GENOSYL- nitric oxide gas

GENOSYL by

Drug Labeling and Warnings

GENOSYL by is a Prescription medication manufactured, distributed, or labeled by VERO BIOTECH, INC.. Drug facts, warnings, and ingredients follow.

Drug Details [pdf]

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use GENOSYL® safely and effectively. See full prescribing information for GENOSYL.

GENOSYL (nitric oxide), for inhalation use
Initial U.S. Approval: 1999

INDICATIONS AND USAGE

GENOSYL is a vasodilator indicated to improve oxygenation and reduce the need for extracorporeal membrane oxygenation in term and near-term (>34 weeks gestation) neonates with hypoxic respiratory failure associated with clinical or echocardiographic evidence of pulmonary hypertension in conjunction with ventilatory support and other appropriate agents (1).

DOSAGE AND ADMINISTRATION

The recommended dose is 20 ppm, maintained for up to 14 days or until the underlying oxygen desaturation has resolved (2.1).

Doses greater than 20 ppm are not recommended (2.1, 5.2).

Administration: Avoid abrupt discontinuation (2.2, 5.1).

DOSAGE FORMS AND STRENGTHS

GENOSYL (nitric oxide) is a gas, available at concentrations up to 800 ppm. (3)

CONTRAINDICATIONS

Neonates dependent on right-to-left shunting of blood (4).

WARNINGS AND PRECAUTIONS

Rebound Pulmonary Hypertension: Abrupt discontinuation of GENOSYL may lead to worsening oxygenation and increasing pulmonary artery pressure (5.1).

Methemoglobinemia: Methemoglobin increases with the dose of nitric oxide; following discontinuation or reduction of nitric oxide, methemoglobin levels return to baseline over a period of hours (5.2).

Elevated NO2 Levels: Monitor NO2 levels (5.3).

Heart Failure: In patients with pre-existing left ventricular dysfunction, GENOSYL may increase pulmonary capillary wedge pressure leading to pulmonary edema (5.4).

ADVERSE REACTIONS

The most common adverse reaction is hypotension (6).

To report SUSPECTED ADVERSE REACTIONS, contact Vero Biotech at 1-877-337-4118 and http://www.vero-biotech.com/ or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS

Nitric oxide donor compounds may increase the risk of developing methemoglobinemia (7).

Revised: 8/2024
Table of Contents

FULL PRESCRIBING INFORMATION: CONTENTS*

1 INDICATIONS AND USAGE

2 DOSAGE AND ADMINISTRATION

2.1 Dosage

2.2 Administration

3 DOSAGE FORMS AND STRENGTHS

4 CONTRAINDICATIONS

5 WARNINGS AND PRECAUTIONS

5.1 Rebound Pulmonary Hypertension Syndrome following Abrupt Discontinuation

5.2 Hypoxemia from Methemoglobinemia

5.3 Airway Injury from Nitrogen Dioxide

5.4 Worsening Heart Failure

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

6.2 Postmarketing Experience

7 DRUG INTERACTIONS

7.1 Nitric Oxide Donor Agents

8 USE IN SPECIFIC POPULATIONS

8.4 Pediatric Use

8.5 Geriatric Use

10 OVERDOSAGE

11 DESCRIPTION

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

12.2 Pharmacodynamics

12.3 Pharmacokinetics

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

14 CLINICAL STUDIES

14.1 Treatment of Hypoxic Respiratory Failure (HRF)

14.2 Ineffective in Adult Respiratory Distress Syndrome (ARDS)

14.3 Ineffective in Prevention of Bronchopulmonary Dysplasia (BPD)

16 HOW SUPPLIED/STORAGE AND HANDLING

* Sections or subsections omitted from the full prescribing information are not listed.

1 INDICATIONS AND USAGE

GENOSYL® is indicated to improve oxygenation and reduce the need for extracorporeal membrane oxygenation in term and near-term (>34 weeks gestation) neonates with hypoxic respiratory failure associated with clinical or echocardiographic evidence of pulmonary hypertension in conjunction with ventilatory support and other appropriate agents.

2 DOSAGE AND ADMINISTRATION

2.1 Dosage

Term and near-term neonates with hypoxic respiratory failure

The recommended dose of GENOSYL is 20 ppm. Maintain treatment up to 14 days or until the underlying oxygen desaturation has resolved and the neonate is ready to be weaned from GENOSYL therapy.

Doses greater than 20 ppm are not recommended [see Warnings and Precautions (5.2)].

2.2 Administration

Nitric Oxide Delivery System

GENOSYL must be administered using a calibrated GENOSYL Delivery System. Only validated ventilator systems should be used in conjunction with GENOSYL [see Description (11)].

Consult the GENOSYL Delivery System Operator's Manual or call 1-877-337-4118 or visit www.vero-biotech.com for needed information on training and technical support for users of GENOSYL with the GENOSYL Delivery System .

Keep available a backup power supply to address power failures. The GENOSYL Delivery System consists of a primary system and a fully functional second system that can be used as backup in the event of primary system failure.

Monitoring

Measure methemoglobin within 4-8 hours after initiation of treatment with GENOSYL and periodically throughout treatment [see Warnings and Precautions (5.2)].

Monitor for PaO2 and inspired NO2 during GENOSYL administration [see Warnings and Precautions 5.3)].

Weaning and Discontinuation

Avoid abrupt discontinuation of GENOSYL [see Warnings and Precautions (5.1)]. To wean GENOSYL, down titrate in several steps, pausing several hours at each step to monitor for hypoxemia.

3 DOSAGE FORMS AND STRENGTHS

GENOSYL (nitric oxide) is a gas available at concentrations up to 800 ppm [see Description (11)].

4 CONTRAINDICATIONS

GENOSYL is contraindicated in neonates dependent on right-to-left shunting of blood.

5 WARNINGS AND PRECAUTIONS

5.1 Rebound Pulmonary Hypertension Syndrome following Abrupt Discontinuation

Wean from GENOSYL [see Dosage and Administration (2.2)]. Abrupt discontinuation of GENOSYL may lead to worsening oxygenation and increasing pulmonary artery pressure, i.e., Rebound Pulmonary Hypertension Syndrome. Signs and symptoms of Rebound Pulmonary Hypertension Syndrome include hypoxemia, systemic hypotension, bradycardia, and decreased cardiac output. If Rebound Pulmonary Hypertension occurs, reinstate GENOSYL therapy immediately.

5.2 Hypoxemia from Methemoglobinemia

Nitric oxide combines with hemoglobin to form methemoglobin, which does not transport oxygen. Methemoglobin levels increase with the dose of GENOSYL; it can take 8 hours or more before steady-state methemoglobin levels are attained. Monitor methemoglobin and adjust the dose of GENOSYL to optimize oxygenation.

If methemoglobin levels do not resolve with decrease in dose or discontinuation of GENOSYL, additional therapy may be warranted to treat methemoglobinemia [see Overdosage (10)].

5.3 Airway Injury from Nitrogen Dioxide

Nitrogen dioxide (NO2) forms in gas mixtures containing NO and O2. Nitrogen dioxide may cause airway inflammation and damage to lung tissues.

If there is an unexpected change in NO2 concentration, or if the NO2 concentration reaches 0.5 ppm when measured in the breathing circuit, then the delivery system should be assessed in accordance with the GENOSYL Delivery System Operator's Manual troubleshooting section, and the NO2 analyzer should be recalibrated. The dose of GENOSYL and/or FiO2 should be adjusted as appropriate.

5.4 Worsening Heart Failure

Patients with left ventricular dysfunction treated with GENOSYL may experience pulmonary edema, increased pulmonary capillary wedge pressure, worsening of left ventricular dysfunction, systemic hypotension, bradycardia and cardiac arrest. Discontinue GENOSYL while providing symptomatic care.

6 ADVERSE REACTIONS

The following adverse reactions are discussed elsewhere in the label;

Hypoxemia [see Warnings and Precautions (5.2)]

Worsening Heart Failure [see Warnings and Precautions (5.4)]

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The adverse reaction information from the clinical studies does, however, provide a basis for identifying the adverse events that appear to be related to drug use and for approximating rates.

Controlled studies have included 325 patients on nitric oxide doses of 5 to 80 ppm and 251 patients on placebo. Total mortality in the pooled trials was 11% on placebo and 9% on nitric oxide gas for inhalation, a result adequate to exclude nitric oxide mortality being more than 40% worse than placebo.

In both the NINOS and CINRGI studies, the duration of hospitalization was similar in nitric oxide gas for inhalation and placebo-treated groups.

From all controlled studies, at least 6 months of follow-up is available for 278 patients who received nitric oxide gas and 212 patients who received placebo. Among these patients, there was no evidence of an adverse effect of treatment on the need for re-hospitalization, special medical services, pulmonary disease, and neurological sequelae.

In the NINOS study, treatment groups were similar with respect to the incidence and severity of intracranial hemorrhage, Grade IV hemorrhage, periventricular leukomalacia, cerebral infarction, seizures requiring anticonvulsant therapy, pulmonary hemorrhage, or gastrointestinal hemorrhage.

In CINRGI, the only adverse reaction (>2% higher incidence on nitric oxide gas for inhalation than on placebo) was hypotension (14% vs. 11%).

6.2 Postmarketing Experience

Post marketing reports of accidental exposure to nitric oxide for inhalation in hospital staff have been associated with chest discomfort, dizziness, dry throat, dyspnea, and headache.

7 DRUG INTERACTIONS

7.1 Nitric Oxide Donor Agents

Nitric oxide donor agents such as prilocaine, sodium nitroprusside and nitroglycerine may increase the risk of developing methemoglobinemia.

8 USE IN SPECIFIC POPULATIONS

8.4 Pediatric Use

The safety and efficacy of nitric oxide for inhalation has been demonstrated in term and near-term neonates with hypoxic respiratory failure associated with evidence of pulmonary hypertension [see Clinical Studies (14.1)]. Additional studies conducted in premature neonates for the prevention of bronchopulmonary dysplasia have not demonstrated substantial evidence of efficacy [see Clinical Studies (14.3)]. No information about its effectiveness in other age populations is available.

8.5 Geriatric Use

Nitric oxide is not indicated for use in the adult population.

10 OVERDOSAGE

Overdosage with nitric oxide gas is manifest by elevations in methemoglobin and pulmonary toxicities associated with inspired NO2. Elevated NO2 may cause acute lung injury. Elevations in methemoglobin reduce the oxygen delivery capacity of the circulation. In clinical studies, NO2 levels >3 ppm or methemoglobin levels >7% were treated by reducing the dose of, or discontinuing, nitric oxide gas.

Methemoglobinemia that does not resolve after reduction or discontinuation of therapy can be treated with intravenous vitamin C, intravenous methylene blue, or blood transfusion, based upon the clinical situation.

11 DESCRIPTION

GENOSYL (nitric oxide) is administered by inhalation. Nitric oxide is a pulmonary vasodilator. Nitric oxide is generated from liquid dinitrogen tetroxide (N2O4) by the Cassette in the GENOSYL Delivery System. Upon initiation of GENOSYL Delivery System, the liquid N2O4 is heated and the equilibrium shifts to nitrogen dioxide (NO2) gas. The NO2 is then converted into nitric oxide (NO) using the antioxidant Cartridges, and nitric oxide is delivered to the patient by means of a ventilator or a nasal cannula. The amount of nitric oxide administered to the patient is set by controlling the temperature of the N2O4 liquid module, which controls the pressure inside the liquid module, which in turn controls the mass of NO2 that is sent to the primary Cartridges, and hence the mass of nitric oxide. The mass flow of nitric oxide, together with the air from the pump, control the nitric oxide concentration. A nitric oxide sensor monitors the nitric oxide in the patient line. GENOSYL Delivery System is designed to deliver a controlled level of nitric oxide blended with breathing air or oxygen-enriched breathing air.

The GENOSYL Delivery System controls the flow of nitric oxide mixed with air delivered to the patient.

The structural formula of nitric oxide (NO) is shown below:

Chemical Structure

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Nitric oxide relaxes vascular smooth muscle by binding to the heme moiety of cytosolic guanylate cyclase, activating guanylate cyclase and increasing intracellular levels of cyclic guanosine 3',5'-monophosphate, which then leads to vasodilation. When inhaled, nitric oxide selectively dilates the pulmonary vasculature, and because of efficient scavenging by hemoglobin, has minimal effect on the systemic vasculature.

GENOSYL appears to increase the partial pressure of arterial oxygen (PaO2) by dilating pulmonary vessels in better ventilated areas of the lung, redistributing pulmonary blood flow away from lung regions with low ventilation/perfusion (V/Q) ratios toward regions with normal ratios.

12.2 Pharmacodynamics

Effects on Pulmonary Vascular Tone in PPHN

Persistent pulmonary hypertension of the newborn (PPHN) occurs as a primary developmental defect or as a condition secondary to other diseases such as meconium aspiration syndrome (MAS), pneumonia, sepsis, hyaline membrane disease, congenital diaphragmatic hernia (CDH), and pulmonary hypoplasia. In these states, pulmonary vascular resistance (PVR) is high, which results in hypoxemia secondary to right-to-left shunting of blood through the patent ductus arteriosus and foramen ovale. In neonates with PPHN, nitric oxide gas for inhalation improves oxygenation (as indicated by significant increases in PaO2).

12.3 Pharmacokinetics

The pharmacokinetics of nitric oxide has been studied in adults.

Absorption and Distribution

Nitric oxide is absorbed systemically after inhalation. Most of it traverses the pulmonary capillary bed where it combines with hemoglobin that is 60% to 100% oxygen-saturated. At this level of oxygen saturation, nitric oxide combines predominantly with oxyhemoglobin to produce methemoglobin and nitrate. At low oxygen saturation, nitric oxide can combine with deoxyhemoglobin to transiently form nitrosylhemoglobin, which is converted to nitrogen oxides and methemoglobin upon exposure to oxygen. Within the pulmonary system, nitric oxide can combine with oxygen and water to produce nitrogen dioxide and nitrite, respectively, which interact with oxyhemoglobin to produce methemoglobin and nitrate. Thus, the end products of nitric oxide that enter the systemic circulation are predominantly methemoglobin and nitrate.

Metabolism

Methemoglobin disposition has been investigated as a function of time and nitric oxide exposure concentration in neonates with respiratory failure. The methemoglobin (MetHb) concentration-time profiles during the first 12 hours of exposure to 0, 5, 20, and 80 ppm nitric oxide are shown in Figure 1.

Methemoglobin concentrations increased during the first 8 hours of nitric oxide exposure. The mean methemoglobin level remained below 1% in the placebo group and in the 5 ppm and 20 ppm nitric oxide gas groups, but reached approximately 5% in the 80 ppm nitric oxide gas group. Methemoglobin levels >7% were attained only in patients receiving 80 ppm, where they comprised 35% of the group. The average time to reach peak methemoglobin was 10 ± 9 (SD) hours (median, 8 hours) in these 13 patients, but one patient did not exceed 7% until 40 hours.

Elimination

Nitrate has been identified as the predominant nitric oxide metabolite excreted in the urine, accounting for >70% of the nitric oxide dose inhaled. Nitrate is cleared from the plasma by the kidney at rates approaching the rate of glomerular filtration.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

No evidence of a carcinogenic effect was apparent, at inhalation exposures up to the recommended dose (20 ppm), in rats for 20 hr/day for up to two years. Higher exposures have not been investigated.

Nitric oxide gas has demonstrated genotoxicity in Salmonella (Ames Test), human lymphocytes, and after in vivo exposure in rats. There are no animal or human studies to evaluate nitric oxide for effects on fertility.

14 CLINICAL STUDIES

14.1 Treatment of Hypoxic Respiratory Failure (HRF)

The efficacy of nitric oxide gas was investigated in term and near-term newborns with hypoxic respiratory failure (HRF) resulting from a variety of etiologies. Inhalation of nitric oxide gas reduces the oxygenation index (OI= mean airway pressure in cm H2O × fraction of inspired oxygen concentration [FiO2]× 100 divided by systemic arterial concentration in mmHg [PaO2]) and increases PaO2 [see Clinical Pharmacology (12.1)].

NINOS Study

The Neonatal Inhaled Nitric Oxide Study (NINOS) was a double-blind, randomized, placebo-controlled, multicenter trial in 235 neonates with hypoxic respiratory failure. The objective of the study was to determine whether inhaled nitric oxide would reduce the occurrence of death and/or initiation of extracorporeal membrane oxygenation (ECMO) in a prospectively defined cohort of term or near-term neonates with hypoxic respiratory failure unresponsive to conventional therapy. Hypoxic respiratory failure was caused by meconium aspiration syndrome (MAS; 49%), pneumonia/sepsis (21%), idiopathic primary pulmonary hypertension of the newborn (PPHN; 17%), or respiratory distress syndrome (RDS; 11%). Infants ≤14 days of age (mean, 1.7 days) with a mean PaO2 of 46 mmHg and a mean oxygenation index (OI) of 43 cm H2O / mmHg were initially randomized to receive 100% O2 with (n=114) or without (n=121) 20 ppm nitric oxide for up to 14 days. Response to study drug was defined as a change from baseline in PaO2 30 minutes after starting treatment (full response = >20 mmHg, partial = 10–20 mmHg, no response = <10 mmHg). Neonates with a less than full response were evaluated for a response to 80 ppm nitric oxide or control gas. The primary results of this study are presented in Table 1.

Table 1: Summary of Clinical Results from Hypoxic Respiratory Failure Study
	Control (n=121)	Nitric Oxide gas (n=114)	P value
* Extracorporeal membrane oxygenation † Death or need for ECMO was the primary end point of this study
Death or ECMO*,†	77 (64%)	52 (46%)	0.006
Death	20 (17%)	16 (14%)	0.60
ECMO	66 (55%)	44 (39%)	0.014

Although the incidence of death by 120 days of age was similar in both groups (NO, 14%; control 17%), significantly fewer infants in the nitric oxide group required ECMO compared with controls (39% vs. 55%, p = 0.014). The combined incidence of death and/or initiation of ECMO showed a significant advantage for the nitric oxide treated group (46% vs. 64%, p = 0.006). The nitric oxide group also had significantly greater increases in PaO2 and greater decreases in the OI and the alveolar-arterial oxygen gradient than the control group (p<0.001 for all parameters). Significantly more patients had at least a partial response to the initial administration of study drug in the nitric oxide group (66%) than the control group (26%, p<0.001). Of the 125 infants who did not respond to 20 ppm nitric oxide control, similar percentages of NO-treated (18%) and control (20%) patients had at least a partial response to 80 ppm nitric oxide gas for inhalation or control drug, suggesting a lack of additional benefit for the higher dose of nitric oxide. No infant had study drug discontinued for toxicity. Inhaled nitric oxide gas had no detectable effect on mortality. The adverse events collected in the NINOS trial occurred at similar incidence rates in both treatment groups [see Adverse Reactions (6.1)]. Follow-up exams were performed at 18-24 months for the infants enrolled in this trial. In the infants with available follow-up, the two treatment groups were similar with respect to their mental, motor, audiologic, or neurologic evaluations.

CINRGI Study

This study was a double-blind, randomized, placebo-controlled, multi-center trial of 186 term and near-term neonates with pulmonary hypertension and hypoxic respiratory failure. The primary objective of the study was to determine whether nitric oxide gas would reduce the receipt of ECMO in these patients. Hypoxic respiratory failure was caused by MAS (35%), idiopathic PPHN (30%), pneumonia/sepsis (24%), or RDS (8%). Patients with a mean PaO2 of 54 mmHg and a mean OI of 44 cm H2O / mmHg were randomly assigned to receive either 20 ppm nitric oxide gas (n=97) or nitrogen gas (placebo; n=89) in addition to their ventilatory support. Patients who exhibited a PaO2 >60 mmHg and a pH < 7.55 were weaned to 5 ppm nitric oxide gas or placebo. The primary results from the CINRGI study are presented in Table 2.

Table 2: Summary of Clinical Results from Persistent Pulmonary Hypertension of the Newborn Study
	Placebo	Nitric oxide gas	P value
* Extracorporeal membrane oxygenation † ECMO was the primary end point of this study
ECMO*,†	51/89 (57%)	30/97 (31%)	<0.001
Death	5/89 (6%)	3/97 (3%)	0.48

Significantly fewer neonates in the nitric oxide gas group required ECMO compared to the control group (31% vs. 57%, p<0.001). While the number of deaths were similar in both groups (Nitric oxide gas, 3%; placebo, 6%), the combined incidence of death and/or receipt of ECMO was decreased in the nitric oxide gas group (33% vs. 58%, p<0.001).

In addition, the nitric oxide gas group had significantly improved oxygenation as measured by PaO2, OI, and alveolar-arterial gradient (p<0.001 for all parameters). Of the 97 patients treated with nitric oxide gas, 2 (2%) were withdrawn from study drug due to methemoglobin levels >4%. The frequency and number of adverse events reported were similar in the two study groups [see Adverse Reactions (6.1)].

In clinical trials, reduction in the need for ECMO has not been demonstrated with the use of inhaled nitric oxide in neonates with congenital diaphragmatic hernia (CDH).

