COBAS B 123 POC SYSTEM, COBAS B 123 AUTOQC PACK TRI-LEVEL, COBAS B 123 AUTOCVC PACK, ROCHE COMBITROL PLUS B

K111188 · Roche Diagnostics · CHL · May 14, 2012 · Clinical Chemistry

Device Facts

• Record ID: K111188
• Device Name: COBAS B 123 POC SYSTEM, COBAS B 123 AUTOQC PACK TRI-LEVEL, COBAS B 123 AUTOCVC PACK, ROCHE COMBITROL PLUS B
• Applicant: Roche Diagnostics
• Product Code: CHL · Clinical Chemistry
• Decision Date: May 14, 2012
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1120
• Device Class: Class 2

Indications for Use

The cobas b 123 POC system is a fully automated POC system for whole blood in vitro measurement of pH, blood gases (BG), electrolytes Na⁺, K⁺, iCa²⁺ (ISE), hematocrit (Hct), metabolites (Glu, Lac), total hemoglobin (tHb), hemoglobin derivatives (O₂Hb, HHb, COHb, MetHb), and oxygen saturation (SO₂). In addition, the cobas b 123 POC system calculates derived parameters. It is dedicated for use in a Point-of-Care environment and laboratory. The integrated AutoQC module and the oximeter module are available as an option. pH, pO₂ and pCO₂: pH, pO₂ and pCO₂ measurements are used in the diagnosis and treatment of life-threatening acid-base disturbances. Sodium (Na⁺): sodium measurements are used in the diagnosis and treatment of aldosteronism, diabetes insipidus, adrenal hypertension, Addison's disease, dehydration, inappropriate antidiuretic secretion, or other diseases involving electrolyte imbalance. Potassium (K⁺): potassium measurements are used to monitor electrolyte balance in the diagnosis and treatment of disease conditions characterized by low or high blood potassium levels. Calcium (Ca²⁺): 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). Hematocrit (Hct): hematocrit measurements are used to distinguish normal from abnormal states of whole blood, such as anemia and erythrocytosis (an increase in the number of red cells). Glucose (Glu): glucose measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus and idiopathic hypoglycemia, and of pancreatic islet cell carcinoma. Lactate (Lac): Lactate measurements are used to evaluate the acid-base status and are used in the diagnosis and treatment of lactic acidosis (abnormally high acidity of the blood.) Total Hemoglobin (tHb): total hemoglobin measurements are used to measure the hemoglobin content of whole blood for the detection of anemia. O₂Hb: oxyhemoglobin as a fraction of total hemoglobin. COHb: carboxyhemoglobin measurements are used to determine the carboxyhemoglobin content of human blood as an aid in the diagnosis of carbon monoxide poisoning. MetHb: methemoglobin as a fraction of total hemoglobin. HHb: reduced hemoglobin as a fraction of total hemoglobin. SO₂: oxygen saturation, more specifically the ratio between the concentration of oxyhemoglobin and oxyhemoglobin plus reduced hemoglobin.

Device Story

The cobas b 123 POC system is a modular, automated analyzer for whole blood analysis. It utilizes thick film electrochemical sensor technology (potentiometric for pH, pCO2, Na+, K+, iCa2+; amperometric for pO2, glucose, lactate) and conductivity for hematocrit. An optional oximeter module uses spectrophotometry and an ultrasonic hemolyzer to measure hemoglobin derivatives (tHb, O2Hb, HHb, COHb, MetHb, SO2). The system features a Linux-based touch screen interface, a self-contained disposable sample/reagent delivery system, and an optional AutoQC module for automated quality control. Smart memory chips in sensors and reagent packs track lot numbers, expiration, and usage. Operated by clinicians in POC or laboratory settings, the device provides rapid results to inform clinical decision-making for critical care patients. It benefits patients by enabling immediate assessment of acid-base status, electrolyte balance, and oxygenation, facilitating timely therapeutic interventions.

Clinical Evidence

Bench testing only. Precision studies (CLSI EP5-A2) conducted with N=80 replicates per level. Linearity studies (CLSI EP6) confirmed measuring ranges. Interference studies (CLSI EP7-A2) evaluated potential substances. Method comparison study across 6 sites (2 lab, 4 POC) compared results against predicate devices, showing high correlation (r > 0.97 for all analytes).

Technological Characteristics

Modular analyzer with thick-film microelectrode array technology. Potentiometric sensors (pH, pCO2, Ca2+, K+, Na+), amperometric sensors (pO2, Glucose, Lactate), and spectrophotometric oximeter module. Conductivity-based hematocrit measurement. Disposable self-contained reagent/sample delivery system with smart memory chip tracking. Linux-based software. Operating temperature 15-32°C.

Indications for Use

Indicated for use in Point-of-Care and laboratory environments for the quantitative measurement of pH, blood gases, electrolytes, hematocrit, metabolites, and hemoglobin derivatives in whole blood to aid in the diagnosis and treatment of acid-base disturbances, electrolyte imbalances, anemia, carbohydrate metabolism disorders, and carbon monoxide poisoning.

Regulatory Classification

Identification

A blood gases (PCO2 , PO2 ) and blood pH test system is a device intended to measure certain gases in blood, serum, plasma or pH of blood, serum, and plasma. Measurements of blood gases (PCO2 , PO2 ) and blood pH are used in the diagnosis and treatment of life-threatening acid-base disturbances.

Predicate Devices

• cobas b 221 (OMNI S) Blood Gas System (K032311)
• Hitachi 902 Analyzer (K921661)
• cobas c 501 Analyzer (K060373/A001)
• COMBITROL PLUS B / AUTOTROL PLUS B (K032453)

Submission Summary (Full Text)

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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION INSTRUMENT AND ASSAY TEMPLATE

A. 510(k) Number:
k111188

B. Purpose for Submission:
New Device

C. Measurand:
pH, pO2, pCO2, sodium, potassium, ionized calcium, Hct, tHb, O2Hb, HHb, COHb, MetHb, SO2, lactic acid, glucose

D. Type of Test:
Quantitative

E. Applicant:
Roche Diagnostics Corporation

F. Proprietary and Established Names:
Cobas® b 123 POC System, Cobas® b 123 AutoQC Pack Tri-Level, Cobas® b 123 AutoCVC Pack, Roche COMBITROL PLUS B

G. Regulatory Information:

| Product Code | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| CHL | Class II | 21 CFR § 862.1120
Blood gases (pCO2, pO2) and blood pH test system | 75 |
| JGS | Class II | 21 CFR § 862.1665
Sodium test system | 75 |
| CEM | Class II | 21 CFR § 862.1600
Potassium test system | 75 |
| JFP | Class II | 21 CFR § 862.1145 | 75 |

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| | | Calcium test system | |
| --- | --- | --- | --- |
| GKF | ass II | 21 CFR § 864.5600
Hematocrit automated instrument | 81 |
| CGA | Class II | 21 CFR § 862.1345
Glucose test system | 75 |
| KHP | Class I, meets limitations of exemptions per 21 CFR § 862.9 (c)(9) | 21 CFR § 862.1450
Lactic acid test system | 75 |
| KHG | Class II | 21 CFR § 864.7500
Whole blood hemoglobin assays (tHb) | 81 |
| GGZ | Class II | 21 CFR § 864.7500
Whole blood hemoglobin assays (Oxyhemoglobin) | 81 |
| GKA | Class II | 21 CFR § 864.7500
Deoxyhemoglobin | 81 |
| GHS | Class II | 21 CFR § 864.7425
Carboxyhemoglobin | 81 |
| KHG | Class II | 21 CFR § 864.5620
Methemoglobin | 81 |
| GLY | Class II | 870.1230 Oximeter
Oxygen Saturation | 81 |
| JJY | Class I, reserved | 21 CFR § 862.1660
Quality control material (assayed and unassayed) | 75 |

H. Intended Use:

1. Intended use(s):

See indications for use statements below.

2. Indication(s) for use:

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Device Name: cobas® b 123 POC System

The cobas b 123 POC system is a fully automated POC system for whole blood in vitro measurement of pH, blood gases (BG), electrolytes Na⁺, K⁺, iCa²⁺ (ISE), hematocrit (Hct), metabolites (Glu, Lac), total hemoglobin (tHb), hemoglobin derivatives (O₂Hb, HHb, COHb, MetHb), and oxygen saturation (SO₂). In addition, the cobas b 123 POC system calculates derived parameters.

It is dedicated for use in a Point-of-Care environment and laboratory. The integrated AutoQC module and the oximeter module are available as an option.

pH, pO₂ and pCO₂: pH, pO₂ and pCO₂ measurements are used in the diagnosis and treatment of life-threatening acid-base disturbances.

Sodium (Na⁺): sodium measurements are used in the diagnosis and treatment of aldosteronism, diabetes insipidus, adrenal hypertension, Addison's disease, dehydration, inappropriate antidiuretic secretion, or other diseases involving electrolyte imbalance.

Potassium (K⁺): potassium measurements are used to monitor electrolyte balance in the diagnosis and treatment of disease conditions characterized by low or high blood potassium levels.

Calcium (Ca²⁺): 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).

Hematocrit (Hct): hematocrit measurements are used to distinguish normal from abnormal states of whole blood, such as anemia and erythrocytosis (an increase in the number of red cells).

Glucose (Glu): glucose measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus and idiopathic hypoglycemia, and of pancreatic islet cell carcinoma.

Lactate (Lac): Lactate measurements are used to evaluate the acid-base status and are used in the diagnosis and treatment of lactic acidosis (abnormally high acidity of the blood.)

Total Hemoglobin (tHb): total hemoglobin measurements are used to measure the hemoglobin content of whole blood for the detection of anemia.

O₂Hb: oxyhemoglobin as a fraction of total hemoglobin.

COHb: carboxyhemoglobin measurements are used to determine the carboxyhemoglobin content of human blood as an aid in the diagnosis of carbon monoxide poisoning.

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MetHb: methemoglobin as a fraction of total hemoglobin.

HHb: reduced hemoglobin as a fraction of total hemoglobin.

$\mathrm{SO}_2$: oxygen saturation, more specifically the ratio between the concentration of oxyhemoglobin and oxyhemoglobin plus reduced hemoglobin.

## Device Name: cobas® b 123 AutoQC Pack Tri-Level

The cobas b 123 AutoQC pack Tri-Level is a multi-analyte control intended for use as control material to monitor the measurement of pH, $\mathrm{PCO}_2$, $\mathrm{PO}_2$, $\mathrm{SO}_2$, $\mathrm{Na}^+$, $\mathrm{K}^+$, $\mathrm{iCa}^{2+}$, Hct, tHb and Hb derivatives as well as glucose and lactate on cobas b 123 systems with an AutoQC module.

## Device Name: cobas® b 123 AutoCVC Pack

The cobas b 123 AutoCVC Pack is a multi-analyte control, intended for use in calibration verification of the measuring range established by the cobas b 123 POC system for pH, $\mathrm{PCO}_2$, $\mathrm{PO}_2$, $\mathrm{SO}_2$, $\mathrm{Na}^+$, $\mathrm{K}^+$, $\mathrm{iCa}^{2+}$, Hct, tHb and Hb derivatives as well as glucose and lactate on cobas b 123 systems with an AutoQC module.

