← Product Code [CGA](/submissions/CH/subpart-b%E2%80%94clinical-chemistry-test-systems/CGA) · K183546

# GEM Premier ChemSTAT (K183546)

_Instrumentation Laboratory CO · CGA · Feb 16, 2019 · Clinical Chemistry · SESE_

**Canonical URL:** https://fda.innolitics.com/submissions/CH/subpart-b%E2%80%94clinical-chemistry-test-systems/CGA/K183546

## Device Facts

- **Applicant:** Instrumentation Laboratory CO
- **Product Code:** [CGA](/submissions/CH/subpart-b%E2%80%94clinical-chemistry-test-systems/CGA.md)
- **Decision Date:** Feb 16, 2019
- **Decision:** SESE
- **Submission Type:** Traditional
- **Regulation:** 21 CFR 862.1345
- **Device Class:** Class 2
- **Review Panel:** Clinical Chemistry

## 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 Glucose (Glu), Lactate (Lac), Hematocrit (Hct), pH and partial pressure of carbon dioxide (pCO2) 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. - Glucose (Glu) measurement is used in the diagnosis, monitoring and treatment of carbohydrate metabolism disturbances including diabetes mellitus, neonatal hypoglycemia, idiopathic hypoglycemia, and of pancreatic islet cell carcinoma. - Lactate (Lac) measurement is used to evaluate the acid-base status of patients suspected of having lactic acidosis, to monitor tissue hypoxia and strenuous physical exertion, and in the diagnosis of hyperlactatemia. - Hematocrit (Hct) measurements in whole blood of the packed red cell volume of a blood sample are used to distinguish normal from abnormal states, such as anemia and erythrocytosis (an increase in the number of red cells). - pH and pCO2 measurements in whole blood are used in the diagnosis and treatment of life-threatening acid-base disturbances.

## Device Story

Portable critical care system; analyzes lithium heparinized whole blood (arterial/venous) at point-of-care or central lab. Input: whole blood sample via disposable GEM Premier ChemSTAT PAK (cartridge). Operation: cartridge contains sensors, process control solutions, sampler, and waste; analyzer uses internal logic/touchscreen to guide user. Principle: amperometry (Glu, Lac), conductivity (Hct), potentiometry (pH, pCO2). Output: quantitative measurements of Glu, Lac, Hct, pH, pCO2. iQM (Intelligent Quality Management) provides continuous monitoring, automatic error detection, correction, and documentation. Healthcare providers use output to diagnose/monitor acid-base status and metabolite balance; aids clinical decision-making for life-threatening disturbances.

## Clinical Evidence

Method comparison study (CLSI EP09c) compared GEM Premier ChemSTAT to GEM Premier 4000 using lithium heparinized whole blood patient samples. Pooled data from 3 POC sites and internal CSL (N=431-559 per analyte) showed high correlation (R=0.995-0.999) across reportable ranges. Precision studies (CLSI EP05-A3) and reproducibility studies (multi-site POC) confirmed performance within specifications. Bench testing included LoB/LoD/LoQ, linearity, and analytical specificity (interference testing).

## Technological Characteristics

Portable analyzer with touch-sensitive screen. Disposable multi-use PAK (cartridge) contains sensors, process control solutions, sampler, and waste. Measurement principles: Amperometry (Glu, Lac), Conductivity (Hct), Potentiometry (pH, pCO2). Calibration: 2-point. iQM (Intelligent Quality Management) system for continuous monitoring. Components traceable to NIST/CLSI standards. EEPROM chip in cartridge stores PC solution values.

## Regulatory Identification

A glucose test system is a device intended to measure glucose quantitatively in blood and other body fluids. Glucose measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus, neonatal hypoglycemia, and idiopathic hypoglycemia, and of pancreatic islet cell carcinoma.

## Special Controls

*Classification.* Class II (special controls). The device, when it is solely intended for use as a drink to test glucose tolerance, is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.

