GEM Premier ChemSTAT

K183555 · Instrumentation Laboratory CO · JFY · Feb 16, 2019 · Clinical Chemistry

Device Facts

• Record ID: K183555
• Device Name: GEM Premier ChemSTAT
• Applicant: Instrumentation Laboratory CO
• Product Code: JFY · Clinical Chemistry
• Decision Date: Feb 16, 2019
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1225
• Device Class: Class 2

Indications for Use

The GEM Premier ChemSTAT is a portable critical care system for use by health care professionals to rapidly analyze lithium 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 Creatinine (Crea), Blood Urea Nitrogen (BUN) and Total Carbon Dioxide (tCO2) from arterial and venous heparinized whole blood. These parameters, along with derived parameters, aid in the diagnosis of a patient's acid/base status and metabolite balance. - Creatinine (Crea) measurements are used in the diagnosis and treatment of renal diseases and in monitoring renal dialysis. - Blood Urea Nitrogen (BUN) or urea measurements are used for the diagnosis, monitoring, and treatment of certain renal and metabolic diseases. - Total carbon dioxide/tCO2 (also referred to as bicarbonate/HCO3-) is used in the diagnosis, monitoring, and treatment of numerous potentially serious disorders associated with changes in body acid-base balance.

Device Story

Portable analyzer for point-of-care or central lab use; processes arterial/venous lithium heparinized whole blood samples. System uses disposable multi-use GEM Premier ChemSTAT Cartridge/PAK containing sensors, solutions, and waste management. Creatinine measured via enzymatic amperometry; BUN via enzymatic potentiometry; tCO2 via potentiometry. Analyzer features touch-screen interface for clinician interaction. Output provides quantitative metabolite concentrations; aids clinicians in diagnosing renal/metabolic disease and acid/base status. Benefits include rapid, on-site diagnostic information for clinical decision-making.

Clinical Evidence

No clinical trials performed. Evidence consists of analytical bench testing: precision (CLSI EP05-A3), linearity (CLSI EP06-A), interference (CLSI EP07), and detection limits (CLSI EP17-A2). Method comparison study (N=405-416) against Roche Cobas analyzers showed high correlation (R=0.986-0.997) across reportable ranges.

Technological Characteristics

Portable analyzer with touch-sensitive screen. Uses disposable, closed-system PAK (cartridge) containing sensors, process control solutions, and waste management. Measurement principles: Enzymatic Amperometry (Creatinine), Enzymatic Potentiometry (BUN), and Potentiometry (tCO2). Calibration via 2-point or 3-point methods. Components traceable to NIST/CLSI standards. Features Intelligent Quality Management (iQM) for continuous monitoring. Connectivity via internal logic/processing.

Indications for Use

Indicated for health care professionals to analyze lithium heparinized whole blood (arterial/venous) for Creatinine, BUN, and tCO2 in clinical/central lab settings. Used for diagnosis/treatment of renal diseases, metabolic diseases, and acid-base balance disorders in patients of all ages.

Regulatory Classification

Identification

A creatinine test system is a device intended to measure creatinine levels in plasma and urine. Creatinine measurements are used in the diagnosis and treatment of renal diseases, in monitoring renal dialysis, and as a calculation basis for measuring other urine analytes.

Predicate Devices

• Cobas Integra Creatinine Plus Ver.2 assay (k024098)
• Cobas Integra Urea/BUN (k954000)
• Cobas Integra Bicarbonate Liquid (k031879)

Submission Summary (Full Text)

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

A. 510(k) Number:
k183555

B. Purpose for Submission:
New device

C. Measurand:
Creatinine, blood urea nitrogen (BUN), and total carbon dioxide (tCO₂)

D. Type of Test:
Quantitative; enzymatic amperometry (creatinine)
Quantitative; enzymatic potentiometry (BUN)
Quantitative; potentiometry (tCO₂)

E. Applicant:
Instrumentation Laboratory Co.

F. Proprietary and Established Names:
GEM Premier ChemSTAT

G. Regulatory Information:
| Analyte | Product Code | Classification | Regulation Section | Panel |
| --- | --- | --- | --- | --- |
| Creatinine | JFY | Class II | 21 CFR 862.1225 Creatinine test system | Chemistry (75) |
| BUN | CDQ | Class II | 21 CFR 862.1770 Urea nitrogen test system | |
| tCO₂ | KHS | Class II | 21 CFR 862.1160 Bicarbonate/carbon dioxide test system | |

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H. Intended Use:

1. Intended use(s):

See indications for use.