## Device Name: Roche COMBITROL PLUS B

COMBITROL PLUS B is a multi-analyte control intended for use as control material to monitor the measurement of pH, $\mathrm{PCO}_2$, $\mathrm{PO}_2$, $\mathrm{SO}_2$, $\mathrm{Na}^+$, $\mathrm{K}^+$, $\mathrm{iCa}^{2+}$, Hct, tHb and Hb derivatives as well as glucose, lactate, urea/BUN and bilirubin on Roche OMNI S or cobas b 221 analyzers with an oximeter module, and cobas b 123 analyzers (except urea/BUN, and bilirubin). COMBITROL PLUS B control material is not intended for use with analyzers from other manufacturers.

3. Special conditions for use statement(s):

For prescription use.

For Point of Care

4. Special instrument requirements:

Cobas b 123 POC System

## I. Device Description:

The cobas b 123 POC system consists of a modular system analyzer which contains the following components:

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An electrochemical sensor system independent of the reagent delivery system for the following analytes:

- pCO2, pH, calcium, potassium, and sodium (potentiometric measurement)
- pO2 (amperometric measurement)
- Hct (conductivity measurement)
- Glucose and Lactate enzyme (amperometric measurement)

An optionally integrated oximeter module consisting of a spectrometer, measurement and calibration light source, respectively, an ultrasonic hemolyzer and thermostatic components measure SO2, tHb, O2Hb, HHb, COHb, and MetHb

A disposable, self-contained sample and reagent delivery system containing liquid reagents, calibrators and waste container, built-in safety shielded sample port, built-in oximeter cuvette, two peristaltic pump fluidics systems, and built in air filter

The system also includes an optional integrated Auto QC module that uses a disposable cassette containing three levels of QC material.

A smart memory chip is incorporated into each biosensor, reagent pack (sample and reagent delivery system) and AutoQC cassette which tracks and monitors the sensor, reagent pack, AutoQC and AutoCVC cassette usage

**Cobas b 123 AutoQC Pack Tri-Level:**

- 24 single glass ampoules of multi-analyte controls in 3 levels

**Cobas b 123 AutoCVC Pack:**

- 24 single glass ampoules of multi-analyte controls in 6 levels

**Roche COMBITROL PLUS B:**

- Multi-analyte controls available in 3 levels

**J. Substantial Equivalence Information:**

The cobas b 123 POC System is equivalent to cobas b 221 (OMNI S Analyzer) k032311 for the following parameters:

- pH
- pO2
- pCO2
- Na+
- K+

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$\mathrm{Ca2 + }$
Hct
tHb
O2Hb
HHb
COHb
MetHb
SO2

The cobas b 123 POC system is equivalent to Roche Gluco-Quant Glucose/HK assay on the Hitachi 902 (k921661) and the Roche Glucose HK Assay on the cobas c 501 analyzer (k060373/A001) for the measurement of glucose.

The cobas b 123 POC system is equivalent to the Roche Lactate assay on the Hitachi 902 analyzer (k921661) and the Lactate Generation 2 (Gen.2) assay on the cobas c 501 analyzer (k060373) for the measurement of lactate.

The cobas b 123 AutoQC Pack Tri-Level, cobas b 123 AutoCVC Pack, and COMBITROL PLUS B materials are substantially equivalent to the Roche AUTOTROL PLUS B and Roche COMBITROL PLUS B materials - k032453.

Similarities between candidate and predicate devices:

| Characteristic | Candidate Device: cobas b 123 POC System | Predicate Device: cobas b 221 (k032311) |
| --- | --- | --- |
| Intended Use | The cobas b 123 POC system is a fully automated POC system to measure pH, blood gases (BG), electrolytes (ISE), hematocrit (Hct), metabolites (Glu, Lac), total hemoglobin (tHb), hemoglobin derivatives (O2Hb, HHb, COHb, MetHb), and oxygen saturation (SO2). In addition, the cobas b 123 POC system calculates derived parameters. It is dedicated for use in a Point-of-Care environment and laboratory. The integrated AutoQC module and the oximeter module are available as an option. Depending on the equipment configuration of the instrument, the Sensor Cartridge and the Fluid Pack used, the following parameters are measured in human whole blood and QC materials. | Same |

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| Test Principle | Enzymatic (Lactate) Enzymatic (Glucose) | Same |
| --- | --- | --- |
| Blood Gas Measurement | pH and pCO2 by potentiometry pO2 by amperometry | Same |
| Electrolyte Measurement | K+, Na+, and Ca2+ by potentiometry | Same |
| Metabolite Measurement | Glucose and Lactate by amperometry | Same |
| Hemoglobin Measurement | tHb, SO2, O2Hb, HHb, COHb, MetHb:Spectrophotometric | Same |
| Hematocrit Measurement | Conductivity | Same |
| Sensor Technology | Amperometric and potentiometric thick film microelectrode array technology for Glucose and Lactate | Same |
| Sample Introduction | Syringe and capillary aspiration | Same |
| On-Board (In-Use) Reagent Stability | Up to 42 days | Same |
| Reagent Tracking | Memory chip technology for identification, lot specifications, usage tracking and traceability allowing pack to be moved from one system to another | Same |
| QC Material | COMBITROL PLUS B (manual QC) and AUTOTROL PLUS B (automated QC) | Same |
| Calibration | Two-point liquid calibration | Same |
| Graphical User Interface | Menu-driven touch screen | Same |
| Additional Analyzer Hardware | Hard drive and printer | Same |
| Operating System Software | Linux-based | Same |
| System Operating Temperature | 15-32°C | Same |

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| Characteristic | Candidate Device cobas b 123 AutoQC Pack Tri-Level | Predicate Device Roche AUTOTROL PLUS B (k032453) |
| --- | --- | --- |
| Intended use | Intended for use as a quality control material | same |
| Number of Levels | 3 | Same |
| Matrix | Buffered, aqueous electrolyte solution equilibrated with carbon dioxide and oxygen gas mixture | Same |
| Technological Characteristics | The material consists of buffered aqueous electrolyte solutions with clinically relevant concentrations of the targeted analytes, tonometered with precision gas mixtures of carbon dioxide and oxygen to achieve pH and blood gas values that span the range of values typical for such products with the same intended use. A mixture of dyes is used to simulate absorbance of hemoglobin derivatives. Hematocrit is simulated by conductivity. | Same |
| Characteristic | Candidate Device Modified COMBITROL PLUS B | Predicate Device Roche AUTOTROL PLUS B (k032453) |
| --- | --- | --- |
| Intended Use | intended for use as a quality control material | same |
| Number of Levels | 3 | Same |
| Fill Volume | 1.7 mL | Same |
| Matrix | Buffered, aqueous electrolyte solution equilibrated with carbon dioxide and oxygen gas mixture | Same |
| Technological Characteristics | The material consists of buffered aqueous electrolyte solutions with clinically relevant concentrations of | Same |

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| | the targeted analytes,
tonometered with precision
gas mixtures of carbon
dioxide and oxygen to
achieve pH and blood gas
values that span the range
of values typical for such
products with the same
intended use. A mixture of
dyes is used to simulate
absorbance of hemoglobin
derivatives. Hematocrit is
simulated by conductivity. | |
| --- | --- | --- |
| Characteristic | Candidate Device cobas b 123 AutoCVC Pack | Predicate Device Roche AUTOTROL PLUS B (k032453) |
| --- | --- | --- |
| Intended use | Intended for use as a quality control material | same |
| Matrix | Buffered, aqueous electrolyte solution equilibrated with carbon dioxide and oxygen gas mixture | Same |
| Technological Characteristics | The material consists of buffered aqueous electrolyte solutions with clinically relevant concentrations of the targeted analytes, tonometered with precision gas mixtures of carbon dioxide and oxygen to achieve pH and blood gas values that span the range of values typical for such products with the same intended use. A mixture of dyes is used to simulate absorbance of hemoglobin derivatives. Hematocrit is simulated by conductivity. | Same |

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Differences between candidate and predicate devices:

| Characteristic | Candidate Device cobas b 123 POC System | Predicate Device cobas b 221 (k032311) |
| --- | --- | --- |
| Sample Volume | 123 μl | 210 μl |
| Electrochemical Sensors | pH, PO2.PCO2, K+, Na+, Ca2+, Glucose, Reference microelectrode array sensor with up to 28 days in-use life Note: Sensors with Lactate are stable up to 21 days. | pH, PO2.PCO2, K+, Na+, Cl, Ca2+ Reference electrodes with 6 to 16 months in-use life, depending on the electrode type. |
| Electrochemical sensor storage stability | Sensor: 2°C – 8°C for 4 months | Sensor: 25°C for 18 or 24 months, depending on electrode type |
| Auto QC Module | AutoQC Module holds one AutoQC Pack, which is comprised of 24 AUTOTROL PLUS B tri-level ampoules. | QC module holds 120 AUTOTROL PLUS B tri-level ampoules. |
| Characteristic | Candidate Device cobas b 123 POC System | Predicate Device Roche Hitachi Glucose HK Assays: Hitachi 902 (k921661) and cobas c 501 (k060373) |
| --- | --- | --- |
| Sample Type | Whole Blood | Serum, plasma, urine, CSF, and hemolysate |
| Measurement Principle | Amperometric measurement of the detectable product (H2O2) under a polarization voltage of 350 mV. | UV photometric measurement of the detectable product (NADPH) at 340 nm. |
| Characteristic | Candidate Device cobas b 123 POC System | Predicate Device Roche Hitachi Lactate Assays: Hitachi 902 (k921661) and cobas c 501 (k060373) |
| --- | --- | --- |
| Measurement Principle | Amperometric measurement of the detectable product (H2O2) under a polarization voltage of 350 mV. | UV photometric measurement of the detectable product (chromogen) at 340 nm. |

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| Characteristic | Candidate Device cobas b 123 AutoQC Pack Tri-Level | Predicate Device Roche AUTOTROL PLUS B (k032453) |
| --- | --- | --- |
| Auto QC Pack | The AutoQC Pack is comprised of 24 AUTOTROL PLUS B tri-level ampoules. The AutoQC Pack also contains a smart memory chip for tracking and traceability, allowing the pack to be moved from one system to another. | The QC Pack holds 120 AUTOTROL PLUS B tri-level ampoules. The QC Pack does not contain a smart memory chip. |
| Fill Volume | 1.0 mL | 1.7 mL |

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

1. EP5-A2: Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline
2. EP6-A: Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline
3. EP7-A2: Interference Testing in Clinical Testing; Approved Guideline – Second Edition
4. EP9-A2: Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline – Second Edition
5. EP17-A: Protocols for Determination of Limits of Detection and Limits of Quantitation; Approved Guideline
6. IEC 61326-1: Electrical Equipment for Measurement, Control and Lab Use-EMC Requirements (Part 1: General Requirements)
7. IEC 61326-2: Electrical Equipment for Measurement, Control and Lab Use- EMC Requirements (Part 2-6: IVD Equipment)

L. Test Principle:

The cobas b 123 POC system measures the analytes pH, K+, Ca2+, and Na+ use potentiometric sensors which transmit direct signals that relate the content of the sample to be measured. A reference electrode is used to provide a stable, fixed

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potential against which other potential differences can be measured.