## Predicate Devices

- GEM Premier 4000 (k133407)

## Submission Summary (Full Text)

> This content was OCRed from public FDA records by [Innolitics](https://innolitics.com). If you use, quote, summarize, crawl, or train on this content, cite Innolitics at https://innolitics.com.
>
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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE

A. 510(k) Number:
k183546

B. Purpose for Submission:
New Device

C. Measurand:
Glucose, Lactate, Hematocrit, pH, pCO2

D. Type of Test:
Quantitative, potentiometry for pH, and pCO2
Quantitative, amperometry for glucose and lactate
Quantitative, electrical conductivity for hematocrit

E. Applicant:
Instrumentation Laboratory Co.

F. Proprietary and Established Names:
GEM Premier ChemSTAT

G. Regulatory Information:

|  Product Code | Classification | Regulation Section | Panel  |
| --- | --- | --- | --- |
|  CGA | Class II | 862.1345 Glucose Test system | Chemistry (75)  |
|  KHP | Class I | 862.1450 Lactic acid test system | Chemistry (75)  |
|  GKF | Class II | 864.5660 Automated hematocrit instrument | Hematology (81)  |
|  CHL | Class II | 862.1120 Blood Gases (pCO2) and Blood pH system | Chemistry (75)  |

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H. Intended Use:

1. Intended use(s):

See indications for use.

2. Indication(s) 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 Glucose (Glu), Lactate (Lac), Hematocrit (Hct), pH and partial pressure of carbon dioxide (pCO2) 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.

- Glucose (Glu) measurement is used in the diagnosis, monitoring and treatment of carbohydrate metabolism disturbances including diabetes mellitus, neonatal hypoglycemia, idiopathic hypoglycemia, and of pancreatic islet cell carcinoma.
- Lactate (Lac) measurement is used to evaluate the acid-base status of patients suspected of having lactic acidosis, to monitor tissue hypoxia and strenuous physical exertion, and in the diagnosis of hyperlactatemia.
- Hematocrit (Hct) measurements in whole blood of the packed red cell volume of a blood sample are used to distinguish normal from abnormal states, such as anemia and erythrocytosis (an increase in the number of red cells).
- pH and pCO2 measurements in whole blood are used in the diagnosis and treatment of life-threatening acid-base disturbances.

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 GEM Premier ChemSTAT system contains 2 key components: GEM Premier ChemSTAT analyzer and a disposable, multiuse GEM Premier ChemSTAT PAK Cartridge/PAK (GEM PAK).

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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.

J. Substantial Equivalence Information:

1. Predicate device name(s):

GEM Premier 4000

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

k133407

3. Comparison with predicate:

|  Similarities  |   |   |
| --- | --- | --- |
|  Item | Candidate Device
GEM Premier ChemSTAT
(k183546) | Predicate Device
GEM Premier 4000
(k133407)  |
|  Intended Use | Quantitative measurement of glucose, lactate, hematocrit, pH and pCO_{2} in arterial and venous heparinized whole blood. | Same  |
|  Intended User | Central Laboratory and Point-of-Care professionals. | Same  |
|  Measurement Principle | Amperometry (Glucose and Lactate)
Potentiometry (pH and pCO_{2})
Conductivity (Hematocrit) | Same  |
|  Measuring Range Glucose | 4-685 mg/dL | Same  |
|  Measuring Range lactate | 0.3 -17.0 mmol/L | Same  |
|  Measuring Range pH | 7 -8.00 | Same  |
|  Measuring Range Hematocrit | 15 – 72% | Same  |
|  Measuring Range pCO_{2} | 6 -125 mmHg | Same  |
|  Calibration | 2-point calibration | Same  |

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|  Differences  |   |   |
| --- | --- | --- |
|  Item | Candidate Device
GEM Premier ChemSTAT
(k183546) | Predicate Device
GEM Premier 4000
(k133407)  |
|  Sample Volume | 65 to 150 μL | 150 μL  |
|  Sample Type | Lithium heparinized whole blood (arterial and venous) | Lithium heparinized whole blood (arterial, venous and capillary)  |

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

- CLSI EP05-A3. Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline, 3rd Edition.
- CLSI EP06-A. Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline.
- CLSI EP07. Interference Testing in Clinical Chemistry; Approved Guideline, 3rd Edition.
- CLSI EP17-A2. Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline, 2nd Edition.
- CLSI EP25-A. Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline.
- CLSI EP37 Supplemental Tables for Interference Testing in Clinical Chemistry, 1st Edition.

## L. Test Principle:

### Glucose and Lactate

The Glucose and Lactate sensors are amperometric biosensors consisting of a platinum electrode operated at a positive potential with respect to the card reference electrode. Glu or Lac determination is accomplished by enzymatic reaction of Glu or Lac with oxygen in the presence of glucose oxidase or lactate oxidase and the electrochemical oxidation of the resulting hydrogen peroxide (H₂O₂) at the platinum electrode. The current flow between the platinum electrode and the ground electrode is proportional to the rate at which H₂O₂ molecules diffuse to the platinum and are oxidized, which in turn is directly proportional to the metabolite (Glu or Lac) concentration.