2. Indication(s) for use:

The GEM Premier ChemSTAT analyzer is a portable system used by health care professionals to analyze arterial and venous lithium heparinized whole blood samples for creatinine, blood urea nitrogen (BUN), and total carbon dioxide (tCO₂) at point of care in a clinical setting or at a central laboratory. These parameters, along with derived parameters, aid in the diagnosis of a patient’s acid/base status and metabolite balance.

Creatinine measurements are used in the diagnosis and treatment of renal diseases and in monitoring renal dialysis.

Blood Urea Nitrogen (BUN) or urea measurements are used for the diagnosis, monitoring and treatment of certain renal and metabolic diseases.

Total carbon dioxide/tCO₂ (also referred to as bicarbonate/HCO3-) is used in the diagnosis, monitoring and treatment of patients’ acid/base status and metabolite balance.

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 ChemSTAT analyzer

I. Device Description:

The GEM Premier ChemSTAT system is a prescription-use-only, portable system used by health care professionals to analyze arterial and venous lithium heparinized whole blood samples at point-of-care or a central laboratory. The system has two primary components: the GEM Premier ChemSTAT analyzer and a disposable, multiuse GEM Premier ChemSTAT Cartridge/PAK (GEM PAK).

The GEM Premier ChemSTAT analyzer has the internal logic and processing power necessary to perform analysis. It employs a touch-sensitive color screen and a set of menus and buttons for user interaction.

The GEM Premier ChemSTAT PAK (or GEM PAK) is a disposable, multi-use PAK that houses all components necessary to operate the instrument. These components include the sensors, solutions, sampler, and waste bag. The GEM PAK enables analysis of 75 to 450 samples.

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J. Substantial Equivalence Information:

1. Predicate device name(s):
Cobas Integra Creatinine Plus Ver.2 assay
Cobas Integra Urea/BUN
Cobas Integra Bicarbonate Liquid

2. Predicate 510(k) number(s):
k024098 - Cobas Integra Creatinine Plus Ver. 2
k954000 - Cobas Integra Urea/BUN
k031879 - Cobas Integra Bicarbonate Liquid

3. Comparison with predicate:

Creatinine

| Similarities and Differences | | |
| --- | --- | --- |
| Device Characteristic | Candidate Device
GEM Premier ChemSTAT | Predicate Device
Cobas Integra Creatinine Plus Ver. 2. |
| Intended Use | Quantitative measurement of creatinine | Same |
| Intended User | Central Laboratory and Point-of-Care | Central Laboratory |
| Measurement Principle | Enzymatic Amperometry | Enzymatic Colorimetry |
| Sample Volume | 150 μL | 2-5 μL |
| Sample Type | Lithium heparinized whole blood (arterial and venous) | Serum, plasma, and urine |
| Reportable Range | 0.20-15 mg/dL | 0.06-30.5 mg/dL |
| Calibration | 3-point | 2-Point |

BUN

| Similarities and Differences | | |
| --- | --- | --- |
| Device Characteristic | Candidate Device
GEM Premier ChemSTAT | Predicate Device
Cobas Integra Urea/BUN |
| Intended Use | Quantitative measurement of BUN | Same |
| Intended User | Central Laboratory and Point-of-Care | Central Laboratory |
| Measurement Principle | Enzymatic Potentiometry | Enzymatic Colorimetry |
| Sample Volume | 150 μL | 2 μL |
| Sample Type | Lithium heparinized whole blood (arterial and venous) | Serum, plasma, and urine |
| Reportable Range | 3.0-112.0 mg/dL | 1.4-112 mg/dL |
| Calibration | 2-point | Same |