Amperometry is used to measure glucose, lactate, and pO2. For this method of measurement, the magnitude of an electrical flow of current proportional to the concentration of the substance being oxidized or reduced at an electrode results in a measurement of glucose, lactate, and pO2 in the blood.

Spectrophotometry is used to measure the analytes: tHb, SO2, O2Hb, HHb, COHb, MetHb. For this method, light passes through the blood samples; specific wavelengths are absorbed and their intensity generates an absorption spectrum used to calculate oximetry parameters.

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

All performance studies were conducted on the cobas b 123 POC system.

# 1. Analytical performance:

# a. Precision/Reproducibility:

A precision study was performed following CLSI EP5-A2 guidance. Within - run and total precision were conducted using control materials and/or tonometered whole blood samples in duplicate in two runs per day for 20 days $(N = 80)$ . Testing was conducted using the cobas b 123 POC syringe mode. Results of the precision studies are as follows:

| pH Precision Data | | | | | | |
| --- | --- | --- | --- | --- | --- | --- |
| Sample | Mean (pH Units) | N | Within run SD | Within run % CV | Total imprecision SD | Total Imprecision %CV |
| Level 1 | 7.149 | 80 | 0.007 | 0.04 | 0.020 | 0.08 |
| Level 2 | 7.393 | 80 | 0.007 | 0.02 | 0.020 | 0.06 |
| Level 3 | 7.543 | 80 | 0.007 | 0.02 | 0.020 | 0.06 |
| Level 4 | 6.883 | 80 | 0.012 | 0.02 | 0.028 | 0.12 |
| Level 5 | 7.731 | 80 | 0.014 | 0.02 | 0.033 | 0.08 |
| pO2 Precision Data | | | | | | |
| --- | --- | --- | --- | --- | --- | --- |
| Sample | Mean (mmHg) | N | Within run SD | Within run % CV | Total imprecision SD | Total Imprecision %CV |
| Blood 1 | 145.4 | 80 | 1.629 | 0.51 | 3.039 | 2.23 |
| Blood 2 | 40.5 | 80 | 1.974 | 1.70 | 3.306 | 6.09 |
| Blood 3 | 352.2 | 80 | 6.614 | 0.59 | 12.553 | 2.49 |
| Level 1 | 58.5 | 80 | 4.550 | 1.79 | 5.076 | 3.00 |

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| pCO2 Precision Data | | | | | | |
| --- | --- | --- | --- | --- | --- | --- |
| Sample | Mean (mmHg) | N | Within run SD | Within run % CV | Total imprecision SD | Total Imprecision % CV |
| Blood 1 | 23.5 | 80 | 1.150 | 0.50 | 1.725 | 2.21 |
| Blood 2 | 72.7 | 80 | 1.570 | 0.51 | 2.180 | 3.18 |
| Blood 3 | 128.6 | 80 | 5.047 | 1.39 | 6.868 | 2.61 |
| Level 1 | 64.2 | 80 | 1.349 | 0.69 | 1.856 | 1.64 |
| Level 2 | 41.9 | 80 | 1.151 | 0.64 | 1.656 | 1.44 |
| Level 3 | 25.7 | 80 | 1.007 | 0.36 | 1.510 | 1.69 |
| Level 4 | 123.5 | 80 | 4.729 | 0.60 | 6.412 | 2.70 |
| Level 5 | 19.2 | 80 | 1.578 | 0.75 | 2.368 | 2.12 |
| Na Precision Data | | | | | | |
| --- | --- | --- | --- | --- | --- | --- |
| Sample | Mean (mmHg) | N | Within run SD | Within run % CV | Total imprecision SD | Total Imprecision % CV |
| Level 1 | 117.4 | 80 | 1.337 | 0.34 | 1.957 | 0.44 |
| Level 2 | 141.0 | 80 | 1.536 | 0.11 | 2.304 | 0.35 |
| Level 3 | 153.7 | 80 | 1.740 | 0.29 | 2.610 | 0.52 |
| Level 4 | 113.2 | 80 | 1.557 | 0.16 | 2.208 | 0.65 |
| Level 5 | 177.5 | 80 | 2.336 | 0.11 | 3.373 | 0.69 |
| K Precision Data | | | | | | |
| --- | --- | --- | --- | --- | --- | --- |
| Sample | Mean (mmHg) | N | Within run SD | Within run % CV | Total imprecision SD | Total Imprecision % CV |
| Level 1 | 2.98 | 80 | 0.051 | 0.37 | 0.102 | 0.57 |
| Level 2 | 4.72 | 80 | 0.066 | 0.15 | 0.134 | 0.37 |
| Level 3 | 7.01 | 80 | 0.088 | 0.32 | 0.177 | 0.74 |
| Level 4 | 9.25 | 80 | 0.153 | 0.16 | 0.352 | 1.26 |
| Level 5 | 2.02 | 80 | 0.088 | 0.30 | 0.198 | 1.44 |

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| iCa Precision Data | | | | | | |
| --- | --- | --- | --- | --- | --- | --- |
| Sample | Mean (mg/dL) | N | Within run SD | Within run % CV | Total imprecision SD | Total Imprecision %CV |
| Level 1 | 6.80 | 80 | 0.040 | 0.61 | 0.067 | 0.77 |
| Level 2 | 4.80 | 80 | 0.030 | 0.24 | 0.050 | 0.37 |
| Level 3 | 2.64 | 80 | 0.030 | 0.74 | 0.050 | 0.92 |
| Level 4 | 8.63 | 80 | 0.062 | 0.25 | 0.103 | 0.78 |
| Level 5 | 1.60 | 80 | 0.030 | 0.63 | 0.050 | 1.89 |
| Hct Precision Data | | | | | | |
| --- | --- | --- | --- | --- | --- | --- |
| Sample | Mean (%) | N | Within run SD | Within run % CV | Total imprecision SD | Total Imprecision %CV |
| Level 1 | 58.9 | 80 | 0.978 | 0.24 | 1.467 | 0.80 |
| Level 2 | 40.9 | 80 | 0.617 | 0.21 | 0.926 | 1.05 |
| Level 3 | 32.5 | 80 | 0.451 | 0.22 | 0.676 | 1.06 |
| Level 5 | 19.0 | 80 | 1.783 | 0.38 | 2.676 | 1.18 |
| Level 6 | 63.6 | 80 | 1.718 | 0.09 | 2.576 | 0.75 |
| Glucose Precision Data | | | | | | |
| --- | --- | --- | --- | --- | --- | --- |
| Sample | Mean (mg/dL) | N | Within run SD | Within run % CV | Total imprecision SD | Total Imprecision %CV |
| Level 1 | 111 | 80 | 0.126 | 0.59 | 0.304 | 1.67 |
| Level 2 | 47.3 | 80 | 0.104 | 0.85 | 0.177 | 2.23 |
| Level 3 | 454.5 | 80 | 0.302 | 0.37 | 1.253 | 2.29 |
| Level 5 | 45.5 | 80 | 0.103 | 0.91 | 0.176 | 3.55 |
| Level 6 | 510 | 80 | 0.329 | 0.77 | 1.307 | 2.77 |
| Lactate Precision Data | | | | | | |
| --- | --- | --- | --- | --- | --- | --- |
| Sample | Mean (mg/dL) | N | Within run SD | Within run % CV | Total imprecision SD | Total Imprecision %CV |
| Level 1 | 96 | 80 | 0.36 | 0.37 | 2.24 | 2.34 |
| Level 2 | 29 | 80 | 0.07 | 0.24 | 0.58 | 2.03 |
| Level 3 | 15 | 80 | 0.05 | 0.32 | 0.42 | 2.65 |
| Level 5 | 57 | 80 | 0.59 | 1.04 | 1.34 | 2.37 |
| Level 6 | 128 | 80 | 0.92 | 0.72 | 3.83 | 3.00 |

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| tHb Precision Data | | | | | | |
| --- | --- | --- | --- | --- | --- | --- |
| Sample | Mean (g/dL) | N | Within run SD | Within run % CV | Total imprecision SD | Total Imprecision % CV |
| Level 1 | 7.1 | 80 | 0.135 | 0.66 | 0.174 | 2.29 |
| Level 2 | 11.5 | 80 | 0.172 | 0.72 | 0.222 | 1.12 |
| Level 3 | 19.6 | 80 | 0.294 | 0.82 | 0.344 | 1.21 |
| Level 5 | 6.1 | 80 | 0.131 | 0.60 | 0.166 | 2.12 |
| Level 6 | 21.7 | 80 | 0.335 | 0.63 | 0.402 | 1.06 |
| O2Hb Precision Data | | | | | | |
| --- | --- | --- | --- | --- | --- | --- |
| Sample | Mean (%) | N | Within run SD | Within run % CV | Total imprecision SD | Total Imprecision % CV |
| Level 1 | 48.3 | 80 | 1.000 | 0.25 | 1.500 | 0.54 |
| Level 2 | 75.8 | 80 | 1.000 | 0.55 | 1.500 | 0.63 |
| Level 3 | 92.0 | 80 | 1.000 | 0.40 | 1.500 | 0.42 |
| Level 5 | 42.1 | 80 | 1.000 | 0.28 | 1.500 | 0.49 |
| Level 6 | 94.3 | 80 | 1.000 | 0.40 | 1.500 | 0.39 |
| HHb Precision Data | | | | | | |
| --- | --- | --- | --- | --- | --- | --- |
| Sample | Mean (%) | N | Within run SD | Within run % CV | Total imprecision SD | Total Imprecision % CV |
| Level 1 | 17.6 | 80 | 1.000 | 0.24 | 1.500 | 0.52 |
| Level 2 | 8.2 | 80 | 1.000 | 1.78 | 1.500 | 2.02 |
| Level 3 | 2.7 | 80 | 1.000 | 4.73 | 1.500 | 4.92 |
| Level 5 | 19.7 | 80 | 1.000 | 0.21 | 1.500 | 0.37 |
| Level 6 | 1.9 | 80 | 1.000 | 6.88 | 1.500 | 6.58 |
| COHb Precision Data | | | | | | |
| --- | --- | --- | --- | --- | --- | --- |
| Sample | Mean (%) | N | Within run SD | Within run % CV | Total imprecision SD | Total Imprecision % CV |
| Level 1 | 22.4 | 80 | 0.350 | 0.24 | 0.510 | 0.52 |
| Level 2 | 10.4 | 80 | 0.250 | 1.78 | 0.500 | 2.03 |
| Level 3 | 3.5 | 80 | 0.250 | 4.63 | 0.500 | 4.82 |
| Level 5 | 25.1 | 80 | 0.350 | 0.21 | 0.520 | 0.37 |
| Level 6 | 2.5 | 80 | 0.250 | 6.65 | 0.500 | 6.36 |

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| SO2 Precision Data | | | | | | |
| --- | --- | --- | --- | --- | --- | --- |
| Sample | Mean (%) | N | Within run SD | Within run % CV | Total imprecision SD | Total Imprecision %CV |
| Level 1 | 73.4 | 80 | 1.500 | 0.13 | 2.000 | 0.28 |
| Level 2 | 90.3 | 80 | 1.500 | 0.23 | 2.000 | 0.26 |
| Level 3 | 97.1 | 80 | 1.500 | 0.15 | 2.000 | 0.15 |
| Level 5 | 68.2 | 80 | 1.500 | 0.16 | 2.000 | 0.27 |
| Level 6 | 98.0 | 80 | 1.500 | 0.15 | 2.000 | 0.14 |