### Hematocrit

Hct 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.

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pH

The pH 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 potential can be described by this simplified form of the Nernst equation  $\mathrm{E} = \mathrm{E}' + (\mathrm{S} \times \log \mathrm{C})$ , where  $\mathrm{E}$  is the electrode potential,  $\mathrm{E}'$  is the standard potential for that membrane,  $\mathrm{S}$  is the sensitivity (slope), and  $\mathrm{C}$  is the ion activity.  $\mathrm{E}'$  and  $\mathrm{S}$  can be determined by the sensor response to the Process Control (PC) Solutions, and the equation can be solved for the activity of the ion of interest.

pCO2

The pCO2 sensor is a patented design that relies on generated potential of the bicarbonate sensor versus the pH sensor. The potential difference between the two sensors is related to the logarithm of pCO2 content in the sample.

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

# 1. Analytical performance:

# a. Precision/Reproducibility:

i. Internal Precision Study - Whole Blood

An internal precision study was performed at an internal site using 5 whole blood samples with different concentrations of analytes for Glucose, Lactate, pH,  $\mathrm{pCO_2}$ , and Hematocrit. Testing was performed on 3 different GEM Premier ChemSTAT analyzers with 3 cartridges for 5 days, with 1 run per day and 8 replicates measured per run per level for a total of 120 data sets per sample.

The results are summarized in the table below:

|  Analyte | Level | Mean | Within Run |   | Between Analyzer |   | Total Imprecision  |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
|   |   |   |  SD | %CV | SD | %CV | SD | %CV  |
|  Glucose (mg/dL) | 1 | 24 | 0.5 | 2.3 | 0.0 | 0.0 | 0.5 | 2.3  |
|   |  2 | 48 | 0.9 | 1.9 | 0.3 | 0.7 | 0.9 | 2.0  |
|   |  3 | 122 | 1.3 | 1.1 | 1.0 | 0.8 | 1.7 | 1.4  |
|   |  4 | 356 | 2.7 | 0.8 | 1.6 | 0.4 | 3.2 | 0.9  |
|   |  5 | 620 | 3.2 | 0.5 | 4.3 | 0.7 | 5.4 | 0.9  |
|  Lactate (mmol/L) | 1 | 0.7 | 0.06 | 8.9 | 0.00 | 0.0 | 0.06 | 8.9  |
|   |  2 | 2.0 | 0.06 | 2.8 | 0.04 | 1.9 | 0.07 | 3.3  |
|   |  3 | 4.9 | 0.05 | 1.1 | 0.10 | 2.1 | 0.11 | 2.3  |
|   |  4 | 7.8 | 0.13 | 1.7 | 0.13 | 1.6 | 0.18 | 2.3  |
|   |  5 | 14.2 | 0.23 | 1.6 | 0.25 | 1.8 | 0.34 | 2.4  |
|  Hct (%) | 1 | 18 | 0.3 | 1.6 | 0.1 | 0.8 | 0.3 | 1.8  |
|   |  2 | 33 | 0.3 | 0.9 | 0.2 | 0.7 | 0.4 | 1.1  |
|   |  3 | 44 | 0.3 | 0.7 | 0.2 | 0.5 | 0.4 | 0.9  |
|   |  4 | 57 | 0.3 | 0.5 | 0.2 | 0.4 | 0.4 | 0.7  |
|   |  5 | 65 | 0.4 | 0.7 | 0.3 | 0.5 | 0.5 | 0.8  |

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|  Analyte | Level | Mean | Within Run |   | Between Analyzer |   | Total Imprecision  |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
|   |   |   |  SD | %CV | SD | %CV | SD | %CV  |
|  pH | 1 | 7.07 | 0.008 | 0.1 | 0.000 | 0.0 | 0.008 | 0.1  |
|   |  2 | 7.25 | 0.007 | 0.1 | 0.000 | 0.0 | 0.007 | 0.1  |
|   |  3 | 7.34 | 0.008 | 0.1 | 0.002 | 0.0 | 0.008 | 0.1  |
|   |  4 | 7.49 | 0.009 | 0.1 | 0.003 | 0.0 | 0.010 | 0.1  |
|   |  5 | 7.69 | 0.010 | 0.1 | 0.008 | 0.1 | 0.013 | 0.2  |
|  pCO2(mmHg) | 1 | 110 | 1.4 | 1.3 | 0.0 | 0.0 | 1.4 | 1.3  |
|   |  2 | 71 | 0.9 | 1.2 | 0.0 | 0.0 | 0.9 | 1.2  |
|   |  3 | 51 | 0.7 | 1.4 | 0.0 | 0.0 | 0.7 | 1.4  |
|   |  4 | 29 | 0.4 | 1.5 | 0.1 | 0.2 | 0.5 | 1.6  |
|   |  5 | 12 | 0.6 | 4.8 | 0.0 | 0.0 | 0.6 | 4.8  |

ii. External Reproducibility Study with Aqueous Controls -Point-of-Care Setting:

An external reproducibility study was performed in 3 clinical point of care sites using aqueous control solutions. Testing was performed by 9 different operators on six different GEM Premier ChemSTAT analyzers, using a single lot of GEM Premier CHEMSTAT PAK's cartridges. Each site tested quality control materials for each analyte with two levels of GEM ChemSTAT CVP and 4 to 5 levels of GEM ChemSTAT PVP. Each control was tested in triplicate, twice a day for five days for a total of 30 replicates per level with  $n = 90$  data sets across all three sites 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 results are summarized in the table below for all 3 sites POC sites.

|  Glucose (mg/dL)  |   |   |   |   |   |   |   |   |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  Control Level | Mean | Repeatability |   | Between Day |   | Between Site |   | Reproducibility  |   |
|   |   |  SD | %CV | SD | %CV | SD | %CV | SD | %CV  |
|  CVP 1 | 392 | 1.0 | 0.2 | 0.7 | 0.2 | 4.3 | 1,1 | 5.9 | 1.5  |
|  CVP 2 | 78 | 1.5 | 1.9 | 0.6 | 0.8 | 0.0 | 0.0 | 1.6 | 2.1  |
|  PVP 1 | 642 | 1.3 | 0.2 | 1.1 | 0.2 | 6.5 | 1.0 | 6.8 | 1.1  |
|  PVP 2 | 393 | 1.6 | 0.4 | 1.3 | 0.3 | 3.3 | 0.8 | 4.2 | 1.1  |
|  PVP 3 | 115 | 1.4 | 1.2 | 0.0 | 0.0 | 0.0 | 0.0 | 1.5 | 1.3  |
|  PVP 4 | 80 | 0.6 | 0.7 | 0.5 | 0.6 | 0.3 | 0.3 | 0.9 | 1.1  |
|  PVP 5 | 14 | 0.5 | 3.6 | 0.2 | 1.6 | 1.4 | 9.7 | 1.5 | 10.5  |

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|  Lactate (mmol/L)  |   |   |   |   |   |   |   |   |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  Control Level | Mean | Repeatability |   | Between Day |   | Between Site |   | Reproducibility  |   |
|  CVP 1 | 8.2 | 0.04 | 0.5 | 0.02 | 0.3 | 0.03 | 0.3 | 0.07 | 0.8  |
|  CVP 2 | 1.7 | 0.03 | 1.8 | 0.01 | 0.7 | 0.04 | 2.4 | 0.05 | 3.1  |
|  PVP 1 | 15.7 | 0.07 | 0.4 | 0.07 | 0.5 | 0.09 | 0.6 | 0.15 | 0.9  |
|  PVP 2 | 8.1 | 0.06 | 0.7 | 0.04 | 0.4 | 0.07 | 0.9 | 0.11 | 1.3  |
|  PVP 3 | 5.0 | 0.03 | 0.6 | 0.04 | 0.8 | 0.03 | 0.6 | 0.6 | 1.2  |
|  PVP 4 | 1.7 | 0.03 | 1.5 | 0.01 | 0.6 | 0.01 | 0.9 | 0.03 | 1.9  |
|  PVP 5 | 0.5 | 0.02 | 4.1 | 0.03 | 5.1 | 0.03 | 5.6 | 0.04 | 8.6  |
|  Hematocrit (%)  |   |   |   |   |   |   |   |   |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  Control Level | Mean | Repeatability |   | Between Day |   | Between Site |   | Reproducibility  |   |
|  CVP 1 | 42 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0  |
|  CVP 2 | 22 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0  |
|  PVP 1 | 18 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0  |
|  PVP 2 | 23 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0  |
|  PVP 3 | 43 | 0.1 | 0.1 | 0.0 | 0.0 | 0.0 | 0.0 | 0.1 | 0.2  |
|  PVP 4 | 68 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0  |
|  pH  |   |   |   |   |   |   |   |   |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  Control Level | Mean | Repeatability |   | Between Day |   | Between Site |   | Reproducibility  |   |
|  CVP 1 | 7.11 | 0.005 | 0.1 | 0.002 | 0.0 | 0.000 | 0.0 | 0.006 | 0.1  |
|  CVP 2 | 7.54 | 0.003 | 0.0 | 0.001 | 0.0 | 0.001 | 0.0 | 0.003 | 0.0  |
|  PVP 1 | 7.59 | 0.004 | 0.1 | 0.002 | 0.0 | 0.002 | 0.0 | 0.005 | 0.1  |
|  PVP 2 | 7.11 | 0.007 | 0.1 | 0.003 | 0.0 | 0.000 | 0.0 | 0.008 | 0.1  |
|  PVP 3 | 7.36 | 0.003 | 0.0 | 0.000 | 0.0 | 0.001 | 0.0 | 0.005 | 0.1  |
|  PVP 4 | 7.55 | 0.004 | 0.1 | 0.002 | 0.0 | 0.002 | 0.0 | 0.005 | 0.1  |
|  pCO2 (mmHg)  |   |   |   |   |   |   |   |   |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  Control Level | Mean | Repeatability |   | Between Day |   | Between Site |   | Reproducibility  |   |
|  CVP 1 | 92 | 1.2 | 1.4 | 0.0 | 0.0 | 0.2 | 0.2 | 2.0 | 2.2  |
|  CVP 2 | 16 | 0.3 | 2.0 | 0.1 | 0.6 | 0.3 | 0.3 | 0.4 | 2.8  |
|  PVP 1 | 60 | 1.1 | 1.9 | 0.2 | 0.3 | 0.5 | 0.5 | 1.3 | 2.1  |
|  PVP 2 | 92 | 2.1 | 2.3 | 0.8 | 0.9 | 0.8 | 0.8 | 2.5 | 2.7  |
|  PVP 3 | 38 | 0.6 | 1.6 | 0.0 | 0.0 | 0.3 | 0.3 | 0.7 | 1.9  |
|  PVP 4 | 16 | 0.4 | 2.4 | 0.1 | 0.5 | 0.2 | 0.2 | 0.4 | 2.8  |

