 at an external point-of-care (POC) site, using venous heparinized whole blood patient samples transferred from syringe to a capillary device and run by 3 POC operators. The study used a minimum of 20 residual whole blood samples run over 5 days. Each sample was run in triplicate. The results are summarized below:

| Analyte | n | Mean | Within Sample precision | |
| --- | --- | --- | --- | --- |
| | | | SD | %CV |
| pCO2(mmHg) | 63 | 42 | 0.9 | 2.0 |
| | 3 | 88 | 0.6 | 0.7 |
| K+(mmol/L) | 66 | 4.0 | 0.05 | 1.2 |
| Cl-(mmol/L) | 66 | 107 | 0.5 | 0.5 |
| Hct (%) | 66 | 30 | 0.7 | 2.4 |
| tHb (g/dL) | 60 | 11.0 | 0.29 | 2.6 |

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b. Linearity/assay reportable range:

Previously established in k160225, k160412, and k160415.

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

As described in k160225, k160412, k160415.

d. Detection limit:

Previously established in k160225, k160412, and k160415.

e. Analytical specificity:

Previously established in k160225, k160412, and k160415.

f. Assay cut-off:

Not applicable

# 2. Comparison studies:

a. Method comparison with predicate device:

A method comparison study for capillary whole blood was performed at an external POC site with 6 POC operators and an internal laboratory with 3 POC operators. Two capillary samples were collected via finger-stick from each patient/donor. One sample was analyzed in singlicate on the GEM Premier 5000 (test device) and the other samples was analyzed in singlicate on the GEM Premier 4000 (predicate device). To span the reportable range for each analyte, $<10\%$ of contrived samples were prepared, transferred into capillary tubes and run in singlicate on the GEM Premier 5000 and GEM Premier 4000. The study results are shown below.

| Analyte | N | Slope | Intercept | R | Sample range |
| --- | --- | --- | --- | --- | --- |
| pCO2(mmHg) | 139 | 1.000 | 1.000 | 0.980 | 11 to 87 |
| K+(mmol/L) | 140 | 1.000 | 0.100 | 0.995 | 1.5 to 17.6 |
| Cl-(mmol/L) | 141 | 1.000 | -1.000 | 0.995 | 45 to 149 |
| Hct (%) | 136 | 1.003 | -0.407 | 0.987 | 15 to 64 |
| tHb (g/dL) | 137 | 1.028 | -0.470 | 0.994 | 4.5 to 20.5 |

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

| Analyte | N | Range Min | Range Max | ML | Bias at MDL | 95% CI of Bias at MDL |
| --- | --- | --- | --- | --- | --- | --- |
| pCO2 (mmHg) | 130 | 26 | 50 | 35 | 1.0 | 1.0 to 2.0 |
| | | | | 50 | 1.0 | 1.0 to 2.0 |
| | | | | 70 | 1.4% | 1.4% to 3.1% |
| K+ (mmol/L) | 130 | 3.1 | 6.7 | 3.0 | 0.1 | -0.03 to 0.19 |
| | | | | 5.8 | 0.1 | 0.05 to 0.30 |
| | | | | 7.5 | 1.3% | 0.7% to 6.8% |
| Cl- (mmol/L) | 129 | 90 | 111 | 90 | -1.1% | -1.1% to 0.0% |
| | | | | 112 | -0.9% | -0.9% to 0.0% |
| Ht (%) | 13 | 24 | 51 | 21 | -0.4 | -1.3 to 0.5 |
| | | | | 33 | -0.3 | -0.7 to 0.1 |
| | | | | 56 | -0.1 | -0.7 to 0.5 |
| tHb (g/dL) | 131 | 6.9 | 17.3 | 7.0 | -0.27 | -0.43 to -0.12 |
| | | | | 10.5 | -0.17 | -0.25 to -0.09 |
| | | | | 18.0 | 0.05 | -0.07 to 0.16 |

b. Matrix comparison:

Not applicable. Sponsor stated that only lithium heparin 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

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

Not applicable

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4. Clinical cut-off:
Not applicable

5. Expected values/Reference range:
k160225, k160412, k160415

N. Proposed Labeling:
The labeling is sufficient and it satisfies the requirements of 21 CFR Parts 801 and 809, as applicable.

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

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