← Product Code [CHL](/submissions/CH/subpart-b%E2%80%94clinical-chemistry-test-systems/CHL) · K151978

# EDAN i15 Blood Gas and Chemistry Analysis System, EDAN i15 Calibrant Fluid Pack, EDAN i15 Blood Gas and Electrolyte Control, EDAN i15 Hematocrit Control (K151978)

_Edan Instruments, Inc. · CHL · Jul 15, 2016 · Clinical Chemistry · SESE_

**Canonical URL:** https://fda.innolitics.com/submissions/CH/subpart-b%E2%80%94clinical-chemistry-test-systems/CHL/K151978

## Device Facts

- **Applicant:** Edan Instruments, Inc.
- **Product Code:** [CHL](/submissions/CH/subpart-b%E2%80%94clinical-chemistry-test-systems/CHL.md)
- **Decision Date:** Jul 15, 2016
- **Decision:** SESE
- **Submission Type:** Traditional
- **Regulation:** 21 CFR 862.1120
- **Device Class:** Class 2
- **Review Panel:** Clinical Chemistry

## Indications for Use

The i15 Blood Gas and Chemistry Analysis System (including Blood Gas and Chemistry Analyzer, Calibrant Fluid Pack, Test Cartridge) is a portable, automated system that measures pH and blood gases (pCO2, pO2), electrolytes (Na+, K+, Ca++, Cl-) and hematocrit in arterial and venous whole blood samples with lithium heparin or calcium balanced heparin. The system is intended for in-vitro diagnostic use only by trained health care professionals in a laboratory environment, near patient or point-of-care settings.

## Device Story

Portable, automated, microprocessor-based system for in-vitro diagnostic analysis of whole blood. Inputs: lithium- or calcium-balanced heparinized whole blood (140 µL) via syringe or capillary. Operation: disposable Test Cartridge integrates sensors, flow path, and waste; Calibrant Fluid Pack provides calibration solutions. Principle: potentiometric (pH, pCO2, Na+, K+, Ca++, Cl-), amperometric (pO2), and conductivity (Hct). Output: quantitative results for measured parameters and various calculated clinical indices (e.g., HCO3, BE, AnGap) displayed on a color touch screen. Used in clinical labs or point-of-care settings by trained professionals. Results assist in diagnosing/treating acid-base, oxygenation, and electrolyte disorders. System includes external multi-analyte quality controls for verification.

## Clinical Evidence

Bench testing only. Precision studies (n=80 per level) and method comparison studies (n=488 samples) against the predicate device were conducted. Linearity, interference, and detection limit studies (LoB/LoD/LoQ for Ca++) were performed per CLSI guidelines. No clinical prospective/retrospective studies were required.

## Technological Characteristics

Potentiometric (pH, PCO2, Na+, K+, Cl-, Ca++), amperometric (PO2), and conductivity (Hct) sensors. Single-use disposable cartridges with barcode-based calibration. Analyzer includes CPU, electronic interfaces, Wi-Fi/wired connectivity, and barcode scanner. Calibrant fluid pack contains NIST-traceable standards. Aqueous controls provided for quality verification.

## Regulatory 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

- Siemens (Bayer) Rapidpoint 400 System (k002738)
- RNA Medical QC823 Blood Gas, Electrolyte, Metabolite Control (k943754)
- RNA Medical QC900 Hematocrit Control (k955630)

## Reference Devices

- Radiometer ABL 800

## 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 AND INSTRUMENT COMBINATION TEMPLATE

A. 510(k) Number:
k151978

B. Purpose for Submission:
New Device

C. Measurand:
pH, pCO2, pO2, Hematocrit (Hct), Sodium (Na⁺), Potassium (K⁺), Chloride (Cl⁻), and Calcium (Ca²⁺)

D. Type of Test:
Potentiometric measurement: pH, PCO2, Na⁺, K⁺, Cl⁻, and Ca²⁺
Amperometric measurement: PO2
Conductivity measurement: Hct

E. Applicant:
EDAN Instruments, Inc.

F. Proprietary and Established Names:
EDAN i15 Blood Gas and Chemistry Analysis System, EDAN i15 Calibrant Fluid Pack, EDAN i15 Blood Gas and Electrolyte Control, and EDAN i15 Hematocrit Control

G. Regulatory Information:

|  Product Code | Classification | Regulation Section | Panel  |
| --- | --- | --- | --- |
|  CHL | II | 862.1120, Blood Gases (pCO2, pO2) and Blood pH system | 75-Chemistry  |
|  JGS | II | 862.1665, Sodium Test System | 75-Chemistry  |
|  CEM | II | 862.1600, Potassium Test System | 75-Chemistry  |
|  JFP | II | 862.1145, Calcium Test System | 75-Chemistry  |

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|  Product Code | Classification | Regulation Section | Panel  |
| --- | --- | --- | --- |
|  CGZ | II | 862.1170, Chloride Test System | 75-Chemistry  |
|  GKF | II | 864.5600, Automated hematocrit instrument | 81-Hematology  |
|  JIX | II | 862.1150, Calibrators | 75-Chemistry  |
|  JJS | I, reserved | 862.1660, Quality Control Materials | 75-Chemistry  |
|  GLK | II | 864.8625, Hematology Quality Control Mixture | 81-Hematology  |

H. Intended Use:

1. Intended use(s):

See Indication(s) for Use below

2. Indication(s) for use:

The i15 Blood Gas and Chemistry Analysis System (including Blood Gas and Chemistry Analyzer, Calibrant Fluid Pack, Test Cartridge) is a portable, automated system that measures pH and blood gases (PCO2, PO2), electrolytes (Na⁺, K⁺, Ca²⁺, Cl⁻) and hematocrit in arterial and venous whole blood samples with lithium heparin or calcium balanced heparin. The system is intended for in-vitro diagnostic use only by trained health care professionals in a laboratory environment, near patient or point-of-care settings.

pH, PCO2, PO2: Whole blood measurement of certain gases in whole blood, or pH of whole blood, is used in the diagnosis and treatment of life-threatening acid-base and/or oxygenation disturbances.

Hct: Whole blood measurements of the packed 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 blood cells)

Na⁺: Sodium measurement is used in the diagnosis and treatment of aldosteronism, diabetes insipidus, adrenal hypertension, Addison’s disease, dehydration, or diseases involving electrolyte imbalance.

K⁺: Potassium measurement is used to monitor electrolyte balance in the diagnosis and treatment of disease conditions characterized by low or high potassium levels

Cl⁻: Chloride measurement is used in the diagnosis and treatment of electrolyte and

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metabolic disorders such as cystic fibrosis and diabetic acidosis.

Ca++: Calcium measurements are used in the diagnosis and treatment of parathyroid disease, a variety of bone diseases, chronic renal disease and tetany (intermittent muscular contractions or spasms).

The EDAN i15 Calibrant Fluid Pack is intended for the calibration of pH, PO2, PCO2, Na+, K+, Ca++, Cl-, and Hct as part of the EDAN i15 Blood Gas and Chemistry Analysis System.

The EDAN i15 Blood Gas and Electrolyte Controls are external multi-analyte quality control material intended to be used for the verification of correct operation and measurement of the EDAN i15 Blood Gas and Electrolyte Analyze, together with i15 Calibrant Fluid Pack and i15 Test Cartridge for the analysis of pH, blood gases (PCO2, PO2), and electrolytes (Na+, K+, Ca++, and Cl-).

The EDAN i15 Hematocrit Controls are intended to be used for the verification of correct operation and measurement of the EDAN i15 Blood Gas and Chemistry Analysis System, together with i15 Calibrant Fluid Pack and i15 Test Cartridge for the analysis of hematocrit.

I. Device Description:

EDAN i15 Blood Gas and Chemistry Analysis System:

The EDAN i15 Blood Gas and Chemistry Analysis System, (including the Blood Gas and Chemistry Analyzer, Calibrant Fluid Pack, Test Cartridge, and Quality Controls) is a system for in-vitro analysis of whole blood, delivering quantitative results for a panel of tests. The analyzer has a user interface module which contains the CPU and all the required electronic interfaces for external communication and data storage. The signals generated by the electrochemical sensors contained in the Test Cartridges are converted into concentration levels which are displayed on the screen of the analyzer, stored in memory, and can be transmitted by communication link or Wi-Fi to the Data Management System (DMS) or HIS/LIS. The analyzer includes a barcode scanner to scan bar codes of test cartridges, calibrant fluid packs, controls, patient and operator ID. The analyzer aspirates the sample directly from a syringe, or capillary fitted with an adaptor, and requires a minimum sample volume of 140 μL for analysis.