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# iii. External Precision - Whole Blood

A precision study was performed at 3 external clinical point-of care (POC) sites, using 5 whole blood patient samples for over 5 days, by 6 different operators on 3 GEM Premier ChemSTAT instruments (one analyzer per site), using a single lot of GEM Premier ChemSTAT PAKs (cartridges). Reproducibility was not assessed for whole blood samples because samples at each clinical site are unique. Each whole blood patient sample was run in triplicate on a single GEM Premier ChemSTAT instrument.

The results are summarized in the table below:

|  Analyte | Site | N | Mean | Within Sample SD or CV%  |
| --- | --- | --- | --- | --- |
|  Glucose (mg/dL) | POC1 | 12 | 38 | 1.7  |
|   |  POC2 | 3 | 23 | 0.6  |
|   |  POC3 | 15 | 49 | 1.7  |
|   |  Pooled | 30 | 42 | 1.6  |
|   |  POC1 | 54 | 122 | 1.0%  |
|   |  POC2 | 63 | 112 | 0.8%  |
|   |  POC3 | 51 | 115 | 1.0%  |
|   |  Pooled | 168 | 116 | 0.9%  |
|  Lactate (mmol/L) | POC1 | 9 | 1.9 | 0.07  |
|   |  POC2 | 27 | 1.8 | 0.08  |
|   |  POC3 | 9 | 2.2 | 0.07  |
|   |  Pooled | 45 | 1.9 | 0.08  |
|   |  POC1 | 57 | 5.7 | 1.7%  |
|   |  POC2 | 39 | 3.7 | 2.5%  |
|   |  POC3 | 54 | 3.8 | 1.8%  |
|   |  Pooled | 150 | 4.5 | 1.9%  |
|  Hematocrit (%) | POC1 | 69 | 32 | 0.5  |
|   |  POC2 | 66 | 40 | 0.4  |
|   |  POC3 | 63 | 31 | 0.6  |
|   |  Pooled | 198 | 35 | 0.5  |
|  pH | POC1 | 63 | 7.26 | 0.008  |
|   |  POC2 | 66 | 7.36 | 0.009  |
|   |  POC3 | 66 | 7.31 | 0.007  |
|   |  Pooled | 195 | 7.31 | 0.008  |
|  pCO2 (mmHg) | POC1 | 54 | 49 | 1.2  |
|   |  POC2 | 60 | 40 | 0.7  |
|   |  POC3 | 60 | 50 | 0.9  |
|   |  Pooled | 174 | 46 | 0.9  |
|   |  POC1 | 18 | 74 | 1.4%  |
|   |  POC2 | 6 | 66 | 1.6%  |
|   |  POC3 | 3 | 78 | 1.5%  |
|   |  Pooled | 27 | 73 | 1.5%  |