14.2 Ineffective in Adult Respiratory Distress Syndrome (ARDS)

In a randomized, double-blind, parallel, multicenter study, 385 patients with adult respiratory distress syndrome (ARDS) associated with pneumonia (46%), surgery (33%), multiple trauma (26%), aspiration (23%), pulmonary contusion (18%), and other causes, with PaO2/FiO2 <250 mmHg despite optimal oxygenation and ventilation, received placebo (n=193) or nitric oxide gas (n=192), 5 ppm, for 4 hours to 28 days or until weaned because of improvements in oxygenation. Despite acute improvements in oxygenation, there was no effect of nitric oxide gas on the primary endpoint of days alive and off ventilator support. These results were consistent with outcome data from a smaller dose ranging study of nitric oxide (1.25 to 80 ppm). GENOSYL (nitric oxide) for inhalation is not indicated for use in ARDS.

14.3 Ineffective in Prevention of Bronchopulmonary Dysplasia (BPD)

The safety and efficacy of nitric oxide gas for the prevention of chronic lung disease [bronchopulmonary dysplasia (BPD)] in neonates ≤ 34 weeks gestational age requiring respiratory support has been studied in four large previously conducted multicenter, double-blind, placebo-controlled clinical trials in a total of 2,600 preterm infants. Of these, 1,290 received placebo, and 1,310 received inhaled nitric oxide at doses ranging from 5-20 ppm, for treatment periods of 7-24 days duration. The primary endpoint for these studies was alive and without BPD at 36 weeks postmenstrual age (PMA). The need for supplemental oxygen at 36 weeks PMA served as a surrogate endpoint for the presence of BPD. Overall, efficacy for the prevention of bronchopulmonary dysplasia in preterm infants was not established. There were no meaningful differences between treatment groups with regard to overall deaths, methemoglobin levels, or adverse events commonly observed in premature infants, including intraventricular hemorrhage, patent ductus arteriosus, pulmonary hemorrhage, and retinopathy of prematurity.

The use of GENOSYL (nitric oxide) for prevention of BPD in preterm neonates ≤34 weeks gestational age is not recommended.

16 HOW SUPPLIED/STORAGE AND HANDLING

GENOSYL Delivery System Cassettes produce at least 216 liters of 800 ppm nitric oxide gas (at standard temperature and pressure, STP) (NDC: 72385-002-01).

GENOSYL Delivery System External Transport Cassettes produce at least 73 liters of 800 ppm nitric oxide gas (at standard temperature and pressure, STP) (NDC: 72385-003-01).

Store at 20°C to 25°C (68°F to 77°F) with excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature].

The GENOSYL Delivery System must be used with antioxidant Cartridges not older than 12 months from the manufacturing date.

Occupational Exposure

The exposure limit set by the Occupational Safety and Health Administration (OSHA) for nitric oxide is 25 ppm, and for NO2 the limit is 5 ppm.

Rx Only

VERO Biotech and GENOSYL are registered trademarks of VERO Biotech.

Manufactured by:

VERO BIOTECH

387 Nerem Street NW

Suite 125

Atlanta, GA 30313, USA
[602604]

INSTRUCTIONS FOR USE

VĒRO
BIOTECH

GENOSYL®
DELIVERY SYSTEM

FOR DELIVERY OF
GENOSYL®
(NITRIC OXIDE)
GAS FOR INHALATION

OPERATOR'S MANUAL

Technical Support: 877.337.4118

Company Confidential
Part No. 602502 Rev. I

DO NOT COPY

VERO Biotech Inc.
387 Nerem Street NW, Suite 125
Atlanta, GA 30313 USA

WARNINGS, CAUTIONS, AND NOTES

Please read all Warnings and Cautions in this Operator's Manual prior to using the GENOSYL DS.

MR Conditional Safety Information

The GENOSYL DS may be safely used in the MR environment under the following conditions. Failure to follow these conditions may result in injury.

Maximum static magnetic field of 100 Gauss (0.01mT)
Device remains outside the scanner bore
Preparation protocols described in the Warnings section titled "Use in the MR Environment" must be followed before MR procedure

Image Artifacts:

When the GENOSYL DS is battery powered, no image artifacts are expected. When powered using a wall outlet, minor noise is expected.

Throughout this Operator's Manual, warnings, cautions, and notes will be displayed in the following manner.

WARNING
The warning box will alert the user to possible injury, death, or serious adverse reactions associated with the use or misuse of the device.

CAUTION
The caution box will alert the user about proper use of the equipment and any conditions that could result in equipment damage or failure. The user should read and adhere to all warnings and cautions.

NOTE
The note box provides information, clarification, or supplemental information to assist and educate the user on the use of the equipment.

A complete list of Warnings and Cautions for the GENOSYL DS are shown below. Where appropriate, some of these will also be shown throughout this manual.

WARNINGS
Please consult the package insert for a complete list of contraindications.
Alarms ALWAYS acknowledge and follow information provided from alarms. An alarm indicates an abnormal condition, and ignoring alarms can result in possible injury, death, or serious adverse reactions. ALWAYS use clinical judgement when setting upper or lower alarm limits. Failure to do so could result in possible injury or death.
Consoles ALWAYS have a second Console present and properly connected when a Dosing Console is connected to the patient. If the Dosing Console malfunctions, switch to the Back-up Console. If the Back-up Console is not available or properly connected, this may result in patient injury or death. DO NOT clean the GENOSYL DS with the power connected and the System turned ON, as this may lead to injury (e.g., shock). Unplug AC/DC power supply external to the System prior to cleaning. NEVER modify the equipment. Modifications of the equipment may result in malfunction, which may result in a fire, shock, injury, or death. NEVER turn the rear power switch OFF until the System has gone through a controlled shutdown or instructed by VERO Technical Support. Turning the rear power switch OFF prematurely (e.g., while it is still in use) will immediately shut down the device. This may result in interruption in NO delivery to the patient, which may cause injury or death.
Cassette DO NOT use the Cassette if the Cassette State Window is not blue. A Cassette State Window that is any color other than blue may affect the Cassette's ability to provide the correct NO dosage to the patient, which may cause injury or death. DO NOT use a Cassette that is beyond its expiration date. Using an expired Cassette may affect the Cassette's ability to provide the correct NO dosage to the patient, which may cause injury or death. MAKE SURE the System stabilizes to the prescribed concentration (ppm) of NO prior to leaving the Console unattended. Failure to do so could result in under delivery of the target NO, leading to injury or harm. ALWAYS replace a Cassette once depleted. A depleted Cassette will interrupt patient dosing and can lead to underdosing and/or injury to the patient. ALWAYS follow Cassette inspection instructions prior to Cassette insertion. Not inspecting the Cassette prior to insertion may lead to using a faulty Cassette, resulting in injury.
Use in the MR Environment The GENOSYL DS is classified as MR Conditional with MR scanners of 1.5 or 3.0 Tesla strength ONLY in areas where the field strength is less than 100 gauss. ALWAYS operate at a fringe field of less than 100 gauss. This device contains ferromagnetic components and may experience strong attraction close to the magnet. DO NOT exceed 100 gauss; System operation may be impacted. Confirm Cart caster lock function. Optionally connect tether. NEVER use the GENOSYL DS in the MR scanner room without gauss alarms installed. ALWAYS verify at least one gauss alarm is functioning properly prior to use in the MR environment. DO NOT use the GENOSYL DS in the MR environment if neither gauss alarm is functional. ALWAYS move System away from the MR scanner if the gauss alarm sounds. The gauss alarm will sound if the System is too close to the MR scanner. Move System away from the MR scanner until the gauss alarm stops sounding. ALWAYS verify that the GENOSYL DS Cart casters are locked after positioning the System in the MR scanner room. ALWAYS verify that the GENOSYL DS is securely attached to the Cart. ALWAYS arrange power cord, MR patient gas sample line, and NO delivery line to avoid entanglement, strangulation and/or a trip hazard. DO NOT use the GENOSYL DS in the MR environment if the Cart moves when the brake caster locks are engaged. NEVER perform NO or NO2 calibration within the MR scanner room. Calibration equipment is a potential projectile hazard.
Transport ALWAYS ensure the GENOSYL DS Dosing and Back-up Consoles are securely affixed to the External Transport Mounts when the System will be used in a transport vehicle. ALWAYS ensure Consoles are placed into External Transport Mode before inserting a Cassette for external transport outside of the hospital. ONLY use External Transport Cassettes, identified by orange color and transport sticker, in external transport outside of the hospital. ALWAYS ensure the External Transport Mounts are secured during patient transport, per hospital protocols.
Use with Anesthesia Gas Machines ALWAYS use the Anesthesia Gas Machine (AGM) in accordance with the manufacturer's instructions. The flow out of the anesthesia gas machine via the INSPIRATORY breathing circuit limb must pass through the GENOSYL DS Gas Injection Assembly. The GENOSYL DS injects and samples gas from the patient respiratory circuit which may affect the triggering sensitivity of the anesthesia gas machine (AGM). ALWAYS ensure the trigger sensitivity of the AGM is checked after connecting the GENOSYL DS to the breathing circuit and starting iNO delivery or when the dose is changed and adjust trigger sensitivity as necessary. Failure to do so may lead to AGM auto cycling or apnea alarm. ALWAYS ensure the patient disconnect and high–pressure alarms are used with the AGM. Ensure the Injection Assembly and the Gas Sample Tee are BOTH inserted on the inspiratory limb of the circuit.
Connections ALWAYS follow pre-use setup instructions for the routing and connections of tubing to avoid patient strangulation. MAKE SURE the System has all tubing connected as described in the instructions. Not connecting all tubing may result in inaccurate dosage and harm the patient. NEVER touch the electrical connectors of the System or its accessories, and the patient simultaneously. If the user touches another device with a ground-fault failure and simultaneously touches the GENOSYL DS, this can result in injury (e.g., shock) should a grounding failure be present.
Battery ONLY properly trained personnel should replace the battery. Incorrectly replacing the battery may result in a hazard such as excessive temperatures, fire, or explosion. MAKE SURE the GENOSYL DS is connected to AC wall power to charge the battery a minimum of once every 3 months to maintain a minimum battery charge. Failure to recharge the Console battery for extended timeframes may result in full discharge of the battery. If a Battery Error message occurs during startup of the System, contact Technical Support at 877-337-4118 for assistance.
User ONLY intended users who are experienced in the use of this System should use this device. US federal law restricts device use to licensed medical professionals. If device is used by unintended users, device can be misused and lead to injury or death.
Alternative Means of Ventilation ALWAYS ensure that the manual flow displayed on the Console matches the flow set into the resuscitation bag. Incorrect flow settings may result in an incorrect estimation of NO delivery. If the flow into the manual equipment is too low, there is risk of overdosing the patient with NO. ALWAYS squeeze the bag several times, after starting fresh gas flow, to empty residual gas in the bag prior to using the System to ventilate a patient. Failure to do so could result in higher NO2 levels being delivered to the patient. ALWAYS use the smallest bag adequate to deliver the desired tidal volume. Failure to do so could result in higher NO2 levels being delivered to the patient.
Patient Monitoring ALWAYS constantly monitor the patient. System malfunctions can occur if device and patient are not monitored and can result in injury or death. Careful monitoring is required by care personnel whenever the System is used on a patient. The use of an alarm and a monitoring system does not give an absolute assurance of warning for every malfunction that may occur. Certain alarms may require immediate response.
Use with Breathing Devices ONLY use a manual resuscitation bag with the GENOSYL DS for a short time (e.g., less than one hour) when on battery only. Otherwise, the System may shut off and may result in injury or death. The GENOSYL DS injects and samples gas from the patient respiratory circuit which may affect the triggering sensitivity of the ventilator. ALWAYS ensure the trigger sensitivity of the ventilator is checked after connecting the GENOSYL DS to the breathing circuit or when the dose is changed and adjust trigger sensitivity as necessary. Failure to do so may lead to ventilator auto cycling or apnea alarm. ALWAYS ensure the patient disconnect and high-pressure alarms are used with the ventilator. ONLY use the GENOSYL DS with Bio-Med Crossvent 2+ with Constant Flow ON. Not doing so may lead to elevated NO2 levels or dose variability.
Set-up ONLY VERO Biotech authorized equipment technicians are to perform the initial System set-up prior to initial use. Failure to use an authorized equipment technician can result in a patient or user injury. ONLY store the GENOSYL DS as outlined in the storage instructions. Not storing the device in alignment with its storage instructions can cause the device to be unsafe and lead to injury or death. AVOID using the GENOSYL DS adjacent to or stacked with other equipment, as it may result in improper operation. If such use is necessary, this equipment and the other equipment should be observed to verify that they are operating normally. DO NOT use accessories or cables other than those specified or provided by the manufacturer of this equipment, as this may result in increased electromagnetic emissions or decreased electromagnetic immunity of this equipment and result in improper operation. DO NOT place portable RF communications equipment (including peripherals such as antenna cables and external antennas) closer than 30cm (12 inches) to any part of the GENOSYL DS, including cables specified. Otherwise, degradation of the performance of this equipment could occur, resulting in injury. Only connect to a power outlet with protective earth. Failure to connect to an outlet with protective earth may result in an electrical shock.
Troubleshooting ALWAYS ensure patient safety before troubleshooting (such as an activated alarm) or replacing a problematic item. Not monitoring the patient prior to attending to an alarm can result in injury or death.
Calibration ONLY use the calibration gas pressure regulators supplied by the manufacturer. Pressure regulators not supplied by the manufacturer may damage the sensors and may lead to patient injury. ALWAYS verify the correct NIST traceable calibration gas is being used and confirm the expiration date of the calibration gas prior to performing calibration. The use of incorrect or expired gas may result in inaccurate sensor readings and can lead to patient injury.
Cleaning and Maintenance NEVER submerge the GENOSYL DS, Cassettes, or non-disposable Adaptive Sensor Cable. Submerging in liquids will damage the System and could cause electrical shorts which may result in injury or death.
Water Trap ALWAYS empty Water Trap when prompted by the System, and when the trap is more than half full. Allowing the Water Trap to completely fill will occlude the Sample Line which will interrupt patient gas NO, NO2, and O2 concentration monitoring. Failure to monitor the patient gas NO, NO2, and O2 concentrations may result in patient injury. ALWAYS conduct Water Trap / Sample Line Leak Test every time you empty and replace the Water Trap, as failure to do so may lead to an incorrect NO reading, which can result in injury or death. ALWAYS use a Water Trap supplied by the manufacturer. Using an incorrect Water Trap could result in non-functioning or inaccurate sensor readings.
Use Outside of Product Labeling ALWAYS use the GENOSYL DS in accordance with the indications, usage, contraindications, warnings, and precautions described in the GENOSYL prescribing information and labeling. Refer to latest approved prescribing information and labeling prior to use. The approved patient population for the GENOSYL DS as specified in the drug labeling for GENOSYL (nitric oxide) for inhalation, is limited to neonates. The GENOSYL DS is not intended to be used in other patient populations. ONLY use the GENOSYL DS, its parts, and accessories as instructed. Using non-specified components may result in product malfunction, injury, or death ONLY trained personnel should operate the GENOSYL DS. Failure to do so can result in injury or death. ONLY mechanical ventilators validated with the GENOSYL DS should be used. Not using a validated ventilator system can result in injury or harm.

CAUTIONS
Supplied Instructions ALWAYS refer to the instructions supplied with all equipment to be used in conjunction with the GENOSYL DS for their intended uses, contraindications, and potential complications. Misuse of the device or its components may damage the device.
Cassette DO NOT remove Cassette from packaging until ready to use. External packaging is designed to protect the Cassette from damage and/or contamination. User should always have a secondary Cassette inserted in the Dosing Console and preheated in order for auto transition to occur. User should replace depleted Cassette as soon as possible after ejection.
Consoles ALWAYS operate the Console on a level surface to avoid potential interruption to nitric oxide (NO) delivery. ONLY use recommended cleaning agents or a damp cloth to clean the Console and limit use of liquids around Console. Excess water can permanently damage the device. ONLY use the GENOSYL DS with the power cord supplied by the manufacturer. Use of a generic power cord may cause output voltage instability leading to a touch screen failure. ALWAYS ensure the power cord is firmly seated into the power supply and the wall outlet. A loose connection can result in damage to the device or faulty operation. Prolonged use in dry environments without humidification will damage the gas sensors. Supplemental humidification providing greater than 20% relative humidity (RH) in the patient circuit is recommended.
Use with Breathing Devices When using spontaneous breathing modes on respiratory device, NO2 levels may exceed 3.0 ppm NO when dosing ≥ 57 ppm NO into 100% FiO2 and maximum bias flow, resulting in nitric oxide delivery interruption. Once sample value of NO2 is below 3.0 ppm, the Console will auto resume delivery of NO at set dose. Refer to Section 12.1.5 Table 13 for additional information. When using non-spontaneous breathing modes on respiratory device NO2 levels may exceed 3.0 ppm when dosing ≥ 63 ppm NO into 100% FiO2 and maximum bias flow, resulting in nitric oxide delivery interruption. Once sample value of NO2 is below 3.0 ppm, the Console will auto resume delivery of NO at set dose. Refer to Section 12.1.5 Table 13 for additional information.
Use with Anesthesia Gas Machines The Adaptive Sensor is recommended for use with anesthesia gas machines (AGMs). When using an AGM without the Adaptive Sensor, transient dose excursions outside of the set NO dose may occur during Cassette transition, and changes in breathing circuit flow may cause fluctuations in measured levels of NO and NO2 when using the manual ventilation bag integrated with the AGM. When using anesthesia gas machines, NO2 levels may exceed 3.0 ppm when dosing ≥ 58 ppm NO into 100% FiO2, resulting in nitric oxide delivery interruption. Once sample value of NO2 is below 3.0 ppm, the Console will auto resume delivery of NO at set dose. DO NOT use in environments with <20% relative humidity (RH) in the absence of supplemental humidification. Prolonged use in dry environments without humidification will damage the gas sensors. GENOSYL DS was validated with listed AGMs using a Heat Moisture Exchanger (HME) and was not tested with heated humidification connected to the respiratory circuit. Rebreathing validation testing was performed with semi-closed breathing systems. Non-rebreathing validation testing was perfumed with semi-open breathing systems. The GENOSYL DS has not been evaluated with fully open or fully closed anesthesia breathing systems.
Gas Sampling During Aerosol Delivery Pneumatic Nebulizers will dilute the delivered nitric oxide dose.
Calibration ALWAYS perform a full-scale calibration of the GENOSYL DS when prompted by the System prior to use. ALWAYS confirm the correct flow direction of the installed one-way check valve in the sampling tee to avoid over pressurization of the sample system and damage to the device.
Cleaning and Maintenance ALWAYS follow maintenance instructions in this manual for your safety and to prevent damage to the System. ALWAYS power down the GENOSYL DS Console when not in use. DO NOT sterilize (e.g., autoclave, gas sterilize) any of the components of the System, as this may compromise performance. DO NOT use harsh cleaning agents. Doing so may impair the structural integrity and/or function of the device. DO NOT touch or rub the display screen with abrasive cleaning compounds, as they may scratch and damage the screens. ALWAYS ensure the System is completely dry after cleaning before powering it ON. Failure to do so could result in equipment damage.
Switching OFF the System NEVER turn the rear power switch OFF until the System has gone through a controlled shutdown or instructed by VERO Technical Support. Turning the rear power switch OFF prematurely (e.g., while it is still in use) will immediately shut down the device and may cause improper operation upon restart.
Cart DO NOT stand or sit on the Cart. Standing or sitting on the Cart can damage the device. ALWAYS push or pull the Cart using the handle only. NOT doing so may result in damage to the device.