An additional precision study was performed between the syringe mode and the capillary mode using whole blood samples. The syringe mode results provided by the sponsor demonstrated comparable results to the capillary mode. Within-run precision for all analytes (parameters) for the capillary mode are summarized below:

| Analyte | Unit of Measure | Sample | Capillary | | | |
| --- | --- | --- | --- | --- | --- | --- |
| | | | Mean | SR | CV (%) | n |
| pH | pH Units | 1 | 7.18 | 0.003 | 0.04 | 24 |
| | | 2 | 7.36 | 0.002 | 0.02 | 32 |
| pO2 | mmHg | 1 | 75.42 | 0.31 | 0.40 | 24 |
| | | 2 | 132.75 | 1.349 | 1.00 | 32 |
| pCO2 | mmHg | 1 | 68.13 | 0.192 | 0.28 | 24 |
| | | 2 | 31.43 | 0.199 | 0.63 | 32 |
| Na+ | mEq/L | 1 | 98.77 | 0.485 | 0.5 | 12 |
| | | 2 | 113.51 | 0.187 | 0.2 | 12 |
| | | 3 | 141.34 | 0.676 | 0.5 | 12 |
| | | 4 | 160.68 | 0.498 | 0.3 | 12 |
| | | 5 | 183.69 | 0.431 | 0.2 | 12 |
| K+ | mEq/L | 1 | 2.08 | 0.020 | 1.0 | 12 |
| | | 2 | 4.88 | 0.048 | 1.0 | 12 |
| | | 3 | 3.93 | 0.019 | 0.5 | 12 |
| | | 4 | 12.48 | 0.041 | 0.3 | 12 |
| | | 5 | 19.40 | 0.042 | 0.2 | 12 |

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| iCa2+ | mg/dL | 1 | 2.20 | 0.020 | 0.9 | 12 |
| --- | --- | --- | --- | --- | --- | --- |
| | | 2 | 4.88 | 0.036 | 0.8 | 12 |
| | | 3 | 11.69 | 0.108 | 0.9 | 12 |
| | | 4 | 7.13 | 0.024 | 0.3 | 12 |
| Hct | % | 1 | 64.81 | 0.123 | 0.20 | 8 |
| | | 2 | 49.97 | 0.305 | 0.61 | 8 |
| | | 3 | 42.10 | 0.080 | 0.20 | 8 |
| | | 4 | 28.70 | 0.062 | 0.20 | 8 |
| | | 5 | 20.39 | 0.134 | 0.70 | 8 |
| Glucose | mg/dL | 1 | 101.44 | 0.025 | 0.5 | 8 |
| | | 2 | 71.71 | 0.031 | 0.8 | 8 |
| | | 3 | 81.08 | 0.032 | 0.7 | 8 |
| | | 4 | 49.55 | 0.008 | 0.3 | 8 |
| | | 5 | 274.05 | 0.071 | 0.5 | 8 |
| Lactate | mg/dL | 1 | 24.68 | 0.033 | 1.2 | 12 |
| | | 2 | 34.77 | 0.034 | 0.9 | 12 |
| | | 3 | 28.92 | 0.052 | 1.6 | 12 |
| | | 4 | 59.82 | 0.028 | 0.4 | 12 |
| | | 5 | 53.96 | 0.047 | 0.8 | 12 |
| tHb | g/dL | 1 | 15.49 | 0.182 | 1.18 | 24 |
| | | 2 | 6.94 | 0.071 | 1.02 | 20 |
| | | 3 | 19.32 | 0.243 | 1.26 | 20 |

# Whole blood precision study (capillary mode):

An additional precision study was conducted following guidance from CLSI EP5-A2. Whole blood was collected for use in an "in-house" precision study and utilized twenty (20) cobas b 123 POC analyzers, two sensor lots, samples tested in one run per day, in two replicates, and with samples at three clinically significant concentrations. The following tables present a summary of results:

Repeatability (Within-Run): Summary of Results for pH

| Sample | Mean (pH Units) | SD (pH Units) | CV (%) | n |
| --- | --- | --- | --- | --- |
| Blood Sample 1 | 7.237 | 0.0029 | 0.04% | 40 |
| Blood Sample 2 | 7.441 | 0.0029 | 0.03% | 40 |
| Blood Sample 3 | 7.568 | 0.0054 | 0.07% | 40 |

Repeatability (Within-Run): Summary of Results for $\mathsf{pO}_2$

| Sample | Mean (mmHg) | SD (mmHg) | CV (%) | n |
| --- | --- | --- | --- | --- |
| Blood 1 | 145.4 | 0.7404 | 0.51 | 80 |
| Blood 2 | 40.5 | 0.6888 | 1.70 | 80 |
| Blood 3 | 352.2 | 2.0866 | 0.59 | 80 |

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Repeatability (Within-Run): Summary of Results for $\mathrm{pCO}_2$

| Sample | Mean (mmHg) | SD (mmHg) | CV (%) | n |
| --- | --- | --- | --- | --- |
| Blood 1 | 23.5 | 0.1174 | 0.50 | 80 |
| Blood 2 | 72.7 | 0.3728 | 0.51 | 80 |
| Blood 3 | 128.6 | 1.7942 | 1.39 | 80 |

Repeatability (Within-Run): Summary of Results for $\mathrm{Na^{+}}$

| Sample | Mean (mEq/L) | SD(mEq/L) | CV (%) | n |
| --- | --- | --- | --- | --- |
| Blood Sample 1 | 117.7 | 0.2845 | 0.24% | 40 |
| Blood Sample 2 | 138.6 | 0.2709 | 0.19% | 40 |
| Blood Sample 3 | 156.2 | 0.5890 | 0.37% | 40 |

Repeatability (Within-Run): Summary of Results for $\mathrm{K}^+$

| Sample | Mean (mEq/L) | SD (mEq/L) | CV (%) | n |
| --- | --- | --- | --- | --- |
| Blood Sample 1 | 3.05 | 0.0221 | 0.72% | 40 |
| Blood Sample 2 | 5.00 | 0.0148 | 0.29% | 40 |
| Blood Sample 3 | 6.10 | 0.0198 | 0.32% | 40 |

Repeatability (Within-Run): Summary of Results for $\mathrm{Ca^{2+}}$

| Sample | Mean (mg/dL) | SD (mg/dL) | CV (%) | n |
| --- | --- | --- | --- | --- |
| Blood Sample 1 | 2.90 | 0.03 | 1.065% | 40 |
| Blood Sample 2 | 4.74 | 0.04 | 0.79% | 40 |
| Blood Sample 3 | 5.60 | 0.07 | 1.25% | 40 |

Repeatability (Within-Run): Summary of Results for Hct

| Sample | Mean (%) | SD (%) | CV (%) | n |
| --- | --- | --- | --- | --- |
| Blood Sample 1 | 22.1 | 0.2461 | 1.11% | 40 |
| Blood Sample 2 | 38.5 | 0.1597 | 0.41% | 40 |
| Blood Sample 3 | 62.3 | 0.2370 | 0.38% | 40 |

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Repeatability (Within-Run): Summary of Results for Glucose

| Sample | Mean (mg/dL) | SD (mg/dL) | CV (%) | n |
| --- | --- | --- | --- | --- |
| Blood Sample 1 | 47 | 1.1 | 2.28% | 40 |
| Blood Sample 2 | 90 | 1.1 | 1.27% | 40 |
| Blood Sample 3 | 488 | 2.8 | 0.56% | 40 |

Repeatability (Within-Run): Summary of Results for Lactate

| Sample | Mean (mg/dL) | SD (mg/dL) | CV (%) | n |
| --- | --- | --- | --- | --- |
| Blood Sample 1 | 8 | 0.10 | 1.18% | 40 |
| Blood Sample 2 | 13 | 0.09 | 0.69% | 40 |
| Blood Sample 3 | 32 | 0.51 | 1.56% | 40 |

Repeatability (Within-Run): Summary of Results for tHb

| Sample | Mean (g/dL) | SD (g/dL) | CV (%) | n |
| --- | --- | --- | --- | --- |
| Blood Sample 1 | 6.5 | 0.1058 | 1.62% | 40 |
| Blood Sample 2 | 12.9 | 0.0874 | 0.67% | 40 |
| Blood Sample 3 | 20.7 | 0.0703 | 0.33% | 40 |

Repeatability (Within-Run): Summary of Results for $\mathrm{O}_2\mathrm{Hb}$

| Sample | Mean (%) | SD (%) | CV (%) | n |
| --- | --- | --- | --- | --- |
| Blood Sample 1 | 80.6 | 1.2296 | 1.52% | 40 |
| Blood Sample 2 | 94.5 | 0.5108 | 0.54% | 40 |
| Blood Sample 3 | 97.4 | 0.1342 | 0.13% | 40 |

Repeatability (Within-Run): Summary of Results for HHb

| Sample | Mean (%) | SD (%) | CV (%) | n |
| --- | --- | --- | --- | --- |
| Blood Sample 1 | 5.2 | 0.1828 | 3.51% | 40 |
| Blood Sample 2 | 9.5 | 0.2190 | 2.31% | 40 |
| Blood Sample 3 | 17.0 | 1.2248 | 7.20% | 40 |

Repeatability (Within-Run): Summary of Results for COHb

| Sample | Mean (%) | SD (%) | CV (%) | n |
| --- | --- | --- | --- | --- |
| Blood Sample 1 | 2.0 | 0.0946 | 4.73% | 40 |
| Blood Sample 2 | 5.4 | 0.0688 | 1.27% | 40 |
| Blood Sample 3 | 13.4 | 0.0894 | 0.66% | 40 |

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Repeatability (Within-Run): Summary of Results for MetHb

| Sample | Mean (%) | SD (%) | CV (%) | n |
| --- | --- | --- | --- | --- |
| Blood Sample 1 | 1.3 | 0.0672 | 5.16% | 40 |
| Blood Sample 2 | 5.8 | 0.1125 | 1.93% | 40 |
| Blood Sample 3 | 30.7 | 0.3221 | 1.04% | 40 |

Repeatability (Within-Run): Summary of Results for $\mathrm{SO}_2$

| Sample | Mean (%) | SD (%) | CV (%) | n |
| --- | --- | --- | --- | --- |
| Blood Sample 1 | 82.6 | 1.2561 | 1.52% | 40 |
| Blood Sample 2 | 96.8 | 0.4976 | 0.51% | 40 |
| Blood Sample 3 | 99.7 | 0.1190 | 0.11% | 40 |