{8}

# b. Linearity/assay reportable range:

A linearity study was performed following CLSI EP06-A guidelines. Nine to ten levels per analyte were prepared by tonometry, spiking or diluting whole blood samples to challenge the claimed measuring ranges. Each level was analyzed in triplicate on six GEM Premier ChemSTAT analyzers, with three different cartridges for all analytes except for pH and pCO2 which were tested on three GEM Premier ChemSTAT analyzers and results compared to reference analyzers.

The results are summarized in the table below:

|  Analyte | Linear regression Equation | R2 | Sample range tested | Claimed Measuring Range  |
| --- | --- | --- | --- | --- |
|  Glucose | y = 1.023x - 0.502 | 1.00 | 3-749 mg/dL | 4-685 mg/dL  |
|  Lactate | y = 1.004x + 0.000 | 0.9998 | 0.2-17.8 mmol/L | 0.3-17.0 mmol/L  |
|  Hct | y = 0.984x + 1.909 | 0.9975 | 13-74 % | 15-72%  |
|  pH | y = 1.006x - 0.042 | 0.9996 | 6.76-8.10 | 7.00-8.00  |
|  pCO2 | y = 1.030x - 0.843 | 0.9994 | 2-137 mmHg | 6-125 mmHg  |

The results of the linearity study support the claimed measuring range as described in the table above.

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

Traceability:

Glucose is traceable by automated spectrophotometry using hexokinase method per CDC no. 77-8660 using secondary standard prepared from NIST #917.

Lactate traceability is established by automated spectrophotometry using lactate oxidase with secondary standard prepared from USP #1614308.

$\mathrm{pCO}_2$  traceability is established through tonometry at  $37^{\circ}\mathrm{C}$  using NIST traceable gas mixtures.

pH traceability is established through a direct potentiometry method which uses secondary standards prepared from NIST SRM 186I & 186II phosphate salts.

Hematocrit traceability is established by centrifugation using whole blood per CLSI H7-A3 for establishing true correlation. Maintained from lot to lot by controlling conductivity through controlling sodium level.

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# d. Detection limit:

The limit of blank (LoB), limit of detection (LoD) and limit of quantitation (LoQ) were evaluated in accordance to CLSI EP17-A2 guideline, for Glu, Lac, Hct, pH, and  $p\mathrm{CO}_2$ .

The LoB was assessed by testing blank samples 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. LoB was independently calculated for each lot using the non-parametric method.

The LoD was determined by testing low-level samples over three days using three cartridge lots on three analyzers. The LoB used for LoD calculation is the maximum value across the three cartridge lots. The is calculated using the formula:

$$
\mathrm {L o D} = \mathrm {L o B} + \frac {1 . 6 4 5}{1 - \left(\frac {1}{4 (L - \bar {J})}\right)} * \mathrm {S D} _ {\mathrm {L}}
$$

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. Sixty replicates of the low-level samples were measured per day on 3 analyzers (N=60/analyte/day) using 3 reagent lots. The LoQ is defined as the lowest concentration at which measured total error is less than the pre-defined total error of  $\pm 6\mathrm{mg / dL}$  for glucose,  $\pm 0.4\mathrm{mmol / L}$  for lactate,  $\pm 4\%$  for hematocrit and  $\pm 5\mathrm{mmHg}$  for  $\mathrm{pCO_2}$ . Total error (TE) for low level sample was calculated using the following formula:

$\mathrm{TE} = \left| \left( \text{meanGEM Premier ChemSTAT} - \text{meanPredicate Device} \right) \right| + 1.96 * \mathrm{SDLowLevel}$

The results are summarized in the table below

|  Analyte | LoB | LoD | LoQ | Claimed Measuring Range  |
| --- | --- | --- | --- | --- |
|  Glucose mg/dL | 0 | 1 | 1 | 4-685 mg/dL  |
|  Lactate(mmol/L) | 0.0 | 0.0 | 0.1 | 0.3-17.0 mmol/L  |
|  Hematocrit (%) | 2 | 3 | 10 | 15-72%  |
|  pCO2(mmHg) | 1 | 3 | 3 | 6-125 mmHg  |

Linearity studies were used to support the lower end of the measuring range for pH (see section M.1.b above).