TABLE OF CONTENTS
WARNINGS, CAUTIONS, AND NOTES		3
TABLE OF CONTENTS		12
LIST OF TABLES		16
LIST OF FIGURES		17
ABBREVIATIONS, TERMINOLOGY, AND DEFINITIONS		19
SYMBOLS		21
GENOSYL DS PARTS / COMPONENTS		23
1.	GENERAL INFORMATION	32
1.1	User Responsibility	32
1.2	General Information and Indications for Use	33
1.3	Principles of Operation	34
1.4	Exposure of Healthcare Providers to NO and NO2	38
2.	SYSTEM OVERVIEW	42
2.1	Frequently Used Functions	42
2.2	GENOSYL DS Cart and Consoles	43
2.3	Cassette	49
2.4	GENOSYL DS Ventilator Circuit Components	51
2.5	Gas Lines (detailed explanation)	54
2.6	Console Dosing Modes of Operation	56
2.7	Display Screen	56
2.8	Display "Menu" Tab Navigation	57
2.9	Display Screen Operational Buttons	61
2.10	Display Screen – Cassette Status Indicators	63
2.11	Display Screen - Adaptive Sensor Status	67
2.12	Cassette Insertion into Console	68
2.13	Water Trap / Sample Line Leak Test	68
2.14	Console Shutdown - Cassette Status Indicator	69
2.15	Battery Charge Status Indicator	70
3.	SYSTEM SET-UP AND CONNECTIONS	74
3.1	GENOSYL DS Set-Up and Mechanical Ventilator Circuit Schematic	74
3.2	Connections to Various Breathing Systems	74
3.2.1	Conventional Ventilators	75
3.2.2	Non-Invasive Gas Delivery Systems	79
3.3	GENOSYL DS Ventilator Circuit Assembly Pre-Check	81
3.4	Assembling GENOSYL DS Injection Assembly with Adaptive Sensor and GENOSYL DS Mixer Assembly with Adaptive Sensor	83
3.4.1	GENOSYL DS Injection Assembly with Adaptive Sensor	83
3.4.2	GENOSYL DS Mixer Assembly with Adaptive Sensor	84
3.5	GENOSYL DS Console Connections	86
3.5.1	GENOSYL DS Gas Line Connections	86
3.5.2	GENOSYL DS Sample Line Extension Connection	87
3.5.3	Sample Line Filter Connection	89
3.5.4	GENOSYL DS Adaptive Sensor Cable Connection	91
3.5.5	GENOSYL DS Respiratory Circuit Connections	91
3.6	Manual Ventilation (Bag) Connection	93
3.7	Mechanical Ventilator Circuit Connections	94
3.8	Gas Sampling During Aerosol Delivery	95
4.	SYSTEM START UP	100
4.1	Console Start-Up	100
4.2	Cassette Insertion & Water Trap / Sample Line Leak Test	101
4.2.1	Water Trap / Sample Line Leak Test Troubleshooting	107
5.	NITRIC OXIDE ADMINISTRATION	110
5.1	Nitric Oxide Dose Set-Up and Administration	110
5.1.1	Setting a Dose when using a Circuit with an Adaptive Sensor	110
5.1.2	Setting a Dose when using a Circuit without an Adaptive Sensor	112
5.2	Adjusting the Dose	113
5.3	Replacement of a Depleted Cassette	115
5.4	Manual Mode	116
5.4.1	Manual Ventilation Use (Bagging)	116
5.4.2	Preset Manual Dosing Mode Flow Rate (OPTIONAL)	119
5.4.3	Resuming Primary Dosing	119
5.5	Console Use as a Back-up	120
6.	CONSOLE SHUTDOWN AND CASSETTE DISPOSAL	124
6.1	Console Shutdown	124
6.2	Cassette Disposal	128
7.	USING THE SYSTEM IN THE MR SCANNER ROOM	132
7.1	Connection to the Ventilator Breathing Circuit	132
7.2	Transferring to and from the MR Scanner Room	133
8.	EXTERNAL TRANSPORT	138
8.1	External Transport Set-Up and Ventilator Circuit Schematics	144
8.1.1	Securing a Console in a Transport Mount	144
8.1.2	Connection to an International Bio-Med External Transport Ventilator Circuit	145
8.1.3	Connection to a Conventional External Transport Ventilator	147
8.1.3.1	Connection to a Conventional External Transport Ventilator using an Injection Assembly with Adaptive Sensor	148
8.1.3.2	Transport Ventilator Circuit Set-Up and Connections using Mixer Assembly with Adaptive Sensor	151
8.2	Using the GENOSYL DS for External Transport	153
8.2.1	Switching External Transport Mode ON	153
8.2.2	Inserting an External Transport Cassette	155
8.2.3	Setting a Dose in External Transport Mode with an Adaptive Sensor	159
8.2.4	Setting a Dose in External Transport Mode without an Adaptive Sensor	161
8.2.5	Adjusting a Dose in External Transport Mode	163
8.2.6	Using Manual Dosing Mode while External Transport Mode is Enabled	164
8.2.7	Resuming Primary Dosing while in External Transport Mode	166
8.2.8	Console Shutdown while in External Transport Mode	167
8.2.9	Switching External Transport Mode OFF	171
9.	USE WITH ANESTHESIA GAS MACHINES	174
8.1	Connection to a Dual Limb Anesthesia Circuit	176
8.2	Connection Instructions for the GENOSYL DS to an Anesthesia Gas Machine	177
10.	ALARMS, ALERTS, AND TROUBLESHOOTING	184
10.1	Alarms, Alerts, and Troubleshooting	184
10.2	On-screen Troubleshooting Module	186
10.3	High Priority Alarms and Messages	189
10.4	Medium Priority Alarms and Messages	200
10.5	Low Priority Alarms and Messages	204
10.6	Informational Messages	205
10.7	GaussAlert™ Alarm	207
10.8	Troubleshooting	208
10.9	Leak Detection Tool	211
11.	SYSTEM MAINTENANCE	216
11.1	Calibration	216
11.1.1	Air Calibration	217
11.1.2	NO Calibration	218
11.1.3	NO2 Calibration	220
11.2	Maintenance Schedule	222
11.3	Testing the GaussAlert™ Function	222
11.4	Water Trap Maintenance	224
11.4.1	Emptying the Water Trap	224
11.4.2	Water Trap Replacement	225
11.5	Battery	225
11.6	Cleaning	226
11.6.1	Enclosure, Connections, and Surfaces Other Than the Display	226
11.6.2	Display Screen	227
11.6.3	Cleaning the Gauss Alarms Mount	227
11.7.1	Cart / Console Storage	228
11.7.2	Cassette / Accessory Storage	228
12.	MECHANICAL VENTILATION	232
12.1	Mechanical Ventilation	232
12.1.1	Oxygen Dilution	232
12.1.2	Minute Volume	234
12.1.3	Trigger Sensitivity	234
12.1.4	Maximum NO Delivery	234
12.1.5	Bias Flow and NO2	234
12.2	Ventilator Compatibility	236
13	PRODUCT SPECIFICATIONS	246
13.1	System Performance	246
13.2	System Classification	246
13.3	Testing	246
13.4	Electrical	247
13.5	Power Supply	247
13.6	Battery	247
13.6.1	Battery Charge Status Indicator	248
13.17	Display	248
13.8	Mechanical	248
13.9	Environmental	249
13.10	GaussAlert™ Specifications	249
13.11	MR Signal-to-Noise Ratio and Artifact Dimension Analysis	249
13.12	EMI/EMC	250
KEY WORD INDEX		258

LIST OF TABLES
Table 1: Conventional Ventilator Compatibility Test Ranges	76
Table 2: Non-Invasive Gas Delivery System Compatibility Test Ranges	79
Table 3: External Transport Ventilation Devices Compatibility Testing Ranges	140
Table 4: External Transport Equipment Specifications	143
Table 5: Anesthesia Gas Machine Validation Compatibility Test Ranges	175
Table 6: Anesthesia Gas Machine Tidal Volume Use Cases	176
Table 7: Alarm Icon Descriptions	184
Table 8: Alarm Characteristics	185
Table 9: Alarm Ranges, Defaults and Dose Interruption Condition	185
Table 10: Alarm conditions included in On-screen Troubleshooting Module	187
Table 11: Recommended Cleaning Agents	227
Table 12: Oxygen Dilution	233
Table 13: NO Dose at which NO2 exceeded 3ppm NO2 Threshold when dosing at 100% FiO2 and Maximum bias flow	235
Table 14: Details of Validated Systems	237
Table 15: Validated Compatibility with and without Inline Mixer	241

LIST OF FIGURES
Figure 1: GENOSYL DS Console Front Panel	34
Figure 2: Cassette Output Range	35
Figure 3: Calculated Time to Hospital Cassette Depletion	36
Figure 4: Calculated Time to External Transport Cassette Depletion	36
Figure 5: GENOSYL DS Assembled Cart	44
Figure 6: MR Conditional GENOSYL DS Front View	45
Figure 7: MR Conditional GENOSYL DS Side View	46
Figure 8: Front View GENOSYL DS Console	47
Figure 9: Back View GENOSYL DS Console	48
Figure 10: Right Side View GENOSYL DS Console	48
Figure 11: Left Side View GENOSYL DS Console	48
Figure 12: GENOSYL Cassette	49
Figure 13: GENOSYL External Transport Cassette	50
Figure 14: GENOSYL DS Gas Lines	55
Figure 15: GENOSYL DS Display Screen	56
Figure 16: Water Trap/Sample Line Leak Test	69
Figure 17: Conventional Ventilator Circuit Set-Up and Connections using Injection Assembly with Adaptive Sensor to the GENOSYL DS and a Manual Bagging System	77
Figure 18: Conventional Ventilator Circuit Set-Up and Connection using the Mixer Assembly with Adaptive Sensor to the GENOSYL DS and a Manual Bagging System	78
Figure 19: Fisher and Paykel Optiflow Jr 2 Breathing Circuit	79
Figure 20: Fisher and Paykel Optiflow Breathing Circuit	80
Figure 21: GENOSYL DS Injection Assembly with Adaptive Sensor	83
Figure 22: GENOSYL DS Mixer Assembly with Adaptive Sensor	84
Figure 23: MR Scanner Room	134
Figure 24: Display Navigation in External Transport Mode	139
Figure 25: GENOSYL DS on External Transport Mount	141
Figure 26: External Transport Cassette	142
Figure 27: International Bio-Med Transport Ventilator Circuit Set-Up and Connections using Injection Assembly with Adaptive Sensor to the GENOSYL DS and a Manual Bagging System	145
Figure 28: Transport Ventilator Circuit Set-Up and Connections using Injection Assembly with Adaptive Sensor to the GENOSYL DS and a Manual Bagging System	148
Figure 29: Transport Ventilator Circuit Set-Up and Connections using Mixer Assembly with Adaptive Sensor to the GENOSYL DS and a Manual Bagging System	151
Figure 30: Anesthesia Gas Machine Circuit Set-up and Connection to the GENOSYL DS without Inline Mixer	177
Figure 31: Anesthesia Gas Machine Circuit Set-up and Connection to the GENOSYL DS with Inline Mixer	177
Figure 32: On-screen Troubleshooting Menu	187
Figure 33: Description of VERO On-screen Troubleshooting Module Navigation	188
Figure 34: Screen displayed if recommended actions cannot address alarm condition, or alarm condition is active and on-screen troubleshooting support is not available	189
Figure 35: "Alarms" tab display when a leak is suspected	212
Figure 36: GaussAlert™ Test	223
Figure 37: Cassette Output Range	236

ABBREVIATIONS, TERMINOLOGY, AND DEFINITIONS
ABBREVIATION / TERMINOLOGY	DEFINITION
Adaptive Sensor Port	Port on the front of the Console that the Adaptive Sensor Cable plugs into.
AGM	Anesthesia Gas Machine
Back-up	A situation whereby the Back-up Console and its Cassette is activated in the event of a failure of the Dosing Console.
Back-up Console	The secondary Console used as a "Back-up" system to administer nitric oxide when the Dosing Console cannot be used.
BPM	Breaths per minute
Cassette	The Cassette contains the material used to make nitric oxide and when inserted into the Console is available for dosing the patient.
cmH20	Centimeters of water / unit of pressure
Display	Electronic information panel located on the front of the Console.
Dosing Console	The Console that is actively dosing NO.
DS	Delivery System
Gas Sample Port	Port on the front of the Console at the Water Trap that measures NO, NO2 and O2 levels within the NO gas path prior to reaching the patient.
GENOSYL	Nitric oxide for inhalation
Hz	Hertz
Keypad	A Graphical User Interface function built into the Console display and used to enter the nitric oxide dose to be administered to the patient.
L/min	Liters per minute
LPM	Liters per minute
Mixer	Ventilator circuit accessory used to mix the ventilator gas with the gas supplied by the GENOSYL DS for specific ventilator and tidal volume use cases, per Section 12.2.
MRI	Magnetic Resonance Imaging
MR Scanner Bore	The MR scanner opening
MR Exclusion Zone	Area in the MR scanner room where the magnetic field is greater than 100 gauss
MR Scanner	The MR device for diagnostic imaging
MR Scanner Room	The room where the MR scanner is located
mT	Millitesla; Unit used to measure magnetic field
NICU	Neonatal Intensive Care Unit
NO	Nitric oxide
NO Injection Port	Port on the front of the Console that introduces the concentrated NO into the respiratory circuit.
NO2	Nitrogen dioxide
N2O4	Dinitrogen tetroxide
O2	Oxygen
OD	Oxygen diameter
PEEP	Positive end-expiratory pressure
ppm	Parts er Million
psi	Pounds per square inch/ unit of pressure
System	The System (GENOSYL DS) consists of a Cart with two Consoles, Cassettes, and component parts used to set up the gas lines
v	Electrical Volts

SYMBOLS
Symbol	Symbol Name	Description
	AC	Indicates power input specification is alternating current (AC).
	Adaptive Sensor Port	Input port for Adaptive Sensor Cable
	Atmospheric pressure limitation	To indicate the acceptable upper and lower limits of atmospheric pressure for transport and storage.
	Attention	Indicates the need for the user to consult the instructions for use for important cautionary information such as warnings and precautions that cannot, for a variety of reasons, be presented on the medical device itself.
	Batch Code	Indicates the batch code so that the batch or lot can be identified.
	Calibration Port	Input port for calibration gas
	Catalog or model number	Indicates the catalog number so that the medical device can be identified.
	Consult instructions for use	Informs the user to consult the instructions for use.
	Date of Manufacture	Indicates the date when the medical device was manufactured.
	Do not reuse	Indicates a medical device that is intended for one use, or for use on a single patient during a single procedure.
	External Transport Symbols	Appears on External Transport Cassettes to indicate Cassette can be used during patient transfer in rescue vehicle, fixed wing, or helicopter.
	Ingression	Code for the level of ingression protection tested. The enclosure was tested to be drip proof.
	Magnetic Resonance (MR) Conditional	Indicates that the System has been demonstrated to pose no known hazards in a specified MRI environment with specified conditions of use.
	Manual Ventilation	Output port for GENOSYL to manual ventilation system
	Manufacturer	Indicates the manufacturer of the item.
	NO Injection	Output port for GENOSYL to patient circuit
	Operating Instructions	Refer to operating instructions for instructions for use, warnings, precautions, and other equipment information.
	RF Interference	Devices marked with this symbol may interfere with the Console.
	Sample Gas Inlet	Attachment point for Sample Line on Water Trap
	Serial Number	Indicates the serial number so that a specific medical device can be identified.
	Storage humidity range	Indicates the range of humidity to which the medical device can be safely exposed.
	Storage temperature range	Indicates the temperature limits to which the medical device can be safely exposed.
	Unlock position	Direction to push to open the Water Trap.
	Use by	Indicates the date after which the medical device is not to be used.
	Water Trap Attachment Point	Indicates the location where the Water Trap with Sample Port is to be attached.

GENOSYL DS PARTS / COMPONENTS
PART	PART NAME
	GENOSYL DS Cart
	GENOSYL DS Console (2 required per System)
	MR Conditional GENOSYL DS System
	Gauss Alarms Mount (2 gauss alarms installed)
	External Transport Mount
	External Transport Mount with Quick Connect Plate
	Adaptive Sensor Cable

The following parts are required to set up the GENOSYL DS and deliver nitric oxide to the patient breathing circuit, using validated ventilators, ventilator circuits, and manual ventilation equipment.

PART	PART NAME
	GENOSYL Hospital Cassette (may be referred to as Cassette or Hospital Cassette)
	GENOSYL External Transport Cassette (may be referred to as Cassette or External Transport Cassette)
	Adaptive Sensor
	NO Gas Injection Adapter 22M/15F × 22F
	Adapter 22F × 22F
	Inline Breathing Circuit Filter
.	GENOSYL DS Mixer
	GENOSYL DS Gas Lines: NO Injection Line (red) Sample Line (blue) Manual Ventilation Line (clear)

	GENOSYL DS Sample Line Extension
	Neonatal Gas Sample Tee
	Water Trap
	22M 22F Elbow Adapter
	Sample Line Filter
	Sample Tee, 3/8" Barbed
	Injection Line Filter
	22M/15F × 22M/15F Adapter
	15M × 4.5 Adapter
	22M/15F × 15M Gas Sample Tee
	22F × 15M Adapter

Note: Physical appearances may vary slightly.

The following parts are required to deliver nitric oxide using a manual ventilation system.

PART	PART NAME
	GENOSYL DS Manual Ventilation Bag NO Adapter

Note: Physical appearances may vary slightly.

The following parts are required for routine maintenance.

PART	PART NAME
	Calibration Gas - 45 ppm NO
	Calibration Gas - 10 ppm NO2
	Calibration Regulator
	Calibration Tee Tubing
	Calibration Extension Tubing
	Calibration Gas Carrying Case
	Calibration Equipment Wrench
	Calibration Regulator Teflon Washer

Note: Physical appearances may vary slightly.

GENOSYL® DS

SECTION 1
GENERAL INFORMATION

1. GENERAL INFORMATION

1.1 User Responsibility

The GENOSYL DS (Console) will perform as described in this Operator's Manual, accompanying inserts, and/or labels when assembled, operated, maintained, and repaired in accordance with the instructions provided. The Console must be set up as described in Section 3. If the Console does not perform as described in Section 3 or during assembly, the parts are found to be broken, missing, contaminated, or visibly worn, they should be replaced immediately.

In the case of repair or replacement of the Console is required, a telephone service request should be made to Technical Support at 877-337-4118. The GENOSYL DS or any of its parts should not be serviced or repaired by anyone other than a VERO Biotech Technical Engineer or without written permission from VERO Biotech Technical Engineering Department.

Any malfunction resulting from faulty maintenance, improper repair, damage, alteration by anyone other than a VERO Biotech Technical Engineer, and/or improper use will be the sole responsibility of the User.

WARNING
The GENOSYL DS must only be used in accordance with the approved indications, usage, contraindications, precautions, and warnings described in the GENOSYL DS labeling. Refer to the labeling prior to use.

CAUTION
U.S. Federal law restricts this device to sale by or on the order of a physician. Outside the U.S., check local laws for any restrictions that may apply.

NOTES
Prior to using the GENOSYL DS, read through this Operator's Manual. Follow all instructions and obey the Warnings and Cautions. Keep this Operator's Manual available to readily answer questions. Read through all manufacturer Operator's Manuals for the ventilator, humidifier and any other accessory items used.

1.2 General Information and Indications for Use

GENOSYL DS generates and delivers NO for inhalation at the point of use. The concentration of NO, as set by the user, is monitored, and adjusted to accurately dose the patient throughout an inspired breath. Only validated devices / components should be used with the GENOSYL DS.

The intended population for inhaled NO treatment is term and near-term neonates in neonatal intensive care units (NICUs). Refer to the GENOSYL (nitric oxide) for inhalation drug label for more detailed information.

The GENOSYL DS is intended for use in the hospital, 1.5 Tesla and 3.0 Tesla diagnostic imaging environments, during patient transfer via rescue vehicle, fixed wing aircraft, or helicopter, and the operating room in conjunction with validated anesthesia gas machines.

The GENOSYL DS is intended for use by healthcare professionals (HCPs) who are licensed and actively practicing pediatric and/or neonatal respiratory therapists (RTs), or HCPs in the operating room with the supervision of RTs in the United States. These users are required to set up, administer inhaled nitric oxide (iNO) and provide respiratory care (including initiation and maintenance of mechanical ventilators) in the critically ill neonatal population.

The GENOSYL DS starts with liquid N2O4/NO2, which is then converted in a proprietary Cassette to NO. The GENOSYL DS delivers NO into the ventilator stream, where the NO joins a stream of air or O2 and is diluted to the prescribed concentration.

The NO concentration (dose) to be delivered to the patient is selected by the user and is set and maintained independently by means of computer-controlled air pumps, Cassette heaters, and a feedback loop that measures the delivered NO concentration.

The GENOSYL DS takes a gas sample removed from the NO gas flow stream immediately prior to the patient and provides real-time output of the NO, NO2, and O2 concentrations that are being delivered to the patient. The continuous integrated gas monitoring includes a comprehensive alarm system.

The NO concentration detected from the sample line is used in a feedback loop to adjust the NO concentration delivered into the ventilator circuit.

The GENOSYL DS includes a redundant Console for complete back-up capability for delivery of NO for inhalation. Each Console has a back-up battery that is expected to last up to four hours under optimal conditions in the absence of an external power source. Console will alarm when less than 15 minutes of battery life remains.

1.3 Principles of Operation

GENOSYL DS. The GENOSYL DS continuously introduces a precisely controlled concentration of nitric oxide (NO) into the inspiratory limb of the ventilator circuit. GENOSYL DS utilizes the known properties of NO and other oxides of nitrogen, namely dinitrogen tetroxide (N2O4) and nitrogen dioxide (NO2), to create a "tankless" drug/device combination System to produce, at the point of use, ultra-high purity NO for inhalation, providing a consistent, prescribed dose to the patient.

Console. The GENOSYL DS Console contains the electronics to control the production and to maintain the constant and precise delivery of NO.

The primary features of the Console front panel are displayed in Figure 1.

Figure 1: GENOSYL DS Console Front Panel

NO generation. The Console uses Cassettes containing liquid N2O4/NO2 inside a stainless-steel vessel (the liquid module) and an antioxidant cartridge. Upon initiation of a Cassette, the liquid N2O4 is heated, producing NO2 gas, which is mixed with up to 0.9 LPM ambient air supplied by the Console. The NO2/air is injected into the antioxidant cartridge inside the Cassette, which converts NO2 to NO.

The Cassette is designed to provide NO in concentrations up to 80 ppm. The maximum and minimum delivered dose for a range of constant inspiratory flow rates is presented in Figure 2.

The maximum combination of dose (ppm) and flow (LPM) output of the System is 800 ppm × LPM (e.g., 20 ppm with 40 LPM, 40 ppm at 20 LPM, etc.). The System is capable of delivering NO at a minimum of 1 ppm × LPM (e.g., 1 ppm at 1 LPM).

Figure 2: Cassette Output Range

The total time to deplete the Cassette N2O4 contents depends on the rate of use. The minimum time to depletion based on use rate for Hospital Cassettes is shown in Figure 3. The minimum time to depletion of the External Transport Cassette based on use rate is shown in Figure 4. The calculated minimum remaining contents at the current output rate is indicated by a gauge presented on the Console display during use.