A POC precision study was conducted at 6 external POC sites. The following table is a summary of precision studies conducted at the external POC sites using the cobas b 123 AutoQC Pack Tri-Level QC material:

| | QC Level | Analyte Concentration (Mean) | Within-Run (SD) | Within-Run (% CV) | Total Precision (SD) | Total Precision (% CV) |
| --- | --- | --- | --- | --- | --- | --- |
| Ca | Level 1 | 6.85 mg/dL | 0.01 mg/dL | 0.17 | 0.04 mg/dL | 0.37 |
| | Level 2 | 4.93 mg/dL | 0.01 mg/dL | 0.24 | 0.02 mg/dL | 0.37 |
| | Level 3 | 2.69 mg/dL | 0.02 mg/dL | 0.57 | 0.04 mg/dL | 0.81 |
| K | Level 1 | 2.99 mEq/L | 0.01 mEq/L | 0.19 | 0.01 mEq/L | 0.45 |
| | Level 2 | 4.71 mEq/L | 0.01 mEq/L | 0.2 | 0.01 mEq/L | 0.26 |
| | Level 3 | 6.97 mEq/L | 0.01 mEq/L | 0.16 | 0.02 mEq/L | 0.34 |
| Na | Level 1 | 117.5 mEq/L | 0.14 mEq/L | 0.12 | 0.33 mEq/L | 0.28 |
| | Level 2 | 140.4 mEq/L | 0.24 mEq/L | 0.17 | 0.34 mEq/L | 0.24 |
| | Level 3 | 153.1 mEq/L | 0.22 mEq/L | 0.14 | 0.33 mEq/L | 0.22 |
| Glu | Level 1 | 110 mg/dL | 0.72 mg/dL | 0.66 | 1.4 mg/dL | 1.29 |
| | Level 2 | 45 mg/dL | 0.72 mg/dL | 1.74 | 0.90 mg/dL | 1.98 |
| | Level 3 | 443 mg/dL | 2.3 mg/dL | 0.55 | 6.3 mg/dL | 1.49 |
| Lac | Level 1 | 94.6 mg/dL | 0.54 mg/dL | 0.56 | 1.4 mg/dL | 1.51 |

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| | Level 2 | 27.9 mg/dL | 0.27 mg/dL | 0.87 | 0.45 mg/dL | 1.56 |
| --- | --- | --- | --- | --- | --- | --- |
| | Level 3 | 15.3 mg/dL | 0.18 mg/dL | 1.21 | 0.36 mg/dL | 2.43 |
| Hct | Level 1 | 59.4% | 0.10% | 0.17 | 0.24% | 0.4 |
| | Level 2 | 41.4% | 0.14% | 0.33 | 0.19% | 0.47 |
| | Level 3 | 33.0% | 0.12% | 0.37 | 0.16% | 0.49 |
| PCO2 | Level 1 | 64.6 mmHg | 0.45 mmHg | 0.7 | 0.76 mmHg | 1.17 |
| | Level 2 | 42.2 mmHg | 0.17 mmHg | 0.4 | 0.37 mmHg | 0.88 |
| | Level 3 | 25.9 mmHg | 0.15 mmHg | 0.57 | 0.42 mmHg | 1.62 |
| PO2 | Level 1 | 60.0 mmHg | 0.92 mmHg | 1.57 | 1.89 mmHg | 3.22 |
| | Level 2 | 100.0 mmHg | 1.00 mmHg | 1.01 | 2.00 mmHg | 2.02 |
| | Level 3 | 148.0 mmHg | 1.47 mmHg | 1 | 2.44 mmHg | 1.66 |
| pH | Level 1 | 7.140 | 0.002 | 0.03 | 0.003 | 0.05 |
| | Level 2 | 7.385 | 0.001 | 0.02 | 0.002 | 0.03 |
| | Level 3 | 7.542 | 0.001 | 0.01 | 0.002 | 0.03 |
| COHb | Level 1 | 22.5% | 0.12% | 0.53 | 0.14% | 0.64 |
| | Level 2 | 10.4% | 0.20% | 1.96 | 0.22% | 2.07 |
| | Level 3 | 3.5% | 0.25% | 6.98 | 0.26% | 7.32 |
| HHb | Level 1 | 17.6% | 0.10% | 0.55 | 0.12% | 0.67 |
| | Level 2 | 8.1% | 0.16% | 1.98 | 0.17% | 2.08 |
| | Level 3 | 2.9% | 0.19% | 7.14 | 0.20% | 7.45 |
| MetHb | Level 1 | 11.8% | 0.06% | 0.51 | 0.07% | 0.61 |
| | Level 2 | 5.7% | 0.10% | 1.69 | 0.10% | 1.82 |
| | Level 3 | 1.9% | 0.12% | 6.12 | 0.12% | 6.3 |
| O2Hb | Level 1 | 48.2% | 0.26% | 0.55 | 0.32% | 0.66 |
| | Level 2 | 76.0% | 0.45% | 0.6 | 0.48% | 0.63 |
| | Level 3 | 92.1% | 0.55% | 0.6 | 0.57% | 0.62 |
| SO2 | Level 1 | 73.2% | 0.20% | 0.28 | 0.25% | 0.34 |
| | Level 2 | 90.3% | 0.23% | 0.25 | 0.24% | 0.27 |
| | Level 3 | 96.9% | 0.21% | 0.22 | 0.22% | 0.23 |
| tHb | Level 1 | 7.1 g/dL | 0.10 g/dL | 1.35 | 0.12 g/dL | 1.64 |
| | Level 2 | 11.6 g/dL | 0.11 g/dL | 0.98 | 0.15 g/dL | 1.28 |
| | Level 3 | 19.8 g/dL | 0.17 g/dL | 0.87 | 0.25 g/dL | 1.25 |

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# b. Linearity/assay reportable range:

A linearity study was designed based on CLSI EP6 guidance for each analyte. Samples were prepared by spiking 10 different levels of analyte into whole blood for each of the analyte tested. Each sample concentration was tonometered to the expected concentrations prior to running samples on the candidate device. Samples were tested in a single run in replicates of 5 on a single instrument. The observed values were plotted against expected values. Results of this study are summarized in the following table:

| Analyte | Slope | Intercept | Correlation Coefficient (r2) | Linear Range Tested | Claimed Measuring Range |
| --- | --- | --- | --- | --- | --- |
| pO2 | 1.011 | -2.993 | 0.9966 | 8.900 – 685.9 mmHg | 10 – 685 mmHg |
| pCO2 | 0.976 | 1.812 | 0.9990 | 9.296 – 167.660 mmHg | 10 – 150 mmHg |
| tHb | 0.9895 | 0.0926 | 0.9972 | 3.132 – 27.013 g/dL | 4 – 25 g/dL |
| O2Hb | 0.9979 | 0.2813 | 0.9991 | 3.2 – 100 % | 30 – 100 % |
| HHb | 1.017 | -0.1198 | 0.9989 | 0.19 – 96.6 % | 0.5 – 70 % |
| COHb | 0.9821 | 0.062 | 0.9999 | 1.0 – 78.9 % | 1.1 – 70 % |
| MetHb | 0.9996 | -0.0898 | 1.00 | 0.6 – 79.2 % | 0.95 – 70 % |
| SO2 | 1.0032 | -0.3379 | 0.9990 | 30 – 100 % | 30 – 100 % |

An additional linearity study was performed using whole blood samples for the following analytes: pH, $\mathrm{Na^{+}}$ , $\mathrm{K^{+}}$ , $\mathrm{Ca^{2+}}$ , glucose, and lactate. The results are as follows:

| Analyte | Slope | Intercept | (r2) | Linear Range Tested | Claimed Measuring Range |
| --- | --- | --- | --- | --- | --- |
| pH | 1.007 | -0.032 | 0.9996 | 6.499 – 8.319 pH units | 6.5 – 8.0 pH units |
| Na+ | 1.006 | -1.456 | 0.9993 | 88.16 – 212.3 mEq/L | 100 – 200 mEq/L |
| K+ | 1.018 | 0.010 | 0.9989 | 0.752 – 16.61 mEq/L | 1.0 – 15 mEq/L |
| iCa2+ | 0.985 | -0.162 | 0.9769 | 0.756 – 12.842 mg/dL | 1.09 – 10.02 mg/dL |
| Glucose | 1.009 | -6.236 | 0.9942 | 11.1 – 543.4 mg/ dL | 18 – 540mg/dL |

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

Traceability:

All the analytes in the control/calibrator solutions are traceable to a reference method and the analyte targets are assigned based on the reference methods or other commercially available methods. See table below for traceability for calibrators and controls.

| Analyte | Traceability |
| --- | --- |
| pH | NIST SRM 2181 HEPES and NIST SRM 2182 Na Salt |
| pO2 | Fresh human blood tonometered with PRMs (Primary Reference Materials): • Linde O2 4.5 : purity =99.995% and • N2 4.6 : purity = 99.996% These standards are prepared gravimetrically by National Standards Institutes using guideline ISO6142 (2) as the primary standard gas mixture. The gas mixture is created by using a high precision gas mixing system from LNI. |
| pCO2 | Fresh human blood tonometered with PRMs (Primary Reference Materials): • Linde CO2 4.5: purity = 99.995% This standard is prepared gravimetrically by National Standards Institutes using guideline ISO6142 (2) as the primary standard gas mixture. The gas mixture is created by using a high precision gas mixing system from LNI. |
| Na+ | • NIST SRM 2201: Sodium Chloride • Merck Sodium Bicarbonate /Sodium Carbonate 1962 (traceable to NIST SRM 191b: Sodium Bicarbonate and NIST |

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| | SRM 192a: Sodium
Carbonate)
• Merck Sodium Acetate Trihydrate (Extra Pure)
6268: purity = 99.5-100% |
| --- | --- |
| K+ | NIST SRM 2202: Potassium Chloride |
| Ca2+ | Merck CertiPUR 119778 Calcium standard
solution (traceable to NIST
SRM 3109a: Spectrometric Standard Solution
Calcium) |
| Hct | There is no standard reference material available.
Fresh human blood samples were analyzed using
the Hemafuge®
(microcentrifuge) according to CLSI H7-A3:
*Procedure for Determining Packed
Cell Volume by the Microhematocrit Method;
Approved Standard—Third
Edition (Vol. 20, No. 18).* |
| Glucose | NIST SRM 917b: D-Glucose (Dextrose) |
| Lactate | There is no reference material available.
The material used was Fluka 71718 Sodium
Lactate: purity ≥ 99.0%. |
| tHb | There is no reference material available.
Oxygenated whole blood samples were analyzed
with a Hellma spectrometer using the
HiCN reference method in accordance with CLSI
H15-A3: *Reference and Selected
Procedures for the Quantitative Determination of
Hemoglobin in Blood; Approved
Standard—Third Edition (Vol. 20, No. 28).*
The Hellma spectrometer was calibrated with
NIST SRM 930e: Glass Filters for
Spectrophotometry. |
| O2Hb | There is no reference material available.
A pool of human blood was tonometered at
sample values of 0% and 100% with PRM
(Primary Reference Material):
– Linde O2 4.5 : purity =99.995%
This standard is prepared gravimetrically by
National Standards Institutes using
guideline ISO6142 (2) as the primary standard
gas mixture. The gas mixture is created
by using a high precision gas mixing system
from LNI. |
| HHb | There is no reference material available.
A pool of human blood was tonometered at
sample values of 0% and 100% with PRM |