EDAN i15 Test Cartridge: single-use disposable cartridge into which the blood sample is introduced. The cartridge consists of fluid paths and electrochemical sensors for potentiometric measurement of pH, PCO2, Na+, K+, Cl-, and Ca++, amperometric measurement for PO2; and conductivity measurement for Hct. The cartridge is packaged into a sealed foil pouch which includes a bar-code label with calibration, lot identification and expiration dating information. The test cartridge is available in three versions with different test menus:

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|  Cartridge Type | Measured Parameters  |
| --- | --- |
|  BG8 | pH, PCO2, PO2, Na+, K+, Cl-, Ca++, Hct  |
|  BG3 | pH, PCO2, PO2  |
|  BC4 | Na+, K+, Cl-, Ca++, Hct  |

# EDAN i15 Calibrant Fluid Pack

The Calibrant Fluid is contained in a replaceable cartridge and is comprised of a flexible pouch containing the calibrant standard with dissolved gases, assembled inside a rigid plastic case, with removable, protective cover. The EDAN i15 Calibrant Fluid Pack consists of one level of calibrator and is intended for the calibration of pH, pCO2, pO2,  $\mathrm{Na^{+}}$ ,  $\mathrm{K^{+}}$ ,  $\mathrm{Ca^{++}}$ ,  $\mathrm{Cl^{-}}$ , and Hct as part of the EDAN i15 Blood Gas and Chemistry System. The typical target values assigned to the calibrant solutions are traceable to NIST standards and are shown in the table below:

Analyte Concentration of the EDAN i15 Calibrant Fluid Pack

|  Analyte | Unit of measure | Target Concentration  |
| --- | --- | --- |
|  pH | pH units | 7.342  |
|  pCO2 | mmHg | 41.3  |
|  pO2 | mmHg | 154.0  |
|  Na | mmol/L | 140.0  |
|  K | mmol/L | 4.80  |
|  Cl | mmol/L | 100  |
|  iCa | mmol/L | 1.22  |
|  Hct | % | 9.5%  |

# EDAN i15Blood Gas and Chemistry Controls

Three, single-level aqueous controls in sealed glass ampoules, packaged in 5- ampoule packages representing the normal, high, and low clinical ranges of each of the tests. Level 1: pH/Blood Gas representing respiratory acidosis with low pH and high PCO2 values and low range physiological values for PO2,  $\mathrm{Na^{+}}$ ,  $\mathrm{K^{+}}$ ,  $\mathrm{Cl^{-}}$ , and elevated  $\mathrm{Ca^{++}}$ . Level 2: Representing normal physiological values for all tests. Level3: pH/Blood Gas resenting respiratory alkalosis with elevated pH and low PCO2 values and elevated physiological values for PO2,  $\mathrm{Na^{+}}$ ,  $\mathrm{K^{+}}$ ,  $\mathrm{Cl^{-}}$ , and decreased  $\mathrm{Ca^{++}}$ .

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EDAN i15 Blood Gas and Chemistry Controls

|  Analyte | Level 1 Target Value (Range) | Level 2 Target Value (Range) | Level 3 Target Value (Range)  |
| --- | --- | --- | --- |
|  pH (pH units) | 7.156
(7.096-7.196) | 7.411
(7.361-7.461) | 7.589
(7.539-7.639)  |
|  PO2 (mmHg) | 74.7
(59.7-89.7) | 108.5
(91.5-125.5) | 148.1
(126.1-170.1)  |
|  PCO2 (mmHg) | 66.9
(58.9-74.9) | 40.4
(33.4-47.4) | 21.8
(15.8-27.8)  |
|  Na⁺ (mmol/L) | 113.5
(108.5-118.5) | 131.5
(126.5-136.5) | 153.6
(148-158)  |
|  K⁺ (mmol/L) | 1.97
(1.47-2.47) | 4.37
(3.87-4.87) | 6.27
(5.67-6.87)  |
|  Ca²⁺ (mmol/L) | 1.52
(1.32-1.72) | 1.16
(1.01-1.31) | 0.57
(0.47-0.67)  |
|  Cl⁻ (mmol/L) | 73
(68.6-78.6) | 94.1
(88.1-100.1) | 120.5
(112.5-128.5)  |

EDAN i15 Hematocrit Controls

Two, single- level aqueous hematocrit controls in sealed glass ampoules representing high and low physiological range of hematocrit simulated by conductivity.

EDAN i15 Hematocrit Controls

|  Hct (%) | Target value | Range  |
| --- | --- | --- |
|  Level 1 | 20 | 17-23  |
|  Level 2 | 47 | 43-51  |

J. Substantial Equivalence Information:

1. Predicate device name(s):

Siemens (Bayer) Rapidpoint 400 System, including calibrators
RNA Medical QC823 Blood Gas, Electrolyte, Metabolite Control
RNA Medical QC900 Hematocrit Control

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

k002738
k943754
k955630

3. Comparison with predicate:

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Analyzer

|  Similarities and Differences  |   |   |
| --- | --- | --- |
|  Item | Candidate Device EDAN i15 Blood Gas and Chemistry Analysts System | Predicate Device Siemens Rapidpoint 400 System (k002738)  |
|  Intended Use | For the measurement of pH and blood gases (PCO2, PO2), electrolytes (Na+, K+, Ca++, Cl-) ;and hematocrit in whole blood. | Same  |
|  Setting for use | Clinical laboratory and point of care settings | Same  |
|  Test Principle | pH and PCO2 and electrolytes: potentiometric PO2: Amperometric Hematocrit: conductivity | Same  |
|  Sample type | Heparinized whole blood | Same  |
|  Sample introduction | Syringe and capillary tube, by aspiration | Same  |
|  Sample volume | 140 μL | 100 μL  |
|  Measurement Range | pH: 6.500-7.800 pCO2: 10-150 mmHg PO2:10-700 mmHg Na+: 100-180 mmol/L K+: 2.0-9.0 mmol/L Cl-: 65-140 mmol/L Ca++: 0.25-2.50 mmol/L Hct: 13-72% | pH: 6.500-7.800 pCO2: 5.0-200.0 mmHg PO2: 10-700 mmHg Na+: 100-200 mmol/L K+: 0.5-15.0 mmol/L Cl-: 65-140 mmol/L Ca++: 0.20-5.00 mmol/L Hct: 12-75%  |

Calibrator

|  Similarities and Differences  |   |   |
| --- | --- | --- |
|  Item | Candidate Device EDAN i15 Blood Gas and Chemistry Calibrant Fluid Pack | Predicate Device Siemens Rapidpoint 400 System (k002738)  |
|  Intended Use | For the calibration of pH and blood gases (PCO2, PO2), electrolytes (Na+, K+, Ca++, Cl-) ;and hematocrit on the blood gas and chemistry analyzer. | Same  |

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|  Similarities and Differences  |   |   |
| --- | --- | --- |
|  Item | Candidate Device
EDAN i15 Blood Gas and Chemistry Calibrant Fluid Pack | Predicate Device
Siemens Rapidpoint 400 System (k002738)  |
|  Calibration level and packaging | One solution for the calibration of the sensors contained in a Mylar and aluminum foil bag, housed in a protective, self-contained, molded plastic disposable container. | Three solutions for the calibration of the sensors and a reference solution contained in Mylar and aluminum foil bags, housed in a protective, self-contained, molded plastic disposable container.  |

Blood gas, pH, and electrolyte controls

|  Similarities and Differences  |   |   |
| --- | --- | --- |
|  Item | Candidate Device
EDAN i15 Blood Gas and Chemistry Quality Control | Predicate Device
RNA Medical QC823 Blood Gas, Electrolyte and Metabolite Quality Control (k943754)  |
|  Intended Use | Quality control material intended to monitor the measurement of pH and blood gases (PCO2, PO2), electrolytes (Na+, K+, Ca++, Cl-). | Same  |
|  Levels | Three | Same  |
|  Configuration | Packaged in sealed glass ampoules, each containing 2.5 mL of solution. | Same  |

Hematocrit controls

|  Similarities and Differences  |   |   |
| --- | --- | --- |
|  Item | Candidate Device
EDAN i15 Blood Gas and Chemistry System
Hematocrit Controls | Predicate Device
RNA Medical Hematocrit Controls (k955630)  |
|  Intended Use | Quality control material intended to monitor the measurement of hematocrit by electrical conductivity. | Same  |
|  Levels | Three | Same  |
|  Configuration | Packaged in sealed glass ampoules, each containing 1.7 mL of solution. | Same  |

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

CLSI EP05-A3: Evaluation of Precision of Quantitative Measurement Methods; Approved Guideline-Second Edition

CLSI EP06-A: Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline

CLSI EP07-A2: Interference Testing in Clinical Testing; Approved Guideline-Second Edition

CLSI EP09-A3: Method Comparison and Bias Estimation Using Patient Samples-Approved Guideline-Second Edition

CLSI EP17-A2: Protocols for Determination of Limits of Detection and Limits of Quantitation; Approved Guideline-Second Edition

L. Test Principle:

Potentiometry is used to measure pH, PCO2 and electrolytes (Na⁺, K⁺, Ca²⁺ and Cl⁻) in the EDAN i15 System. Potentiometry is based on the measurement of the difference in electrical signal resulting from a chemical reaction between the analyte and an electrochemical sensor. The electrical signal generated by the reaction is proportional to the amount of analyte in the sample.

Amperometry is used to measure PO2 in the EDAN i15 System. PO2 is measured by applying a fixed voltage to an electrode and then measuring the current resulting in the reaction. The current is proportional to the amount of the analyte in the sample.

Conductance is used to measure hematocrit in the EDAN i15 System. Conductance is the ease with which a conducting substance transmits an electrical current. The conductance is inversely proportional to the concentration of hematocrit in the sample.