Figure 3: Calculated Time to Hospital Cassette Depletion

Figure 4: Calculated Time to External Transport Cassette Depletion

NO Injection into the Ventilator Circuit. After NO is produced in the Cassette, the NO injector introduces the concentrated NO into the ventilator circuit where the NO is diluted to the prescribed concentration (dose) and mixed with the O2 or air supplied to the patient.

GENOSYL Smart Feedback System™ Before the gas mixture reaches the patient, a sample line removes a small gas sample and sends it back to the Console, where gas sensors continuously measure the supplied NO, NO2 and O2. The Console software then compares the measured NO concentration to the set NO concentration and continuously adjusts the delivery of NO to maintain the prescribed NO concentration (dose) delivered to the patient (closed loop control). The Console software commands the NO injection flow rate into the ventilator circuit with a maximum flow rate of 0.9 LPM. Changes in the ventilator settings by the user may cause brief transient changes in the measured NO value. The Console software will adjust the injected flow rate and the internal temperature of the Cassette to compensate for the changes in the total ventilator flow rate. For example, a higher minute ventilation will require a higher injection flow rate to produce the same NO concentration.

Mixer. An inline Mixer is used in the applicable ventilator circuit after the NO injection site and before the gas sample site to mix NO from the Console with the gas supplied by the ventilator, for specific ventilator and tidal volume use cases per Section 12.2.

Gas Monitoring. The gas mixture delivered to the patient by the GENOSYL DS is continuously monitored with two NO detectors, with one providing redundant back-up, as well as a detector for NO2 and O2. A sample of inspired gas is taken from the inspiratory limb, close to the patient, and is measured by the gas sensor within the Console. The gas monitoring sensors are electrochemical; they are specific to each gas and provide an electronic signal that is proportional to the concentration of gas present.

Adaptive Sensor. The Adaptive Sensor is used to detect flow in the patient breathing circuit. When flow is not detected by the Adaptive Sensor, nitric oxide delivery will be interrupted until flow is detected. The Console will provide a visual and audible low priority alarm when flow is not detected to alert the user (see Section 10.5). Once flow is detected, the Console will auto resume delivery of nitric oxide at the previously set dose. An Adaptive Sensor is recommended for use with certain breathing devices. Refer to Section 3 for recommended set up diagrams. The GENOSYL DS will properly deliver and control nitric oxide dose in the absence of an Adaptive Sensor.

Alarms and Dosing Safeguard Fallback Modes. The GENOSYL DS alerts the user in the event of excursions of NO, NO2, and Oxygen from their expected ranges. Nitric oxide delivery interruption conditions are as follows:

1. Press the gray "Set" button on the display screen.
2. Enter the prescribed dose in ppm on the electronic keypad.
3. Press OK to confirm the entry.
1. Press the gray "Set" button on the display screen.
2. Confirm Total Flow range is appropriately selected.
3. Enter the prescribed dose in ppm on the electronic keypad.
4. Press OK to confirm the entry.
1. Press the gray "Set" button to access the electronic keypad on the display screen on the Dosing Console.
2. Enter the prescribed dose using the electronic keypad.
3. Press "OK" to confirm the dose and to start dosing administration.
1. Press the gray "Set" button to access the electronic keypad on the display screen on the Dosing Console.
2. Enter the prescribed ppm dose using the numeric keypad.
3. Adjust Total Flow range, if necessary.
4. Press "OK" to confirm the dose and to start dosing administration.
1. Follow onscreen instructions to replace Cassette.
1. Ensure the oxygen flow source is set appropriately or adjust as needed.
2. Press the button "Switch to Manual" on the Dosing Console.
3. Press "Confirm" to switch to Manual Dosing.
4. To resume primary dosing, see Section 5.4.3.
1. Navigate to the "Settings" Tab.
2. Select the Flow Rate from the drop-down menu.
1. Press the "Switch to Primary" button at the top of the Manual Mode screen.
2. Press "Confirm" to start dosing or "Cancel" to cancel.
1. Press the "Set" button on the Back-up Console which will display the NO dose electronic keypad and Flow Selection menu.
2. Confirm Dose and Total Flow range is appropriately selected.
3. Press "OK" to confirm entry
4. Connect the Adaptive Sensor Cable to the front of the new Dosing Console.
1. Press the gray "Set" button to access the electronic keypad on the display screen.
2. Set the dose to "0" using the electronic keypad.
3. Press "OK" to confirm the entry.
4. If the "Settings" tab is not displayed, press the "Menu" tab to access the sub-level tabs.
5. Press the "Settings" tab on the display menu.
6. Press the red "System Shutdown" icon.
7. Review on screen prompt.
8. Press "Confirm" to confirm shutdown.
9. Wait until the Console shuts down, the display screen appears blank, and the Console emits an audible beep.
10. Open the Cassette Access Door.
11. Remove the Cassettes by pulling the Cassette straight out.
12. Dispose the inerted Cassettes per hospital policy.
13. Press the Black Rocker Power Switch to the "OFF" position.
14. Repeat steps 1-13 for the other Console.
1. Check to make sure nothing is connected to the CAL port during Air Calibration.
2. If the "Calibration" tab is not displayed, press the "Menu" tab to access the sub-level tabs.
3. Press the "Calibration" tab on the display menu.
4. Press the Low Range "Air" button.
5. Press the blue "Start Calibration" button.
6. Press "OK" to continue once calibration is complete.
1. If the "Calibration" tab is not displayed, press the "Menu" tab to access the sub-level tabs.
2. Press the "Calibration" tab on the display menu.
3. Press the High Range "NO" button.
4. Press the gray "Start Calibration" button.
5. Follow the onscreen instructions.
6. Follow the onscreen instructions
7. Press "Accept" to continue once calibration is complete.
1. If the "Calibration" tab is not displayed, press the "Menu" tab to access the sub-level tabs.
2. Press the "Calibration" tab on the display menu.
3. Press the High Range "NO2" button.
4. Press the gray "Start Calibration" button.
5. Follow the onscreen instructions.
6. Follow the onscreen instructions.
7. Press "OK" once calibration is complete.
1. Place the test magnet tool on the GaussAlert™ alarm bracket in the area identified in Figure 36.
2. The alarm will activate and a short flash (less than two seconds) of the LED indicates proper function.
3. Move the test magnet tool away from the GaussAlert™ until the alarm stops sounding.
4. Repeat this procedure on the second GaussAlert™.
1. Remove Water Trap from Console by lifting latch and pulling the base of the Water Trap away from the Console.
2. Remove the lid by pulling the lid from the base.
3. Empty the liquid contents.
4. Reattach the lid by pushing it back onto base.
5. Slide the Water Trap back on the Console until it clicks into place.
1. Remove old Water Trap from Console by lifting the latch and pulling the base of the Water Trap away from the Console.
2. Slide new Water Trap back on the Console until it clicks into place. Replace sample line to Water Trap.
3. Discard the old Water Trap.

WARNING
NEVER use the MR Unsafe GENOSYL DS Cart in the MR scanner room. ALWAYS verify at least one gauss alarm is functioning properly prior to use in the MR environment.

CAUTION
ALWAYS operate the Console on a level surface to avoid potential interruption to nitric oxide (NO) delivery. DO NOT stand or sit on the Cart. Standing or sitting on the Cart can damage device. ALWAYS push or pull the Cart using the handle only. NOT doing so may result in damage to the device.

NOTE
A System has a top and bottom Console. Both Consoles will start-up in Primary Dosing Mode. One Console will be used for dosing and the other will remain in Primary Dosing Mode as a Back-up Console. (See Section 5.5)

CAUTION
DO NOT remove Cassette from packaging until ready to use. External packaging is designed to protect the Cassette from damage and/or contamination.

PART	PART NAME	FUNCTION
	Adaptive Sensor	Used to measure flow from the ventilator into the circuit.
	Adaptive Sensor Cable	Used to communicate flow readings to the Console.
	GENOSYL DS Gas Lines NO Injection Line (red) Sample Line (blue) NO Manual Ventilation Line (clear)	Used to deliver nitric oxide to the ventilator circuit and manual ventilation bag, and to sample gas within the ventilator circuit.
	GENOSYL DS Manual Ventilation Bag NO Adapter	Used to connect oxygen tubing to manual ventilation bagging system to deliver nitric oxide. Includes an NO Injection Port to connect to the NO Injection Line.
	GENOSYL DS Mixer	Used to mix the NO gas with the gas supplied by the ventilator through a filter containing silica gel to provide intra-breath NO delivery for certain scenarios.
	Adapter 22F × 22F	Used as a coupler between the Mixer and the Gas Injection Adapter when a Mixer is required.
	GENOSYL DS Sample Line Extension	Used when the distance between the patient and the DS exceeds the length of the standard sample gas line in the MR Environment.
	Injection Line Filter	Used to filter air from the Injection Line.
	Inline Breathing Circuit Filter	Used to filter air from the Injection Line, and on the expiratory limb when used with an anesthesia gas machine.
	Neonatal Gas Sample Tee	Used to connect the Sample Line to the ventilator circuit.
	NO Gas Injection Adapter 22M/15F × 22F	Used between the Adaptive Sensor and the Inline Breathing Circuit Filter, and to connect to the NO Injection Line (red).
	Sample Tee, 3/8" Barbed	Used to accommodate gas sampling in some ventilator circuits, (e.g., Crossvent Infant Circuit).
	Sample Line Filter	Used to protect sampling system during use with aerosol medications (refer to Section 3.8).
	Water Trap	Used to protect sample system by collecting condensation and filtering contaminants from the sampled gas. The Water Trap may need to be emptied or changed while in use (refer to Section 11.4).
	22M/15F × 22M/15F Adapter	Used to create GENOSYL DS sampling port 6 to 12 inches from the patient wye.
	15M × 4.5 Adapter	Used between Oxygen Tubing and NO Gas Injection Adapter with some non-invasive gas delivery systems.
	22M/15F × 15M Gas Sample Tee	Used to connect the Sample Line to the ventilator circuit.
	22F × 15M Adapter	Used to assist with connection of the NO Delivery Injection Assembly to various ventilator circuits.

MODE	FUNCTIONAL CHARACTERISTICS
Primary Dosing	The dosing mode of operation for controlled dosing with Smart Feedback System™.
Manual Dosing	The dosing mode of operation used for manual ventilation. Manually adjustable fixed dosing without the need of feedback for certain conditions.

NOTE
Some confirmation display screens (e.g., "Confirm", "Yes", "Accept", etc.) will be semi-transparent after dosing has been initiated to allow the Operator to continue to see important information on the underlying screen (e.g., NO values, Alarms, Alerts, etc.).

MENU TAB DISPLAY	TAB / BUTTON	DESCRIPTION
		Press this tab to access the sub-level tabs (Main, Alarms, Calibration, Events, and Settings).
		Displayed when the "Alarms" tab is selected, this screen is used to set the Upper and Lower Alarm Limits for NO (ppm), NO2 (ppm), and O2 (%). A list of Alarms that have occurred since the last reset for the Console will be displayed on this tab.
NOTE
See Section 10 for additional information on alarms and alerts.
	Displayed after pressing the "Alarms" tab, press this button to switch to the default upper and lower limits for NO (ppm), NO2 (ppm), and O2 (%).
	Pressing this button will clear the alarm history from the alarm log visible on this tab. The alarm will remain logged in the Console's permanent logs.
	Press this tab to return to the main screen. Pressing the Main Tab will collapse the tab menu.
		Press this tab to access the calibration screen.
NOTE
See Section 11.1 for additional information on Calibration.
	Press this button to calibrate the low range of the NO and NO2 sensor.
	Press this button to calibrate the high range for the NO sensor.
	Press this button to calibrate the high range for the NO2 sensor.
	Press this button to initiate calibration for the selected gas.
	Press this button to stop the calibration in the middle of a calibration process. The previous calibration will remain to be used.
	Press this button to display the history of calibration.
		Press this tab to access the events menu.
	Press this button to clear the events listed on the events screen.
		Press this tab to access the settings screen.
	Press this button to begin the process of shutting down the Console.
	Press this button to switch display to day (light) display view. This will switch the display to a lighter gray background instead of the dark blue background.
	This drop-down menu allows operator to preset the dilution flow rate for Manual Mode. If no rate is selected, Console will default to 10 LPM.
	Press this button to enter the screen to adjust the date and time. This button is only present when logged in as an Administrator
	Press this button to adjust the date and time. This button is only present when logged in as an Administrator
	Press this button to perform a "Water Trap/ Sample Line Leak Test".
	Used by service personnel only. Password controlled.
NOTE
Contact Technical Support at 877-337-4118 for additional support.
	Press this button to display a window to enter date ranges to retrieve dosing usage over a period of time and number of Cassette activations.
	Press this button to enable External Transport Mode. This button is gray when External Transport Mode is OFF.
NOTE
This will require the transport PIN. Contact Technical Support for additional support.
		Press this button to disable External Transport Mode. This button is orange when External Transport Mode is ON.
NOTE
This will require the transport PIN. Contact Technical Support for additional support.
		When External Transport Mode is ON, the External Transport animated icons will rotate between these three icons in the upper right corner of the screen next to the Alarm icon.


		Day (Light) display view Main Menu: Press this tab to access the sub-level tabs (Main, Alarms, Calibration, Events, and Settings).
	Press this button to switch display to regular night (dark) display view. This button is located on the "Settings" tab.

BUTTON	DESCRIPTION
	Press this button to set the targeted NO (ppm) dose when in Primary Dosing Mode.
	Press this button to pre-silence alarms. Pushing this button will pre-silence specific alarms for 120 seconds. When active, a red "X" will appear through the alarm icon with a countdown of how much longer alarms will be pre-silenced for. When tapping the icon with the red "X", the user will cancel the pre-silence.
	Press this button to cancel the Water Trap / Sample Line Leak Test.
	Press this button to switch a Console to Primary Dosing Mode from Manual Dosing Mode. When in Primary Dosing Mode, the dosage can be set to a user selected (prescribed) level.
	Press this button to switch from Primary Dosing Mode to Manual Dosing Mode. See Section 5.4 for information about dosing in Manual Dosing Mode.
	Electronic keypad used to set and adjust the prescribed targeted nitric oxide dose to be delivered to the patient. Includes buttons to confirm "OK", "Cancel", or "Clear" the entry.
	The Total Flow range is selected by the user if the Adaptive Sensor is not connected to the Console. These buttons will only appear if the Console does not detect an Adaptive Sensor when setting or adjusting dose. Total Flow range is the sum of the ventilator (or ancillary equipment) Bias Flow and the minute ventilation of the patient.
	Displayed when in Manual Dosing Mode, press the green up or down arrows to adjust the dose to the patient, from the default dose. Pressing the down arrow will decrease the dose in increments of 1 ppm for 24 ppm and below. Pressing the up arrow will increase the dose in increments of 2 ppm above 24 ppm. Press the green LPM (liters per minute) button to activate a drop-down menu and set a different dilution flow rate.
	Press this button to confirm the action specified on the screen.
	Press this button to cancel the action specified on the screen.
	Press this button to acknowledge the information message displayed on the screen.
	Press this button to move to the next step.
	Press this button to cancel the current step.

CASSETTE STATUS INDICATOR DISPLAY	DESCRIPTION
	This Cassette Status Indicator will be displayed when a Cassette is not loaded into the Console. The Cassette Status Indicator will display "REPLACE" and will alternate between a dark red and light red. The user is prompted to "Replace"
	This Cassette Status Indicator is displayed during the warmup phase when a new Cassette is inserted. This indicator will display "WARMING" alternating with "READY". Dose may be initiated while the Cassette is warming.
	This Cassette Status Indicator is displayed once the Cassette has achieved a fully preheated status.
	This Cassette Status Indicator is displayed during dosing. If a secondary Cassette has been inserted, the Cassette Status Indicator will display "Dosing" for the dosing Cassette and "Ready" for the secondary Cassette. If a secondary Cassette has not been inserted, the Cassette Status Indicator will display the percentage of nitric oxide remaining in the dosing Cassette and the secondary Cassette Status Indicator will be red and display "Replace". A low priority tone will also sound in ten second intervals until a secondary Cassette is inserted.
	This Cassette Status Indicator will be displayed when the Console is transitioning from the dosing Cassette to the secondary Cassette. The direction of the arrow indicates the Cassette that is being transitioned to.
	This Cassette Status Indicator will be displayed when less than one hour of Cassette life remains and no secondary Cassette is inserted. The indicator will display the percentage of life remaining in the dosing Cassette and the estimated time before depletion. The Cassette Status Indicator for the dosing Cassette will appear yellow and display "Dosing" and the other Cassette Status Indicator will appear red and display "Replace"
	This Cassette Status Indicator is displayed when a Cassette is depleted and no secondary Cassette is inserted in the Console. This status will only display if another Cassette is not present in the Console. The Cassette Status Indicator for the dosing Cassette will appear red and display "Dosing 0%" and "0m". The empty Cassette Status Indicator will appear red and display "Replace". Both indicators will alternate between a dark and light red color.
	This Cassette Status Indicator will be displayed when a Cassette that has previously been used is inserted in a Console. The Cassette display will alternate between "USED" and an "X" through the Cassette icon. The Console will automatically eject a previously used Cassette.
	This Cassette Status Indicator will be displayed two minutes after inserting one Cassette into the Back-up Console. The secondary Cassette Status Indicator on the screen will switch from a red flashing "REPLACE" to an empty gray Cassette outline. Once a dose is entered, and the inserted Cassette is activated, the outline will switch back to the red flashing "REPLACE" so the user is prompted to insert a secondary Cassette in the dosing Console.
	This Cassette Status Indicator is displayed when a Cassette is non-operational. A white X will appear over a red Cassette Status Indicator. The Console will eject a non-operational Cassette and dose from the secondary Cassette, if properly inserted. User will be prompted to replace Cassette after ejection.
	This Cassette Status Indicator is displayed when a Cassette is past its expiration date. The display will read "EXPIRED". An expired Cassette cannot be used for dosing and will be automatically ejected from the Console. User will then be prompted to replace the ejected Cassette via the Cassette Status Indicator.
	This Cassette Status Indicator will be displayed when the wrong Cassette type is inserted into the Console. The display will read "WRONG TYPE" then proceed to eject the incorrect Cassette from the Console. A Hospital Cassette will be ejected while External Transport Mode is turned ON and an External Transport Cassette will be ejected while External Transport Mode is turned OFF.

ADAPTIVE SENSOR DISPLAY	DESCRIPTION
	The Console has detected flow through the Adaptive Sensor.
	The Console has detected an Adaptive Sensor without flow. To initiate delivery, the Console requires flow detection. The Set button will not appear until flow is detected through the Adaptive Sensor. The screen will appear as pictured below. Once flow is detected, the "Set" button will appear and allow the user to set the dose. If the Adaptive Sensor stops detecting flow while dosing, the Console will interrupt delivery of NO into the circuit and display a turquoise "Flow Not Detected-Nitric Oxide Delivery Interrupted" message. This message will be accompanied by a low tone every 10 seconds. See Section 10.5 Low Priority Alarms and Messages.
	The Console does not detect an Adaptive Sensor is connected
	An Adaptive Sensor is detected but the Adaptive Sensor is either malfunctioning or not properly connected to the Adaptive Sensor Cable.

WARNING
ONLY use External Transport Cassettes, identified by orange color and transport sticker, in external transport outside of the hospital.

PHOTO	DESCRIPTION
	Insert the Cassette into the receptacle. Push in until you hear the Cassette click into the mechanism.
	The on-screen Cassette Status Indicator will switch to say "READY" and then prompt the user to begin a Water Trap/ Sample Line Leak Test.

TEST IN PROCESS	TEST PASSED

Figure 16: Water Trap / Sample Line Leak Test

CASSETTE STATUS INDICATOR	DESCRIPTION
	This Cassette Status Indicator will display "SAVE" on the shutdown screen to note which Cassette should be retained for future use. This Cassette has not been activated for dosing.
	This Cassette Status Indicator will display "DISPOSE" on the shutdown screen to note which Cassette should be disposed of per hospital policy. This Cassette was used for dosing or has been activated.
	This Cassette Status Indicator will appear on the shutdown screen to note no Cassette was inserted into the receptacle.

CHARGE STATUS INDICATOR	DESCRIPTION
Solid Red	Battery Power Supply Error. See Battery Error Alarm in Section 10.3.
Blinking Red	Communication Failure or Hardware Error. See Hardware Failure Alarm in Section 10.3.
Solid Amber	Console is unplugged and using battery power. See System is running on low Battery Alarm in Section 10.5.
Blinking Amber	Console is using battery power and running on low battery. See Low Battery Alarm in Section 10.5.
Solid Green	Console is plugged in and battery is fully charged.
Blinking Green	Console is plugged in and the battery is charging.

NOTE
Naming conventions: The GENOSYL DS accessories and components consist of the GENOSYL DS Injection Assembly with Adaptive Sensor, (Section 3.4.1), or the GENOSYL DS Mixer Assembly with Adaptive Sensor (Section 3.4.2), and the GENOSYL DS Gas Lines (Section 3.5). Refer to Section 12.2 Table 15 for when use of the Mixer Assembly with Adaptive Sensor is recommended. Connections and disposable circuits to breathing systems may vary and are unique to individual manufacturers. Example circuit diagrams are provided for reference.