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$tCO_{2}$

| Similarities and Differences | | |
| --- | --- | --- |
| Device Characteristic | Candidate Device
GEM Premier ChemSTAT | Predicate Device
Cobas Integra Bicarbonate Liquid |
| Intended Use | Quantitative measurement of tCO_{2} | Same |
| Intended User | Central Laboratory and Point-of-Care | Central Laboratory |
| Measurement Principle | Potentiometry | Enzymatic Colorimetry |
| Sample Volume | 150 μL | 2 μL |
| Sample Type | Lithium heparinized whole blood (arterial and venous) | Serum and plasma |
| Reportable Range | 5-50 mmol/L | 2-50 mmol/L |
| Calibration | 2-point | Same |

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

Clinical and Laboratory Standards Institute (CLSI). EP05-A3: Evaluation of Precision of Quantitative Measurement Procedures, 3rd Edition.

Clinical and Laboratory Standards Institute (CLSI). EP06-A: Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline.

Clinical and Laboratory Standards Institute (CLSI). EP07: Interference Testing in Clinical Chemistry, 3rd Edition.

Clinical and Laboratory Standards Institute (CLSI). EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guidelines – Second edition.

Clinical and Laboratory Standards Institute (CLSI). EP25-A: Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline

Clinical and Laboratory Standards Institute (CLSI). C46-A2: Blood Gas and pH Analysis and Related Measurements; Approved Guideline – Second Edition.

## L. Test Principle:

### Creatinine

The creatinine electrode measures a series of coupled enzymatic reactions involved in the conversion of creatinine to hydrogen peroxide (shown below in equations 1-3). The creatine electrode measures a series of coupled enzymatic reactions involved in the conversion of creatine to hydrogen peroxide (shown below in Equations 2-3).

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The hydrogen peroxide resulting from these reactions is oxidized at the platinum electrode operated at a positive potential (shown above in Equation 4), with respect to the card reference electrode. The oxidation current is proportional to the concentration of creatinine and creatine in the sample.

## BUN

The urea sensor consists of immobilized urease enzyme on a PVC-based ion selective electrode, consisting of an internal $\mathrm{Ag / AgCl}$ reference electrode and an internal electrolyte layer. The urease catalyzes the hydrolysis of urea to ammonium ion. It is detected by an ammonium-ion selective electrode. The sensor potential is measured against the card reference electrode $(\mathrm{Ag / Ag^{+}})$ and is proportional to logarithm of urea concentration.

$$
\mathrm{CO(NH_2)_2 + 2H_2O \xrightarrow{Urease} CO_2 + 2NH_4OH}
$$

## $tCO_2$

The sensor for $\mathrm{HCO_3^-}$ relies on a pH selective polymer as a gas permeable outer membrane and an internal bicarbonate buffer. The generated potential against the reference electrode is related to the logarithm of bicarbonate in the sample, as described per the following formula:

$$
\mathrm{tCO_2 = HCO_3^- (m) + 0.03 * pCO_2}
$$

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

### 1. Analytical performance:

#### a. Precision/Reproducibility:

Precision studies were conducted following the CLSI EP05-A3 guideline.

#### Internal Precision Study – Whole Blood

An internal precision study was performed by testing samples of whole blood for creatinine, blood urea nitrogen, and total carbon dioxide. Samples were analyzed by 2 operators using 3 different GEM Premier ChemSTAT analyzers over 5 days. A single run evaluating 8 replicates of 5 predetermined quantities per analyte (n=120 per level of analyte) was completed per day. The results of the precision study are present in the table below:

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| Analyte | Level | Mean | Within run | | Between Instruments | | Within Lab (Total) | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | | SD | %CV | SD | %CV | SD | %CV |
| Creatinine (mg/dL) | 1 | 0.48 | 0.014 | 2.9 | 0.010 | 2.1 | 0.017 | 3.6 |
| | 2 | 1.53 | 0.016 | 1.0 | 0.028 | 1.8 | 0.032 | 2.1 |
| | 3 | 2.83 | 0.019 | 0.7 | 0.064 | 2.3 | 0.067 | 2.4 |
| | 4 | 5.67 | 0.028 | 0.5 | 0.118 | 2.1 | 0.121 | 2.1 |
| | 5 | 9.36 | 0.056 | 0.6 | 0.228 | 2.4 | 0.235 | 2.5 |
| Blood Urea Nitrogen (mg/dL) | 1 | 6.5 | 0.06 | 1.0 | 0.04 | 0.6 | 0.08 | 1.1 |
| | 2 | 25.7 | 0.24 | 0.9 | 0.12 | 0.5 | 0.27 | 1.1 |
| | 3 | 50.0 | 0.88 | 1.8 | 0.00 | 0.0 | 0.88 | 1.8 |
| | 4 | 81.9 | 1.37 | 1.7 | 0.00 | 0.0 | 1.37 | 1.7 |
| | 5 | 102.4 | 1.44 | 1.4 | 0.63 | 0.6 | 1.57 | 1.5 |
| tCO₂ (mmol/L) | 1 | 8.0 | 0.11 | 1.3 | 0.06 | 0.7 | 0.12 | 1.5 |
| | 2 | 14.8 | 0.22 | 1.5 | 0.00 | 0.0 | 0.22 | 1.5 |
| | 3 | 21.2 | 0.23 | 1.1 | 0.20 | 0.9 | 0.30 | 1.4 |
| | 4 | 32.8 | 0.23 | 0.7 | 0.49 | 1.5 | 0.54 | 1.7 |
| | 5 | 43.5 | 0.30 | 0.7 | 0.83 | 1.9 | 0.88 | 2.0 |

External Reproducibility Study with Aqueous Controls – Point-of-Care Setting

A reproducibility study was performed at 3 external clinical point-of-care (POC) sites by 9 different operators using a single lot of cartridges on 6 different analyzers. Each site used the same lots of aqueous control materials. Each aqueous control level was run in triplicate twice a day for 5 days, for a total of 30 replicates per level (N= 3 sites x 5 days x 2 runs x 3 replicates = 90 per analyte/ per control level). Individual POC site statistics were analyzed by two-way nested ANOVA with factors day and run nested within day. Multisite statistics were determined via three-way nested ANOVA with the factors being site, day and nested within site and run nested within site and day. The pooled results of the study are present in the tables below:

| Creatinine (mg/dL) | | | | | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Control | Mean | Repeatability | | Between Run | | Between Day | | Within Site | | Reproducibility | |
| | | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| CVP 1 | 0.96 | 0.016 | 1.6 | 0.025 | 2.7 | 0.020 | 2.1 | 0.054 | 5.7 | 0.065 | 6.8 |
| CVP 2 | 5.17 | 0.105 | 2.0 | 0.116 | 2.2 | 0.000 | 0.0 | 0.048 | 0.9 | 0.164 | 3.2 |
| CVP 3 | 0.98 | 0.015 | 1.6 | 0.023 | 2.3 | 0.000 | 0.0 | 0.014 | 1.4 | 0.031 | 3.1 |
| CVP 4 | 0.62 | 0.011 | 1.8 | 0.32 | 5.2 | 0.000 | 0.0 | 0.052 | 8.4 | 0.063 | 10.1 |
| PVP 1 | 0.46 | 0.011 | 2.3 | 0.011 | 2.3 | 0.010 | 2.1 | 0.037 | 7.9 | 0.041 | 8.8 |
| PVP 2 | 1.03 | 0.017 | 1.7 | 0.015 | 1.5 | 0.029 | 2.8 | 0.068 | 6.6 | 0.077 | 7.5 |
| PVP 3 | 3.02 | 0.036 | 1.2 | 0.041 | 1.4 | 0.000 | 0.0 | 0.102 | 3.4 | 0.116 | 3.8 |
| PVP 4 | 5.37 | 0.093 | 1.7 | 0.054 | 1.0 | 0.000 | 0.0 | 0.073 | 1.4 | 0.13 | 2.4 |
| PVP 5 | 8.31 | 0.083 | 1.0 | 0.094 | 1.1 | 0.039 | 0.5 | 0.045 | 0.5 | 0.139 | 1.7 |