# e. Analytical specificity:

An interference study was performed based on CLSI EP17-A guideline. The interference 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:

{10}

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

The results are summarized in the table below for substances that showed non-significant interference when tested at the concentrations listed.

|  Test substances | Tested concentrations | Tested analytes where interference was not observed  |
| --- | --- | --- |
|  Acetaminophen | 1030 μmol/L | Glucose, Lactate  |
|  Acetoacetate | 2 mmol/L | Glucose, Lactate  |
|  Albumin (Human) | 60 g/L | Hct  |
|  Ascorbic acid | 298 μmol/L | Glucose, Lactate  |
|  Atracurium | 50 mg/dL | Glucose, Lactate, Hct, pH, pCO2  |
|  Bilirubin | 40 mg/dL | Glucose, Lactate, Hct, pH, pCO2  |
|  Ceftriaxone | 1510 μmol/L | Glucose, Lactate, Hct, pH, pCO2  |
|  Chlorpromazine | 10.3 μmol/L | Glucose, Lactate  |
|  Dobutamine | 0.121 mg/dL | Glucose, Lactate  |
|  Dopamine | 4.06 μmol/L | Glucose, Lactate  |
|  Epinephrine | 0.5 μmol/L | Glucose, Lactate, Hct, pH, pCO2  |
|  Ethanol | 130 mmol/L | Glucose, Lactate  |
|  Ethylene glycol | 8.8 mmol/L | Glucose, Lactate  |
|  Etomidate | 50 mg/L | Glucose, Lactate, Hct, pH, pCO2  |
|  Fentanyl | 0.03 μg/mL | Glucose, Lactate, Hct, pH, pCO2  |
|  Fructose | 1 mmol/L | Glucose  |
|  Furosemide | 48.1 μmol/L | Glucose, Lactate, Hct, pH, pCO2  |
|  Gadodiamide | 1.4 mmol/L | Glucose, Lactate, Hct, pH, pCO2  |
|  Glycolic acid | 1.0 mmol/L | Glucose  |
|  Hematocrit | 25% | pH, pCO2, Glucose, Lactate  |
|  Hematocrit | 60% | pH, pCO2, Glucose, Lactate  |
|  Hemoglobin (Hemolysis) | 1000 mg/dL | Glucose, Lactate, Hct, pH, pCO2  |
|  Heparin | 100,000 U/L | Glucose, Lactate  |
|  β-hydroxybutyrate | 2 mmol/L | Glucose, Lactate, pH  |
|  Ibuprofen | 1060 μmol/L | Glucose, Lactate, Hct, pH, pCO2  |
|  Icodextrin | 20 mg/dL | Glucose, Lactate  |
|  Isoniazid | 438 μmol/L | Glucose, Lactate  |
|  Leukocytes / Platelets | 24.81 / 452 (x103/μl) | Hct 30%  |
|   |  27.60 / 564 (x103/μl) | Hct 60%  |
|  Maltose | 360 mg/dL | Glucose, Lactate  |
|  Maltose | 1000 mg/dL | Glucose, Lactate  |
|  Maltose | 10000 mg/dL | Glucose, Lactate  |
|  Maltose | 100000 mg/dL | Glucose, Lactate  |

{11}

The table below lists substances that demonstrated interference with Glu, Lac, Hct, pH and/or  $p\mathrm{CO}_2$  and the concentration of the interfering substance, as well as the bias observed and its direction (positive / negative):

|  Interfering Substance | Affected Analytes | Analyte Conc. | Interfering Conc. Tested | Bias Observed (Mean) | Lowest Interfering Conc. with Analyte Impact | Bias Observed at the Lowest Concentration  |
| --- | --- | --- | --- | --- | --- | --- |
|  Galactose | Glucose | 40 mg/dL | 3.33 mmol/L | +13 % | 2.77 mmol/L | +10 %  |
|   |   |  220 mg/dL |   | No interference Observed  |   |   |
|  Glycolic acid | Lactate | 1.0 mmol/L | 1.0 mmol/L | +1.5 mmol/L | 0.3 mmol/L | +0.4 mmol/L  |
|   |   |  1.7 mmol/L |   | +1.6 mmol/L | 0.3 mmol/L | +0.4 mmol/L  |
|  Hydroxyurea | Glucose | 40 mg/dL | 3.08 mg/dL | +207 % | 0.15 mg/dL | +10 %  |
|   |   |  220 mg/dL |   | +34 % | 0.90 mg/dL | +10 %  |
|  Hydroxyurea | Lactate | 1.0 mmol/L | 3.08 mg/dL | +3.8 mmol/L | 0.30 mg/dL | +0.4 mmol/L  |
|   |   |  1.7 mmol/L |   | +3.5 mmol/L | 0.33 mg/dL | +0.4 mmol/L  |
|  Mannose | Glucose | 40 mg/dL | 20 mg/dL | +12 % | 19 mg/dL | +10 %  |
|   |   |  220 mg/dL |   | No Interference Observed  |   |   |
|  Thiopental | pH | 7.40 | 1660 μmol/L | +0.04 | 789 μmol/L | +0.02  |
|   |   |  7.25 |   | +0.03 | 1175 μmol/L | +0.02  |
|  Mannitol | pH | 7.40 | 1660 μmol/L | +0.04 | 789 μmol/L | +0.02  |
|  Mannose | Glucose | 40 mg/dL | 3.08 mg/dL | +207 % | 0.15 mg/dL | +10 %  |
|  Mannose | Lactate | 1.0 mmol/L | 3.08 mg/dL | +3.8 mmol/L | 0.30 mg/dL | +0.4 mmol/L  |

