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.

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

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

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)]

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.

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:

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).

Rx Only

VERO Biotech and GENOSYL are registered trademarks of VERO Biotech.

© 2022 VERO Biotech

Manufactured by:
VERO BIOTECH
387 Technology Circle NW
Suite 125
Atlanta, GA 30313, USA
[602604]

Vero Biotech Inc.
387 Technology Circle 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, warning, cautions, and notes will be displayed in the following manner.

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.

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.

The following parts are required to deliver Nitric Oxide using a manual ventilation system.

The following parts are required for routine maintenance.

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.

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 and 1.5 Tesla and 3.0 Tesla diagnostic imaging environments.

The GENOSYL DS is intended for use by healthcare professionals (HCPs) who are licensed and actively practicing pediatric and/or neonatal respiratory therapists (RTs) in the United States. These users are required to set up, administer inhaled Nitric Oxide 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 provides at least 1 hour of NO delivery in the absence of an external power source.

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.

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).

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

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.

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 10.2.

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 high priority alarm when flow is not detected to alert the user (see Section 8.2). 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:

a)

NO > 100 ppm

b)

NO2 reaches 3 ppm

c)

The measured respiratory circuit dilution flow drops below 0.3 SLPM as measured by the Adaptive Sensor.

The Console will provide a visual and audible high priority alarm. When detecting a sustained gas level higher than the above limits for 11 consecutive seconds, the Console will interrupt delivery of NO until the sampled levels of NO and/or NO2 decrease to a safe level. Once sampled levels are in acceptable range, the Console will resume delivery with previously set dose.

If the cause of the high gas cannot be resolved, the use of the Back-up Console may be required. Refer to Section 8.1 for additional information on alarms and dosing safeguards.

If NO delivery was interrupted due to the GENOSYL DS Adaptive Sensor reading dropping below 0.3 SLPM, the Console will resume delivery with the previously set dose once the Adaptive Sensor reading exceeds 0.35 SLPM. The automatic resumption of dose delivery after the interruption conditions listed above are cleared is one of the safety fallback modes of the GENOSYL DS.

Back-up NO Delivery. The Back-up Console is used to administer Nitric Oxide when the Dosing Console cannot be used. This Console has a separate power supply, and at least one Cassette loaded and preheated. If the Dosing Console fails to deliver NO, the Back-up Console is ready to begin dosing to continue NO delivery.

Transition to a new Cassette. When a Cassette approaches depletion, the Dosing Console will automatically transition to the second Cassette in the Console. Once the dosing Cassette is depleted, the Dosing Console will eject the depleted Cassette and alert the user to replace via the Cassette Status Indicator.

Disposal of the Cassette. Following use, any remaining Cassette contents are purged into an inerting chamber, where the contents are chemically neutralized, rendering the Cassette safe for disposal.

1.4 Exposure of Healthcare Providers to NO and NO2

Occupational exposure of healthcare providers to NO or NO2 may occur during Inhaled NO therapy for patients. Below are examples of calculated and observed exposure to NO or NO2, in the context of guideline workplace exposure limits.

Calculated and observational methods show that the exposure levels to NO or NO2 from an NO delivery System are significantly less than the levels recommended by the National Institute for Occupational Safety and Health (NIOSH).

Workplace Limits: NIOSH has recommended workplace exposure limits as follows1.

Theoretical Calculation. The build-up of NO in a well-ventilated ICU room, with NO flowing directly into the room, can be evaluated using the following calculation:

Observations of NO Exposure. The theoretical calculation has been supplemented by actual measurements in three independent studies in actual therapeutic use settings.2,3,4 The studies found that detectable exposures to NO and NO2 were brief, infrequent, and well below recommended exposure limits.

If the location for using NO has uncertain ventilation, then the location should be evaluated for NO and NO2 build-up prior to use.