24

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| | (Primary Reference Material):
–Linde CO2 4.5: purity = 99.995%
This standard is prepared gravimetrically by National Standards Institutes using guideline ISO6142 (2) as the primary standard gas mixture. The gas mixture is created by using a high precision gas mixing system from LNI. |
| --- | --- |
| COHb | There is no reference material available.
A pool of human blood was tonometered at sample values of 0% and 100% with PRM (Primary Reference Material):
• Linde CO 3.7 : purity =99.97%
This standard is prepared gravimetrically by National Standards Institutes using guideline ISO6142 (2) as the primary standard gas mixture. The gas mixture is created by using a high precision gas mixing system from LNI. |
| MetHb | There is no reference material available.
A pool of human blood was tonometered with at sample values of 0% and 100% with PRM (Primary Reference Material):
– Linde N2 4.6 : purity = 99.996%
– Linde NO 2.5 : purity =99.5%
These standards are prepared gravimetrically by National Standards Institutes using guideline ISO6142 (2) as the primary standard gas mixture. The gas mixture is created by using a high precision gas mixing system from LNI. |
| SO2 | There is no reference material available.
Whole blood samples were tonometered at sample values of 30% and 100% with PRMs (Primary Reference Materials):
• Linde O2 4.5 : purity =99.995% %
This standard is prepared gravimetrically by National Standards Institutes using guideline ISO6142 (2) as the primary standard gas mixture. The gas mixture is created by using a high precision gas mixing system from LNI.
The primary standard is used to calibrate the reference instrument, the AVL OMNI 12. |

25

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26

# Stability:

## Shelf life Stability Study:

For this study, three lots of sensor cartridges (BG/ISE/Glu/Lac) were evaluated using five sensors from each lot. Each sensor lot was stored at 2 – 8 °C and after 4 months the following materials were tested in singlet: Quality Control (QC) material, Calibration Verification Control material, plasma, and whole blood. The results of the study supports the shelf life stability claim of up to 4 months based on real-time testing on three lots for the sensor cartridges.

## Shelf life Stability Study (Fluid pack):

For this study, the fluid pack was stored at 15 – 25°C and tested at the following time intervals: T=0, 6, 9, and 13 months. Each result obtained at each time point was compared back to baseline (t=0). The results of the study support a shelf life of 9 months when stored unopened at 15 - 25°C.

## On-board stability study:

Six sensor (BG/ISE/Glu/Lac) cartridge lots were stored on-board the system at 37 °C. Three quality control levels were tested at regular time intervals over a total of 28 days.

The results of the study support an on-board stability of the following:

- Stability of up to 28 days at 37°C for BG (blood gas sensor cartridges)
- Stability of up to 28 days at 30°C for glucose (sensor cartridges) and ISE (ion selective electrode sensor cartridges)
- Stability of up to 21 days at 30°C for lactate sensor cartridges.

## On-board stability study (fluid pack):

A study was conducted evaluating the cobas b 123 fluid pack which contains five components: calibration solution 1, calibration solution 2, standby solution, reference solution, and sol-wet solution. The fluid pack’s stability was carried out at 32°C for 42 days. This study supports the on-board stability claim of 42 days.

## Value Assignment for Roche AUTOTROL 123:

For lot-specific value assignment, each autoQC pack (containing 8 ampoules per level, 5 of the new lot and 3 of the reference lot) were tested in two runs

{26}

on at least three (3) cobas b 123 POC systems. The following table represents the target values for the Roche AUTOTROL 123 levels:

| | | Target Value | | |
| --- | --- | --- | --- | --- |
| | | Level 1 | Level 2 | Level 3 |
| Analyte | Units | Mean | Mean | Mean |
| pH | pH units | 7.100 – 7.180 | 7.345 – 7.425 | 7.502 – 7.582 |
| pO2 | mmHg | 48 - 72 | 88 – 112 | 136 – 160 |
| pCO2 | mmHg | 60.6 – 68.6 | 38.7 – 45.7 | 22.4 – 29.4 |
| Na | mEq/L | 113.0 – 122.0 | 135.4 – 145.4 | 147.6 – 158.6 |
| K | mEq/L | 2.79 – 3.19 | 4.41 – 5.01 | 6.62 – 7.32 |
| Ca | mg/dL | 6.252 – 7.455 | 4.529 – 5.331 | 2.285 – 3.086 |
| Hct | % | 54.4 – 64.4 | 36.4 – 46.4 | 28.0 – 38.0 |
| Glucose | mg/dL | 94 - 126 | 36 – 54 | 389 – 497 |
| Lactate | mg/dL | 77 - 113 | 23 – 32 | 12 – 19 |
| tHb | g/dL | 6.4 – 7.8 | 10.6 – 12.6 | 18.4 – 21.2 |
| O2Hb | % | 44.2 – 52.2 | 72.0 – 80.0 | 88 .1 – 96.1 |
| HHb | % | 14.6 – 20.6 | 5.1 – 11.1 | 0.0 – 5.7 |
| COHb | % | 20.0 – 25.0 | 7.9 – 12.9 | 1.0 – 6.0 |
| MetHb | % | 10.3 – 13.3 | 4.2 – 7.2 | 0.4 – 3.4 |
| SO2 | % | 71.7 – 75.2 | 87.8 – 93.4 | 94.4 – 100.0 |

Value Assignment for Combitrol Plus B:

For lot- specific value assignment, each COMBITROL PLUS B (levels 1, 2, 3) were tested in duplicate using 8 ampoules per level (5 of the new lot, 3 of the reference lot) with two (2) runs per system. At least three (3) cobas b 123 POC systems were used for the study. The following table represents the target values for the Roche AUTOTROL 123 levels:

| | | Target Value | | |
| --- | --- | --- | --- | --- |
| | | Level 1 | Level 2 | Level 3 |
| Analyte | Units | Target range | Target range | Target range |
| pH | pH units | 7.159 – 7.239 | 7.393 – 7.473 | 7.515 – 7.595 |
| pO2 | mmHg | 40 – 64 | 82 – 106 | 131 – 155 |
| pCO2 | mmHg | 61.1 – 69.1 | 39.1 – 46.1 | 19.4 – 26.4 |
| Na | mEq/L | 120.1 – 129.1 | 137.8 – 147.8 | 156.0 – 167.0 |
| K | mEq/L | 2.82 – 3.22 | 4.44 – 5.04 | 6.77 – 7.47 |
| Ca | mg/dL | 6.373 – 7.575 | 4.569 – 5.371 | 1.884 – 2.685 |
| Hct | % | 47.8 – 57.8 | 34.8 – 44.8 | 24.1 – 34.1 |
| Glucose | mg/dL | 86 – 119 | 38.- 56 | 339 – 447 |
| Lactate | mg/dL | 70 – 106 | 23 – 32 | 11 - 18 |
| tHb | g/dL | 6.7 – 8.1 | 11.1 – 13.1 | 18.6 – 21.4 |
| O2Hb | % | 43.2 – 51.2 | 71.0 – 79.0 | 87.6 – 95.6 |
| HHb | % | 15.0 – 21.0 | 5.5 – 11.5 | 0.0 – 5.8 |

{27}

Value Assignment for Calibration Verification Control (CVC):

The six levels of cobas b 123 CVC material are assigned based on the measuring range established by the cobas b 123 POC system. The following table represents the target values of each analyte (parameter):

| | | Target Value | | |
| --- | --- | --- | --- | --- |
| | | Level 1 | Level 2 | Level 3 |
| | | Mean | Mean | Mean |
| pH | pH Units | 7.12 – 7.18 | 7.38 - 7.42 | 7.52 – 7.58 |
| PO2 | mmHg | 55 – 75 | 92 – 107 | 135 – 160 |
| PCO2 | mmHg | 60 – 70 | 38 – 46 | 21 – 27 |
| Na | mEq/L | 110-122 | 133 – 143 | 150 – 160 |
| K | mEq/L | 2.50 – 3.50 | 4.30 – 5.30 | 6.30 – 7.50 |
| iCa | mg/dL | 6.012 – 6.81 | 4.329 – 5.13 | 2.00 – 3.20 |
| Hct | % | 54 – 62 | 36 – 44 | 26 – 34 |
| Glu | mg/dL | 99 – 117 | 41 – 49 | 351 – 451 |
| Lac | mg/dL | 81 - 99 | 25 - 29 | 13 – 15 |
| tHb | g/dL | 6.7 – 8.7 | 11.5 – 13.5 | 19.5 – 22.5 |
| O2Hb | % | 40 – 54 | 68 – 82 | 88 – 98 |
| HHb | % | 14 – 22 | 5 – 12 | 0 – 6 |
| COHb | % | 19 – 27 | 7 – 15 | 0 – 6 |
| MetHb | % | 8 - 16 | 2 – 10 | 0 – 6 |
| SO2 | % | 65 – 79 | 85 – 94 | 94 – 100 |

d. Detection limit:

Refer to the linearity study data above in M.2.b. for the detection limits claim for all analytes. In addition, the sponsor conducted a Limit of Blank (LoB), Limit of Detection (LoD), and Limit of Quantitation (LoQ) study following the CLSI EP - 17A guideline for the following analytes: Glucose, ICa, and Lactate. To determine LoB, zero level samples were prepared and measured on ten cobas b 123 POC instruments to obtain blank measurements $(N = 60)$ . To determine the LoD and LoQ, whole blood samples with low levels of analyte (approximately $4\times$ LoB) were measured on ten instruments $(N = 200)$ . The LoQ was determined based on the inter-assay precision (%CV). Results of the study are presented in the following table:

{28}

| Analyte | LoB | LoD | LoQ | %CV for LoQ | Claimed Measuring Range |
| --- | --- | --- | --- | --- | --- |
| Glucose | 3.1 mg/dL | 5.4 mg/dL | 13.1 mg/dL | 12.1% | 18 – 540 |
| iCa | 0.000 mg/dL | 0.1907 mg/dL | 1.057 mg/dL | 11.8% | 1.09 – 10.02 |
| Lactate | 0.00 mg/dL | 0.84 mg/dL | 5.6 mg/dL | 8.5% | 9 – 180 |

# e. Analytical specificity:

The interference study was performed according to the CLSI guideline EP7-A2. The study used spiked and diluted human whole blood samples containing potential interferents for pH, pO2, pCO2, sodium, potassium, calcium, Hct, tHb, O2Hb, HHb, COHb, MetHb, SO2, lactic acid, and glucose. Each sample containing interferent was evaluated against a reference whole blood sample without interferent. The following table represents substances that were tested without significant effects on test results:

| Interference substance test | Highest concentration tested | Analyte |
| --- | --- | --- |
| 3- beta - Hydroxybutyrate | 20 mmol/L | pH, ISE, Glu, Lac |
| Acetoacetate | 2 mmol/L | pH, ISE, Glu, Lac |
| Acetone | 12.00 mmol/L | BG, pH, ISE, Glu, Lac |
| Acetylcysteine | 10.2 mmol/L | Na, K, , Hct |
| Albumin | >9.0% | BG, pH, ISE, Glu, Lac, Hct |
| Ammonium Chloride | 0.107 mmol/L | BG, pH, ISE Glu, Lac |
| Ampicillin | 0.15 mmol/L | BG, pH, ISE, Glu, Lac |
| Ascorbic Acid | 0.34 mmol/L | ISE, Glu, Lac |
| Aspirin (Acetylsalicylic acid) | 3.62 mmol/L | Na, K, , Glu, Lac |
| Benzalkonium chloride | 0.028 mmol/L | pH, K, Ca, , Glu, Lac |
| Beta-Carotene | 2.0 mg/L | tHB, HHb, O2Hb, COHb, MetHb, SO2 |
| Bilirubin | 0.342 mmol/L | BG, pH, ISE, Glu, Lac |
| Calcium chloride | 5.0 mmol/L | ISE, Glu, Lac |
| Cefoxitin | 1.546 mmol/L | ISE, Glu, Lac |

