GEM PREMIER 4000

K112995 · Instrumentation Laboratory CO · CEM · May 3, 2012 · Clinical Chemistry

Device Facts

• Record ID: K112995
• Device Name: GEM PREMIER 4000
• Applicant: Instrumentation Laboratory CO
• Product Code: CEM · Clinical Chemistry
• Decision Date: May 3, 2012
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1600
• Device Class: Class 2
• Attributes: Pediatric

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, sodium, potassium, chloride, ionized calcium, glucose, lactate, hematocrit, total bilirubin and CO-Oximetry (tHb, O2Hb, COHb, MetHb, HHb) parameters. Total bilirubin can also be quantitated from heparinized plasma samples when analyzed in the tBili/CO-Ox mode. 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. Total bilirubin measurements are used in the diagnosis and management of biliary tract obstructions, liver disease and various hemolytic diseases and disorders involving the metabolism of bilirubin. In neonates, the level of total bilirubin is used to aid in assessing the risk of kernicterus. 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. Facilities should follow local, state and federal regulatory guidelines to ensure that a total quality management system is followed. As part of this program, GEM CVP (Calibration Valuation Product) with CO-Ox, GEM CVP tBili and GEM CVP Hematocrit are external solutions intended to complete the calibration process and final accuracy assessment of the iQM cartridge calibration following warm-up. The reported values for GEM CVP (two levels for pH, blood gases, electrolytes, metabolites, total bilirubin, CO-Oximetry and hematocrit) must meet IL's 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 for rapid whole blood analysis at point-of-care or central lab. Inputs: whole blood (syringe, full capillary, micro capillary) or heparinized plasma. Principle: potentiometric measurement for electrolytes (K+ sensor). iQM (Intelligent Quality Management) provides continuous monitoring, real-time error detection, automatic system correction, and documentation, replacing traditional external QC. Output: quantitative measurements of pH, blood gases, electrolytes, metabolites, hematocrit, total bilirubin, and CO-Oximetry. Used by clinicians to aid diagnosis of acid/base, electrolyte, and oxygenation status. Benefits: rapid clinical decision-making via automated quality control and point-of-care testing.

Clinical Evidence

Bench testing only. Precision studies (N=160 per level) across three sample modes showed total imprecision %CV ranging from 0.86% to 3.55%. Linearity confirmed across 0.2–19.0 mmol/L range (R^2 > 0.999). Method comparison vs. GEM Premier 3000 (N=220 per mode) and field site testing (N=304-454) demonstrated comparable performance (slopes 0.978–1.050). Sodium citrate identified as an interferent at ≥ 7.3 mmol/L.

Technological Characteristics

Potentiometric ion-selective electrode (ISE) system. Modified K+ sensor membrane with reduced valinomycin and counterion. Connectivity: standalone/networked. Software: iQM for automated quality control. Standards: CLSI EP5-A2, EP6-A, EP7-A2, EP9-A2, EP17-A, EP25-A, C29-A2.

Indications for Use

Indicated for use by healthcare professionals in clinical settings or central laboratories to analyze whole blood samples for pH, blood gases, electrolytes, metabolites, hematocrit, total bilirubin, and CO-Oximetry. Used for diagnosis/management of acid/base status, electrolyte/metabolite balance, oxygen delivery capacity, biliary/liver disease, hemolytic disorders, and kernicterus risk in neonates. Prescription use only.

Regulatory Classification

Identification

A potassium test system is a device intended to measure potassium in serum, plasma, and urine. Measurements obtained by this device are used to monitor electrolyte balance in the diagnosis and treatment of diseases conditions characterized by low or high blood potassium levels.

Predicate Devices

• GEM Premier 4000 with iQM and CVP (k061974)

Submission Summary (Full Text)

{0}

1

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

A. 510(k) Number:
k112995

B. Purpose for Submission:
Modification of a cleared device (k061974 and k093623) -Potassium sensor change

C. Measurand:
Potassium

D. Type of Test:
Quantitative, potentiometric method

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
GEM CVP 5 (Calibration Valuation Product) tBili

G. Regulatory Information:

- GEM Premier 4000 with iQM (Intelligent Quality Management):

| Description | CFR Section | Device Class | Product Code |
| --- | --- | --- | --- |
| Blood gases and blood pH | 862.1120 | Class II | CHL |
| Sodium test system | 862.1665 | Class II | JGS |
| Potassium test system | 862.1600 | Class II | CEM |
| Calcium test system | 862.1145 | Class II | JFP |