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| BUN (mg/dL) | | | | | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Control | Mean | Repeatability | | Between Run | | Between Day | | Within Site | | Reproducibility | |
| | | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| CVP 1 | 15.5 | 0.26 | 1.7 | 0.14 | 0.9 | 0.00 | 0.0 | 0.08 | 0.5 | 0.31 | 2.0 |
| CVP 2 | 57.2 | 0.44 | 0.8 | 0.18 | 0.3 | 1.14 | 2.0 | 1.31 | 2.3 | 1.80 | 3.1 |
| PVP 1 | 5.7 | 0.10 | 1.9 | 0.00 | 0.0 | 0.01 | 0.1 | 0.08 | 1.5 | 0.13 | 2.4 |
| PVP 2 | 15.5 | 0.24 | 1.6 | 0.05 | 0.3 | 0.00 | 0.0 | 0.09 | 0.6 | 0.26 | 1.7 |
| PVP 3 | 38.2 | 0.33 | 0.9 | 0.19 | 0.5 | 0.67 | 1.8 | 0.68 | 1.8 | 1.03 | 2.7 |
| PVP 4 | 56.5 | 0.61 | 1.1 | 0.00 | 0.0 | 1.08 | 1.9 | 1.21 | 2.1 | 1.73 | 3.1 |
| PVP 5 | 96.2 | 1.26 | 1.3 | 0.00 | 0.0 | 1.78 | 1.9 | 1.93 | 2.0 | 2.91 | 3.0 |
| tCO2 (mmol/L) | | | | | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Control | Mean | Repeatability | | Between Run | | Between Day | | Within Site | | Reproducibility | |
| | | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| CVP 1 | 25.4 | 0.15 | 0.6 | 0.10 | 0.4 | 0.25 | 1.0 | 0.55 | 2.2 | 0.63 | 2.5 |
| CVP 2 | 13.0 | 0.13 | 1.0 | 0.00 | 0.0 | 0.21 | 1.6 | 0.53 | 4.0 | 0.58 | 4.5 |
| PVP 1 | 41.1 | 0.42 | 1.0 | 0.00 | 0.0 | 0.50 | 1.2 | 1.05 | 2.6 | 1.23 | 3.0 |
| PVP 2 | 25.7 | 0.25 | 1.0 | 0.00 | 0.0 | 0.14 | 0.5 | 0.52 | 2.0 | 0.60 | 2.3 |
| PVP 3 | 18.7 | 0.18 | 1.0 | 0.00 | 0.0 | 0.04 | 0.2 | 0.08 | 0.4 | 0.20 | 1.1 |
| PVP 4 | 13.0 | 0.12 | 0.9 | 0.00 | 0.0 | 0.18 | 1.4 | 0.53 | 4.1 | 0.57 | 4.4 |
| PVP 5 | 8.0 | 0.10 | 1.2 | 0.00 | 0.0 | 0.15 | 1.9 | 0.40 | 5.0 | 0.44 | 5.5 |

## External Precision - Whole Blood

A precision study was performed at 3 external clinical POC sites by 6 different operators using a single lot of cartridges on 3 different analyzers. Reproducibility was not assessed for whole blood samples as the whole blood samples at each clinical site are unique.

| Analyte | Site | N | | Mean | | Within Sample Precision | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | SD | %CV | SD | %CV | SD | %CV |
| Creatinine (mg/dL) | 1 | 33 | 36 | 0.91 | 3.50 | 0.011 | 1.4 |
| | 2 | 60 | 6 | 0.88 | 5.13 | 0.014 | 1.4 |
| | 3 | 54 | 12 | 0.72 | 3.52 | 0.013 | 0.6 |
| | Pooled | 147 | 54 | 0.83 | 3.69 | 0.013 | 1.2 |
| BUN (mg/dL) | 1 | 36 | 33 | 15.2 | 45.6 | 0.18 | 2.8 |
| | 2 | 54 | 12 | 12.4 | 36.4 | 0.18 | 0.7 |
| | 3 | 42 | 21 | 11.8 | 52.1 | 0.12 | 0.9 |
| | Pooled | 132 | 66 | 13.0 | 46.0 | 0.16 | 1.9 |
| tCO2 (mmol/L) | 1 | 33 | 39 | 14.8 | 24.6 | 0.11 | 1.1 |
| | 2 | 30 | 36 | 17.4 | 22.9 | 0.12 | 0.9 |
| | 3 | 18 | 45 | 15.4 | 23.2 | 0.12 | 0.5 |
| | Pooled | 81 | 120 | 15.9 | 23.6 | 0.12 | 0.9 |