{29}

| Chlorpromazine | 0.0063 mmol/L | BG, pH, ISE, Glu, Lac |
| --- | --- | --- |
| Cyclosporine | 0.0043 mmol/L | BG, pH, ISE, Glu, Lac |
| Creatinine | 0.442 mmol/L | BG, pH, ISE, Glu, Lac |
| Cyanide | 0.1 mmol/L | BG, pH, ISE, Glu, Lac |
| Dobesilate | 0.880 mmol/L | BG, ISE, Glu, Lac |
| Dopamine | 0.00587 mmol/L | BG, pH, ISE, Glu, Lac |
| Dobutamine | 0.66 mmol/L | pH, K, Ca, , Glu, Lac |
| Doxycycline | 0.068 mmol/L | BG, pH, ISE, Glu, Lac |
| EDTA | 0.0003 mmol/L | ISE, Glu, Lac |
| Ethanol | 86.80 mmol/L | BG, pH |
| Ethylene glycol | 2.425 mmol/L | BG, pH, ISE, Glu, Lac |
| Evans blue | 5 mg/L | tHB, HHb, O2Hb, COHb, MetHb, SO2 |
| Gelfusine | Dilution 1:1 | tHB, HHb, O2Hb, COHb, MetHb, SO2 |
| Gentamicin | 0.021 mmol/L | BG, pH, ISE, Glu, Lac |
| Gentisic Acid | 0.117 mmol/L | BG, pH, ISE, Glu, Lac |
| Glutathione, reduced | 3.0 mmol/L | ISE, Glu, Lac |
| Glycolic Acid | 13.05 mmol/L | PO2, Na, K, , Glu |
| Guaiaco | 0.4 mmol/L | BG, pH, ISE, Glu, Lac |
| HAES-sterile 10% | Dilution 1:1 | tHB, HHb, O2Hb, COHb, MetHb, SO2 |
| HAES (Hydroxyethylstarch) | 50.0% | BG, ISE, Glu, Lac |
| Halothane | 0.759 mmol/L | PO2 |
| Hemoglobin | 2.00 g/L | BG, pH, ISE, Glu, Lac |
| Hydroxycarbamide (Hydroxyurea) | 2.50 mmol/L | BG, pH,ISE |
| Hydroxocobalmin | 0.25 mg/mL | tHb, HHb, O2Hb, COHb, MetHb, SO2 |
| Ibuprofen | 2.425 mmol/L | ISE, Glu, Lac |

30

{30}

| Indocyanine green | 5 mg/mL | tHb, HHb, O2Hb, COHb, MetHb, SO2 |
| --- | --- | --- |
| Isoflurane | 3.00 % | BG, pH, ISE, Glu, Lac |
| Isoniazid | 0.29 mmol/L | BG, pH, ISE, Glu, Lac |
| Intralipid 20% | 10 mg/mL | tHB, HHb, O2Hb, COHb, MetHb, SO2 |
| Lactate | 6.6 mmol/L | ISE, Glu |
| Levodopa (L-Dopa) | 0.12 mmol/L | BG, pH, ISE, Glu, Lac |
| Lipfundin 20% with MCT | 10 mg/ mL | tHB, HHb, O2Hb, COHb, MetHb, SO2 |
| Lipidem | 10 mg/mL | tHB, HHb, O2Hb, COHb, MetHb, SO2 |
| Lithium acetate | 3.20 mmol/L | BG, pH, ISE, Glu, Lac |
| Maltose | 13.62 mmol/L | BG, pH, ISE, Glu, Lac |
| Methyldopa | 0.071 mmol/L | BG, pH, ISE, Glu, Lac |
| Methylene blue | 2.5 mg/L | tHB, HHb, O2Hb, COHb, MetHb, SO2 |
| Metronidazole | 0.701 mmol/L | pH, ISE, Glu, Lac |
| Monosodium phosphate | 9.0 mmol/L | ISE, Glu, Lac |
| Norepinephrine | 0.12 mmol/L | BG, pH, ISE, Lac |
| Nitrous Oxide | 85% | PO2 |
| Omegaven | 5 mg/mL | tHB, HHb, O2Hb, COHb, MetHb, SO2, tHB, HHb, O2Hb, COHb, MetHb, SO2, |
| Paracetamol(Acetaminophen) | 1.320 mmol/L | BG, pH, ISE, Glu, Lac |
| Patent blue | 2.5 mg/L | tHB, HHb, O2Hb, COHb, MetHb, SO2 |
| Perphenazine | 0.0.223 μmol/L | BG, pH, ISE, Glu, Lac |
| pH low | 7.1 | tHB, HHb, O2Hb, COHb, MetHb, |

31

{31}

| | | SO2 |
| --- | --- | --- |
| pH high | 7.9 | tHB, HHb, O2Hb, COHb, MetHb, SO2 |
| Phenobarbital | 0.431 mmol/L | BG, pH, ISE, Glu, Lac |
| Phenylbutazone | 1.3 mmol/L | ISE, Glu, Lac |
| Phenytoin | 0.198 mmol/L | BG, pH, ISE, Glu, Lac |
| Potassium Thiocyanate | 6.88 mmol/L | BG, pH, Na, Ca, Lac |
| Propofol | 1.00 % | BG |
| Propofol 2% | 0.11 mg/mL | tHB, HHb, O2Hb, COHb, MetHb, SO2 |
| pCO2 | 0.00 mm Hg | pO2, ISE, Glu, Lac |
| pCO2 | 85.0 mmHg | ISE, Glu, Lac |
| pO2 | 600.0 mmHg | BG, pH, ISE, Glu, Lac |
| pO2 | <25 mmHg | BG, pH, ISE, Glu, Lac |
| Rifampicin | 0.078 mmol/L | BG, pH, ISE, Glu, Lac |
| SMOF Lipid 20% | 10 mg/mL | tHB, HHb, O2Hb, COHb, MetHb, SO2 |
| Sodium Bicarbonate | 35 mmol/L | ISE, Glu, Lac |
| Sodium Bromide | 37.5 mmol/L | pH, K, Ca, Lac |
| Sodium Chloride | 45 mmol/L | BG, pH, ISE, Glu, Lac |
| Sodium Fluoride | 0.105 mmol/L | BG, pH, ISE, Glu, Lac |
| Sodium glutamate | 0.86 mmol/L | ISE, Glu, Lac |
| Sodium heparin | 3000 IU/L | BG, ISE, Glu, Lac |
| Sodium Pyruvate | 0.309 mmol/L | BG, pH, ISE, Glu, Lac |
| Albumin | 12 g/dL | tHB, HHb, O2Hb, COHb, MetHb, SO2 |
| Triglyceride | 37.00 mmol/L | BG, pH, ISE, Glu, Lac |
| Urea | 49.20 mmol/L | BG, pH, ISE, Glu, Lac |
| Uric Acid | 1.40 mmol/L | ISE, Glu |
| Vancomycin | 0.069 mmol/L | BG, pH, ISE, Glu, |
| | | Lac |
| Bifenthrin | 0.005 mmol/L | BG, pH, ISE, Glu, Lac |
| Bifenthrin 2% | 0.005 mmol/L | BG, pH, ISE, Glu, Lac |
| Bifenthrin 3% | 0.005 mmol/L | BG, pH, ISE, Glu, Lac |
| Bifenthrin 5% | 0.005 mmol/L | BG, pH, ISE, Glu, Lac |
| Bifenthrin 7% | 0.005 mmol/L | BG, pH, ISE, Glu, Lac |
| Bifenthrin 10% | 0.005 mmol/L | BG, pH, ISE, Glu, Lac |
| Bifenthrin 15% | 0.005 mmol/L | BG, pH, ISE, Glu, Lac |
| Bifenthrin 20% | 0.005 mmol/L | BG, pH, ISE, Glu, Lac |

{32}

Additional interference study testing the following analytes at two levels (low and high) against additional potential interferents was performed. The following is a summary of what was tested:

$\mathrm{Na+}$ , $\mathrm{K+}$ , and $\mathrm{Ca2+}$ : potential interference with benzalkonium, thiocyanate, salicylate, bromide, iodide

Glucose and Lactate: potential interference with uric acid, ascorbic acid, acetaminophen, dopamine, sodium fluoride, and oxalate

pO2: potential interference with nitrous oxide, halothane, and isoflurane

The results of this adjunctive study showed that there was interference with benzalkonium chloride at low and high sodium concentrations.

The following table represents substances which interfered:

| Interference substance tested | Highest concentration of interfering substance (mmol/L) | Analyte (Na)/ concentration (mEq/L) | Effect of the interferent (mEq/L) | ± Trueness (mean bias) mEq/L |
| --- | --- | --- | --- | --- |
| Benzalkonium chloride | 0.0280 | 116.47 | 2.81 ± 0.42 | 2.9 |
| | 152.20 | 152.20 | 4.07 ± 0.83 | 3.6 |
| Dobutamine | 0.66 | 137.4 | 21.2 ± 2.3 | 3.1 |
| Interference substance tested | Highest concentration of interfering substance (mmol/L) | Analyte (Hct)/ concentration (%) | Effect of the interferent (%) | ± Trueness (mean bias) (%) |
| Sodium Chloride | 45.0 | 43.3 | -9.4 ± 0.2 | 3.000 |
| Interference substance tested | Highest concentration interfering substance (mmol/L) | Analyte (Glucose)/ concentration (mg/dL)) | Effect of the interferent (mg/dL) | ± Trueness (mean bias) (mg/dL) |
| Acetylcysteine | 4 10.2 | 73.88 | - 25.2 ± 9.01 | 9.163 |

{33}

| Hydroxycarbamide
(Hydroxyurea) | 2.50 | 72.08 | 21.6 ± 12.6 | 9.010 |
| --- | --- | --- | --- | --- |
| Norepinephrine | 0.118 | 73.88 | -9.01 ± 3.6 | 9.848 |
| Potassium
Thiocyanate | 6.88 | 72.08 | 21.6 ± 7.2 | 9.010 |
| Sodium
Bromide | 37.50 | 72.08 | 9.01 ± 5.4 | 9.010 |
| Interference
substance tested | Highest
concentration of
interfering
substance
(mmol/L) | Analyte (Lactate)/
concentration
(mg/dL)) | Effect of the
interferent
(mg/dL) | ± Trueness
(mean bias)
(mg/dL) |
| Acetylcysteine | 10.20 | 49.54 | -12.6 ± 2.7 | 6.513 |
| Glycolic acid | 13.05 | 46.84 | 6.3±4.5 | 6.313 |
| Hydroxycarbamide
(hydroxyurea) | 2.50 | 43.24 | -10.8±5.4 | 6.046 |
| Uric Acid | 1.4 | 54.05 | -8.1±0.9 | 6.760 |
| Interference
substance tested | Highest
concentration of
interfering
substance | Analyte (tHb)/
concentration
(g/dL) | Effect of the
interferent
(g/dL) | ± Trueness
(mean bias)
(g/dL) |
| Methylene blue | 40 mg/L | 13.7 | -1.1 | 0.5 |
| Hydroxycobalamin | 0.90 mg/mL | 13.6 | -0.5 | 0.5 |
| Sulfhemoglobin | 10% | 17.41 | “spectral interference detected” | 0.5 |
| Cyanomethemoglobin | 10% | 14.21 | “spectral interference detected” | 0.5 |
| Fluorescein | 0.4 mg/mL | 14.53 | “spectral interference detected” | 0.5 |
| Interference
substance tested | Highest
concentration of
interfering
substance | Analyte (O2Hb)/
concentration (%) | Effect of the
interferent
(%) | ± Trueness
(mean bias)
(%) |
| Sulfhemoglobin | 10% | 94.22 | “spectral interference detected” | 3.00 |
| Cyanomethemoglobin | 10% | 95.81 | “spectral interference detected” | 3.00 |