{1}

2

| Chloride test system | 862.1170 | Class II | CGZ |
| --- | --- | --- | --- |
| Glucose test system | 862.1345 | Class II | CGA |
| Lactic acid test system | 862.1450 | Class I, meets limitations of exemptions per 21 CFR 862.9 (c)(9) | KHP |
| Automated hematocrit instrument | 864.5600 | Class II | GKF |
| Carboxyhemoglobin assay | 864.7425 | Class II | GHS |
| Automated hemoglobin system | 864.5620 | Class II | GKR |
| Whole blood hemoglobin assays | 864.7500 | Class II | GLY |
| Bilirubin (Total or Direct) Test System | 862.1110 | Class II | CIG |
| (Total and Unbound) in the Neonate Test System | 862.1113 | Class I, Reserved | MQM |

- GEM CVP 1 and 2 (Calibration Valuation Product) with CO-Ox:
- GEM CVP 5 (Calibration Valuation Product) tBili:

| Description | CFR Section | Device Class | Product Code |
| --- | --- | --- | --- |
| Quality Control Material | 862.1660 | Class I, reserved | JJY |

- GEM CVP 3 and 4 (Calibration Valuation Product) Hematocrit:

| Description | CFR Section | Device Class | Product Code |
| --- | --- | --- | --- |
| Hematocrit Control | 864.8625 | Class II | GLK |

## H. Intended Use:

1. Intended use(s):

Refer to indications for use below.

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, $p\mathrm{CO}_2$, $p\mathrm{O}_2$, sodium, potassium, chloride, ionized calcium, glucose, lactate, hematocrit, total bilirubin and CO-Oximetry (tHb, $\mathrm{O}_2\mathrm{Hb}$, COHb, MetHb, HHb)

{2}

parameters. Total bilirubin can also be quantitated from heparinized plasma samples when analyzed in the tBili/CO-Ox mode. 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. Total bilirubin measurements are used in the diagnosis and management of biliary tract obstructions, liver disease and various hemolytic diseases and disorders involving the metabolism of bilirubin. In neonates, the level of total bilirubin is used to aid in assessing the risk of kernicterus.

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. Facilities should follow local, state and federal regulatory guidelines to ensure that a total quality management system is followed.

As part of this program, GEM CVP (Calibration Valuation Product) with CO-Ox, GEM CVP tBili and GEM CVP Hematocrit are external solutions intended to complete the calibration process and final accuracy assessment of the iQM cartridge calibration following warm-up. The reported values for GEM CVP (two levels for pH, blood gases, electrolytes, metabolites, total bilirubin, CO-Oximetry and hematocrit) must meet IL's 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 only

At point-of-care or central laboratory settings.

4. Special instrument requirements:

GEM Premier 4000 Analyzer

I. Device Description:

The GEM Premier 4000 analyzer utitilizes an ion-selective electrode for the measurement of potassium. The potassium (K+) electrode has a sensor membrane on the surface of the electrode. The GEM Premier 4000 K sensor membrane is being modified to lower the Valinomycin concentration, along with a proportional decrease in the amount of counterion. This modification is to the Potassium sensor for the K+ assay on the GEM Premier 4000. There are no changes to other analyte measurements and device components.

{3}

J. Substantial Equivalence Information:

1. Predicate device name:
GEM Premier 4000 with iQM and CVP

2. Predicate 510(k) number:
k061974

3. Comparison with predicate:
| Comparison Table: Potassium | | |
| --- | --- | --- |
| Item | New Device (k112995) | Predicate (k061974) |
| Intended Use | Quantitative measurement of potassium | Same |
| Test Principle | Potentiometric ion-selective electrode | Same |
| Specimen Type | Whole blood | Same |
| Assay Range | 0.2 to 19.0 mmol/L | Same |
| Membrane Formulation | Modified | Unmodified |

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

1. CLSI EP5-A2. Evaluation of Precision Performance of Clinical Chemistry Devices; Approved Guideline Second edition
2. CLSI EP6-A. Evaluation of the Linearity of Quantitative Analytical Methods; Approved Guideline
3. CLSI EP7-A2. Interference Testing in Clinical Chemistry; Approved Guideline- Second edition
4. CLSI EP9-A2. Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline Second edition
5. CLSI EP17-A. Protocols for Determination of Limits of Detection and Limits of Quantitation; Approved Guideline.
6. CLSI C29-A2. Standardization of Sodium and Potassium Ion-selective electrode systems to the flame photometric reference method; Approved Guideline, Second Edition

{4}

L. Test Principle:

The GEM Premier 4000 potassium sensor technology is based on ion selective electrode methodology. Valinomycin is an ionophore that functions as the potassium recognition component in the sensor. When the sensor is exposed to solutions containing potassium, an electrical signal response (change in electrode potential in millivolts) proportional to the concentration of potassium in the sample is measured. The measured response is converted into potassium concentration based on the slope from the sensor calibration.