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# b. Linearity/assay reportable range:

A linearity study was performed following the CLSI EP06-A guideline. 9 levels per analyte were prepared by spiking or diluting whole blood from healthy volunteers to challenge the claimed measurement range for each analyte. At least 2 levels exceeded the claimed measurement range at the low and high ends. Each blood level was analyzed in triplicate on 6 different analyzers using cartridges from 3 different production lots (N=18 per level). The observed values were plotted against the expected values and linear regression analysis was performed. The results from a representative lot for each analyte are present below. The results of the linear regression analysis support the following claimed measuring ranges for the creatinine, BUN, and tCO $_2$ assays:

| Analyte | Claimed Measuring Range | Tested Range | Slope | Intercept | R² |
| --- | --- | --- | --- | --- | --- |
| Creatinine (mg/dL) | 0.20-15 | 0.10-16.40 | 0.986 | -0.039 | 0.9963 |
| BUN (mg/dL) | 3.0-112 | 2.4-122.0 | 1.016 | -0.323 | 0.9997 |
| tCO₂ (mmol/L) | 5-50 | 3.6-51.3 | 1.015 | -1.346 | 0.9997 |

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

# Traceability

The traceability of the parameters measured by GEM Premier ChemSTAT are listed below:

Creatinine: Traceable to NIST Standard 967a

BUN: Traceable to NIST SRM 912

$\mathrm{tCO_2}$ : Per CLSI guideline C46-A2, calculated from pH and pCO2 concentrations of aqueous secondary standard.

# d. Detection limit:

The limit of blank (LoB), limit of detection (LoD), and limit of quantitation (LoQ) were determined according to CLSI EP17-A2 guideline.

For LoB studies, 60 blank samples per cartridge lot were tested on 3 days with 3 different cartridge lots (N=60/analyte/lot). After recording 60 blank sample measurements, the results were ranked from lowest to highest. The LoB was determined as the maximal LoB value for each of the three cartridge lots per analyte.

The LoD was determined using a "low" sample with a target analyte concentration 1-5x greater than the estimated LoB.

$$
\mathrm{LoD} = \mathrm{LoB} + \frac{1.645}{1 - \left(\frac{1}{4(L - \bar{P})}\right)} * \mathrm{SD_L}
$$

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# Where:

$\mathrm{L} =$ total number of all low level sample results across all cartridge lots $\mathrm{J} =$ number of low level samples (number of days)

The LoQ was assessed by testing low-level whole blood samples. 60 replicates of the low-level samples were measured per day by 3 analyzers (N=60/analyte/day). LoQ was defined as the lowest concentration that met the total error goal of $0.3\mathrm{mg / dL}$ or $15\%$ for creatinine, $2.0\mathrm{mg / dL}$ or $9\%$ for BUN and $2.0\mathrm{mmol / L}$ or $10\%$ for tCO2.

The overall results of LoB, LoD, and LoQ are summarized below:

| Analyte | LoB | LoD | LoQ | Claimed Measuring Range |
| --- | --- | --- | --- | --- |
| Creatinine (mg/dL) | 0.04 | 0.07 | 0.10 | 0.20-15 |
| BUN (mg/dL) | 0.3 | 0.3 | 1.2 | 3.0-112 |
| tCO2(mmol/L) | 0.0 | 0.2 | 2.0 | 5-50 |

# e. Analytical specificity:

To determine the effects of potential endogenous and exogenous interference, the sponsor conducted an analytical specificity study according to the CLSI EP07 guideline. Testing was conducted using whole blood samples at two different analyte concentrations. Substances were considered not interfering if the difference between the test and control samples was less than or equal to the following clinically significant interference limits set for each analyte:

| Analyte | Clinically significant interference |
| --- | --- |
| Creatinine (mg/dL) | ≤0.20 mg/dL |
| BUN (mg/dL) | ≤±10% |
| tCO2(mmol/L) | ≤±10% |

Substances identified as interfering substances were further characterized to determine the concentration that produces a clinically significant interference.