M. Performance Characteristics (if/when applicable):

1. Analytical performance:

a. Precision/Reproducibility:

i.) A within run and total precision study was conducted in-house by with the 3 levels of EDAN i15 blood gas and chemistry control materials by testing two samples per day in 2 runs per day for 20 days on one EDAN i15 Blood Gas and Electrolyte analyzer (n=80). Results are summarized below:

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|   |   | Within-Run |   | Total  |   |
| --- | --- | --- | --- | --- | --- |
|  Analyte | Mean (n=80) | SD | CV% | SD | CV%  |
|  pH (pH units) | 7.153 | 0.012 | 0.17 | 0.012 | 0.17  |
|   |  7.410 | 0.013 | 0.18 | 0.013 | 0.18  |
|   |  7.598 | 0.008 | 0.11 | 0.009 | 0.12  |
|  PCO2 (mmHg) | 62.8 | 2.11 | 3.36 | 2.40 | 3.82  |
|   |  38.8 | 2.11 | 5.45 | 2.33 | 6.02  |
|   |  20.5 | 0.80 | 3.91 | 0.85 | 4.13  |
|  pO2 (mmHg) | 71.4 | 2.67 | 3.73 | 2.68 | 3.75  |
|   |  106.2 | 1.84 | 1.73 | 2.50 | 2.35  |
|   |  149.2 | 2.59 | 1.74 | 3.33 | 2.23  |
|  Na+ (mmol/L) | 111.8 | 1.29 | 1.15 | 1.32 | 1.18  |
|   |  133.0 | 0.95 | 0.71 | 1.14 | 0.86  |
|   |  158.5 | 1.51 | 0.95 | 1.44 | 0.91  |
|  K+ (mmol/L) | 1.91 | 0.040 | 2.11 | 0.040 | 2.07  |
|   |  4.34 | 0.047 | 1.09 | 0.052 | 1.20  |
|   |  6.34 | 0.073 | 1.16 | 0.065 | 1.02  |
|  Cl- (mmol/L) | 75.9 | 0.91 | 1.20 | 0.93 | 1.22  |
|   |  92.3 | 1.07 | 1.16 | 1.08 | 1.17  |
|   |  121.7 | 0.66 | 0.54 | 0.69 | 0.57  |
|  Ca++ (mmol/L) | 1.37 | 0.04 | 3.09 | 0.05 | 3.47  |
|   |  1.23 | 0.02 | 1.54 | 0.03 | 2.42  |
|   |  0.61 | 0.02 | 3.10 | 0.02 | 3.66  |
|  Hct (%) | 19.2 | 0.57 | 2.97 | 0.73 | 3.82  |
|   |  46.8 | 0.58 | 1.24 | 0.54 | 1.16  |

ii.) A precision study was performed with the intended POC operators following CLSI EP5-A3. The precision study took place at four point-of-care (POC) locations comprised of a respiratory medical unit, two intensive care units, and an anesthesia unit. Testing was performed by 11 POC operators (2 or 3 operators per site). Within-run and total precision were performed using 3 levels of blood gas/electrolyte control material as well as 3 levels of hematocrit control material. Four EDAN i15 analyzers and 4 number of cartridge lots (one analyzer and one lot per site). The duration of testing varied between 4 and 14 days among the sites. Each of the control materials were run twice a day at each site. Each site produced similar precision results. Results of precision studies from a representative site (POC site 1) are shown below:

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|  pH Precision |   |   | Within-Run |   | Total  |   |
| --- | --- | --- | --- | --- | --- | --- |
|  Sample | N | Mean (pH units) | SD | CV% | SD | CV%  |
|  Level 1 | 24 | 7.139 | 0.007 | 0.097 | 0.007 | 0.104  |
|  Level 2 | 24 | 7.399 | 0.006 | 0.081 | 0.005 | 0.072  |
|  Level 3 | 24 | 7.584 | 0.007 | 0.089 | 0.006 | 0.073  |
|  PCO2 Precision |   |   | Within-Run |   | Total  |   |
|  Sample | N | Mean (mmHg) | SD | CV% | SD | CV%  |
|  Level 1 | 24 | 72.1 | 2.84 | 3.94 | 3.04 | 4.21  |
|  Level 2 | 24 | 43.3 | 1.22 | 2.82 | 1.48 | 3.42  |
|  Level 3 | 24 | 24.0 | 0.44 | 1.85 | 0.62 | 2.57  |
|  The combined rate total imprecision results from all 4PCC sites are summarized in the table below |   |   |  |   |   |   |
|  PO2 Precision |   |   | Within-Run |   | Total  |   |
|  Sample | N | Mean (mmHg) | SD | CV% | SD | CV%  |
|  Level 1 | 24 | 69.9 | 1.83 | 2.62 | 2.32 | 3.32  |
|  Level 2 | 24 | 105.6 | 1.83 | 1.73 | 1.69 | 1.60  |
|  Level 3 | 24 | 148.5 | 2.17 | 1.46 | 1.97 | 1.33  |
|  Na+ Precision |   |   | Within-Run |   | Total  |   |
|  Sample | N | Mean (mmol/L) | SD | CV% | SD | CV%  |
|  Level 1 | 24 | 121.1 | 1.17 | 0.97 | 1.11 | 0.92  |
|  Level 2 | 24 | 142.5 | 0.89 | 0.62 | 1.23 | 0.86  |
|  Level 3 | 24 | 166.1 | 1.71 | 1.03 | 1.49 | 0.90  |
|  K+ Precision |   |   | Within-Run |   | Total  |   |
|  Sample | N | Mean (mmol/L) | SD | CV% | SD | CV%  |
|  Level 1 | 24 | 2.10 | 0.000 | 0.000 | 0.000 | 0.000  |
|  Level 2 | 24 | 4.59 | 0.029 | 0.629 | 0.028 | 0.614  |
|  Level 3 | 24 | 6.79 | 0.054 | 0.796 | 0.054 | 0.790  |
|  Cl- Precision |   |   | Within-Run |   | Total  |   |
|  Sample | N | Mean (mmol/L) | SD | CV% | SD | CV%  |
|  Level 1 | 24 | 78.3 | 0.65 | 0.82 | 0.64 | 0.81  |
|  Level 2 | 24 | 99.3 | 0.41 | 0.41 | 0.57 | 0.57  |
|  Level 3 | 24 | 127.6 | 0.58 | 0.45 | 0.72 | 0.57  |
|  Ca++ Precision |   |   | Within-Run |   | Total  |   |
|  Sample | N | Mean (mmol/L) | SD | CV% | SD | CV%  |
|  Level 1 | 24 | 1.448 | 0.065 | 4.49 | 0.063 | 4.38  |
|  Level 2 | 24 | 1.108 | 0.022 | 2.02 | 0.027 | 2.47  |
|  Level 3 | 24 | 0.56 | 0.013 | 2.93 | 0.016 | 3.55  |
|  Hct Precision |   |   | Within-Run |   | Total  |   |
|  Sample | N | Mean (%) | SD | CV% | SD | CV%  |
|  Level 1 | 24 | 21.5 | 0.29 | 1.34 | 0.52 | 2.41  |
|  Level 2 | 24 | 34.0 | 0.00 | 0.00 | 0.00 | 0.00  |
|  Level 3 | 24 | 47.0 | 0.00 | 0.00 | 0.00 | 0.00  |

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The combined-site total imprecision from all 4 POC sites are summarized in the tables below:

Combined POC Sites Precision Level 1 Control

|  Analyte | N | Mean | Total SD | Total CV%  |
| --- | --- | --- | --- | --- |
|  pH (pH units) | 80 | 7.135 | 0.007 | 0.10  |
|  PCO2 (mmHg) | 80 | 73.2 | 2.56 | 3.5  |
|  PO2 (mmHg) | 80 | 70.9 | 2.3 | 3.2  |
|  Na+(mmol/L) | 80 | 121.3 | 0.99 | 0.8  |
|  K+(mmol/L) | 80 | 2.23 | 0.03 | 1.3  |
|  Ca++(mmol/L) | 80 | 1.46 | 0.07 | 4.5  |
|  Cl-(mmol/L) | 80 | 78.1 | 0.8 | 1.0  |
|  Hct (%) | 80 | 21.0 | 0.7 | 3.2  |

Combined POC Sites Precision Level 2 Control

|  Analyte | N | Mean | Total SD | Total CV%  |
| --- | --- | --- | --- | --- |
|  pH (pH units) | 80 | 7.399 | 0.006 | 0.08  |
|  PCO2 (mmHg) | 80 | 43.1 | 1.66 | 3.9  |
|  PO2 (mmHg) | 80 | 104.8 | 2.13 | 2.0  |
|  Na+(mmol/L) | 80 | 143.1 | 1.0 | 0.7  |
|  K+(mmol/L) | 80 | 4.63 | 0.05 | 1.0  |
|  Ca++(mmol/L) | 80 | 1.10 | 0.04 | 3.3  |
|  Cl-(mmol/L) | 80 | 99.9 | 0.6 | 0.6  |
|  Hct (%) | 80 | 33.7 | 0.3 | 0.9  |

Combined POC Sites Precision Level 3 Control

|   | N | Mean | Total SD | Total CV%  |
| --- | --- | --- | --- | --- |
|  Analyte | 80 | 7.583 | 0.006 | 0.08  |
|  PCO2 (mmHg) | 80 | 24.7 | 0.9 | 3.6  |
|  PO2 (mmHg) | 80 | 146.3 | 2.1 | 1.4  |
|  Na+(mmol/L) | 80 | 166.0 | 1.4 | 0.9  |
|  K+(mmol/L) | 80 | 6.84 | 0.06 | 0.8  |
|  Ca++(mmol/L) | 80 | 0.48 | 0.02 | 3.7  |
|  Cl-(mmol/L) | 80 | 126.6 | 1.0 | 0.8  |
|  Hct (%) | 80 | 47.0 | 0.22 | 0.5  |

iii.) Hematocrit venous whole blood precision: An in-house with-in run precision study was performed on heparinized venous whole blood samples collected from eight volunteers. Six levels were prepared (one on each day of 6 days) in order to cover the measuring range of hematocrit. Each sample was run in replicates of 10 on 3 EDAN i15 analyzers, using 3 reagent lots, over a period of 6 days (one level run per day) for a total of 30 results per level. The with-in run precision results from the six

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levels of whole blood tested from both syringe and capillary tube is presented in the table below.