WARNING
ALWAYS use the GENOSYL DS in accordance with the indications, usage, contraindications, warnings, and precautions described in the GENOSYL prescribing information and labeling. Refer to latest approved prescribing information and labeling prior to use. The approved patient population for the GENOSYL DS as specified in the drug labeling for GENOSYL (nitric oxide) for inhalation, is limited to neonates. The GENOSYL DS is not intended to be used in other patient populations. ONLY use the GENOSYL DS, its parts, and accessories as instructed. Using non-specified components may result in product malfunction, injury or death. ALWAYS follow pre-use setup instructions for the routing and connections of tubing to avoid patient strangulation. MAKE SURE the System has all tubing connected as described in the instructions. Not connecting all tubing may result in inaccurate dosage and harm to the patient. DO NOT use accessories or cables other than those specified or provided by the manufacturer of this equipment, as this may result in increased electromagnetic emissions or decreased electromagnetic immunity of this equipment and result in improper operation.

CAUTION
Prolonged use in dry environments without humidification will damage the gas sensors. Supplemental humidification providing greater than 20% relative humidity (RH) in the patient circuit is recommended.

NOTE
All circuit components, including GENOSYL DS circuit components, should be changed out and disposed of according to hospital protocol. Refer to Section 8 for use of the GENOSYL DS with an external transport ventilation device. Refer to Section 9 for use of the GENOSYL DS with an anesthesia gas machine.

WARNING
ALWAYS ensure the trigger sensitivity of the ventilator is checked after connecting the GENOSYL DS to the breathing circuit or when the dose is changed. The GENOSYL DS injects and samples gas from the patient respiratory circuit which may affect the triggering sensitivity of the ventilator. ALWAYS ensure the patient disconnect and high–pressure alarms are used with the ventilator. ONLY use the GENOSYL DS with Bio-Med Crossvent 2+ with Constant Flow ON. Not doing so may lead to elevated NO2 levels or dose variability.

CAUTION
When using spontaneous breathing modes on respiratory device, NO2 levels may exceed 3.0 ppm when dosing ≥ 57 ppm NO into 100% FiO2 and maximum bias flow, resulting in nitric oxide delivery interruption. Once sample value of NO2 is below 3.0 ppm, the Console will auto resume delivery of NO at set dose. Refer to Section 12.1.5 Table 13 for additional information. When using non-spontaneous breathing modes on respiratory device, NO2 levels may exceed 3.0 ppm when dosing ≥ 63 ppm NO into 100% FiO2 and maximum bias flow, resulting in nitric oxide delivery interruption. Once sample value of NO2 is below 3.0 ppm, the Console will auto resume delivery of NO at set dose. Refer to Section 12.1.5 Table 13 for additional information.

NOTE
If a higher than desired level of NO2 is measured in the patient circuit, increasing respiratory device bias flow, if applicable, may result in decreased NO2 levels.

Table 2: Non-Invasive Gas Delivery System Compatibility Test Ranges
Setting	Range	Unit
Optiflow Jr 2 Flow Rate	0.5 - 25	LPM
Optiflow Flow Rate	5-60	LPM

ILLUSTRATION	ACTION	Warnings, Cautions and Notes
Cassettes – 3 ea. Adaptive Sensor – 1 ea. Adaptive Sensor Cable – 1 ea. Gas Injection Adapter – 1 ea. Inline Breathing Circuit Filter 1ea. (2 Inline Breathing Circuit Filters will be needed for use with an AGM. Refer to Section 9 for more information about use with an AGM) Mixer Assembly Mixer – 1 ea. Adapter (22mm ID × 22mm ID) – 1ea. Inline Breathing Circuit Filter– 1 ea. Gas Lines – 1 ea. Gas Sample Tee – 1 ea. Manual Ventilation Bag NO Adapter – 1 ea.	1. Remove all items of the GENOSYL DS Parts / Components from packaging. 2. Confirm that the appropriate Cassettes for the intended use environment have been selected. 3. Check the expiration date for each Cassette and the Inline Breathing Circuit Filter to ensure use is within the expiration date.	WARNING
DO NOT use a Cassette that is beyond its expiration date. Using an expired Cassette may affect the Cassette's ability to provide the correct NO dosage to the patient, which may cause injury or death. ONLY use External Transport Cassettes, identified by orange color and transport sticker, in external transport outside of the hospital.
NOTE
A Mixer Assembly is not required for all use cases. Refer to Section 12.2, Table 15
	4. Visually inspect the Water Traps on both Consoles to ensure they are installed and empty.	WARNING
ALWAYS empty Water Trap before each use, when prompted by the System, and when the trap is more than half full. Allowing the Water Trap to completely fill will occlude the Sample Line which will interrupt patient gas NO, NO2, and O2 concentration monitoring. Failure to monitor the patient gas NO, NO2, and O2 concentrations may result in patient injury. ALWAYS conduct Water Trap / Sample Line Leak Test every time you empty and replace the Water Trap, as failure to do so may lead to an incorrect NO reading, which can result in injury or death.
NOTE
To empty the Water Trap, see Section 11.4.1.

INSTRUCTIONS FOR USE

VĒRO
BIOTECH

GENOSYL®
DELIVERY SYSTEM

FOR DELIVERY OF
GENOSYL®
(NITRIC OXIDE)
GAS FOR INHALATION

QUICK REFERENCE GUIDE

Technical Support: 877.337.4118

GENOSYL® DS

QUICK REFERENCE GUIDE

TABLE OF CONTENTS
TABLE OF CONTENTS		2
LIST OF TABLES		3
LIST OF FIGURES		4
1.	SYSTEM SET-UP AND CONNECTIONS	6
1.1.	GENOSYL DS Set-Up and Mechanical Ventilator Circuit Schematic	6
1.2.	Connections to Various Breathing Systems	7
1.2.1	Conventional Ventilators	7
1.2.2	Non-Invasive Gas Delivery Systems	10
1.3	GENOSYL DS Ventilator Circuit Assembly Pre-Check	12
1.4	Assembling GENOSYL DS Injection Assembly with Adaptive Sensor	13
1.4.1	GENOSYL DS Injection Assembly with Adaptive Sensor	13
1.4.2	GENOSYL DS Mixer Assembly with Adaptive Sensor	13
1.5	GENOSYL DS Console Connections	14
1.5.1	GENOSYL DS Gas Lines Connections	14
1.5.2	GENOSYL DS Sample Line Extension Connection	16
1.5.3	GENOSYL DS Respiratory Circuit Connections	17
1.6	Manual Ventilation (Bag) Connection	18
1.7	Mechanical Ventilator Circuit Connections	18
2.	SYSTEM START UP	19
2.1	Console Start-Up	19
2.2	Cassette Insertion & Water Trap / Sample Line Leak Test	20
3	NITRIC OXIDE ADMINISTRATION	21
3.1	Nitric Oxide Dose Set-Up and Administration	21
3.1.1	Setting a dose when using a circuit with an Adaptive Sensor	21
3.1.2	Setting the dose when using a circuit without an Adaptive Sensor	22
3.2	Replacement of a Depleted Cassette	22
3.3	Manual Dosing Mode	23
3.3.1	Manual Ventilation Use (Bagging)	23
3.4	Resuming Primary Dosing	24
3.5	Adjusting the Dose	24
3.5.1	Adjusting the Dose when using a Circuit with an Adaptive Sensor	24
3.5.2	Adjusting the Dose and Flow Range when using a Circuit without an Adaptive Sensor	24
3.6	Console Use as a Back-Up	25
4	CONSOLE SHUTDOWN AND CASSETTE DISPOSAL	25
4.1	Console Shutdown	25
4.2	Cassette Disposal	27
5	ALARMS, ALERTS, AND TROUBLESHOOTING	27
5.1	Alarms, Alerts, and Troubleshooting	27
6	MAINTENANCE	28
6.1	Calibration	28
6.1.1	Air Calibration	29
6.1.2	NO Calibration	29
6.1.3	NO2 Calibration	30
6.2	Maintenance Schedule	30
6.3	Water Trap Maintenance	31
6.3.1	Emptying the Water Trap	31
6.3.2	Water Trap Replacement	31
6.4	Battery	32
6.5	Cleaning	32
6.5.1	Enclosure, Connections, and Surfaces Other Than the Display	32
6.5.2	Display Screen	33
6.6	Storage	33
6.6.1	Cart / Console Storage	33
6.6.2	Cassette / Accessory Storage	34
6.7	Ventilator Compatibility	34

LIST OF TABLES
Table 1:	Conventional Ventilator Compatibility Test Ranges	8
Table 2:	Non-Invasive Gas Delivery System Compatibility Test Ranges	10
Table 3:	Details of Validated Systems	35
Table 4:	Validated Compatibility with and without Inline Mixer	39

LIST OF FIGURES
Figure 1:	Front View GENOSYL DS Console	5
Figure 2:	GENOSYL DS Display Screen	5
Figure 3:	Conventional Ventilator Circuit Set-Up and Connections using Injection Assembly with Adaptive Sensor to the GENOSYL DS and a Manual Bagging System	9
Figure 4:	Conventional Ventilator Circuit Set-Up and Connection using the Mixer Assembly with Adaptive Sensor to the GENOSYL DS and a Manual Bagging System	9
Figure 5:	Fisher and Paykel Optiflow Jr 2 Breathing Circuit Diagram	11
Figure 6:	Fisher and Paykel Optiflow Breathing Circuit	11
Figure 7:	GENOSYL DS Injection Assembly with Adaptive Sensor	13
Figure 8:	GENOSYL DS Mixer Assembly with Adaptive Sensor	14
Figure 9:	Manual Ventilation System	18

Figure 1: Front View GENOSYL DS Console

Figure 2: GENOSYL DS Display Screen

1. SYSTEM SET-UP AND CONNECTIONS

1.1. GENOSYL DS Set-Up and Mechanical Ventilator Circuit Schematic

NOTE: Naming conventions: The GENOSYL DS accessories and components consist of the GENOSYL DS Injection Assembly with Adaptive Sensor or GENOSYL DS Mixer Assembly with Adaptive Sensor, and the GENOSYL DS Gas Lines. Refer to Section 6.7 Table 4 for when use of the Mixer Assembly with Adaptive Sensor is recommended.

NOTE: All circuit components, including GENOSYL DS circuit components, should be changed out according to hospital protocol.

WARNING:

ALWAYS use the GENOSYL DS in accordance with the indications, usage, contraindications, warnings, and precautions described in the GENOSYL prescribing information and labeling. Refer to latest approved prescribing information and labeling prior to use.
The approved patient population for the GENOSYL DS as specified in the drug labeling for GENOSYL (nitric oxide) for inhalation, is limited to neonates. The GENOSYL DS is not intended to be used in other patient populations.
ONLY use the GENOSYL DS, its parts, and accessories as instructed. Using non-specified components may result in product malfunction, injury or death.
ALWAYS follow pre-use setup instructions for the routing and connections of tubing to avoid patient strangulation.
MAKE SURE the System has all tubing connected as described in the instructions. Not connecting all tubing may result in inaccurate dosage and harm to the patient.
DO NOT use accessories or cables other than those specified or provided by the manufacturer of this equipment, as this may result in increased electromagnetic emissions or decreased electromagnetic immunity of this equipment and result in improper operation.

1.2. Connections to Various Breathing Systems

1.2.1 Conventional Ventilators

Bio-Med Devices CrossVent 2+
Bio-Med Device MVP-10
Dräger V500
Dräger VN500
Dräger V600
Dräger VN600
Dräger V800
Dräger VN800
Hamilton C1/T1
Hamilton C6
Hamilton G5
Hamilton MR1
Puritan Bennett 980
Vyaire AVEA

WARNING:

ONLY use the GENOSYL DS with Bio-Med Crossvent 2+ with Constant Flow ON. Not doing so may lead to elevated NO2 levels or dose variability.
The GENOSYL DS injects and samples gas from the patient respiratory circuit which may affect the triggering sensitivity of the ventilator. ALWAYS ensure the trigger sensitivity of the ventilator is checked after connecting the GENOSYL DS to the breathing circuit or when the dose is changed and adjust trigger sensitivity as necessary. Failure to do so may lead to ventilator auto cycling or apnea alarm.
ALWAYS ensure the patient disconnect and high–pressure alarms are used with the ventilator.

CAUTION:

When using spontaneous breathing modes on respiratory device, NO2 levels may exceed 3.0 ppm when dosing ≥ 57 ppm NO into 100% FiO2 and maximum bias flow resulting in nitric oxide delivery interruption. Once sample value of NO2 is below 3.0 ppm, the Console will auto resume delivery of NO at set dose. Refer to the Operator's Manual Section 12.1.5 Table 13 for additional information.
When using non-spontaneous breathing modes on respiratory device, NO2 levels may exceed 3.0 ppm when dosing ≥ 63 ppm NO or greater into 100% FiO2 and maximum bias flow resulting in nitric oxide delivery interruption. Once sample value of NO2 is below 3.0 ppm, the Console will auto resume delivery of NO at set dose. Refer to the Operator's Manual Section 12.1.5 Table 13 for additional information.

Table 1: Conventional Ventilator Compatibility Test Ranges
Setting	Range	Unit
Inspiratory Flow Rate	2-120	LPM
Respiratory Rate	6-60	BPM
Peak Inspiratory Pressure	0-70	cmH2O
Positive End-Expiratory Pressure (PEEP)	0-20	cmH2O

For applicable use scenarios, and when use of a mixer is required, see Section 6.7, Table 4.

Figure 3: Conventional Ventilator Circuit Set-Up and Connections using Injection Assembly with Adaptive Sensor to the GENOSYL DS and a Manual Bagging System

Figure 4: Conventional Ventilator Circuit Set-Up and Connection using the Mixer Assembly with Adaptive Sensor to the GENOSYL DS and a Manual Bagging System

1.2.2 Non-Invasive Gas Delivery Systems

Fisher and Paykel Optiflow Jr Breathing Circuit
Fisher and Paykel Optiflow Breathing Circuit

Table 2: Non-Invasive Gas Delivery System Compatibility Test Ranges
Setting	Range	Unit
Fisher and Paykel Optiflow Jr 2 Flow Rate	0.5 - 25	LPM
Fisher and Paykel Optiflow Flow Rate	5-60	LPM

For applicable use scenarios, see Section 6.7, Table 4.

Figure 5: Fisher and Paykel Optiflow Jr 2 Breathing Circuit Diagram

Figure 6: Fisher and Paykel Optiflow Breathing Circuit

1.3 GENOSYL DS Ventilator Circuit Assembly Pre-Check

Follow the steps listed below for the initial System pre-check prior to completing the ventilator circuit assembly.

Remove all items of the GENOSYL DS Parts / Components from packaging.
Check the expiration date for each Cassette and Inline Breathing Circuit Filter to ensure use is within the expiration date.

WARNING: DO NOT use a Cassette that is beyond its expiration date. Using an expired Cassette may affect the Cassette's ability to provide the correct NO dosage to the patient, which may cause injury or death.

3. Visually inspect the Water Traps on both Consoles to ensure they are installed and empty (Note: To empty the Water Trap, see Section 6.3.1).

WARNING:

ALWAYS empty Water Trap before each use, when prompted by the System, and when the trap is more than half full. Allowing the Water Trap to completely fill will occlude the Sample Line which will interrupt patient gas NO, NO2, and O2 concentration monitoring. Failure to monitor the patient gas NO, NO2, and O2 concentrations may result in patient injury.
ALWAYS conduct Water Trap /Sample Line Leak Test every time you empty and replace the Water Trap, as failure to do so may lead to an incorrect NO reading, which can result in injury or death.

1.4 Assembling GENOSYL DS Injection Assembly with Adaptive Sensor

The Injection Assembly with Adaptive Sensor or the Mixer Assembly with Adaptive Sensor is the point of nitric oxide injection into the patient respiratory circuit. Only one type of assembly is required for each patient circuit. For certain scenarios, the Mixer Assembly with Adaptive Sensor is recommended to mix the NO gas with the gas supplied by the ventilator through a filter containing silica gel to provide intra-breath NO delivery. Refer to Table 4 for scenarios when a Mixer is recommended for use.

NOTE: When using a Mixer, an Inline Breathing Circuit Filter must be used. If a Mixer is not used, an Inline Breathing Circuit Filter as presented in Figure 8 may be used, or an Injection Line Filter connected to the port on the Gas Injection Adapter may be used.

1.4.1 GENOSYL DS Injection Assembly with Adaptive Sensor

Connect the Inline Breathing Circuit Filter to the Gas Injection Adapter (22mm ID × 22 mm OD).
Connect Adaptive Sensor to the inlet end of Gas Injection Adapter (22mm ID × 22 mm OD).

Figure 7: GENOSYL DS Injection Assembly with Adaptive Sensor

1.4.2 GENOSYL DS Mixer Assembly with Adaptive Sensor

1. Connect the Inline Breathing Circuit Filter to the Adapter (22mm ID × 22 mm OD).
2. Connect the Adapter (22mm ID × 22 mm ID) to the distal end of the Mixer.
3. Connect the Gas Injection Adapter to the proximal end of the Mixer.
4. Connect Adaptive Sensor to the proximal end of the Gas Injection Adapter.

Figure 8: GENOSYL DS Mixer Assembly with Adaptive Sensor

NOTE: To determine if the Injection Assembly with Adaptive Sensor or the Mixer Assembly with Adaptive Sensor is recommended, see Section 6.7, Table 4.

1.5 GENOSYL DS Console Connections

1.5.1 GENOSYL DS Gas Lines Connections

Follow the steps listed below to connect the Gas Lines to both Consoles.

Push and twist clockwise the short Y-end of the NO Injection Line (red) to the "NO" port (red) on the front panel of the dosing Console.
Push and twist the short Y-end of the Sample Line (blue) to the Gas Sample Port (blue) on the front of the Water Trap, attached to the dosing Console.

NOTE: Ensure the Sample Lines are connected to the Water Traps on both Consoles.
Push and twist the short Y-end of the Manual Ventilation Line (clear) to the Manual Bagging Port on the front of the dosing Console.
Repeat steps 1, 2, and 3 on the Back-up Console.
Connect Adaptive Sensor Cable to Adaptive Sensor Port on front of the dosing Console.

1.5.2 GENOSYL DS Sample Line Extension Connection

For use in the MR Environment when a longer sample line may be required, follow the steps listed below to connect a Sample Line Extension. It is recommended to install the extension prior to initiation of dose.

	If actively dosing, switch to Manual Dosing Mode prior to completing the following steps.
		WARNING: Failure to switch to Manual Dosing Mode prior to installing a Sample Line Extension when the System is actively dosing may result in a spike in the NO dose delivered to the patient.
	2. Turn the blue Stopcock Valve, attached at the Gas Sample Tee, to the closed position as shown.
	3. Push and twist counterclockwise the Luer-Lock Collar of the Sample Line to remove from the blue Stopcock Valve at the Gas Sample Tee.
	4. Push and twist clockwise the Luer-Lock Collar of the Sample Line onto the Sample Line Extension female connection. 5. Push and twist clockwise the Luer-Lock Collar of the Sample Line onto the blue Stopcock Valve at the Gas Sample Tee. 6. Perform Water Trap/Sample Line Leak test, as instructed.
	7. If actively dosing, switch back to Primary Dosing Mode

1.5.3 GENOSYL DS Respiratory Circuit Connections

Follow the steps listed below to connect the Gas Lines to the Injection Assembly, Sample Tee, and Adaptive Sensor. If a Sample Tee already exists within the ventilator circuit, the Sample Line may be connected directly to the existing Sample Tee.

	Push and twist clockwise the Luer-Lock Collar from the NO Injection Line onto the NO Injection Assembly.
		NOTE: After connecting, the valve assembly may have rotated such that the orientation may appear different from what is shown here and on the display screen.

	2. Push and twist clockwise the Luer-Lock Collar of the Sample Line onto the Sampling Port of the Gas Sample Tee.
		NOTE: Skip this step if a Gas Sample Tee is already connected and in-line with the ventilator circuit.
	3. Ensure the blue Stopcock Valve is in the open position as shown.
	4. Connect the distal end of the Adaptive Sensor Cable to the Adaptive Sensor on the Injection Assembly

1.6 Manual Ventilation (Bag) Connection

Figure 9: Manual Ventilation System

1. Attach the barbed end of the Manual Ventilation Bag NO Adapter into the oxygen tubing from the oxygen source.

2. Attach the other end of the NO Adapter to the oxygen port on the side of the Manual Ventilation Bag.

3. Connect the Manual Ventilation Line (clear) to the NO Injection Port of the Manual Ventilation Bag NO Adapter.

4. Place the Manual Ventilation Assembly in a clean accessible place if needed for future use.

1.7 Mechanical Ventilator Circuit Connections

Follow the steps outlined in this section to connect the GENOSYL DS Ventilator Circuit Assembly to the Mechanical Ventilator Circuit.

WARNING:

The GENOSYL DS injects and samples gas from the patient respiratory circuit which may affect the triggering sensitivity of the ventilator. ALWAYS ensure the trigger sensitivity of the ventilator is checked after connecting the GENOSYL DS to the breathing circuit or when the dose is changed and adjust trigger sensitivity as necessary. Failure to do so may lead to ventilator auto cycling or apnea alarm.
ALWAYS ensure the patient disconnect and high–pressure alarms are used with the ventilator.

NOTE: All ventilator connections should be assembled and inspected prior to connecting to the mechanical ventilator circuit.

Disconnect the Inspiratory Tubing from the humidifier and attach it to the proximal end of the Injection Assembly to the Adaptive Sensor.
Attach the distal end of the Injection Assembly to the humidifier.
Insert the Sample Tee into the ventilator circuit at the proximal end of the temperature probe closest to the patient.