# Summary of interference studies for creatinine:

The interferences tested and found to be clinically non-significant are summarized below:

| Substance tested | Highest concentration tested showing no significant interference |
| --- | --- |
| Acetaminophen | 1,030 μmol/L |
| Acetoacetate | 2 mmol/L |
| L-Ascorbic acid | 298 μmol/L |
| Atracurium | 50 mg/L |
| Bilirubin | 40 mg/dL |
| Ceftriaxone | 1,510 μmol/L |
| Chlorpromazine | 10.3 μmol/L |

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| Substance tested | Highest concentration tested showing no significant interference |
| --- | --- |
| Diatrizoate sodium | 301 μmol/L |
| Dobutamine | 0.121 mg/dL |
| Dopamine | 4.06 μmol/L |
| Epinephrine | 0.5 μmol/L |
| Ethanol | 130 mmol/L |
| Ethylene Glycol | 8.8 mmol/L |
| Etomidate | 50 mg/L |
| Fentanyl | 0.03 μg/mL |
| Furosemide | 48.1 μmol/L |
| Gadodiamide | 1.4 mmol/L |
| Glycolic acid | 1.0 mmol/L |
| Hct | 25% |
| Hct | 60% |
| Hemoglobin | 1,000 mg/dL |
| Heparin | 100,000 U/L |
| β-Hydroxybutyrate | 2 mmol/L |
| Ibuprofen | 1,060 μmol/L |
| Icodextrin | 20 mg/dL |
| Isoniazid | 438 μmol/L |
| Methadone | 10.3 μmol/L |
| Midazolam | 0.376 mg/mL |
| Morphine | 27.3 μmol/L |
| N-Acetyl-L-cysteine | 920 μmol/L |
| Phenobarbital | 2,970 μmol/L |
| Piperacillin | 110 mg/mL |
| pO2 | 30 mmHg |
| Pralidoxime Iodide | 4 mg/mL |
| Propofol | 4.8 mg/mL |
| Suxamethonium | 68 μmol/L |
| Tazobactam | 3.05 mg/mL |
| Thiocyanate | 898 μmol/L |
| Intralipid | 2,000 mg/dL |
| Uric acid | 1.4 mmol/L |
| Vancomycin | 82.8 μmol/L |

Clinically significant interfering substances for creatinine measurements are itemized below:

- Creatinine concentrations are increased by 0.20 mg/L when 0.77 mg/dL hydroxyurea is present in the sample.
- Creatinine concentrations are increased by 0.20 mg/dL when 0.382 mmol/L creatine is present in the sample.

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# Summary of interference studies for BUN

The interferences tested and found to be clinically non-significant are summarized below:

| Substance tested | Highest concentration tested showing no significant interference |
| --- | --- |
| Ammonium | 151 μmol/L |
| Atracurium | 50 mg/L |
| Benzalkonium | 5 mg/L |
| Bilirubin | 40 mg/dL |
| Ceftriaxone | 1,510 μmol/L |
| Diatrizoate sodium | 301 μmol/L |
| Epinephrine | 0.5 μmol/L |
| Etomidate | 50 mg/L |
| Fentanyl | 0.03 μg/mL |
| Furosemide | 48.1 μmol/L |
| Gadodiamide | 1.4 mmol/L |
| Hemoglobin | 1,000 mg/dL |
| Heparin | 100,000 U/L |
| Hydroxyurea | 3.08 mg/dL |
| Ibuprofen | 1,060 μmol/L |
| Leflunomide | 100 μg/mL |
| Methadone | 10.3 μmol/L |
| Midazolam | 0.376 mg/mL |
| Morphine | 27.3 μmol/L |
| N-Acetyl-L-cysteine | 920 μmol/L |
| Perchlorate | 20 mg/dL |
| Phenobarbital | 2,970 μmol/L |
| Piperacillin | 110 mg/mL |
| Propofol | 4.8 mg/mL |
| Salicylic acid | 0.207 mmol/L |
| Suxamethonium | 68 μmol/L |
| Tazobactam | 3.05 mg/mL |
| Teriflunomide | 100 μg/mL |
| Thiocyanate | 898 μmol/L |
| Thiopental | 1,660 μmol/L |
| Triglycerides | 2,000 mg/dL |
| Vancomycin | 82.8 μmol/L |