Venous whole blood with-in run precision studies for Hct

|   | Syringe |   |   | Capillary Tube  |   |   |
| --- | --- | --- | --- | --- | --- | --- |
|  Hct Level | Mean (%) (n=30) | SD | %CV | Mean (%) (n=30) | SD | %CV  |
|  1 | 18.0 | 1.1 | 6.3 | 18.4 | 1.1 | 5.9  |
|  2 | 30.6 | 0.6 | 1.8 | 31.1 | 0.8 | 2.4  |
|  3 | 47.1 | 0.8 | 1.7 | 48.0 | 0.7 | 1.3  |
|  4 | 51.4 | 0.6 | 1.2 | 52.5 | 0.7 | 1.3  |
|  5 | 54.0 | 0.6 | 1.2 | 53.9 | 0.9 | 1.6  |
|  6 | 62.9 | 0.9 | 1.4 | 63.1 | 0.8 | 1.3  |

iv. An in-house precision study was performed utilizing 3 EDAN i15 Blood Gas and Chemistry Analysis System with venous whole blood collected from 3 healthy volunteers. The whole blood was tonometered to nominal gas values. The remainder of the analytes were not altered. The samples were run in replicates of 10 on each of the three analyzers for a total of 30 results. The results of the combined precision data is summarized below:

Venous whole blood with-in run precision studies

|  N=30 | Syringe values |   |   | Capillary Tube values  |   |   |
| --- | --- | --- | --- | --- | --- | --- |
|  Parameter | Mean | SD | %CV | Mean | SD | %CV  |
|  pH | 7.325 | 0.015 | 0.20 | 7.322 | 0.016 | 0.21  |
|  PCO2 (mm/Hg) | 44.3 | 1.1 | 2.6 | 43.7 | 1.2 | 3.8  |
|  PO2 (mm/Hg) | 150.8 | 4.5 | 3.0 | 148.7 | 4.1 | 2.8  |
|  Na+ (mmol/L) | 139.1 | 0.9 | 0.7 | 139.2 | 0.9 | 0.6  |
|  K+ (mmol/L) | 3.24 | 0.06 | 1.9 | 3.35 | 0.08 | 2.5  |
|  Ca++ (mmol/L) | 1.19 | 0.03 | 2.7 | 1.17 | 0.03 | 2.3  |
|  Cl- mmol/L) | 103.5 | 1.8 | 1.7 | 103.5 | 2.0 | 1.1  |
|  Hct (%) | 47.1 | 0.8 | 1.7 | 48.1 | 1.1 | 2.2  |

b. Linearity/assay reportable range:

A linearity study was performed based on CLSI EP6 guidance for each analyte using lithium heparinized venous whole blood with sampling from a syringe and from a capillary tube. Samples aspirated into the instrument from a syringe or from a capillary tube require the same volume of blood (140 μL), travel through the same aspiration port and tubing, and are measured exactly the same by the analyzer. The only difference is the sample tube type and the manner in which the samples are collected. For each parameter, 7 levels were prepared by tonometry to achieve

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expected concentrations and by spiking or diluting the samples to span the claimed measuring range. The target values were based on results from a reference measurement procedure; Radiometer ABL 800 (pH), microhematocrit centrifuge (HCT). Samples were tested in a single run in replicates of 3 on a single analyzer. The linearity results are summarized in the table below:

Linearity results from Lithium-heparinized whole blood samples from a syringe

|  Analyte | Slope | Intercept | r | Range tested  |
| --- | --- | --- | --- | --- |
|  pH (pH units) | 0.9842 | 0.11 | 0.9996 | 6.455-7.944  |
|  PO2 (mmHg) | 0.9969 | -6.16 | 0.9993 | 6-716  |
|  PCO2 (mmHg) | 0.9533 | 0.62 | 0.9969 | 3-149  |
|  Na+ (mmol/L) | 0.9923 | -1.38 | 0.9983 | 94-185  |
|  K+ (mmol/L) | 0.9886 | 0.08 | 0.9997 | 1.7-10.2  |
|  Cl- (mmol/L) | 1.0028 | -1.59 | 0.9993 | 58-176  |
|  Ca++ (mmol/L) | 0.9848 | -0.05 | 0.9981 | 0.23-2.94  |
|  Hct (%) | 0.9687 | 1.54 | 0.9981 | 3-77  |

Linearity results from Lithium-heparinized, whole blood samples from a capillary tube

|  Analyte | Slope | Intercept | r | Range tested  |
| --- | --- | --- | --- | --- |
|  pH (pH units) | 1.0039 | -0.03 | 0.9995 | 6.464-8.00  |
|  PO2 (mmHg) | 1.0174 | -5.40 | 0.9997 | 7-717  |
|  PCO2 (mmHg) | 0.9999 | -0.06 | 0.9992 | 2-150  |
|  Na+ (mmol/L) | 1.0059 | -3.06 | 0.9986 | 94-185  |
|  K+ (mmol/L) | 1.0013 | -0.01 | 0.9998 | 1.9-10.0  |
|  Cl- (mmol/L) | 0.9965 | -1.59 | 0.9992 | 59-175  |
|  Ca++ (mmol/L) | 0.9771 | -0.06 | 0.9968 | 0.24-2.97  |
|  Hct (%) | 0.9623 | 1.51 | 0.9984 | 4-76  |

The results of the linearity study support the sponsor's claimed measuring ranges below:

pH: 6.500-7.800

PO2: 10-700 mmHg

PCO2: 10-150 mmHg

$\mathrm{Na^{+}}$  : 100-180 mmol/L

$\mathrm{K}^{+}$  : 2-9 mmol/L

$\mathrm{Cl}^{-}$  : 65-140 mmol/L

$\mathrm{Ca}^{++}$  : 0.25-2.50 mmol/L

Hct:  $13 - 72\%$

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

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Traceability: The traceability of the EDAN i15 Blood Gas and Chemistry Calibrant Fluid Pack are listed in the chart below:

Traceability EDAN i15 Blood Gas and Chemistry Calibrant Cartridge

|  Analyte | Traceability  |
| --- | --- |
|  pH | NIST HEPES SRM 2181 and 2182  |
|  PO2 | NIST traceable pure gases prepared gravimetrically  |
|  PCO2 | NIST traceable pure gases prepared gravimetrically  |
|  Na+ | NIST SRM 919b Sodium Chloride  |
|  K+ | NIST SRM 918b Potassium Chloride  |
|  Ca++ | NIST SRM 915b Calcium Carbonate  |
|  Cl- | NIST SRM 919b Sodium Chloride  |
|  Hct | No standard reference material available. Values based on micro hematocrit centrifuge method according to CLSI H7-A3, Procedure for Determining Packed Cell Volume by the Microhematocrit Method  |

# Value Assignment:

EDAN i15 Calibrant Fluid Pack is value assigned by testing at least 20 replicates pre analyte/per level on the EDAN i15 Blood Gas and Chemistry Analysis System and comparing the results to those obtained on the reference methods (Rapidpoint 400 and ABL 800). The analyte concentrations of the EDAN i15 calibrant fluid must meet internal specifications for acceptable bias as compared to the reference methods. The typical target values assigned to the calibrant solutions are traceable to NIST standards and are shown in the table below:

EDAN i15 Calibrant Fluid Pack Target Values

|  Analyte | Unit of measure | Target Concentration  |
| --- | --- | --- |
|  pH | pH units | 7.342  |
|  pCO2 | mmHg | 41.3  |
|  pO2 | mmHg | 154.0  |
|  Na+ | mmol/L | 140.0  |
|  K+ | mmol/L | 4.80  |
|  Cl- | mmol/L | 100  |
|  iCa++ | mmol/L | 1.22  |
|  Hct | % | 9.5%  |