M. Performance Characteristics (if/when applicable):

1. Analytical performance:

a. Precision/Reproducibility:

Precision studies were performed to evaluate the performance of the modified K+ sensor using three levels of whole blood samples under the syringe mode (150 μL), the full capillary mode (150 μL) and the micro capillary (65 μL) mode. Due to the instability of whole blood, fresh levels of whole blood were prepared (using 0.1M KCL as the spiking solution) for each run, each day, with a target concentration of 3.0, 4.0 and 7.0 mmol/L of potassium. Testing was completed in replicates of 8 per run, twice a day for 5 days on 2 GEM Premier 4000 instruments. The mean, standard deviation (SD), and coefficients of variation (CV) were determined for each level and each mode as summarized below:

| Precision Data Summary | | | | | | |
| --- | --- | --- | --- | --- | --- | --- |
| Whole Blood- Syringe Mode | | | | | | |
| Sample | N | Within Run | | | Total | |
| | | Mean (mmol/L) | SD (mmol/L) | CV (%) | SD (mmol/L) | CV (%) |
| 1 | 160 | 2.90 | 0.04 | 1.51 | 0.04 | 1.51 |
| 2 | 160 | 3.88 | 0.05 | 1.32 | 0.05 | 1.32 |
| 3 | 160 | 7.41 | 0.06 | 0.86 | 0.06 | 0.86 |
| Whole Blood- Full Capillary Mode | | | | | | |
| Sample | N | Within Run | | | Total | |
| | | Mean (mmol/L) | SD (mmol/L) | CV (%) | SD (mmol/L) | CV (%) |
| 1 | 160 | 3.06 | 0.11 | 3.55 | 0.11 | 3.55 |
| 2 | 160 | 4.06 | 0.11 | 2.71 | 0.11 | 2.71 |
| 3 | 160 | 7.44 | 0.12 | 1.58 | 0.16 | 2.16 |
| Whole Blood- Micro Capillary Mode | | | | | | |
| Sample | N | Within Run | | | Total | |
| | | Mean (mmol/L) | SD (mmol/L) | CV (%) | SD (mmol/L) | CV (%) |
| 1 | 160 | 3.34 | 0.11 | 3.31 | 0.11 | 3.31 |
| 2 | 158 | 4.25 | 0.11 | 2.66 | 0.11 | 2.66 |
| 3 | 160 | 7.83 | 0.10 | 1.27 | 0.10 | 1.27 |

{5}

# b. Linearity/assay reportable range:

A linearity study was performed using whole blood samples according to the CLSI EP6-A guideline. 7 different concentrations of potassium were measured in triplicate on 3 different GEM Premier 4000 analyzers using 3 different sample modes. The measured values were plotted against the expected values measured by the reference method (Flame Photometer). The linear regressions analysis is summarized in the table below:

| Linearity Data Summary | | | |
| --- | --- | --- | --- |
| Testing Mode | Linear regression equation | R2 | Sample range tested |
| Syringe mode | Y= 1.0144X - 0.0612 | 0.9999 | 0.18-24.17 mmol/L |
| Full capillary | Y= 1.0115X + 0.0251 | 0.9997 | 0.13-24.57 mmol/L |
| Micro capillary | Y= 1.0791X - 0.2189 | 0.9998 | 0.17-26.14 mmol/L |

The results of the study support the sponsor's claim that the assay is linear from 0.2 to $19.0\mathrm{mmol / L}$

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

Traceability:

Potassium is traceable to a reference material (NIST standard). See k061974

GEM CVP 1 and 2 (Calibration Valuation Product) with CO-Ox, GEM CVP 3 and 4 (Calibration Valuation Product) Hematocrit, and GEM CVP 5 (Calibration Valuation Product) tBili are part of the iQM quality control and assessment system for the GEM Premier 4000 system. They have been previously cleared in k061974 and k093623.

Potassium sensor stability:

The shelf life stability study was performed on three lots of sensors and the in-use (cartridge use life) stability study was performed on six lots of sensors. Real-time stability study is still on-going. Based on the results, the sponsor claims that the K sensor has a shelf life stability of 2 months at 15 to $25^{\circ}\mathrm{C}$ and an in-use stability of at least 600 samples. The stability study protocol and acceptance criteria were found to be adequate.