GENOSYL® DS

SECTION 2
SYSTEM OVERVIEW

2. SYSTEM OVERVIEW

2.1 Frequently Used Functions

Detailed instructions are provided in this manual for the primary user interaction and frequently used functions of the GENOSYL DS, which include:

System Set-Up and Connections (Section 3)

• Connections to Various Breathing Systems
• GENOSYL DS Ventilator Circuit Assembly Pre-Check
• GENOSYL DS Injection Assembly with Adaptive Sensor
• GENOSYL DS Mixer Assembly with Adaptive Sensor
• GENOSYL DS Console Connections
• GENOSYL DS Gas Line Connections
• GENOSYL DS Sample Line Extension Connection
• GENOSYL DS Adaptive Sensor Cable Connection
• GENOSYL DS Ventilator Circuit Connection
• GENOSYL DS Manual Ventilation Connections
• GENOSYL DS Mechanical Ventilator Circuit Connections

System Start-Up (Section 4)

• Console Start-Up
• Cassette Insertion
• Water Trap / Sample Line Leak Test

Nitric Oxide Administration (Section 5)

• Setting a Dose when using a Circuit with an Adaptive Sensor
• Setting a Dose when using a Circuit without an Adaptive Sensor
• Adjusting the Dose
• Manual Mode
  • Manual Ventilation Use (Bagging)
  • Preset Manual Mode Flow Rate (Optional0
  • Resuming Primary Dosing
• Console Use as Back-up

Console Shutdown (Section 6)

• Console Shutdown
• Cassette Removal
• Cassette Disposal

Using the System in the MR Scanner Room (Section 7)

• Connection to the Ventilator Circuit
• Transferring to and from the MR Scanner Room

Alarms, Alerts, and Troubleshooting (Section 8)

• Alarms (High, Medium, and Low Priority)
• Informational messages
• Troubleshooting

System Maintenance (Section 9)

• Calibration
• Maintenance Schedule
• Testing the GaussAlert™ Function
• Water Trap Maintenance
• Battery
• Cleaning
• Storage

2.2 GENOSYL DS Cart and Consoles

The following pages contain photos of the GENOSYL DS Consoles. The specific sections of the GENOSYL DS are numbered with the respective description listed below the photo.

2.3 Cassette

The Cassette contains the material that will be converted to nitric oxide during the activation process. It is inserted into the GENOSYL DS Console, and its shape helps ensure proper orientation during the insertion process. A Cassette State Window is located on the front of the Cassette to indicate if the Cassette is available for use (blue), or if it has been inerted and unavailable for use (bleached and reddened).

2.4 GENOSYL DS Ventilator Circuit Components

The following parts are used to set up the GENOSYL DS portion of the patient respiratory circuit, as specified in Section 3.2.

2.5 Gas Lines (detailed explanation)

Gas lines are used to deliver nitric oxide from the GENOSYL DS Consoles to the ventilator circuit and manual ventilation bag, and to sample gas within the ventilator circuit. The lines are color coded and labeled with icons corresponding to colors and icons on each Console.

The NO Injection Line (red) delivers Nitric Oxide from the Console to the mechanical ventilation circuit (described in Section 3.5).

The Sample Line (blue) also contains a stopcock to conduct the Water Trap / Sample Line Leak Test (described in Section 4.2).

A Sample Line Extension is available when additional distance between the patient circuit and the Console is required (e.g., use in the MR environment) (described in Section 3.5.2).

The Manual Ventilation Line (clear) delivers Nitric Oxide from the Console to the Manual Ventilation Bag NO adapter (described in Section 3.6).

2.6 Console Modes of Operation

During operation, a Console can be in one of two modes; Primary or Manual. The user can switch the modes during normal operation to perform specific functions for certain conditions. The following table summarizes key characteristics of each mode.

2.7 Display Screen

The GENOSYL DS display screen is presented below (Figure 13) followed by a table with descriptive text corresponding to the numbers shown around the display screen.