EDAN i15 Blood Gas and Electrolyte Controls and EDAN i15 Hematocrit Controls are value assigned by testing 60 replicates per analyte/ per level on the EDAN i15 Blood Gas and Chemistry Analysis System after verification of correct measurement on traceable standard methods. The following represents an example of target values and ranges for the EDAN i15 Blood Gas and Electrolyte Control and EDAN i15 Hematocrit Controls:

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EDAN i15 Blood Gas and Electrolyte Control

Level 1

|  Analyte | Target value | Range  |
| --- | --- | --- |
|  pH (pH units) | 7.156 | 7.096-7.196  |
|  PO2 (mmHg) | 74.7 | 59.7-89.7  |
|  PCO2 (mmHg) | 66.9 | 58.9-74.9  |
|  Na⁺ (mmol/L) | 113.5 | 108.5-118.5  |
|  K⁺ (mmol/L) | 1.97 | 1.47-2.47  |
|  Ca²⁺ (mmol/L) | 1.52 | 1.32-1.72  |
|  Cl⁻ (mmol/L) | 73 | 68.6-78.6  |

Level 2

|  Analyte | Target value | Range  |
| --- | --- | --- |
|  pH (pH units) | 7.411 | 7.361-7.461  |
|  PO2 (mmHg) | 108.5 | 91.5-125.5  |
|  PCO2 (mmHg) | 40.4 | 33.4-47.4  |
|  Na⁺ (mmol/L) | 131.5 | 126.5-136.5  |
|  K⁺ (mmol/L) | 4.37 | 3.87-4.87  |
|  Ca²⁺ (mmol/L) | 1.16 | 1.01-1.31  |
|  Cl⁻ (mmol/L) | 94.1 | 88.1-100.1  |

Level 3

|  Analyte | Target value | Range  |
| --- | --- | --- |
|  pH (pH units) | 7.589 | 7.539-7.639  |
|  PO2 (mmHg) | 148.1 | 126.1-170.1  |
|  PCO2 (mmHg) | 21.8 | 15.8-27.8  |
|  Na⁺ (mmol/L) | 153.0 | 148-158  |
|  K⁺ (mmol/L) | 6.27 | 5.67-6.87  |
|  Ca²⁺ (mmol/L) | 0.57 | 0.47-0.67  |
|  Cl⁻ (mmol/L) | 120.5 | 112.5-128.5  |

EDAN i15 Hematocrit Control

|  Hct (%) | Target value | Range  |
| --- | --- | --- |
|  Level 1 | 20 | 17-23  |
|  Level 2 | 47 | 43-51  |

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16

# Stability:

The stability studies performed to support the stability claims of the EDAN i15 Blood Gas and Electrolyte Control and EDAN i15 Hematocrit Control were reviewed and the study protocol and acceptance criteria were found to be acceptable. Stability studies support EDAN's shelf life claim of 36 months when stored at 2-8°C for the blood gas and electrolyte controls; and for the hematocrit controls, a 24 month shelf life when stored at 2-25°C.

EDAN i15 Calibrant Fluid Pack: Real time stability studies support the sponsor's shelf life claim of 12 months when stored at 2-8°C and in-use life of 30 days after installation in the analyzer. The stability study protocol and acceptance criteria were found to be acceptable.

## d. Detection limit:

Refer to the linearity study above in M.2.b for the measuring range claim for all analytes except ionized calcium, for which detection limit studies were performed and are described below.

Detection limit studies were performed on the ionized calcium analyte to determine the limit of blank (LoB), limit of detection (LoD) and limit of quantitation (LoQ). The detection limit studies were performed according to CLSI EP17-A guidelines.

Limit of blank: Five venous whole blood samples depleted of ionized calcium were tested in replicates of 12 on two i15 systems separately to obtain a total of 60 results. Each of the two analyzers used a different lot of reagent and calibrant fluid packs. LoB was calculated using the following equation: $\mathrm{LoB} = \mu \mathrm{B} + 1.645\mathsf{GB}$. Using the highest LoB value of the two analyzers, the LoB was determined to be $0.09\mathrm{mmol / L}$.

Limit of detection: The limit of detection was determined by testing 5 venous whole blood samples with low level calcium levels (~4 times LoB) using 2 sets of i15 systems with different lots of test cartridges and calibrant fluid over a period of 3 days for a total of 60 results. Using the following equation: $\mathrm{LoD} = \mu \mathrm{B} + 1.645\mathsf{GB} + 1.645\mathsf{GB}$. The LoD was determined to be $0.11\mathrm{mmol / L}$.

Limit of quantitation: The limit of quantitation was determined by analyzing the 60 results from the LoD study using 4 low samples. The sponsor determined that the LoQ is $0.11\mathrm{mmol / L}$.

Ionized Calcium detection limits results:

|  Limit of Blank | Limit of Detection | Limit of Quantitation  |
| --- | --- | --- |
|  0.09 mmol/L | 0.11 mmol/L | 0.11 mmol/L  |

The measuring range of $\mathrm{Ca}^{++}$ is 0.25-2.50 mmol/L.

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# e. Analytical specificity:

An interference study was performed in accordance with CLSI EP7-A2. Heparinized human venous whole blood samples containing low and high concentrations (see chart below) of each analyte were spiked with one or two levels of each potential interfering substance.

Concentrations of analytes tested

|  Analyte | Low test concentration | High test concentration  |
| --- | --- | --- |
|  pH | 7.300 | 7.500  |
|  PCO2 (mmHg) | 40 | 70  |
|  PO2 (mmHg) | 70 | 100  |
|  Na+ (mmol/L) | 130 | 150  |
|  K+ (mmol/L) | 3.0 | 5.0  |
|  Ca++ (mmol/L) | 1.0 | 2.0  |
|  Cl- (mmol/L) | 90 | 110  |
|  Hct (%) | 35 | 55  |

Seven replicates of both the spiked sample and the unspiked sample were tested on two i15 Blood Gas and Chemistry Systems with one lot of test cartridges. The samples containing interferent were evaluated against the same whole blood sample without the interferent. Significant interference is presented as absolute bias for pH and as percent bias for all other analytes and the sponsor's acceptance criteria for defining non-significant interference are provided below:

|  Measurand | Evaluation method | Definition of non-significant interference  |
| --- | --- | --- |
|  pH | Absolute difference | < 0.02 pH units  |
|  pCO2 | Percent bias | < 8%  |
|  pO2 | Percent bias | < 9%  |
|  Na+ | Percent bias | < 3%  |
|  K+ | Percent bias | < 10%  |
|  Ca++ | Percent bias | < 10%  |
|  Cl- | Percent bias | < 5%  |
|  Hct | Percent bias | < 6%  |

The table below indicates which analytes were tested with each potentially interfering substance:

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|  Substance | Test Concentration(s) | Analyte(s) tested | Analytes not tested  |
| --- | --- | --- | --- |
|  Acetaminophen | 20.0 mg/dL | pH, PCO2, PO2, Na+, K+, Ca++, Cl-, Hct | none  |
|  Acetylsalicylic acid | 39 mg/dL 65mg/dL | PCO2, PO2, Na+, Ca++, Cl-, Hct | pH  |
|  Albumin | +1.5 g/dl (total albumin approximately 6.5 g/dL) +3.0 g/dL (total albumin approximately 8.0 g/dL) | Na+, K+, Ca++, Cl-, Hct | pH, PCO2, PO2  |
|  Ascorbic acid | 6.0 mg/dL | PCO2, PO2, Na+, K+, Cl-, Hct | pH  |
|  Benzylkonium Chloride | 0.80 mg/dL | Na+, K+, Ca++, Cl-, Hct | pH, PCO2, PO2  |
|  Bilirubin | 15 mg/dL | pH, PCO2, PO2, Na+, K+, Ca++, Cl-, Hct | none  |
|  Sodium Bromide | 185 mg/dL | pH, PCO2, PO2, K+, Ca++, Hct | Na+  |
|  Bicarbonate (NaHCO3) | 58.8 mg/dL 294 mg/dL | PCO2, PO2, K+, Ca++, Hct | pH, Na+  |
|  Calcium Chloride | 27.8 mg/dL 55.5 mg/dL | pH, PCO2, PO2, Na+, K+, Hct | Cl-, Ca++  |
|  Cholesterol | 250 mg/dL 500 mg/dL | pH, PCO2, PO2, Na+, K+, Ca++, Cl-, Hct | none  |
|  Cysteine | 12 mg/dL | pH, PCO2, PO2, Na+, K+, Ca++, Cl-, Hct | none  |
|  Dextran | 3 g/dL | pH, PCO2, PO2, Na+, K+, Ca++, Cl- | none  |
|  Dobutamine hydrochloride | 22 mg/dL | Na+, K+, Ca++, Cl-, Hct | pH, PCO2, PO2  |
|  Ethanol | 400 mg/dL | pH, PCO2, PO2, Na+, K+, Ca++, Cl-, Hct | none  |
|  Holothane | 14.95 mg/dL | pH, PCO2, PO2, Na+, K+, Ca++, Cl-, Hct | none  |
|  Hydrogen | 1.5 g/dL | pH, PCO2, PO2, Na+, K+, Ca++, Cl-, Hct | none  |
|  Hydrogenated carbon dioxide | 1.5 g/dL | pH, PCO2, PO2, Na+, K+, Ca++, Cl-, Hct | none  |
|  Hydrogenated nitrogen | 1.5 g/dL | pH, PCO2, PO2, Na+, K+, Ca++, Cl-, Hct | none  |
|  Hydrogenated sulfur | 1.5 g/dL | pH, PCO2, PO2, Na+, K+, Ca++, Cl-, Hct | none  |
|  Hydrogenated sulfuric acid | 1.5 g/dL | pH, PCO2, PO2, Na+, K+, Ca++, Cl-, Hct | none  |
|  Hydrogenated sulfuric acid | 1.5 g/dL | pH, PCO2, PO2, Na+, K+, Ca++, Cl-, Hct | none  |
|  Hydrogenated sodium | 1.5 g/dL | pH, PCO2, PO2, Na+, K+, Ca++, Cl-, Hct | none  |
|  Hydrogenated sodium | 1.5 g/dL | pH, PCO2, PO2, Na+, K+, Ca++, Cl-, Hct | none  |
|  Hydrogenated sodium | 1.5 g/dL | pH, PCO2, PO2, Na+, K+, Ca++, Cl-, Hct | none  |
|  Hydrogenated sodium | 1.5 g/dL | pH, PCO2, PO2, Na+, K+, Ca++, Cl-, Hct | none  |
|  Hydrogenated sodium | 1.5 g/dL | pH, PCO2, PO2, Na+, K+, Ca++, Cl-, Hct | none  |
|  Hydrogenated sodium | 1.5 g/dL | pH, PCO2, PO2, Na+, K+, Ca++, Cl-, Hct | none  |