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Summary of interference studies for $\mathrm{tCO_2}$ :

The interferences tested and found to be clinically non-significant are summarized below:

| Substance tested | Highest concentration tested showing no significant interference |
| --- | --- |
| Atracurium | 50 mg/L |
| Bilirubin | 40 mg/dL |
| Ceftriaxone | 1,510 μmol/L |
| Epinephrine | 0.5 μmol/L |
| Etomidate | 50 mg/L |
| Fentanyl | 0.03 μg/mL |
| Furosemide | 48.1 μmol/L |
| Gadodiamide | 1.4 mmol/L |
| Hemoglobin | 1,000 mg/dL |
| Ibuprofen | 1,060 μmol/L |
| Methadone | 10.3 μmol/L |
| Midazolam | 0.376 mg/mL |
| Morphine | 27.3 μmol/L |
| N-Acetyl-L-cysteine | 920 μmol/L |
| Phenobarbital | 2,970 μmol/L |
| Piperacillin | 110 mg/mL |
| Propofol | 4.8 mg/mL |
| Suxamethonium | 68 μmol/L |
| Tazobactam | 3.05 mg/mL |
| Thiopental | 1,660 μmol/L |
| Triglycerides | 2,000 mg/dL |
| Vancomycin | 82.8 μmol/L |

f. Assay cut-off:

Not applicable.

2. Comparison studies:

a. Method comparison with predicate device:

Method comparison studies were performed at 3 external POC sites by 2 POC operators at each site. Lithium heparinized whole blood samples were tested in singlicate on a single GEM Premier ChemSTAT Analyzer. The same samples were then centrifuged, and the plasma portions were tested in singlicate on 2 Roche Cobas analyzers for creatinine, BUN, and $\mathrm{tCO_2}$ . The results for each sample measured by the Roche Cobas analyzers were averaged. Additional contrived samples ( $<10\%$ ) were prepared and tested when necessary to span the reportable range for each analyte.

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Regression Analysis Summary for GEM Premier ChemSTAT Analyzer vs. Roche Cobas Analyzer:

| Analyte | Sample Range | N | Slope | Intercept | R |
| --- | --- | --- | --- | --- | --- |
| Creatinine (mg/dL) | 0.20-14.18 | 405 | 1.009 | -0.027 | 0.997 |
| BUN (mg/dL) | 3.0-109.7 | 405 | 0.965 | 0.441 | 0.997 |
| tCO2 (mmol/L) | 5.5-47.2 | 416 | 0.979 | 0.535 | 0.986 |

b. Matrix comparison:

Not applicable. The creatinine, BUN and tCO2 assays are for use with lithium heparinized whole blood only.

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:

The following expected values are provided in the product inert for arterial blood (unless otherwise noted) based on the literature:

| Analyte | Reference Range |
| --- | --- |
| Creatinine | 0.04-0.33 (0-1 yr) mg/dL |
| | 0.04-0.45 (2-5 yr) mg/dL |
| | 0.20-0.52 (6-9 yr) mg/dL |
| | 0.22-0.59 (10 yr) mg/dL |
| | 0.62-1.10 (male adult) mg/dL |
| | 0.45-0.75 (female adult) mg/dL |

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| Analyte | Reference Range |
| --- | --- |
| BUN | 3-25 (1 wk) mg/dL
4-19 (< 1 yr) mg/dL
5-18 (infant/child) mg/dL
6-20 (18-60 yr) mg/dL
8-23 (60-90 yr) mg/dL
10-31 (> 90 yr) mg/dL |
| tCO_{2} | 19.0-24.0 mmol/L
22.0-26.0 (venous) mmol/L |

- Burtis, Carl and David Bruns, Tietz Textbook of Clinical Chemistry and Molecular Diagnostics, Elsevier Saunders, 7th Edition, 2015, pp 952-982.
- Wu, A., Tietz Clinical Guide to Laboratory Tests, W.B. Saunders Co., St. Louis MO, 4th Edition, 2006, page 316 and 1096.

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.