2.8 Display Menu Tab Navigation

The table below consists of the available Menu tabs (Main, Alarms, Calibration, Events, and Settings) along with the functional description of each tab, and the buttons within each tab.

2.9 Display Screen Operational Buttons

The following buttons on the display screens allow the Operator to operate and adjust the GENOSYL DS prior to and during the delivery of nitric oxide.

Note: the following are shown in "regular mode" but are also available in "day" mode.

2.10 Display Screen – Cassette Status Indicators

The following describes the Cassette Status Indicators that will be shown on the display screen prior to, during, and post-delivery of nitric oxide. The Cassette Status Indicators consist of two Cassette icons, which correspond to the left and right Cassette receptacles.

2.11 Display Screen - Adaptive Sensor Status

The following describes the Adaptive Sensor status that will be shown on the display screen. The Adaptive Sensor Icon is located on the top left of the Console display screen.

2.12 Cassette Insertion into Console

When inserting a Cassette into a Console, it is important to push the Cassette fully into the receptacle and confirm the Cassette has been registered on the screen.

2.13 Water Trap / Sample Line Leak Test

A Water Trap / Sample Line Leak Test is initiated when a Cassette has been inserted into the Console and fully seated, and if the measured NO is less than 1.0 ppm. Its purpose is to test the integrity of the Water Trap seal, the proper seating of the Water Trap, and the Sample Line connection to each Console, prior to operation. This is important to ensure an accurate measurement of NO within the ventilator circuit.

After the test has been initiated, the screen will prompt the Operator to close the Stopcock Valve and the Operator will have 60 seconds within which to do this. A numerical timer and a horizontal progress bar provide a visual representation of the time elapsed (red) and time remaining (gray). Once the Stopcock Valve has been closed and if the test has been successfully completed, the entire progress bar will turn green.

If the test has failed, the progress bar will remain red throughout the full 60 seconds. The Operator will be notified and prompted to troubleshoot the potential cause

Prior to completion of the leak test and if a condition exists in which immediate NO delivery is required, the Operator may cancel the leak test. The GENOSYL DS will allow a dose of 20 ppm to be set in Primary Mode. If a different dose is required, a Water Trap/Sample Line Leak test must be completed.

The Water Trap/ Sample Line Leak Test may also be initiated manually via the Settings Tab and pressing the "Perform Leak Test" button. This may be useful to test the integrity of the Water Trap and Sample Line independent of the need to initiate the delivery of Nitric Oxide (see Settings in Section 2.8).

GENOSYL® DS

SECTION 3
SYSTEM SET-UP AND CONNECTIONS

3. SYSTEM SET-UP AND CONNECTIONS

3.1 GENOSYL DS Set-Up and Mechanical Ventilator Circuit Schematic

The schematic in Figure 15 shows an example ventilator circuit set-up and connection to the GENOSYL DS, and a manual ventilation bagging system.

All required GENOSYL DS Parts / Components are listed in the front of this manual and should be removed from their packaging prior to set-up.

3.2 Connections to Various Breathing Systems

3.2.1 Conventional Ventilators

Compatibility testing has demonstrated performance meeting requirements for the GENOSYL DS operating range of 0 to 80 ppm with the following conventional ventilators at the operating ranges shown in Table 1. For further information on the use of the GENOSYL DS with validated MR conditional ventilators in the MR environment, refer to Section 7.

• Bio-Med Devices CrossVent 2+/2i+
• Bio-Med Devices MVP-10
• Dräger V500
• Dräger VN500
• GE Healthcare R860
• Hamilton C1/T1
• Hamilton C2/C3
• Hamilton G5
• Hamilton MR1
• Maquet Servo-U/N/I
• Maquet Servo-I MR
• Puritan Bennett 840
• Puritan Bennett 980
• Vyaire AVEA

The ventilator circuit diagram for use without the Inline Mixer Accessory, required in certain scenarios, is shown in Figure 15. See Section 10.2, Table 10 for applicable use scenarios.