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|  Substance | Test Concentration(s) | Analyte(s) tested | Analytes not tested  |
| --- | --- | --- | --- |
|  Hydroxbutyrate | 104 mg/dL 208 mg/dL | PCO2, PO2, Na+, Ca++, Cl-, Hct | pH  |
|  Hydroxyurea | 183 mg/dL | pH, PCO2, PO2, Na+, K+, Ca++, Cl-, Hct | none  |
|  Hematocrit | 10%PCV 20% PCV | pH, PCO2, PO2, Na+, K+, Ca++, Cl- | Hct  |
|  Hemolysis | 100 mg/dL 500mg/dL | pH, PCO2, PO2, Na+, K+, Ca++, Cl-, Hct | none  |
|  Heparin | 11.8 mg/dL 58.8 mg/dL | pH, PCO2, PO2, Na+, K+, Ca++, Cl-, Hct | none  |
|  Ibuprofen | 50 mg/dL | pH, PCO2, PO2, Na+, K+, Ca++, Cl-, Hct | none  |
|  Iodine | 38 mg/dL | pH, PO2, PO2,Na+, K+, Cl-,Ca++, Hct | none  |
|  Lactic acid | 59 mg/dL 90 mg/dL | PCO2, PO2, Na+, Ca++, Cl-, Hct | pH  |
|  Lithium | 2.22 mg/dL | pH, PCO2, PO2, Na+, K+, Ca++, Cl-, Hct | none  |
|  Magnesium Chloride | 47.6 mg/dL | Na+, K+, Ca++, Cl-, Hct | pH, PCO2, PO2  |
|  Ofloxacin | 6 μg/L | pH, PCO2, PO2, Na+, K+, Ca++, Cl-, Hct | none  |
|  PCO2 | 60 mm/Hg PCO2 | PO2, Na+, K+, Ca++ Cl-, Hct | pH, PCO2  |
|  Phosphate | 24mg/dL 48 mg/mL | PCO2, PO2, K+, Ca++, Hct | pH, Na+  |
|  Potassium Chloride | 60 mg/dL | pH, PCO2, PO2, Na+, Ca++, Hct | K+, Cl-  |
|  Potassium thiocyanate | 20 mg/dL | Na+, Ca++, Cl-, Hct | pH, PCO2, PO2, K+  |
|  Salicylic Acid | 30 mg/dL 60 mg/dL | PCO2, PO2, Na+, Cl-,Ca++,Hct | pH  |
|  Sodium Chloride | 117 mg/dL | pH, PCO2, PO2, K+, Ca++, Hct | Na+, Cl-  |
|  Sodium Chloride | 100 mg/dL | PCO2, PO2, Na+, K+, Ca++, Hct | pH  |
|  Sodium Chloride | 100 mg/dL | PCO2, PO2, Na+, K+, Ca++, Hct | pH  |
|  Sodium Chloride | 100 mg/dL | PCO2, PO2, Na+, K+, Ca++, Hct | pH  |

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The following table indicates the lowest concentration of substance tested that resulted in significant interference on the results of either one or both levels of analyte. An asterisk in the result column indicates that the result was not significantly affected by the concentration of substance tested.

|  Measurand | Interfering Substance | Concentration of substance tested | Blood Sample Value | Absolute Difference in pH Units  |
| --- | --- | --- | --- | --- |
|  pH | Acetaminophen | 20.01 mg/dL | pH: 7.5 | -0.034  |
|   |   |   |  pH: 7.3 | *  |
|   |  Bromide | 185.20 mg/dL | pH: 7.5 | -0.027  |
|   |   |   |  pH: 7.3 | *  |
|   |  Calcium Chloride | 27.27 mg/dL | pH: 7.5 | *  |
|   |   |   |  pH: 7.3 | -0.024  |
|   |  Ethanol | 400 mg/dL | pH: 7.5 | -0.024  |
|   |   |   |  pH: 7.3 | *  |
|   |  Hematocrit | 20% | pH: 7.5 | -0.022  |
|   |   |   |  pH: 7.3 | *  |
|   |  Hemoglobin | 500 mg/dL | pH: 7.5 | 0.029  |
|   |   |   |  pH: 7.3 | 0.036  |
|   |  Heparin | 58.82 mg/dL | pH: 7.5 | *  |
|   |   |   |  pH: 7.3 | -0.034  |
|   |  Hydroxycarbamide (Hydroxyurea) | 182.52 mg/dL | pH: 7.5 | *  |
|   |   |   |  pH: 7.3 | -0.031  |
|   |  Iodide | 37.94 mg/dL | pH: 7.5 | *  |
|   |   |   |  pH: 7.3 | -0.025  |
|   |  Potassium Chloride | 59.64 mg/dL | pH: 7.5 | -0.036  |
|  pH: 7.3 |   |   | *  |   |

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|   | Sodium Chloride | 117 mg/dL | pH: 7.5 | -0.024  |
| --- | --- | --- | --- | --- |
|   |   |   |  pH: 7.3 | -0.021  |
|   |  Sodium Oxalate | 168 mg/dL | pH: 7.5 | *  |
|   |   |   |  pH: 7.3 | -0.032  |
|  Measurand | Interfering Substance | Concentration of Substance Tested | Blood Sample Value | Percent Bias  |
|  PCO2 | Acetaminophen | 20.01 mg/dL | PCO2: 70 mmHg | 10.15%  |
|   |   |   |  PCO2: 40 mmHg | *  |
|   |  Acetylsalicylic acid | 39.09 mg/dL | PCO2: 70 mmHg | 8.01%  |
|   |   |   |  PCO2: 40 mmHg | *  |
|   |  Ethanol | 400 mg/dL | PCO2: 70 mmHg | 9.54%  |
|   |   |   |  PCO2: 40 mmHg | *  |
|   |  Hydroxybutyrate | 104 mg/dL | PCO2: 70 mmHg | 8.49%  |
|   |   |   |  PCO2: 40 mmHg | *  |
|   |  Iodide | 37.94 mg/dL | PCO2: 70 mmHg | -10.00%  |
|   |   |   |  PCO2: 40 mmHg | -8.69%  |
|   |  Lactic Acid | 59.40 mg/dL | PCO2: 70 mmHg | 8.67%  |
|   |   |   |  PCO2: 40 mmHg | *  |
|   |  Potassium Chloride | 59.64 mg/dL | PCO2: 70 mmHg | 11.15%  |
|   |   |   |  PCO2: 40 mmHg | *  |
|   |  Bicarbonate (NaHCO3) | 294 mg/dL | PCO2: 70 mmHg | -14.46%  |
|   |   |   |  PCO2: 40 mmHg | -17.44%  |
|  Measurand | Interfering Substance | Concentration of Substance Tested | Blood Sample Value | Percent Bias  |
|  PO2 | Acetylsalicylic acid | 39.09 mg/dL | PO2: 100 mg/dL | *  |
|   |   |   |  PO2: 70 mg/dL | -10.11%  |
|   |  Hematocrit | 20% PCV | PO2: 100 mg/dL | *  |
|   |   |   |  PO2: 70 mg/dL | 12.13%  |
|   |  Lactic Acid | 90 mg/dL | PO2: 100 mg/dL | *  |
|   |   |   |  PO2: 70 mg/dL | 9.74%  |
|   |  PCO2 | 60 mmHg | PO2: 100 mg/dL | *  |
|   |   |   |  PO2: 70 mg/dL | 9.60%  |
|   |  Salicylic acid | 59.94 mg/dL | PO2: 100 mg/dL | *  |
|   |   |   |  PO2: 70 mg/dL | 14.98%  |
|   |  Sodium Chloride | 117 mg/dL | PO2: 100 mg/dL | *  |
|   |   |   |  PO2: 70 mg/dL | 9.22%  |