2. SYSTEM START UP

2.1 Console Start-Up

CAUTION:

ONLY use the GENOSYL DS with the power cord supplied by the manufacturer. Use of a generic power cord may cause output voltage instability leading to a touch screen failure.
ALWAYS ensure the power cord is firmly seated into the power supply and the wall outlet. A loose connection can result in damage to the device or faulty operation.

Push the Circular Power Connectors into the back of the top and bottom Consoles.
Connect the main power cord to a grounded 120 V electrical outlet.
Press the Black Rocker Power Switch, located on the back of each Console, to the right (ON position) to power on both Consoles.
Press the Silver Power Button, located at the top left corner on the front panel of each Console, to turn on the display screens on both Consoles. The display screen will illuminate, and the Consoles will beep, indicating the power is on.

CAUTION: The System will conduct an internal self-test. If an alarm or failure message should occur, refer to Section 10 in the Operator's Manual to resolve the issue.

NOTE: If the display screen does not turn on, see Troubleshooting, Section 10 of the Operator's Manual.

2.2 Cassette Insertion & Water Trap / Sample Line Leak Test

The following steps should be taken on both the top and bottom Consoles. Upon the insertion of the Cassette, a test will be initiated on each Console to check and ensure the integrity of the Water Traps and Sample Line.

The Water Trap / Sample Line Leak Test is automatically initiated when a Cassette has been inserted, and the measured NO is less than 1.0 ppm.

WARNING: ALWAYS follow Cassette insertion instructions prior to Cassette insertion. Not inspecting the Cassette prior to insertion may lead to using a faulty Cassette, resulting in injury.

Confirm the Cassette State Window on each Cassette is blue.

WARNING: DO NOT use the Cassette if the Cassette State Window is not blue. A Cassette State Window that is any color other than blue may affect the Cassette's ability to provide the correct NO dosage to the patient, which may cause injury or death.

NOTE: If the Cassette State Window is not blue, see Troubleshooting, Section 10.8 of the Operator's Manual.

2. Open the Cassette Access Doors and insert two Cassettes into the Dosing Console and at least one Cassette into the Back-Up Console. Push until it clicks.

NOTE: The Water Trap / Sample Line Leak Test is automatically initiated when a Cassette has been inserted, and the measured NO is less than 1.0 ppm
After the first Cassette is fully inserted, the Operator will have 60 seconds to close the blue Stopcock Valve to perform the test.

3. Follow the onscreen instructions on both Consoles.

NOTE:

The screen will indicate the Water Trap / Sample Line Leak Test has started and the progress bar will be red until the stopcock valve has been closed, upon which it will then turn green if there is no leak detected.
See Section 3.5 for detail around dosing in Manual Dosing Mode.

4. Follow the onscreen instructions on both Consoles.

CAUTION: Open the blue Stopcock Valve prior to pressing "Accept". Failure to do so will result in a line occlusion error.

NOTE: If the Water Trap / Sample Line Leak Test fails, follow the onscreen instructions to resolve the issue. Also see Troubleshooting, Section 10.8 of the Operator's Manual.

5. If this screen is displayed, follow the onscreen instructions on both Consoles.

6. Press Yes on both Consoles to begin a new Water Trap / Sample Line Leak Test.

3 NITRIC OXIDE ADMINISTRATION

3.1 Nitric Oxide Dose Set-Up and Administration

WARNING:

MAKE SURE the System stabilizes to the prescribed concentration (ppm) of NO prior to leaving the Console unattended. Failure to do so could result in under delivery of the target NO, leading to injury or harm.
ALWAYS constantly monitor the patient. System malfunctions can occur if device and patient are not monitored and can result in injury or death. Careful monitoring is required by care personnel whenever the System is used on a patient. The use of an alarm and a monitoring system does not give an absolute assurance of warning for every malfunction that may occur. Certain alarms may require immediate response.
If the gas flow of the patient's respiratory device/ventilator should be interrupted or discontinued, the NO dose should be maintained by switching to Manual Dosing Mode or the target NO dose should be set to zero.

3.1.1 Setting a dose when using a circuit with an Adaptive Sensor

Press the gray "Set" button on the display screen.
Enter the prescribed dose in ppm on the electronic keypad.
Press OK to confirm the entry.

3.1.2 Setting the dose when using a circuit without an Adaptive Sensor

Press the gray "Set" button on the display screen.
Confirm Total Flow Range is appropriately selected.
Enter the prescribed dose in ppm on the electronic keypad.
Press OK to confirm the entry.

NOTE:

The time to reach target dose may vary up to 10 minutes.
If unable to set the dose in Primary Dosing Mode, see Troubleshooting, Section 10.8 of the Operator's Manual.

3.2 Replacement of a Depleted Cassette

The GENOSYL DS automatically switches from the dosing Cassette to the secondary Cassette in the Dosing Console once the Cassette is depleted, when a secondary Cassette is properly inserted and preheated. After transition, the depleted Cassette is automatically ejected.

CAUTION: User should always have a secondary Cassette inserted in Dosing Console and preheated in order for auto transition to occur. User should replace depleted Cassette as soon as possible after ejection.

ILLUSTRATION	ACTION	Warnings, Cautions and Notes
		NOTE
		The Console will automatically transition to the secondary Cassette if properly inserted and preheated. The screen to the left will be displayed during the transition process.

3.3 Manual Dosing Mode

NOTE: When entering Manual Dosing Mode, the set target dose in Primary Dosing Mode will carry over to Manual Mode if 5 ppm or greater. Less than 5 ppm set target dose in Primary Dosing Mode will default to 5 ppm dose in Manual Dosing Mode. However, dose and flow rate be adjusted for specific situations. The GENOSYL DS Smart Feedback System™ is disabled while in Manual Dosing Mode. To reinitiate the feedback loop, switch back to Primary Dosing Mode as soon as the situation permits

3.3.1 Manual Ventilation Use (Bagging)

WARNING:

ALWAYS ensure that the manual flow displayed on the Console matches the flow set into the resuscitation bag. Incorrect flow settings may result in an incorrect estimation of NO delivery. If the flow into the manual equipment is too low, there is risk of overdosing the patient with NO.
ALWAYS squeeze the bag several times, after starting fresh gas flow, to empty residual gas in the bag prior to using the System to ventilate a patient. Failure to do so could result in higher NO2 levels being delivered to the patient.
ALWAYS use the smallest bag adequate to deliver the desired tidal volume. Failure to do so could result in higher NO2 levels being delivered to the patient.
ONLY use a manual resuscitation bag with the GENOSYL DS for a short time (e.g., less than one hour) when on battery only. Otherwise, the System may shut off and may result in injury or death.
If the dilution flow rate displayed on the screen does not match the wall source, then the estimated NO may be inaccurate.

Ensure the oxygen source is set appropriately or adjust as needed.
Press the button "Switch to Manual" on the Dosing Console.
Press "Confirm" to switch to Manual Dosing Mode
To resume primary dosing, see Section 3.4.

NOTE:

When switching to Manual Dosing Mode, dosing has been initiated at the same dose (ppm) as set in Primary Dosing Mode. If the dosing was set at "0" prior to pressing the "Switch to Manual" button, the estimated NO will also be at "0" and will need to be adjusted. If the primary dosing was set between 1 and 5 ppm prior to pressing the "Switch to Manual" button, the estimated NO dose will also be 5 ppm and may be adjusted.
If an adjustment of the NO concentration is required, press the green up and down arrows.
If an adjustment to the Dilution Flow Rate is required, press the LPM value and a drop-down menu will expand. Press the prescribed value. The new value will be highlighted in blue and the drop-down menu will collapse.
In the event dose is initiated in Manual Dosing Mode, the Console will default to 20 ppm, which can be adjusted as needed.

3.4 Resuming Primary Dosing

Press the "Switch to Primary" button at the top of the Manual Dosing Mode screen.
Press "Confirm" to start dosing or "Cancel" to cancel.

NOTE: The NO dose used in Manual Dosing Mode will become the set target dose in Primary Dosing Mode.

3.5 Adjusting the Dose

To adjust the dose of nitric oxide administered per hospital protocol/physician order. Follow the instructions listed below.

3.5.1 Adjusting the Dose when using a Circuit with an Adaptive Sensor

Press the gray "Set" button to access the electronic keypad on the display screen on the Dosing Console.
Enter the prescribed (ppm) dose using the electronic keypad.
Press "OK" to confirm the dose and to start dosing administration.

3.5.2 Adjusting the Dose and Flow Range when using a Circuit without an Adaptive Sensor

Press the gray "Set" button to access the electronic keypad on the display screen on the Dosing Console.
Enter the prescribed (ppm) dose using the electronic keypad.
Adjust Total Flow Range, if necessary.
Press "OK" to confirm the dose and to start dosing administration.

3.6 Console Use as a Back-Up

This section describes the process of activating the Cassette in the Back-Up Console. Delivery of NO will begin immediately upon Cassette activation.

Press the "Set" button on the Back-Up Console which will display the NO dose electronic keyboard and Flow Section menu.
Confirm Dose and Total Flow range is appropriately selected.
Press "OK" to confirm entry
Connect Adaptive Sensor to the front of the new Dosing Console

NOTE:

The default Total Flow range displayed will be <2.5 LPM unless otherwise selected by the user.
The Back-Up Console is now the and Flow Range Console.
Dosing has been initiated at the default setting of 20 ppm.

4 CONSOLE SHUTDOWN AND CASSETTE DISPOSAL

WARNING: NEVER turn the rear power switch OFF until the System has gone through a controlled shutdown or instructed by VERO Technical Support. Turning the rear power switch OFF prematurely (e.g., while it is still in use) will immediately shut down the device. This may result in interruption in NO delivery to the patient, which may cause injury or death.

CAUTION:

NEVER turn the rear power switch OFF until the System has gone through a controlled shutdown or instructed by VERO Technical Support. Turning the rear power switch OFF prematurely (e.g., while it is still in use) will immediately shut down the device and may cause improper operation upon restart.

4.1 Console Shutdown

If the administration of NO must be stopped, then the dose level must be set to "0" and the Cassette must be removed prior to shutting down the Console.

Press the gray "Set" button to access the electronic keypad on the display screen.
Set the dose to "0" using the electronic keypad.
Press "OK" to confirm the entry.
If the "Settings" tab is not displayed, press the "Menu" tab to access the sub-level tabs.
Press the "Settings" tab on the display menu.
Press the red "System Shut Down" icon.
Review on screen prompt.

NOTE: The screen will inform user if Cassette should be saved or disposed of.
Press "Confirm" to confirm shutdown.

Wait until the Console shuts down, the display screen appears blank, and the Console emits an audible beep.

NOTE: The Console will inert any remaining contents from a dosing Cassette upon ejection rendering it unusable. If a Cassette has only been preheated, and not used for dosing, the contents have not been inerted and it can still be used.

Open the Cassette Access Door.
Remove the Cassette by pulling the Cassette straight out.
Dispose the Cassette per hospital policy.
Press the Black Rocker Power Switch to the "OFF" position.
Repeat steps 1-12 for the other Console.

CAUTION: NEVER turn the rear power switch OFF until the System has gone through a controlled shutdown or instructed by VERO Technical Support. Turning the rear power switch OFF prematurely (e.g., while it is still in use) may cause improper operation.

NOTE: If the System does not shut down, see Troubleshooting, Section 10.8 of the Operator's Manual.

4.2 Cassette Disposal

Following dosing use, any remaining Cassette liquid contents are purged into an inerting chamber that is built into the Cassette, where the contents are chemically neutralized, rendering the Cassette safe for disposal. When the Cassette liquid contents are emptied into the inerting chamber, the Cassette State Window on the front of the Cassette reddens and bleaches from its original blue color, indicating the Cassette is depleted. The Cassette can now be disposed of per hospital policy.

5 ALARMS, ALERTS, AND TROUBLESHOOTING

WARNING: ALWAYS ensure patient safety before troubleshooting (such as an activated alarm) or replacing a problematic item. Not monitoring the patient prior to attending to an alarm can result in injury or death.

5.1 Alarms, Alerts, and Troubleshooting

Section 10 of the Operator's Manual contains the system alarms and message in order of High (red), Medium (yellow), and Low Priority (turquoise) followed by Informational Messages (green). The table shows the alarm/symptom, the possible cause(s) of the alarm and recommended action to resolve the alarm. Additionally, on-screen troubleshooting support is available by either tapping an active alarm banner or by selecting the "Alarm Info" button on the "Alarms" tab. If the alarm/issue cannot be resolved, contact Technical Support at 877-337-4118.

A sample screen with an active alarm is shown below:

The alarm banner contains a drop-down menu containing a list of all alarms should there be multiple activated. The alarm icon is always present on the top right of the screen and tapping the icon will pre-silence or silence alarms. Refer to the table below for descriptions of each alarm status:

ALARM ICON DISPLAY	DESCRIPTION
	No active alarm condition is detected on the Console. Tap this icon to activate the pre-silence feature.
	Alarms are actively pre-silenced. Countdown of time remaining appears under the icon. Pre-silence lasts for 120 seconds. Low/High NO, High NO2, Low/High O2, Water Trap Removed and Dosing Cassette Removed alarms are pre-silenced. Alarms will still be visible on alarm banner but audible alarm will not sound.
	Console has an active alarm condition that requires attention. Tap the icon to silence the alarm for 120 seconds.
	Console has an active alarm condition that requires attention and the alarms have been silenced. Countdown of time remaining appears under the icon.

6 MAINTENANCE

6.1 Calibration

WARNING:

ONLY use the calibration gas pressure regulators supplied by the manufacturer. Pressure regulators not supplied by the manufacturer may damage the sensors and may lead to patient injury.
ALWAYS verify the correct NIST traceable calibration gas is being used and confirm the expiration date of the calibration gas prior to performing calibration. The use of incorrect or expired gas may result in inaccurate sensor readings and can lead to patient injury.
NEVER perform NO or NO2 calibration within the MR scanner room. Calibration equipment is a potential projectile hazard.

CAUTION:

ALWAYS perform a full-scale calibration of the GENOSYL DS when prompted by the System prior to use.
ALWAYS confirm the correct flow direction of the installed one-way check valve in the sampling tee to avoid over pressurization of the sampling system and damage to the device.

6.1.1 Air Calibration

Air Calibration will take up to 2 minutes. A progress bar is displayed in the lower lefthand corner of the display screen during the calibration process.

Check to make sure nothing is connected to the CAL port during Air Calibration.
If the "Calibration" tab is not displayed, press the "Menu" tab to access the sub-level tabs.
Press the "Calibration" tab on the display menu.
Press the Low Range "Air" button.
Press the blue "Start Calibration" button.
Press "Accept " to continue once calibration is complete.

NOTE: If calibration fails, ensure that nothing is connected to or blocking the CAL port.

6.1.2 NO Calibration

WARNING:

DO NOT open the valve prior to connecting to the CAL port. Opening the valve first will expose the user to NO gas.
DO NOT interrupt calibration until finished. If interrupted, calibration will be cancelled.
DO NOT disconnect tubing from the calibration port prior to closing the valve. Disconnecting the tubing first will expose the user to NO gas.

NOTE: NO calibration takes approximately 2 minutes if not dosing, or five minutes if actively dosing. A progress bar is displayed in the lower left-hand corner of the display screen during the calibration process.

If the Calibration Tab is not displayed, press the "Menu" tab to access the sub-level tabs.
Press the "Calibration" tab on the display menu.
Press the High Range "NO" button.
Press the blue "Start Calibration" button.
Follow the onscreen instructions.
Press "Accept " to continue once calibration is complete.

6.1.3 NO2 Calibration

WARNING:

DO NOT open the valve prior to connecting to the CAL port. Opening the valve first will expose the user to NO2 gas.
DO NOT interrupt calibration until finished. If interrupted, calibration will be cancelled.
DO NOT disconnect tubing from the calibration port prior to closing the valve. Disconnecting the tubing first will expose the user to NO2 gas.

NOTE: NO2 calibration takes approximately 2.5 minutes. A progress bar is displayed in the lower left-hand corner of the display screen during the calibration process.

If the Calibration Tab is not displayed, press the "Menu" tab to access the sub-level tabs.
Press the "Calibration" tab on the display menu.
Press the High Range "NO2" button.
Press the blue "Start Calibration" button
Follow the onscreen instructions.
Press "Accept " once calibration is complete.

6.2 Maintenance Schedule

The Console components require the following maintenance:

COMPONENT	SCHEDULE
Water Trap	Per patient or as required (per Sample Line / Leak Test)
Console	24 months or 10,000 pump hours, which ever is first

The Console requires factory service every 24 months or 10,000 pump hours, whichever is first. The System will display an Information Message to remind the operator when service is required. Call Technical Support at 877-337-4118 to schedule service.

6.3 Water Trap Maintenance

6.3.1 Emptying the Water Trap

WARNING: ALWAYS empty Water Trap before each use, when prompted by the System, and when the trap is more than half full. Allowing the Water Trap to completely fill will occlude the Sample Line which will interrupt patient gas NO, NO2, and O2 concentration monitoring. Failure to monitor the patient gas NO, NO2, and O2 concentrations may result in patient injury.

Remove Water Trap from Console by lifting latch and pulling the base of the Water Trap away from the Console.
Remove the lid by pulling the lid from the base.
Empty the liquid contents.
Clean the Water Trap per hospital policy and cleaning instructions in the Operator's Manual.
Reattach the lid by pushing it back onto base.
Slide the Water Trap back on the Console until it clicks into place.

6.3.2 Water Trap Replacement

WARNING:

ALWAYS use a Water Trap supplied by the manufacturer. Using an incorrect water trap could result in non-functioning or inaccurate sensor readings.
ALWAYS conduct a Water Trap test every time you empty and replace the Water Trap, as failure to do so may lead to an incorrect NO reading, which can result in injury or death.

If the Water Trap / Sample Line Leak Test does not meet requirements and the Sample Line integrity is confirmed or remains occluded, replace the Water Trap.

Remove old Water Trap from Console by lifting the latch and pulling the base of the Water Trap away from the Console.
Slide new Water Trap back on the Console until it clicks into place.
Discard the old Water Trap.

6.4 Battery

The battery will be serviced during scheduled maintenance performed by the manufacturer. If the need arises to replace the battery sooner than scheduled contact Technical Support at 877-337-4118 to schedule a maintenance appointment.

During storage, the GENOSYL DS may be stored with the power off, but the external power supply should be connected at least once every 3 months to ensure a minimum charge is maintained on the internal battery.

WARNING: ONLY properly trained personnel should replace the battery. Incorrectly replacing the battery may result in a hazard such as excessive temperatures, fire, or explosion.

6.5 Cleaning

CAUTION:

ALWAYS power down the GENOSYL DS Console and disconnect the power to the Console when not in use. Failure to do so may lead to permanent damage to the Console.
DO NOT sterilize (e.g., autoclave, gas sterilize) any of the components of the System, as this may compromise performance.
DO NOT use harsh cleaning agents on the GENOSYL DS. Doing so may impair the structural integrity and/or function of the device.
ONLY use a damp cloth to clean the Console and limit use of liquids around Console. Excess water can permanently damage the device.
ALWAYS ensure the System is completely dry after cleaning before powering it ON. Failure to do so could result in equipment damage.

6.5.1 Enclosure, Connections, and Surfaces Other Than the Display

Prior to performing any cleaning or maintenance operations ensure that the GENOSYL DS Console has been completely powered down and that the AC/DC power supply external to the GENOSYL DS Console has been unplugged. Apply any mild detergent to cloth prior to wiping down the System. Gently clean the outer surface of the Console, Cart, and Adaptive Sensor Cable with a soft damp cloth and mild detergent or isopropyl alcohol (70%).

WARNING:

NEVER submerge the GENOSYL DS, Cassette, or non-disposable Adaptive Sensor Cable. Submerging in liquid will damage the System and could cause electrical shorts which may result in injury or death.
DO NOT clean the GENOSYL DS with the power connected and the System turned ON, as this may lead to injury (e.g., shock). Unplug AC/DC power supply external to the System prior to cleaning.

6.5.2 Display Screen

Turn off Console and disconnect from AC power. Gently clean with a damp cloth.

CAUTION:

DO NOT touch or rub the display screen with abrasive cleaning compounds or organic solvents, as they may scratch and damage the screen.
DO NOT spray or pour liquids directly on the controller or the display, as they may damage the screen.

6.6 Storage

6.6.1 Cart / Console Storage

The acceptable storage conditions for the cart/Console are shown in the following table.

Cart / Console Storage	Temperature	-20°C to 60°C
	Humidity	15% to 95%, non-condensing
	Pressure	57kPa to 110kPa

During storage, the GENOSYL DS may be stored with the power off, but with the external power supply connected in which case the internal battery will be kept fully charged.

WARNING:

MAKE SURE the GENOSYL DS is connected to AC wall power to charge the battery a minimum of once every 3 months to maintain a minimum battery charge. Failure to recharge the Console battery for extended timeframes may result in full discharge of the battery. If a Battery Error message occurs during startup of the System, contact Technical Support at 877-337-4118 for assistance.
ONLY properly trained personnel should replace the battery. Incorrectly replacing the battery may result in a hazard such as excessive temperatures, fire, or explosion.
ONLY store the GENOSYL DS as outlined in the storage instructions. Not storing the device in alignment with its storage instructions can cause the device to be unsafe and lead to injury or death.