{6}

d. Detection limit:

See linearity study in section M.1.b above.

e. Analytical specificity:

An interference study was performed based on the CLSI EP7-A guideline. A comprehensive interference screen was conducted, followed by a dose-response evaluation to characterize the interference according to the CLSI EP7-A. Two levels of human whole blood pooled samples (K approximately 3.0 and $5.0\mathrm{mmol / L}$ ) were spiked with various potential interference substances (48 drugs and endogenous compounds). All samples were analyzed in triplicates on the GEM Premier 4000 and the reference method (flame photometer). The sponsor defines non-significant interference as difference within $\pm 0.1\mathrm{mmol / L}$ when compared to the reference method. Results are summarized in the table below for non-significant interference when tested at the concentrations listed:

Potential Interfering Substances and the Concentrations Tested

| Substance | “Worst Case” Test Concentration | Substance | “Worst Case” Test Concentration |
| --- | --- | --- | --- |
| Acetaminophen | 20 mg/dL | Hydroxyurea | 0.8 mg/dL |
| Acetoacetate | 2 mmol/L | Ibuprofen | 2.425 mmol/L |
| Ammonium | 107 μmol/L | Icodextrin | 20 mg/dL |
| Aprotinin | 50 mg/L | Iodide | 3 mmol/L |
| Ascorbic acid | 6 mg/dL | Isoniazide | 4 mg/dL |
| Atracurium | 50 mg/L | Lactate | 6.6 mmol/L |
| Benzalkonium | 5 mg/L | Lithium | 3.2 mmol/L |
| Bromide | 37.5 mmol/L | Ionized Magnesium | 15 mmol/L |
| Ionized Calcium | 2.5 mmol/L | Maltose | 0.2 mg/dL |
| Chlorpromazine | 0.0063 mmol/L | Mannose | 20 mg/dL |
| Creatinine | 5 mg/dL | Oxalate | 500 mg/dL |
| Dobutamine | 2 mg/dL | Perchlorate | 20 mg/dL |
| Dopamine | 0.1 mg/dL | pH | 6.80 |
| Ethanol | 400 mg/dL | Pralidoxime iodide | 40 μg/mL |
| Etomidate | 50 mg/L | Pyruvate | 0.309 mmol/L |
| Flaxedil | 5 mg/dL | Salicylate | 4.34 mmol/L |
| Fluoride | 0.4 mg/dL | Sodium | 180 mmol/L |
| Fructose | 18 mg/dL | Thiocyanate | 56 mg/dL |
| Galactose | 15 mg/dL | Thiopental | 66 mg/L |

{7}

8

| Substance | “Worst Case” Test Concentration | Substance | “Worst Case” Test Concentration |
| --- | --- | --- | --- |
| Glucose | 1000 mg/dL | Triglycerides | 3250 mg/dL |
| Glycolic acid | 1 mmol/L | Urea | 42.9 mmol/L |
| Heparin | 300 IU/mL | Uric acid | 23.5 mg/dL |
| β-hydroxybutyrate | 2 mmol/L | Xylose | 20 mg/dL |

Because hemolysis and sodium citrate have shown significant interference, the sponsor stated the following limitations in the labeling:

“Hemolyzed samples may result in falsely elevated potassium levels.”

“Blood collection tubes containing sodium citrate as an additive will produce clinically significant interference on Potassium and should not be used.”

f. Assay cut-off:

Not applicable

2. Comparison studies:

a. Method comparison with predicate device:

A method comparison study was performed for potassium according to the CLSI EP9-A guideline. Six GEM Premier 400 analyzers were tested with two in each sample mode, over a period of 18 days, against the results performed with a commercially available blood gases analyzer. A total of 109 samples were tested. Approximately 10% to 14% of the samples were altered in order to cover the hard-to-find sample range. The linear regressions analysis is summarized in below:

| Test mode | N | Slope (95%CI) | Intercept (95% CI) | R² | Sample range tested (mmol/L) |
| --- | --- | --- | --- | --- | --- |
| Syringe | 109 | 1.002 (0.994-1.011) | 0.052 (0.012-0.1092) | 0.998 | 0.2-18.6 |
| Full capillary | 109 | 1.001 (0.992-1.011) | 0.092 (0.047-0.137) | 0.997 | 0.2-18.2 |
| Micro capillary | 109 | 1.016 (1.006-1.027) | 0.148 (0.095-0.200) | 0.997 | 0.2-18.2 |

b. Matrix comparison:

Not applicable

{8}

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

4. Clinical cut-off:
Not applicable

5. Expected values/Reference range:
K: 3.4 to 4.5 mmol/L

The reference range for potassium was taken from the literature.

References: Wu, A., Tietz Clinical Guide to Laboratory Tests, W.B. Saunders Co., St. Louis MO, 4th, 2006.

N. Proposed Labeling:
The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

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