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|  Measurand | Interfering Substance | Concentration of Substance Tested | Blood Sample Value | Percent Bias  |
| --- | --- | --- | --- | --- |
|  Na+ | Calcium Chloride | 55.50 mg/dL | Na+: 150 mmol/L | 3.26%  |
|   |   |   |  Na+: 130 mmol/L | 4.99%  |
|   |  Dobutamine hydrochloride | 22.30 mg/dL | Na+: 150 mmol/L | *  |
|   |   |   |  Na+: 130 mmol/L | 5.62%  |
|  Measurand | Interfering Substance | Concentration of Substance Tested | Blood Sample Value | Percent Bias  |
|  K+ | Acetylsalicylic acid | 65.22 mg/dL | K+: 5 mmol/L | 17.21%  |
|   |   |   |  K+: 3 mmol/L | *  |
|   |  Dobutamine hydrochloride | 22.30 mg/dL | K+: 5 mmol/L | *  |
|   |   |   |  K+: 3 mmol/L | 13.97%  |
|   |  Hemoglobin | 100 mg/dL | K+: 5 mmol/L | 30.10%  |
|   |   |   |  K+: 3 mmol/L | 28.16%  |
|   |  Hydroxybutyrate | 208 mg/dL | K+: 5 mmol/L | 12.28%  |
|   |   |   |  K+: 3 mmol/L | 16.87%  |
|   |  Iodide | 37.94 mg/dL | K+: 5 mmol/L | *  |
|   |   |   |  K+: 3 mmol/L | 24.20%  |
|   |  Lactic Acid | 90 mg/dL | K+: 5 mmol/L | 13.05%  |
|   |   |   |  K+: 3 mmol/L | *  |
|   |  PCO2 | 60 mmHg | K+: 5 mmol/L | 10.13%  |
|   |   |   |  K+: 3 mmol/L | *  |
|   |  Salicylic acid | 29.97 mg/dL | K+: 5 mmol/L | 10.54%  |
|   |   |   |  K+: 3 mmol/L | *  |
|   |  Bicarbonate (NaHCO3) | 294 mg/dL | K+: 5 mmol/L | 21.51%  |
|  K+: 3 mmol/L |   |   | 10.31%  |   |

{22}

|  Measurand | Interfering Substance | Concentration of Substance Tested | Blood Sample Value | Percent Bias  |
| --- | --- | --- | --- | --- |
|  iCa++ | Halothane | 14.98 mg/dL | Ca++: 2 mmol/L | *  |
|   |   |   |  Ca++: 1 mmol/L | 11.20%  |
|   |  Heparin | 58.82 mg/dL | Ca++: 2 mmol/L | -12.68%  |
|   |   |   |  Ca++: 1 mmol/L | -14.06%  |
|   |  Magnesium Chloride | 47.61 mg/dL | Ca++: 2 mmol/L | 13.91%  |
|   |   |   |  Ca++: 1 mmol/L | 16.86%  |
|   |  Bicarbonate (NaHCO3) | 294 mg/dL | Ca++: 2 mmol/L | -27.07%  |
|   |   |   |  Ca++: 1 mmol/L | -21.17%  |
|   |  Phosphate (NaH2PO4) | 24 mg/dL | Ca++: 2 mmol/L | -12.14%  |
|   |   |   |  Ca++: 1 mmol/L | -12.34%  |
|   |  Sodium Oxalate | 168 mg/dL | Ca++: 2 mmol/L | -94.16%  |
|  Ca++: 1 mmol/L |   |   | -86.21%  |   |
|  Measurand | Interfering Substance | Concentration of Substance Tested | Blood Sample Value | Percent Bias  |
|  Cl- | Acetylsalicylic acid | 39.09 mg/dL | Cl-: 110 mmol/L | 7.72%  |
|   |   |   |  Cl-: 90 mmol/L | 5.11%  |
|   |  Albumin | +3 g/dL (added to whole blood sample for a total albumin concentration of approx. 8.0 g/dL) | Cl-: 110 mmol/L | 5.13%  |
|   |   |   |  Cl-: 90 mmol/L | 7.19%  |
|   |  Bromide (NaBr) | 185.20 mg/dL | Cl-: 110 mmol/L | *  |
|   |   |   |  Cl-: 90 mmol/L | 6.38%  |
|   |  Iodide | 37.94 mg/dL | Cl-: 110 mmol/L | -7.60%  |
|   |   |   |  Cl-: 90 mmol/L | -11.76%  |
|   |  Potassium Thiocyanate | 20.06 mg/dL | Cl-: 110 mmol/L | 10.81%  |
|   |   |   |  Cl-: 90 mmol/L | 13.41%  |
|   |  Salicylic acid | 29.97 mg/dL | Cl-: 110 mmol/L | 11.28%  |
|  Cl-: 90 mmol/L |   |   | 9.88%  |   |

{23}

|   | Bicarbonate (NaHCO3) | 294 mg/dL | Cl-: 110 mmol/L | 7.72%  |
| --- | --- | --- | --- | --- |
|   |   |   |  Cl-: 90 mmol/L | 8.79%  |
|   |  Sodium Oxalate | 168 mg/dL | Cl-: 110 mmol/L | 5.01%  |
|   |   |   |  Cl-: 90 mmol/L | 6.47%  |
|  Measurand | Interfering Substance | Concentration of Substance Tested | Blood Sample Value | Percent Bias  |
|  Hct | Albumin | +3 g/dL (added to whole blood sample for a total albumin concentration of approx. 8.0 g/dL) | Hct: 55% | * 10.29%  |
|   |   |   |  Hct: 35% | 6.03%  |
|   |  Bromide (NaBr) | 185.20 mg/dL | Hct: 55% | * 13.65%  |
|   |   |   |  Hct: 35% | -6.98%  |
|   |  Calcium Chloride | 55.50 mg/dL | Hct: 55% | -6.11%  |
|   |   |   |  Hct: 35% | *  |
|   |  Dextran | 3 g/dL | Hct: 55% | *  |
|   |   |   |  Hct: 35% | 10.24%.  |
|   |  Dobutamine hydrochloride | 22.30 mg/dL | Hct: 55% | *  |
|   |   |   |  Hct: 35% | 7.76%  |
|   |  Ethanol | 400 mg/dL | Hct: 55% | *  |
|   |   |   |  Hct: 35% | -6.61%  |
|   |  Magnesium Chloride | 47.61 mg/dL | Hct: 55% | -6.40%  |
|   |   |   |  Hct: 35% | -9.39%  |
|   |  Potassium Chloride | 59.64 mg/dL | Hct: 55% | -6.27%  |
|   |   |   |  Hct: 35% | *  |
|   |  Sodium Chloride | 117 mg/dL | Hct: 55% | *  |
|   |   |   |  Hct: 35% | -6.36%  |
|   |  Bicarbonate (NaHCO3) | 58.8 mg/dL | Hct: 55% | *  |
|   |   |   |  Hct: 35% | -7.72%  |

*indicates that no significant interference was observed at the concentration of substance tested.

{24}

The following table represents substances that were tested without significant effects on test results:

|  Interfering substance | Highest concentration tested that did not demonstrate significant interference | Analytes tested  |
| --- | --- | --- |
|  Albumin | + 1.5 g/dL (for a total albumin concentration of approx. 6.5 g/dL) | Na+, K+, Ca++, Cl-, Hct  |
|  Ascorbic acid | 6.02 mg/dL | PCO2, PO2, Na+, K+, Ca++, Cl-, Hct  |
|  Benzylkonium Chloride | 0.80 mg/dL | Na+, K+, Ca++, Cl-, Hct  |
|  Bilirubin | 15 mg/dL | pH, PCO2, PO2, Na+, K+, Ca++, Cl-, Hct  |
|  Cysteine | 12.12 mg/dL | pH, PCO2, PO2, Na+, K+, Ca++, Cl-, Hct  |
|  Lithium | 2.24 mg/dL | pH, PCO2, PO2, Na+, K+, Ca++, Cl-, Hct  |
|  Ofloxacin | 6 ug/mL | pH, PCO2, PO2, Na+, K+, Ca++, Cl-, Hct  |
|  Glyceryl tridodecanoate | 358 mg/dL | Na+, K+, Ca++, Cl-, Hct  |
|  Hydroxycarbamide | 182.52 mg/dL | PCO2, PO2, Na+, K+, Ca++, Cl-, Hct  |
|  Cholesterol | 500 mg/dL | pH, PCO2, PO2, Na+, K+, Ca++, Cl-, Hct  |
|  Triglycerides | 1500 mg/dL | pH, PCO2, PO2, Na+, K+, Ca++, Cl-, Hct  |

The sponsor included the following limitation in the labeling regarding interference of hemolysis on the potassium results:

"Hemolysis will increase the potassium measurement on i15 system due to release of potassium from the red blood cells. When the amount of hemoglobin in plasma is increased by 500 mg/dL, the increase in K⁺ measurement tested on i15 system is about 36%; when the amount of hemoglobin in plasma is increased by 100 mg/dL, the increase in K⁺ measurement tested on i15 system is about 29%."