6.6.2 Cassette / Accessory Storage

The GENOSYL DS may not function correctly if the Cassette or any of the System Accessories have been exposed to high levels of heat or humidity. Cassettes are supplied in a plastic container and should remain unopened until use. Cassettes should be stored at 25°C (77°F) with excursions permitted between 15°C to 30°C (59°F to 86°F). (See USP Controlled Room Temperature)

6.7 Ventilator Compatibility

Vero Biotech performs validation testing which determines the compatibility of ventilator/gas delivery systems with the GENOSYL DS. During this compatibility testing, the GENOSYL DS is evaluated for the following parameters while connected to each ventilator/gas delivery system:

NO Dose Accuracy: Continuous and accurate delivery of a targeted dose of nitric oxide within ± 20% of setpoint or within +/- 2 ppm, whichever is greater.
Respiratory Device Gas Delivery and Alarms: The respiratory device breath delivery and alarms continue to function as intended by the manufacturer across the range of operating conditions.
NO2 Performance: NO2 remains within acceptable limits less than 1.0 ppm with 60% FiO2 and ≤40 ppm NO.
O2 Dilution: Post dilution O2 level delivery is maintained within acceptable limits and conforms with the information presented in the GENOSYL DS Operator's Manual, Section 12.1.1, "Oxygen Dilution".
NO Concentration Transients: NO concentration transients are ≤150% of mean concentration and as low as 0.0 ppm as long as the transient duration does not exceed 10% of the volumetric duration of the breath.

The testing performed demonstrated conformance with all specified requirements.

WARNING:

ALWAYS use the GENOSYL DS in accordance with the indications, usage, contraindications, warnings, and precautions described in the GENOSYL prescribing information and labeling. Refer to latest approved prescribing information and labeling prior to use.
The approved patient population for the GENOSYL DS as specified in the drug labeling for GENOSYL (nitric oxide) for inhalation, is limited to neonates. The GENOSYL DS is not intended to be used in other patient populations.

The following ventilators and non-invasive gas delivery systems have been validated for use with the GENOSYL DS. Validated ventilators were not tested with a nebulizer. See Section 1 for assembly instructions for Injection Assembly with Adaptive Sensor and Mixer Assembly with Adaptive Sensor.

Table 3: Details of Validated Systems
Manufacturer	Model	Modes
* Refer to the Operator's Manual for additional Warnings, Cautions, and general information about use of the GENOSYL DS in the Hospital. Refer to Rev I, Section 7 for additional Warnings, Cautions, and information about use of the GENOSYL DS in the MR Scanner Room. † Refer to the Operator's Manual Rev I, Section 8 for additional Warnings, Cautions, and general information about use of the GENOSYL DS in External Transport. ‡ Refer to the Operator's Manual Rev I, Section 9 for additional Warnings, Cautions, and general information about use of the GENOSYL DS with Anesthesia Gas Machines.
Bio-Med Devices	Crossvent 2+	Cycle CPAP
Bio-Med Devices	MVP-10	Cycle CPAP
Dräger	Fabius GS, Fabius GS Premium, Fabius Tiro	VC PC PS SIMV/PS Manual/ Spontaneous
Dräger	V500, VN 500, V600, VN 600, V800, VN800	VC-AC VC-SIMV VC-CMV PC-AC PC-SIMV PC-CMV PC-BIPAP VC-MMV PC-APRV PC-PSV SPN-CPAP/PS SPN-CPAP/VS SPN-PPS
GE	Aisys CS2	VCV PCV PCV-VG PSVPro CPAP+PSV SIMV PCV SIMV VCV SIMV PCV-VG Manual
Hamilton	C1/MR1	PCV+ PSIMV+ APVcmv APVsimv/SIMV+ ASV DuoPAP APRV SPONT NIV NIV ST nCPAPA nCPAP PC
Hamilton	C6	APVcmv APVsimv PCV+ PSIMV+ DuoPAP APRV SPONT ASV NIV NIV-ST nCPAP-PS
Hamilton	G5	(S)CMV P-CMV P-SIMV APVcmv APVsimv ASV DuoPAP APRV SPONT VS NIV NIV-ST nCPAP-PS SIMV
Hamilton	T1	PCV+ PSIMV+ APVcmv APVsimv/SIMV+ ASV DuoPAP APRV SPONT NIV NIV ST nCPAP nCPAP PC
Puritan Bennett	980	A/C PC A/C VC A/C VC+ NIV AC PC NIV AC VC BiLevel BiLevel PC PS BiLevel PC TC NIV CPAP SPONT VS NIV SPONT PS SPONT TC SPONT PAV+
Vyaire Medical Inc.	AVEA	Volume A/C Pressure A/C Volume SIMV Pressure SIMV CPAP/PSV PRVC A/C PRVC SIMV APRV/BiPhasic TCPL A/C TCPL SIMV Nasal CPAP/IMV
Fisher & Paykel	Optiflow Jr 2 Breathing Circuit	N/A
Fisher and Paykel	Optiflow Breathing Circuit	N/A

Table 4: Validated Compatibility with and without Inline Mixer

At the lowest tested rate of 6 BPM, a Mixer may be used to reduce intra-breath dose variability as outlined in Table 4 below. Intra-breath dose variability was not observed at a respiratory rate of 60 BPM.

See Section 1 for assembly instructions for Injection Assembly with Adaptive Sensor and Mixer Assembly with Adaptive Sensor.

VERO Biotech and GENOSYL are registered trademarks of VERO Biotech Inc.
© 2025 VERO Biotech. Printed in U.S.A. LBL-602503 Rev H JUNE 2025
Please read full prescribing information enclosed.
877.337.4118 | vero-biotech.com

INSTRUCTIONS FOR USE

USING THE GENOSYL® DELIVERY SYSTEM WITH AN ANESTHESIA GAS MACHINE

STEP 1: POWER ON THE GENOSYL DELIVERY SYSTEM
Refer to Operator's Manual Section 4.1 for detailed instructions.

Push circular power connectors into the back of the top and bottom Consoles.
Connect the main power cord to a grounded 120V electrical outlet.
Press the black rocker power switch on the back of each Console to the right (ON Position).
Press the silver power button, located in the top left corner of the front panel of each Console.

NOTE
Refer to Operator's Manual for use of the GENOSYL DS in the MR environment

* Specific use cases may require the use of an Inline Mixer which is used to mix the NO gas with the gas supplied by the AGM through a filter containing silica gel to provide intra-breath NO delivery for certain scenarios. Refer to Table 6 in the Operator's Manual for specific use cases and Section 3.4.2 for additional assembly instructions.
STEP 2: REMOVE ALL GENOSYL DS COMPONENTS FROM PACKAGING Refer to Operator's Manual Section 3.3 for detailed instructions. This includes a Gas Injection Adapter, two Inline Breathing Circuit filters, Adaptive Sensor, Adaptive Sensor Cable, Sample Tee (if not already present in dual limb circuit), Manual Bag Adapter, Gas Lines and two Cassettes.*

STEP 3: ATTACH GAS LINES TO CONSOLES
Refer to Operator's Manual Section 3.5 for detailed instructions.

Push and twist clockwise the short Y-end of the NO Injection Line (red) to the "NO" port (red) on the front panel of both Consoles.
Push and twist clockwise the short Y-end of the Sample Line (blue) to the Gas Sample Port (blue) on the Water Trap attached to both Consoles.
Push and twist clockwise the end of the clear Manual Ventilation Line (clear) to the Manual Ventilation Port (clear) on the front of both Consoles.
Connect the Adaptive Sensor Cable to the Adaptive Sensor Port on the front of the Dosing Console.

STEP 4: ATTACH GAS LINES TO ANESTHESIA CIRCUIT INSPIRATORY LIMB
Refer to Operator's Manual Section 9.2 for detailed instructions.
An Inline Mixer may be required under some ventilation settings to assure NO dosing accuracy.
The settings where use of Inline Mixer is recommended are found in Section 9, Table 6 and instructions for the Inline Mixer Assembly with Adaptive Sensor are found in Section 3.4.2 of the Operator's Manual.

Check the expiration date for each Inline Breathing Circuit Filter to ensure use is within the expiration date.
Connect the Inline Breathing Circuit Filter to the Gas Injection Adapter (22 mm ID × 22 mm OD).
Connect the Adaptive Sensor to the inlet end of the Gas Injection Adapter (22mm ID × 22mm OD).
Attach the Injection Assembly with Adaptive Sensor to the Gas Injection Adapter on the Inspiratory Port on the AGM.
Attach the inspiratory limb of the breathing circuit to the Inline Breathing Circuit Filter. If the breathing circuit has a Sample Gas Tee inserted, ensure this limb of the circuit is attached to the Inline Breathing Circuit Filter.
Insert the Gas Sample Tee into the inspiratory limb of the breathing circuit, 6-12" from the patient wye.
Insert the Inline Breathing Circuit Filter between the Expiratory Port and expiratory limb. Skip this step if a bacterial filter is already present in the expiratory limb of the breathing circuit.
Attach the expiratory limb of the breathing circuit to the Inline Breathing Circuit Filter on the Expiratory Port on the Anesthesia Machine.
Push and twist clockwise the luer-lock collar from the NO injection line onto the NO injection port of the Gas Injection Adapter on the Injection Assembly.
Push and twist clockwise the luer-lock collar of the Stopcock on the Sample Line onto the Sampling Port of the Gas Sample Tee.
Connect the distal end of the Adaptive Sensor Cable to the Adaptive Sensor on the Injection Assembly.

NOTE

Connections to various AGMS are unique to each manufacturer as well as their corresponding disposable circuits.
A dual limb anesthesia breathing circuit should be used for iNO delivery with the GENOSYL DS.
The GENOSYL DS Sample Line must be placed on the INSPIRATORY limb of the breathing circuit between 6 and 12 inches from the patient wye. If the sampling line is placed greater than 6 inches from the patient wye it minimizes the sampling of mixed inspired/expired gas concentrations and if placed less than 12 inches from the patient wye it ensures correct iNO and NO2 measurement.

To ensure assembly setup is correct, refer to Figure 1. Anesthesia Machine Setup on reverse side.

STEP 5: ASSEMBLE MANUAL VENTILATION WITH THE GENOSYL DS
Refer to Operator's Manual Section 3.6 for detailed instructions.

Attach the barbed end of the Manual Ventilation Bag NO Adapter into the oxygen tubing from the oxygen source.
Attach the other end of the NO Adapter to the oxygen port on the side of the Manual Ventilation Bag.
Connect the Manual Ventilation Line (clear) to the NO Injection Port of the Manual Ventilation Bag NO Adapter.
Place the Manual Ventilation Assembly in a clean accessible place if needed for future use.

To ensure assembly setup is correct, refer to Figure 1. Anesthesia Machine Setup below.

Figure 1. Anesthesia Machine Setup

WARNING

ALWAYS use the GENOSYL DS in accordance with the indications, usage, contraindications, warnings, and precautions described in the GENOSYL prescribing information and labeling. Refer to latest approved prescribing information and labeling prior to use.
ALWAYS use the Anesthesia Gas Machine (AGM) in accordance with the manufacturer's instructions.
The approved patient population for the GENOSYL DS as specified in the drug labeling for GENOSYL (nitric oxide for inhalation (iNO)) is limited to neonates. The GENOSYL DS is not intended to be used in other patient populations.
Ensure the Injection Assembly and the Gas Sample Tee are BOTH inserted on the inspiratory limb of the circuit.
The flow out of the anesthesia gas machine via the INSPIRATORY breathing circuit limb must pass through the GENOSYL DS Gas Injection Assembly.
The GENOSYL DS injects and samples gas from the patient respiratory circuit which may affect the triggering sensitivity of the anesthesia gas machine (AGM). ALWAYS ensure the trigger sensitivity of the AGM is checked after connecting the GENOSYL DS to the breathing circuit and starting iNO delivery or when the dose is changed, and adjust trigger sensitivity as necessary. Failure to do so may lead to AGM auto cycling or apnea alarm.
ALWAYS ensure the patient disconnect and high-pressure alarms are used with the AGM.

CAUTION

Pneumatic Nebulizers will dilute the delivered nitric oxide dose.
The Adaptive Sensor is recommended for use with anesthesia gas machines (AGMs). When using an AGM without the Adaptive Sensor, transient dose excursions outside of the set NO dose may occur during Cassette transition, and changes in breathing circuit flow may cause fluctuations in measured levels of NO and NO2 when using the manual ventilation bag integrated with the AGM.
When using anesthesia gas machines, NO2 levels may exceed 3.0 ppm when dosing ≥ 58 ppm NO into 100% FiO2, resulting in nitric oxide delivery interruption. Once sample value of NO2 is below 3.0 ppm, the Console will auto resume delivery of NO at set dose.
Rebreathing validation testing was performed with semi-closed breathing systems. Non-rebreathing validation testing was performed with semi-open breathing systems. The GENOSYL DS has not been evaluated with fully open or fully closed anesthesia breathing systems.

NOTE

The GENOSYL DS performs as specified in this Operator's Manual independent of anesthetic agent, anesthetic agent concentration, and fresh gas flow rate.
Changes in the AGM ventilator settings, fresh gas flow rate, or pushing the Oxygen Flush button by the user may cause brief transient changes in the measured NO value.
Use of an Adaptive Sensor is recommended for use with AGMs. If not using an Adaptive Sensor:
- And using rebreathing fresh gas flow rates, it is recommended that the < 2.5 LPM Total Flow setting be selected.
- And using non-rebreathing fresh gas flow rates, it is recommended that the Total Flow selection based on the minute volume be selected.
When using the manual ventilation bag integrated with the AGM, nitric oxide can be delivered by leaving the Console in Primary Dosing Mode. Nitric oxide will be delivered through the Injection Assembly into the anesthesia gas circuit.
In the event of anesthesia gas machine failure, NO delivery can be continued using Manual Dosing Mode on the GENOSYL DS with a manual bag connected to the manual ventilation port on the front of the Console and an alternative gas source than the AGM.

INSERTING A CASSETTE
Refer to Operator's Manual Section 4.2 for detailed instructions.

STEP 1: CHECK THE CASSETTE Remove Cassettes from packaging. Check the expiration date for each Cassette to ensure use is within the expiration date. Confirm Cassette status indicator on each Cassette is blue.
STEP 2: INSERT CASSETTE INTO THE CONSOLE Open the Cassette Access Door and insert two Cassettes into the Dosing Console and at least one Cassette into the Back-up Console. Push until it clicks.
STEP 3: COMPLETE WATER TRAP / SAMPLE LINE LEAK TEST Follow on-screen instructions on both Consoles to complete Water Trap / Sample Line Leak Test.

INITIATING A NITRIC OXIDE DOSE
Refer to Operator's Manual Section 5.1.1 for detailed instructions.

STEP 1: INITIATE NITRIC OXIDE ADMINISTRATION 1. Press the gray Set button on the display screen.
2. Enter the prescribed dose in ppm on the electronic keypad. 3. Press OK to confirm entry.

ADJUSTING THE NITRIC OXIDE DOSE
Refer to Operator's Manual Section 5.2.1 for detailed instructions.

STEP 1: SET FLOW

Press the gray "Set" button to access the electronic keypad on the display screen on the Dosing Console.
Enter the prescribed ppm dose using the electronic keypad.
Press "OK" to confirm the dose and to start dosing administration.

MANUAL VENTILATION MODE USING EXTERNAL RESUSCITATION BAG
Refer to Operator's Manual Section 5.4.1 for detailed instructions.

WARNING

ALWAYS ensure that the manual flow displayed on the Console matches the flow set into the resuscitation bag. Incorrect flow settings may result in an incorrect estimation of NO delivery. If the flow into the manual equipment is too low, there is risk of overdosing the patient with NO.
ALWAYS squeeze the bag several times, after starting fresh gas flow, to empty residual gas in the bag prior to using the System to ventilate a patient. Failure to do so could result in higher NO2 levels being delivered to the patient.
ALWAYS use the smallest bag adequate to deliver the desired tidal volume. Failure to do so could result in higher NO2 levels being delivered to the patient.
ONLY use a manual resuscitation bag with the GENOSYL DS for a short time (e.g., less than one hour) when on battery only. Otherwise, the System may shut off and may result in injury or death.

STEP 1: SWITCHING TO MANUAL DOSING MODE

Ensure the oxygen flow source is set appropriately or adjust as needed.
Press the button "Switch to Manual" on the Dosing Console.
Press Confirm to switch to Manual Dosing Mode.

WARNING
If the dilution flow rate displayed on the screen does not match the wall source, then the estimated NO may be inaccurate.

STEP 2: SWITCHING BACK TO PRIMARY DOSING MODE 1. Press the "Switch to Primary" button at the top of the Manual Dosing Mode screen.
2. Press "Confirm" to start dosing or "Cancel" to cancel.

GAS SAMPLING DURING AEROSOL DELIVERY
Refer to Operator's Manual Section 3.8 for detailed instructions.

1. Place the medication nebulizer downstream of the Gas Sample Tee on the inspiratory limb.

2. Insert and connect the Sample Line Filter between the Sample Line and blue Stopcock. Refer to Operator's Manual Section 3.5.3 for detailed instructions to connect a Sample Line Filter.

	NOTE		NOTE
	This placement avoids contamination of the sample system and prevents Line Occlusion Alarm from occurring.		Replace filter after each treatment period. Change the filter if necessary due to Line Occlusion Alarm.

CAUTION
Pneumatic Nebulizers will dilute the delivered nitric oxide dose.

CONSOLE USE AS A BACK-UP
Refer to Operator's Manual Section 5.5 for detailed instructions.

1. Press the "Set" button on the Back-up Console which will display the NO dose electronic keypad and Flow Selection menu. 2. Confirm Dose and Total Flow range is appropriately selected.
3. Press "OK" to confirm entry 4. Connect the Adaptive Sensor Cable to the front of the new Dosing Console.

POWERING DOWN THE SYSTEM
Refer to Operator's Manual Section 6.1 for detailed instructions.

STEP 1: POWERING DOWN THE SYSTEM 1. Press the gray "Set" button to access the electronic keypad on the display screen. 2. Set the dose to "0" using the electronic keyboard. 3. Press "OK" to confirm the entry. 4. If the Settings Tab is not displayed, press the "Menu" tab to access the sub-level tabs.
5. Press the "Settings" tab on the display menu. 6. Press the red "System Shutdown" icon.
7. Review on-screen prompt. 8. Press "Confirm" to confirm shutdown. 9. Wait until the Console shuts down, the display screen appears blank, and the Console emits an audible beep. STEP 2: REMOVE THE CASSETTE Open the Cassette Access Door. Remove the Cassettes by pulling the Cassette straight out. Dispose of the inerted Cassette per hospital policy.

NOTE
The Console will inert any remaining contents from a dosing Cassette upon ejection, rendering it unusable. If a Cassette has only been preheated, and not used for dosing, the contents have not been inerted and it can still be used. The Cassette State Window will remain blue on Cassettes that have not been inerted.

EMPTY AND REPLACE WATER TRAP
Refer to Operator's Manual Section 11.4 for detailed instructions.

STEP 1: EMPTY THE WATER TRAP

Remove Water Traps from both Consoles by lifting latch and pulling the base of the Water Trap away from the Console.
Remove the lids by pulling the lid away from the base.
Empty the liquid contents.
Reattach the lids by pushing back onto base.
Slide the Water Traps back on both Consoles until they click into place.

CRITICAL ALARM TROUBLESHOOTING
Refer to Operator's Manual Section 10 for detailed instructions.

ALARM CONDITION	TROUBLE SHOOTING
LINE OCCLUSION (Sample) Message Box: None Banner:	In this fallback mode, the Console will continue delivering nitric oxide in an open loop mode at the last commanded dose until the line occlusion is resolved. Ensure blue Sample Line Stopcock is in the open position. Remove Sample Line Filter, replace if needed. Empty Water Tap. If occlusion persists after emptying, replace Water Trap. Inspect entire length of blue sample line for kinks or occlusions. Replace gas lines if kink or occlusion cannot be resolved. If issue is still not resolved, switch over to Back-up Console. Contact Technical Support.
WATER TRAP NOT DETECTED Message Box: Banner:	In this fallback mode, the console will continue delivering nitric oxide in an open loop mode at the last commanded dose until the water trap is replaced and the leak check is passed. Re-seat Water Trap. Insert new Water Trap. Switch over to Back-up Console. Call Technical Support.
LOW NO ALARM Message Box: None Banner:	Verify GENOSYL DS gas line connections are tight by loosening then retightening each connection on the red injection and blue sample lines. Verify proper placement of Injection Assembly and Sample adapter within the respiratory circuit. Ensure gas sample tee is placed 6 to 12 inches from the patient wye adapter. Replace adapters that have evidence of excessive condensation. Check the respiratory circuit for the presence of leaks. If not using an Adaptive Sensor, confirm total flow range is properly selected. Allow time for the sensor measurement to adjust while completing the next steps. Push on Cassette to ensure it is fully seated. Empty Water Trap. Replace Water Trap if necessary. If Cassette is depleted, insert a second Cassette if not already present. If auto transition does not occur, switch to Back-up Console. Ensure dose and flow are set within specifications. (see Operator's Manual Section 12.1.4) Liters per minute multiplied by ppm should not exceed 800. (Example 40 LPM × 20ppm = 800) Go to alarms screen and check the NO alarm setting. Set the alarm to the desired setting. If sensor measurement does not adjust, switch over to Back-up Console. Contact Technical Support.
HIGH NO ALARM Message Box: None Banner:	Verify flow is present in the patient's respiratory circuit. Allow time for the sensor measurement to adjust while completing the next steps. Verify GENOSYL DS gas line connections are tight by loosening then retightening each connection on the red injection and blue sample lines. Verify proper placement of injection assembly and sample adapter within the respiratory circuit. Replace adapters that have evidence of excessive condensation. Go to the Alarms screen and check the NO alarm setting. Set alarm to the desired setting. If the sensor measurement does not adjust, switch to Back-up Console. Contact Technical Support.
HIGH NO2 ALARM Message Box: None Banner:	Verify flow is present in the patient's respiratory circuit. Consider increasing bias flow, if applicable Allow time for the sensor measurement to adjust while completing the next steps. Verify GENOSYL DS gas line connections are tight by loosening then retightening each connection on the red injection and blue sample lines. Verify proper placement of injection assembly and sample adapter within the respiratory circuit. Replace adapters that have evidence of excessive condensation. Go to the Alarms screen and check the NO2 alarm setting. Set alarm to the desired setting. If the sensor measurement does not adjust, switch to Back-up Console Contact Technical Support.