{34}

| Fluorescein | 0.4 mg/mL | 96.91 | “spectral interference detected” | 3.00 |
| --- | --- | --- | --- | --- |
| Interference substance tested | Highest concentration of interfering substance | Analyte (HHb)/ concentration (%) | Effect of the interferent (%) | ± Trueness (mean bias) (%) |
| Sulfhemoglobin | 10% | 3.53 | “spectral interference detected” | 2.00 |
| Cyanomethemo globin | 10% | 2.06 | “spectral interference detected” | 2.00 |
| Fluorescein | 0.4 mg/mL | 1.34 | “spectral interference detected” | 2.00 |
| Interference substance tested | Highest concentration of interfering substance | Analyte (COHb)/ concentration (%) | Effect of the interferent (%) | ± Trueness (mean bias) (%) |
| | | | | |
| Sulfhemoglobin | 10% | 1.68 | “spectral interference detected” | 1.17 |
| Cyanomethemo globin | 10% | 1.45 | “spectral interference detected” | 1.15 |
| Fluorescein | 0.4 mg/mL | 1.31 | “spectral interference detected” | 1.13 |
| Interference substance tested | Highest concentration of interfering substance | Analyte (MetHb)/ concentration (%) | Effect of the interferent (%) | ± Trueness (mean bias) (%) |
| Sulfhemoglobin | 10% | 0.58 | “spectral interference detected” | 1.12 |
| Cyanomethemo globin | 10% | 0.68 | “spectral interference detected” | 1.14 |
| Fluorescein | 0.4 mg/mL | 0.44 | “spectral interference detected” | 1.09 |
| Interference substance tested | Highest concentration of interfering | Analyte (SO2)/ concentration (%) | Effect of the interferent (%) | ± Trueness (mean bias) (%) |

{35}

f. Assay cut-off: Not applicable.

# 2. Comparison studies:

# a. Method comparison with predicate device:

A multi-center clinic evaluation consisting of a total of six clinics ( 2 laboratory and 4 point-of-care sites) was conducted for the following analytes: pO2, pCO2, pH, Na, K, Ca, Hct, Glucose, Lactate, tHb, O2Hb, HHb, COHb, MetHb, and SO2. Method comparison studies were performed using Roche cobas b 123 and other commercially available devices. In order to cover the hard-to-find sample range, an internal method comparison study was performed using some altered samples that span the entire claimed measuring ranges for all the analytes. Singlet set of data was used for the linear regression analysis. Results are summarized in the table below:

| Analyte | Unit of Measure | n | Range | Slope | Intercept | r |
| --- | --- | --- | --- | --- | --- | --- |
| pH | pH Units | 764 | 6.59 – 7.89 | 0.9930 | 0.0607 | 0.9940 |
| pO2 | mmHg | 737 | 13.3 – 638.0 | 0.9685 | -0.2771 | 0.9977 |
| pCO2 | mmHg | 731 | 16.6 – 149.5 | 0.9698 | 1.100 | 0.9921 |
| Na+ | mEq/L | 822 | 102.0 – 199.2 | 1.0367 | -4.855 | 0.9793 |
| K+ | mEq/L | 814 | 1.43 – 13.54 | 0.9638 | 0.1242 | 0.9982 |
| iCa2+ | mg/dL | 817 | 1.180 – 9.535 | 0.9878 | 0.0199 | 0.9808 |
| Hct | % | 747 | 12.5 – 68.7 | 0.9521 | 1.506 | 0.9881 |
| Glucose | mg/dL | 719 | 18.9 – 539.0 | 1.000 | -3.11 | 0.9880 |
| Lactate | mg/dL | 622 | 9.0 – 171.8 | 1.0227 | 0.2406 | 0.9945 |
| tHb | g/dL | 750 | 4.24 – 22.6 | 0.9643 | -0.0035 | 0.9888 |
| O2Hb | % | 734 | 31.5 – 98.3 | 0.9908 | 1.3011 | 0.9976 |
| HHb | % | 608 | 0.5 – 69.5 | 1.0200 | -0.7370 | 0.9948 |
| COHb | % | 695 | 1.1 – 63.1 | 1.0000 | 0.0000 | 0.9997 |
| MetHb | % | 87 | 1.0 – 59.3 | 0.9896 | 0.1093 | 0.9999 |
| SO2 | % | 734 | 32.0 – 100.0 | 1.0106 | -0.4291 | 0.9931 |
| pCO2 | % | 731 | 1.0 – 10.0 | 0.9900 | 0.0000 | 0.9999 |
| Na+ | mEq/L | 822 | 102.0 – 199.2 | 1.0367 | -4.855 | 0.9793 |
| K+ | mEq/L | 814 | 1.43 – 13.54 | 0.9638 | 0.1242 | 0.9982 |
| iCa2+ | mg/dL | 817 | 1.180 – 9.535 | 0.9878 | 0.0199 | 0.9808 |
| Hct | % | 747 | 12.5 – 68.7 | 0.9521 | 1.506 | 0.9881 |
| Glucose | mg/dL | 719 | 18.9 – 539.0 | 1.000 | -3.11 | 0.9880 |
| Lactate | mg/dL | 622 | 9.0 – 171.8 | 1.0227 | 0.2406 | 0.9945 |
| tHb | g/dL | 750 | 4.24 – 22.6 | 0.9643 | -0.0035 | 0.9888 |
| O2Hb | % | 734 | 31.5 – 98.3 | 0.9908 | 1.3011 | 0.9976 |
| HHb | % | 608 | 0.5 – 69.5 | 1.0200 | -0.7370 | 0.9948 |
| COHb | % | 695 | 1.1 – 63.1 | 1.0000 | 0.0000 | 0.9997 |
| MetHb | % | 87 | 1.0 – 59.3 | 0.9896 | 0.1093 | 0.9999 |
| SO2 | % | 734 | 32.0 – 100.0 | 1.0106 | -0.4291 | 0.9931 |

{36}

b. Matrix comparison:

Not applicable. Only heparinized whole blood samples are used with this device.

# 3. Clinical studies:

a. Clinical Sensitivity:

Not applicable.

b. Clinical specificity:

Not applicable.

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

Not Applicable.

# 4. Clinical cut-off:

Not Applicable.

5. Expected values/Reference range:

| Analyte | Population | Reference range | Cited from |
| --- | --- | --- | --- |
| Sodium | Adult | 136- 145 mmol/L136- 145 mEq/L | Tietz 20061 |
| | Adult> 90 years | 132- 146 mmol/L132- 146 mEq/L | Tietz 20062 |
| Potassium (serum) | Adult | 3.5 - 5.1 mmol/L 3.5- 5.1 mEq/L | Tietz 20063 |
| Ionized Calcium | Adult, female & male | 1.15 - 1.33 mmol/L4.6 - 5.3 mg/dL | Tietz 20064 |
| Methemoglobin | --- | 0.06- 0.24 g/dL9.3 - 37.2 μmol/L0.04 - 1.52 % of total Hb0.0004- 0.0152 mass fraction of total Hb | Tietz 20065 |
| Glucose (whole | Adult | 65- 95 mg/dL | Tietz 20066 |
| | | mEq/L | |
| | | 132- 146 mmol/L | |
| | | 132- 146 mEq/L | |

{37}

| blood, heparin) | | 3.5 - 5.3 mmol/L | |
| --- | --- | --- | --- |
| Lactate (whole blood) | --- | venous (at bed rest)5- 15 mg/dL3-7 mg/dLarterial (at bed rest)0.56 - 1.39 mmol/L0.36 - 0.75 mmol/L | Tietz 20067 |
| Analyte | Population | Reference range | Cited from |
| pH | Arterial whole blood: Adult, children | 7.35 - 7.45 | Tietz 20068 |
| PO2 | Arterial whole blood: Adult, children (2 days-60 years) | 83 - 108 mmHg | Tietz 20068 |
| PCO2 | Adult (male) arterial whole blood | 35 - 48 mmHg | Tietz 20069 |
| | Adult (female) arterial whole blood | 32 - 45 mmHg | Tietz 20069 |
| Hct | Adult MaleAdult Female | 39 - 50 %35 - 47 % | Tietz 198710 |
| tHb (arterial whole blood) | Adult MaleAdult Female | 13.1 - 17.2 g/dL11.7 - 16.0 g/dL | Tietz 198710 |
| SO2 | Newborn | 40 - 90% | Tietz 20068 |
| | Thereafter(Arterial whole blood) | 94 - 98% | Tietz 20068 |
| O2Hb | Whole Blood (Nonsmoker) | 94 - 98% | American Environmental Laboratory11 |
| HHb | Whole Blood | 1 - 5% | American Environmental Laboratory11 |
| COHb | Whole Blood (Nonsmoker) | 0.5 - 1.5% | Tietz 20069 |

# Citations

1. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics: 4th Edition 2006, p. 2294
2. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics: 4th Edition 2006, p.2295
3. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics: 4th Edition 2006, p.2291
4. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics: 4th Edition 2006, p.2258

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5. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics: 4th Edition 2006, p.2317
6. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics: 4th Edition 2006, p.2271
7. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics: 4th Edition 2006, p.2282
8. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics: 4th Edition 2006, p.2289
9. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics: 4th Edition 2006, p.2259
10. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics: 3rd Edition 1987, p.1817
11. American Environmental Laboratory: The Laboratory Assessment of Oxygenation: Robert F. Morgan 1993, 5(4), p. 147 - 153

N. Instrument Name:
Cobas® b 123 POC System

O. System Descriptions:

1. Modes of Operation:
Single sample
Does the applicant’s device transmit data to a computer, webserver, or mobile device using wireless transmission?
Yes ______ or No ☐ X

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:
Single sample barcode reader

4. Specimen Sampling and Handling:
This device is intended to be used with whole blood samples.

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5. Calibration:
Two point calibration of all parameters.

6. Quality Control:
QC consists of the following materials: AutoQC module with AutoQC pack for automated QC measurements

Combitrol Plus B – control material for manual QC measurements

P. Other Supportive Instrument Performance Characteristics Data Not Covered In The “Performance Characteristics” Section above:
None

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.

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