Interference of Elevated WBC count on Hematocrit:

The sponsor performed a study to evaluate the effects of an elevated WBC count on the devices hematocrit measurement. Whole blood collected from a single healthy adult volunteer in lithium heparin, was processed to obtain an elevated WBC count as determined by analysis on Siemens XP-300 by centrifuging to allow collection of WBC and platelets. This WBC concentrate was added to otherwise untreated, heparinized whole blood to achieve a bias between the treated and untreated whole blood of approximately 50,000 WBC cu/mm. The study demonstrated that the

{25}

addition of 50,000 WBC cu/mL results in an increase in HCT %PCV measured by the EDAN i15 relative to spun hematocrit %PCV by 4.43% PCV (absolute) or 11% (relative).

The sponsor included the following limitation in the labeling:

“NOTE:
The addition of 50,000 WBC cu/mL to a blood sample with 6.1 x 10⁹ WBC cu/mL causes an increase in Hct %PCV measured by the EDAN i15 relative to spun hematocrit %PCV by 4.43% PVC (absolute) (4.02 to 4.84% PCV) or 11% (relative) exceeding the Total Allowable Error defined in CLIA’88.”

f. Assay cut-off:

Not applicable.

2. Comparison studies:

a. Method comparison with predicate device:

The method comparison study was performed at 4 point-of-care (POC) sites by 11 POC personnel, and three clinical laboratory sites to compare the results obtained from the candidate device to those obtained with the predicate device, Siemens Rapidpoint 400 Systems. At least 50 patient samples were selected from venous whole blood and arterial whole blood left over from clinical analysis were tested at each of the 4 POC sites. In order to cover the claimed measuring range, 8% of the specimens were altered. Calcium balanced heparin was used as the anticoagulant in the arterial whole blood samples and lithium heparin was used in the whole blood venous samples. The tables below shows the data from the 4 POC sites, the three clinical lab sites, and the combined POC and clinical lab data.

EDAN i15 vs Siemens Rapidpoint 400 Method Comparison Data

|  Analyte | Site | N | Range | Slope | Intercept | r-value  |
| --- | --- | --- | --- | --- | --- | --- |
|  pH | POC 1-4 | 257 | 6.826 - 7.675 | 1.0130 | -0.0961 | 0.9909  |
|   |  all Lab | 228 | 6.531 - 7.791 | 1.0085 | -0.640 | 0.9940  |
|   |  all Sites | 488 | 6.531 - 7.791 | 1.0105 | -0.0778 | 0.9933  |
|  PCO2 (mmHg) | POC 1-4 | 257 | 18.0 - 144.8 | 1.0285 | -1.5528 | 0.9841  |
|   |  all Lab | 226 | 10.9 - 144.9 | 0.9523 | 1.0417 | 0.9916  |
|   |  all Sites | 483 | 10.9 - 144.9 | 0.9843 | 0.1813 | 0.9879  |

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|  Analyte | Site | N | Range | Slope | Intercept | r-value  |
| --- | --- | --- | --- | --- | --- | --- |
|  PO2 (mmHg) | POC 1-4 | 257 | 17 - 585 | 1.0368 | -4.1355 | 0.9974  |
|   |  all Lab | 229 | 10 - 661 | 1.0018 | 0.2151 | 0.9989  |
|   |  all Sites | 486 | 10 - 661 | 1.0119 | -1.0639 | 0.9983  |
|  Na+ (mmol/L) | POC 1-4 | 257 | 110 - 170 | 0.9787 | 2.5631 | 0.9802  |
|   |  all Lab | 229 | 101 - 180 | 0.9909 | 0.8032 | 0.9952  |
|   |  all Sites | 486 | 101 - 180 | 0.9886 | 1.1358 | 0.9923  |
|  K+ (mmol/L) | POC 1-4 | 257 | 2.4 - 9.0 | 0.9838 | 0.0250 | 0.9968  |
|   |  all Lab | 230 | 2.6 - 8.2 | 0.9868 | 0.0450 | 0.9963  |
|   |  all Sites | 487 | 2.4 - 9.0 | 0.9895 | 0.0164 | 0.9968  |
|  Cl- (mmol/L) | POC 1-4 | 257 | 77 - 137 | 1.0188 | -2.2648 | 0.9821  |
|   |  all Lab | 227 | 66 - 139 | 1.0000 | 0.2599 | 0.9899  |
|   |  all Sites | 484 | 66 - 139 | 1.0012 | -0.1469 | 0.9875  |
|  Ca++ (mmol/L) | POC 1-4 | 257 | 0.47 - 1.82 | 0.9568 | 0.0428 | 0.9695  |
|   |  all Lab | 228 | 0.30 - 2.42 | 0.9919 | 0.0228 | 0.9921  |
|   |  all Sites | 485 | 0.30 - 2.42 | 0.9848 | 0.0200 | 0.9854  |
|  Hct (%) | POC 1-4 | 257 | 21 - 60 | 0.9853 | 0.8173 | 0.9891  |
|   |  all Lab | 230 | 13 - 72 | 0.9842 | 0.6787 | 0.9933  |
|   |  all Sites | 487 | 13 - 72 | 0.9827 | 0.8306 | 0.9917  |

b. Matrix comparison:

Not applicable. For use with 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.

{27}

# 5. Expected values/Reference range:

The reference range values included in the labeling are cited from literature and are shown in the table below.

|  Parameter | Reference Range  |   |   |   |
| --- | --- | --- | --- | --- |
|   |  Arterial |   | Venous  |   |
|  pH | 7.35 - 7.45[1] |   | 7.31 - 7.41[1]  |   |
|  pO2(mmHg) | 80 - 105[1] |   | 35 - 40[1]  |   |
|  pCO2(mmHg) | 35 - 45[1] |   | 41 - 51[1]  |   |
|  Na+(mmol/L) | 138 - 146[1] |   | 138 - 146[1]  |   |
|  K+(mmol/L) | 3.5 - 4.9[1] |   | 3.5 - 4.9[1]  |   |
|  Cl-(mmol/L) | 98 - 109[1] |   | 98 - 109[1]  |   |
|  Ca++(mmol/L) | 1.12 - 1.32[1] |   | 1.12 - 1.32[1]  |   |
|  Parameter | Reference Range  |   |   |   |
|   |  Male | Female | Male | Female  |
|  Hct (%) | 41- 53[2] | 36 - 46[2] | 41- 53[2] | 36 - 46[2]  |

# References:

1. Burtis, Carl A. and Ashwood, Edward R., ed. 1994. Tietz Textbook of Clinical Chemistry. Philadelphia, PA: W. B. Saunders Co.
2. Reference Ranges Table in Laboratory Medicine: the selection and interpretation of clinical laboratory studies, D.A. Noe and R.C. Rock, eds., William &amp; Wilkins, Baltimore, 1994, pg. 878.

# N. Instrument Name:

EDAN i15 Blood Gas and Chemistry Analyzer

# O. System Descriptions:

# 1. Modes of Operation:

Does the applicant's device contain the ability to transmit data to a computer, webserver, or mobile device?

Yes __X__ or No ______

{28}

Does the applicant’s device transmit data to a computer, webserver, or mobile device using wireless transmission?

Yes ☐ X ☐ or No ☐

2. Software:

FDA has reviewed applicant’s Hazard Analysis and software development processes for this line of product types:

Yes ☐ X ☐ or No ☐

3. Specimen Identification:

Bar code

4. Specimen Sampling and Handling:

Lithium heparinized and calcium balanced heparinized whole blood from syringes and capillary tubes.

5. Calibration:

Each lot of EDAN i15 Test Cartridge is calibrated during the manufacturing process, and bar coded with relevant calibration information as well as product identification, lot number and expiration date. Prior to running a sample, the cartridge’s bar code is read into the analyzer by scanning the cartridge bar code label. Once inserted into the analyzer, a calibration of all electrochemical sensors is performed using the precision buffer solution contained in the EDAN i15 Calibrator Fluid Pack. During the calibration and measurement processes, diagnostic tests are automatically performed to assure correct operation of the instrument and measurement of the cartridge. These tests include automatic checks of the cartridge for packaging integrity, proper cartridge temperature control, and proper equilibration behavior of the sensors during calibration and measurement, automatic detection of bubbles and short sample during aspiration.

6. Quality Control:

EDAN i15 Blood Gas and Electrolyte Control: an ampouled, three level aqueous quality control solutions.

EDAN i15 Hematocrit control: Two, single- level aqueous hematocrit controls in sealed glass ampoules representing high and low physiological range of hematocrit simulated by conductivity.

29

{29}

P. Other Supportive Instrument Performance Characteristics Data Not Covered In The "Performance Characteristics" Section above:

Not applicable.

Q. Proposed Labeling:

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

R. Conclusion:

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

30

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**Source:** [https://fda.innolitics.com/submissions/CH/subpart-b%E2%80%94clinical-chemistry-test-systems/CHL/K151978](https://fda.innolitics.com/submissions/CH/subpart-b%E2%80%94clinical-chemistry-test-systems/CHL/K151978)

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