This section contains troubleshooting instructions for common high priority alarms and messages and common possible causes in the OR setting of use. For other high priority alarms and messages and possible causes please refer to the Operator's Manual Section 10.3.

For technical support, contact the Partnership365™ Care Team at 1.877.337.4118

VERO Biotech and GENOSYL are registered trademarks of VERO Biotech Inc.
© 2025 VERO Biotech Inc. All rights reserved. MMC-602936 Rev. B June 2025
Please refer to full Prescribing Information and Operators Manual
vero-biotech.com | 1.877.337.4118

aarc
ZENITH AWARD
2024

PRINCIPAL DISPLAY PANEL - 216 L Cartridge Label

GENOSYL® (nitric oxide)
for inhalation

Recommended dosage: see prescribing information

For use with GENOSYL Delivery System only

LOT
Z-XXXX-YYYY

SN
ZZXXZXXX

EXP
YYYY-MM-DD

VĒRO
BIOTECH

PRINCIPAL DISPLAY PANEL - 216 L Cartridge Label

INGREDIENTS AND APPEARANCE

GENOSYL
nitric oxide gas

Product Information
Product Type	HUMAN PRESCRIPTION DRUG	Item Code (Source)	NDC: 72385-002
Route of Administration	RESPIRATORY (INHALATION)

Ingredient Name	Basis of Strength	Strength
Active Ingredient/Active Moiety
NITRIC OXIDE (UNII: 31C4KY9ESH) (NITRIC OXIDE - UNII:31C4KY9ESH)	NITRIC OXIDE	0.98 mg in 1 L

#	Item Code	Package Description	Marketing Start Date	Marketing End Date
Packaging
1	NDC: 72385-002-01	216 L in 1 CARTRIDGE; Type 0: Not a Combination Product	12/28/2022

Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
Marketing Information
NDA	NDA202860	12/28/2022

Labeler - VERO BIOTECH, INC. (872672477)

Registrant - VERO BIOTECH, INC. (872672477)

Name	Address	ID/FEI	Business Operations
Establishment
VERO BIOTECH, INC.		872672477	manufacture(72385-002)

Trademark Results [GENOSYL]

Mark Image Registration \| Serial	Company Trademark Application Date
GENOSYL 87772550 not registered Live/Pending	VERO BIOTECH, LLC 2018-01-26
GENOSYL 85981080 4496333 Live/Registered	GeNO LLC 2011-12-02
GENOSYL 85485604 4700107 Live/Registered	VERO BIOTECH, LLC 2011-12-02

Room size	1000 ft3
Room volume	28,300 L
Room ventilation (6 complete exchanges/hour)	2,830 L/min
NO flow into the room	80 ppm at 14 L/min
Average NO room concentration	0.4 ppm of NO

ILLUSTRATION	ACTION	Warnings, Cautions and Notes
	1. Close the blue stopcock to the position as shown
	2. Disconnect the blue sample line from the blue stopcock, keeping the blue stopcock connected to the patient circuit.
	3. Push and twist counterclockwise the Luer-Lock Collar of the Sample Line to remove from the blue Stopcock Valve at the Gas Sample Tee.
	4. Push and twist clockwise the male Luer-Lock Collar of the Sample Line Filter to the blue stopcock.
	5. Open the blue stopcock valve to the position as shown.
	6. Perform Water Trap / Sample Line Leak test, as detailed in Section 2.13.

ILLUSTRATION	ACTION	Warnings, Cautions and Notes
	The following steps should be taken to insert the Cassettes into the Consoles.	WARNING
		ALWAYS follow Cassette inspection instructions prior to insertion. Not inspecting the Cassette prior to insertion may lead to using a faulty Cassette, resulting in injury.
		NOTE
		Upon turning on the Consoles, the Cassette Indicator will display "Replace"
	1. Confirm the Cassettes are blue.	WARNING
		Only use the orange External Transport Cassettes identified by orange color and transport sticker for use in external transport outside of the hospital.
		NOTE
		See Section 8 for information about using the GENOSYL DS for external patient transfer outside of the hospital.
	2. Confirm the Cassette State Window on each Cassette is blue.	WARNING
		DO NOT use the Cassette if the window is not blue. A Cassette State Window that is any color other than blue may affect the Cassette's ability to provide the correct NO dosage to the patient, which may cause injury or death.
		NOTE
		Cassette is inserted front first. The Cassette State Window is not visible when properly inserted. If the Cassette State Window is not blue, see Troubleshooting, Section 9.8
	3. Open the Cassette Access Doors and insert two Cassettes into the Dosing Console and at least one Cassette into the Back-up Console. Push until it clicks.	NOTE
		Make sure Consoles are turned on before inserting the Cassette. The Water Trap / Sample Line Leak Test is automatically initiated when the Cassette has been inserted and the measured NO is less than 1.0 ppm. After the first Cassette is fully inserted, the Operator will have 60 seconds to close the blue Stopcock Valve to perform the test (Step 4 below). Gas lines will need to be connected to the Console in order to pass the Water Trap / Sample Line Leak Test.
		NOTE
		The Display Screen will temporarily indicate the Cassette has been detected, then automatically transition to the Water Trap / Sample Line Leak Test screen.
	4. Follow the onscreen instructions on both Consoles.	NOTE
	4. Follow the onscreen instructions on both Consoles.	The screen will indicate the Water Trap / Sample Line Leak Test has started and the progress bar will be red until the Stopcock Valve has been closed, upon which it will then turn green if there is no leak detected. Pressing "Cancel Leak Test", will allow for dosing in Manual Dosing Mode. See Section 5.4 for detail around dosing in Manual Dosing Mode.
	5. Follow the onscreen instructions on both Consoles.	CAUTION
	5. Follow the onscreen instructions on both Consoles.	Open the blue Stopcock Valve prior to pressing "Accept". Failure to do so will result in a line occlusion alarm.

Part Description	Weight per Unit	Dimensions	Number Required	Total Weight
Console	8.85 kg (19.75 lb)	40.6 cm × 34.29 cm × 17 cm (16 in × 13.5 in × 6.75 in)	2	17.7 kg (39.5 lb)
External Transport Cassette	0.42 kg (0.93 lb)	11.4 cm × 3.8 cm × 13 cm (4.5 in × 1.5 in × 5.1in)	3	1.26 kg (2.79 lb)
External Transport Mount	2.22 kg (4.89lb)	40.64 cm × 32.77 cm × 8.89 cm (16 in × 12.9 in × 3.5 in)	2	4.44 kg (9.78 lb)
Quick Connect Plate	1.52 kg (3.35 lb)	46.36 cm × 27.18 cm × 0.64 cm (18.25 in × 10.70 in × 0.25 in)	(1 Optional)	1.52 kg (3.35 lb)
Power Supply	2.07 kg (4.56 lb)	14.6 ft	1	2.07 kg (4.56 lb)

ILLUSTRATION	ACTION
	1. Obtain one (1) Sample Tee, 3/8" Barbed, one (1) GENOSYL DS Adaptive Sensor, one (1) NO Gas Injection Adapter, and one (1) Injection Line Filter.
	2. Connect the GENOSYL DS Adaptive Sensor, NO Gas Injection Adapter, and the Injection Line Filter to create the Gas Injection Assembly.
	3. Connect the GENOSYL DS Adaptive Sensor of the Gas Injection Assembly with Injection Line Filter to the ventilator outlet port.
	4. Connect the inspiratory limb inlet to the NO Gas Injection Adapter of the Gas Injection Assembly with Injection Line Filter.
	5. Locate and cut the noncorrugated tubing at the center of the smooth segment closest to the patient wye.
	6. Insert the barbed ends of the Sample Tee, 3/8" Barbed into both ends of the cut tubing.
	7. Push and twist clockwise the Luer-Lock Collar from the NO Injection Line onto the Injection Assembly with Injection Line Filter. 8. Push and twist clockwise the Luer-Lock Collar of the Sample Line Stopcock onto the Sampling Port of the Sample Tee, 3/8" Barbed.

NO	time-weighted (8 hours) average concentration limit of 25 ppm
NO2	Recommended exposure limit of 1 ppm

ILLUSTRATION	ACTION
	1. Connect the Inline Breathing Circuit Filter to the Gas Injection Adapter (22 mm ID × 22 mm OD).
	2. Connect the Adaptive Sensor to the inlet end of Gas Injection Adapter (22mm ID × 22 MM OD).

ILLUSTRATION	ACTION
	1. Connect the Inline Breathing Circuit Filter to the Adapter 22 mm ID × 22 mm ID.
	2. Connect the Adapter 22mm ID × 22 mm ID to the distal end of the Mixer.
	3. Connect the Gas Injection Adapter to the proximal end of the Mixer.
	4. Connect the Adaptive Sensor to the proximal end of the Gas Injection Adaptor

ILLUSTRATION	ACTION	Warnings, Cautions and Notes
	1. Push and twist clockwise the short Y-end of the NO Injection Line (red) to the "NO" port (red) on the front panel of the Dosing Console.
	2. Push and twist the short Y-end of the Sample Line (blue) to the Gas Sample Port (blue) on the front of the Water Trap, attached to the Dosing Console.	NOTE
		Ensure the Sample Lines are connected to the Water Traps on both Consoles.
	3. Push and twist clockwise the end of the Manual Ventilation Line (clear) to the Manual Ventilation Port (clear) on the front panel of the Dosing Console 4. Repeat steps 1, 2, and 3 on the Back-up Console.

ILLUSTRATION	ACTION	Warnings, Cautions and Notes
	1. If actively dosing, switch to Manual Dosing Mode prior to completing the following steps (see Section 5.4 for details on Manual Dosing Mode).	WARNING
		Failure to switch to Manual Dosing Mode prior to installing a Sample Line Extension when the System is actively dosing may result in a spike in the NO dose delivered to the patient.
	2. Turn the blue Stopcock Valve, attached at the Gas Sample Tee, to the closed position as shown.
	3. Push and twist counterclockwise the Luer-Lock Collar of the Sample Line to remove from the blue Stopcock Valve at the Gas Sample Tee.
	4. Push and twist clockwise the Luer-Lock Collar of the Sample Line onto the Sample Line Extension female connection. 5. Push and twist clockwise the Luer-Lock Collar of the Sample Line onto the blue Stopcock Valve at the Gas Sample Tee.
	6. Perform Water Trap / Sample Line Leak Test, as detailed in Section 2.13.
	7. If actively dosing, switch back to Primary Dosing Mode (see Section 5.4.2 for details on resuming Primary dosing).

ILLUSTRATION	ACTION	Warnings, Cautions and Notes
	1. Connect the Adaptive Sensor Cable to the Adaptive Sensor Port on front of the Dosing Console.	NOTE
		The Adaptive Sensor should only be connected to the Dosing Console.

ILLUSTRATION	ACTION	Warnings, Cautions and Notes
	1. Push and twist clockwise the Luer-Lock Collar from the NO Injection Line onto the Injection Assembly.	NOTE
		After connecting, the valve assembly may have rotated such that the orientation may appear different from what is shown here and on the display screen.
	2. Push and twist clockwise the Luer-Lock Collar of the Sample Line onto the Sampling Port of the Gas Sample Tee.	NOTE
		Skip this step if a Gas Sample Tee is already connected and in-line with the ventilator circuit.
	3. Ensure the blue Stopcock Valve is in the open position as shown.
	4. Connect the distal end of the Adaptive Sensor Cable to the Adaptive Sensor on the Injection Assembly

ILLUSTRATION	ACTION	Warnings, Cautions and Notes
	1. Disconnect the Inspiratory Tubing from the humidifier and attach it to the proximal end of the Injection Assembly to the Adaptive Sensor. 2. Attach the distal end of the Injection Assembly to the humidifier.
	3. Insert the Sample Tee into the ventilator circuit at the proximal end of the temperature probe closest to the patient.	NOTE
		If a Gas Sample Tee is already connected and in-line with the ventilator circuit, connect the blue Sample Line directly to the existing Gas Sample Tee.

ILLUSTRATION	ACTION	Warnings, Cautions and Notes
	1. Push the Circular Power Connectors into the back of the top and bottom Consoles. 2. Connect the main power cord to a grounded 120 V electrical outlet.	CAUTION
		ONLY use the GENOSYL DS with the power cord supplied by the manufacturer. Use of a generic power cord may cause output voltage instability leading to a touch screen failure. ALWAYS ensure the power cord is firmly seated into the power supply and the wall outlet. A loose connection can result in damage to the device or faulty operation.
	3. Press the Black Rocker Power Switch, located on the back of each Console, to the right (ON position) to power on both Consoles.
	4. Press the Silver Power Button, located at the top left corner on the front panel of each Console, to turn on the display screens on both Consoles. The display screen will illuminate, and the Consoles will beep, indicating the power is on.	CAUTION
		The System will conduct an internal self-test. If an alarm or failure message should occur, refer to Section 10 to resolve the issue.
		NOTE
		If the display screen does not turn on, see Troubleshooting, Section 10.8.

ILLUSTRATION	ACTION	Warnings, Cautions and Notes
	1. If this screen is displayed, follow the onscreen instructions on both Consoles.
	2. Press "Confirm" on both Consoles to begin a new Water Trap / Sample Line Leak Test.	NOTE
		NO Injection is held at 20 ppm until the completion of a successful Water Trap / Sample Line Leak Test.

ILLUSTRATION	ACTION	Warnings, Cautions and Notes
	1. Press the gray "Set" button on the display screen.	Note
	1. Press the gray "Set" button on the display screen.	The Adaptive Sensor must detect flow through the breathing circuit to set a dose.
	2. Enter the prescribed dose in ppm on the electronic keypad. 3. Press OK to confirm the entry.	NOTE
		The time to reach target dose may vary up to 10 minutes.
		If unable to set the dose in Primary Dosing Mode, see Troubleshooting, Section 10.8.
		NOTE
		If manual ventilation is required, proceed to Section 5.4. When adjusting dose, proceed to Section 5.2. If dosing is completed, proceed to Section 6.1.
		NOTE
		The display screen will look as shown after completing steps 1-3.
		NOTE
		The NO2 sensor reading may appear as "—" for the first 30 seconds of dosing while the sample System is preparing.

ILLUSTRATION	ACTION	Warnings, Cautions and Notes
	1. Press the gray "Set" button on the display screen.
	2. Confirm Total Flow range is appropriately selected. 3. Enter the prescribed dose in ppm on the electronic keypad. 4. Press OK to confirm the entry.	NOTE
		The time to reach target dose may vary up to 10 minutes. If unable to set the dose in Primary Dosing Mode, see Troubleshooting, Section 10.8.
		NOTE
		If manual ventilation is required, proceed to Section 5.4. When adjusting dose, proceed to Section 5.2. If dosing is completed, proceed to Section 6.1.
		NOTE
		The display screen will look as shown after completing steps 1-3.
		NOTE
		The NO2 sensor reading may appear as "--" for the first 30 seconds of dosing while the sample system is preparing.

ILLUSTRATION	ACTION	Warnings, Cautions and Notes
	1. Press the gray "Set" button to access the electronic keypad on the display screen on the Dosing Console.
	2. Enter the prescribed dose using the electronic keypad. 3. Press "OK" to confirm the dose and to start dosing administration.	NOTE
		If dosing is complete, proceed to Section 6.

ILLUSTRATION	ACTION	Warnings, Cautions and Notes
	1. Press the gray "Set" button to access the electronic keypad on the display screen on the Dosing Console.
	2. Enter the prescribed ppm dose using the numeric keypad. 3. Adjust Total Flow range, if necessary. 4. Press "OK" to confirm the dose and to start dosing administration.	NOTE
		If dosing is complete, proceed to Section 6.

ILLUSTRATION	ACTION	Warnings, Cautions and Notes
		NOTE
		The Console will automatically transition to the secondary Cassette if properly inserted and preheated. The screen to the left will be displayed during the transition process.
	1. Follow onscreen instructions to replace Cassette.

ILLUSTRATION	ACTION	Warnings, Cautions and Notes
	1. Ensure the oxygen flow source is set appropriately or adjust as needed. 2. Press the button "Switch to Manual" on the Dosing Console.
	3. Press "Confirm" to switch to Manual Dosing.	WARNING
	3. Press "Confirm" to switch to Manual Dosing.	If the dilution flow rate displayed on the screen does not match the wall source, then the estimated NO may be inaccurate.
		NOTE
		Dosing has been initiated at the same dose (ppm) as set in Primary Dosing Mode. If the primary dosing was set at "0" prior to pressing the "Switch to Manual" button, the estimated NO will also be at "0" and will need to be adjusted. If the dose was set between 1 and 5 ppm prior to pressing the "Switch to Manual" button, the estimated NO dose will also be at"5 ppm" and may be adjusted. In the event dose is initiated in Manual Dosing Mode, the console will default to 20 ppm, which can be adjusted as needed.
	4. To resume primary dosing, see Section 5.4.3.	NOTE
	4. To resume primary dosing, see Section 5.4.3.	If an adjustment of the NO concentration is required, press the green up and down arrows. If an adjustment to the Dilution Flow Rate is required while in Manual Dosing Mode, press the LPM value and a dropdown menu will expand. Press the prescribed value. The new value will be highlighted in blue and the dropdown menu will collapse.

ILLUSTRATION	ACTION	Warnings, Cautions and Notes
	1. Navigate to the "Settings" Tab.
	2. Select the Flow Rate from the drop-down menu.	NOTE
	2. Select the Flow Rate from the drop-down menu.	The Console will default to a Flow Rate of 10 LPM if not adjusted. Any adjustment will be retained until the Console is powered down.

ILLUSTRATION	ACTION	Warnings, Cautions and Notes
	1. Press the "Switch to Primary" button at the top of the Manual Mode screen.
	2. Press "Confirm" to start dosing or "Cancel" to cancel.	NOTE
	2. Press "Confirm" to start dosing or "Cancel" to cancel.	The NO dose used in Manual Mode will become the set target dose in Primary Mode.
		NOTE
		The display screen will look as shown after completing steps 1-2.

DISPLAY	ACTION	Warnings, Cautions and Notes
	1. Press the "Set" button on the Back-up Console which will display the NO dose electronic keypad and Flow Selection menu.
	2. Confirm Dose and Total Flow range is appropriately selected. 3. Press "OK" to confirm entry	NOTE
		The Back-up Console screen will be as shown. The default Total Flow range displayed will be <2.5LPM and the default dose will be 20 ppm unless otherwise selected by the user. See Section 5.1.2 The Back-up Console is now the Dosing Console.
	4. Connect the Adaptive Sensor Cable to the front of the new Dosing Console.

DISPLAY	ACTION	Warnings, Cautions and Notes
	1. Press the gray "Set" button to access the electronic keypad on the display screen.
	2. Set the dose to "0" using the electronic keypad. 3. Press "OK" to confirm the entry.
	4. If the "Settings" tab is not displayed, press the "Menu" tab to access the sub-level tabs. 5. Press the "Settings" tab on the display menu. 6. Press the red "System Shutdown" icon.
	7. Review on screen prompt. 8. Press "Confirm" to confirm shutdown. 9. Wait until the Console shuts down, the display screen appears blank, and the Console emits an audible beep.	NOTE
		If the System does not shut down, see Troubleshooting , Section 10.8. The screen will inform user if Cassette should be saved or disposed of. Refer to Section 2.14 Shutdown Cassette Status Indicator description.
	10. Open the Cassette Access Door.
	11. Remove the Cassettes by pulling the Cassette straight out. 12. Dispose the inerted Cassettes per hospital policy.	NOTE
		The Console will inert any remain contents from a dosing Cassette upon ejection, rendering it unusable. If a Cassette has only been preheated, and not used for dosing, the contents have not been inerted and it can still be used. The Cassette State Window will remain blue on Cassettes that have not been inerted.
	13. Press the Black Rocker Power Switch to the "OFF" position. 14. Repeat steps 1-13 for the other Console.	WARNING
		NEVER turn the rear power switch OFF until the System has gone through a controlled shutdown or instructed by VERO Technical Support. Turning the rear power switch OFF prematurely (e.g., while it is still in use) will immediately shut down the device. This may result in interruption in NO delivery to the patient, which may cause injury or death.
		CAUTION
		NEVER turn the rear power switch OFF until the System has gone through a controlled shutdown or instructed by VERO Technical Support. Turning the rear power switch OFF prematurely (e.g., while it is still in use) will immediately shut down the device and may cause improper operation upon restart.