{12}

f. Assay cut-off:

Not applicable

2. Comparison studies:

a. Method comparison with predicate device:

A method comparison study was performed at 3 external POC sites using lithium heparinized arterial and venous whole blood samples. Each sample was analyzed in singlicate on the GEM Premier ChemSTAT and on the GEM Premier 4000. To span the reportable range for each analyte, $< 10\%$ of contrived samples were spiked for each analyte.

The results are summarized in the table below:

|  Analyte | N | Slope | Intercept | R | Sample Range  |
| --- | --- | --- | --- | --- | --- |
|  Glucose (mg/dL) | 432 | 1.019 | -0.558 | 0.999 | 35 to 684  |
|  Lactate (mmol/L) | 432 | 1.000 | -0.100 | 0.997 | 0.6 to 16.0  |
|  Hematocrit (%) | 431 | 1.032 | -0.626 | 0.997 | 16 to 71  |
|  pH | 552 | 1.006 | -0.038 | 0.995 | 7.03 to 7.87  |
|  pCO_{2} (mmHg) | 559 | 1.000 | 0.000 | 0.996 | 7 to 120  |

b. Matrix comparison:

Not applicable. The glucose, lactate, hematocrit, pH and $\mathrm{pCO_2}$ 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

{13}

# 5. Expected values/Reference range:

The following are the reference ranges from published literature:

|  Analyte | Reference Range | Unit  |
| --- | --- | --- |
|  Glu* | 65 to 95 | mg/dL  |
|   |  3.6 to 5.3 | mmol/L  |
|  Lac* | 0.36 to 0.75 (arterial at rest) | mmol/L  |
|   |  2.24 to 6.76 (arterial at rest) | mg/dL  |
|   |  0.56 to 1.39 (venous at rest) | mmol/L  |
|   |  5.0 to 12.5 (venous at rest) | mg/dL  |
|  Hct* | 39-51 (male) and 35-47 (female) | %  |
|  pH* | 7.35 to 7.45 | pH  |
|  cH* | 44.7 to 35.5 | nmol/L  |
|  cH* | 44.7 to 35.5 | nEq/L  |
|  pH* | 7.32 to 7.43 (venous) | pH  |
|  cH* | 47.9 to 37.2 (venous) | nmol/L  |
|  cH* | 47.9 to 37.2 (venous) | nEq/L  |
|  pCO2** | 35 to 48 (male) and 32 to 45 (female) | mmHg  |
|   |  4.6 to 6.4 (male) and 4.3 to 6.0 (female) | kPa  |
|   |  6 to 7 mmHg (0.80 to 0.93 kPa) higher than arterial pCO2 (venous blood, right atrium) |   |

The sponsor recommends that each laboratory establish their own reference ranges applicable to their patient population.

# References:

* Burtis, Carl and David Bruns, Tietz Textbook of Clinical Chemistry and Molecular Diagnostics, Elsevier Saunders, 7th Edition, 2015, pages 952-982.
** Wu, A., Tietz Clinical Guide to Laboratory Tests, W.B. Saunders Co., St. Louis MO, 4th Edition, 2006, pages 216.

# 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.

---

**Source:** [https://fda.innolitics.com/submissions/CH/subpart-b%E2%80%94clinical-chemistry-test-systems/CGA/K183546](https://fda.innolitics.com/submissions/CH/subpart-b%E2%80%94clinical-chemistry-test-systems/CGA/K183546)

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