The ventilator circuit diagram for use with the Inline Mixer Accessory, required in certain scenarios, is shown in Figure 16. See Section 10.2, Table 10 for applicable use scenarios.

3.2.2 Non-Invasive Gas Delivery Systems

Compatibility testing has demonstrated performance meeting requirements for the GENOSYL DS operating range of 0 to 80 ppm with the following non-invasive gas delivery systems at operating ranges shown in Table 2.

• Fisher and Paykel Optiflow Jr Breathing Circuit
• Fisher and Paykel Optiflow Breathing Circuit
• Infant Bubble Continuous Positive Airway Pressure (CPAP)

The Fisher and Paykel Optiflow Jr Breathing Circuit for use with the GENOSYL DS is shown in Figure 17.

The Fisher and Paykel Optiflow Breathing Circuit for use with the GENOSYL DS is shown in Figure 18.

The infant bubble CPAP diagram for use with the GENOSYL DS is shown in Figure 19.

3.3 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.

3.4 Assembling GENOSYL DS Injection Assembly with Adaptive Sensor and GENOSYL DS Mixer 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 Section 10.2, Table 10 for scenarios when a Mixer is recommended for use.

3.4.1 GENOSYL DS Injection Assembly with Adaptive Sensor

Follow the instructions outlined below to assemble the GENOSYL DS Injection Assembly as shown in Figure 20.

3.4.2 GENOSYL DS Mixer Assembly with Adaptive Sensor

If required, follow the instructions outlined below to assemble the GENOSYL DS Mixer Assembly with Adaptive Sensor as shown in Figure 21.

3.5 GENOSYL DS Console Connections

3.5.1 GENOSYL DS Gas Line Connections

Follow the steps listed below to connect the GENOSYL DS to both Consoles.

3.5.2 GENOSYL DS Sample Line Extension Connection

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

3.5.3 GENOSYL DS Adaptive Sensor Cable Connection

Follow the step below to connect the Adaptive Sensor Cable to the Dosing Console.

3.5.4 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.

3.6 Manual Ventilation (Bag) Connection

Follow the steps listed below to connect the Manual Ventilation Line to a manual bagging system.

3.7 Mechanical Ventilator Circuit Connections

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

GENOSYL® DS

SECTION 4
SYSTEM START-UP

4. SYSTEM START UP

4.1 Console Start-Up

Follow the instructions in this section to turn on both the Dosing and Back-up Consoles.

4.2 Cassette Insertion & Water Trap / Sample Line Leak Test

The following steps should be taken on both the top and bottom Consoles. Initiating Console Start-Up and inserting a Cassette for the bottom Console at this stage will prepare it to serve as a Back-up for the top Console.

Upon the insertion of a Cassette, a test will be initiated on each Console to check and ensure the integrity of the Water Traps and Sample Line (see Section 2.13). This helps ensure the accuracy of NO being delivered to the ventilator circuit.

The Water Trap/ Sample Line Leak Test is automatically initiated upon one or both of the following conditions: 1) Insertion and seating of the Cassette if the measured NO is less than 1.0 ppm and/or 2) Insertion and seating of the Water Trap.

4.2.1 Water Trap / Sample Line Leak Test Troubleshooting

GENOSYL® DS

SECTION 5
NITRIC OXIDE ADMINISTRATION

5. NITRIC OXIDE ADMINISTRATION

5.1 Nitric Oxide Dose Set-Up and Administration

The following steps are a continuation of Section 4.2, in which the Cassette will now be activated for Nitric Oxide administration.

5.1.1 Setting a Dose when using a Circuit with an Adaptive Sensor

This section describes how to set a Nitric Oxide dose when an Adaptive Sensor is used in the patient circuit. Refer to Section 3.2 for recommended set up diagrams.

5.1.2 Setting a Dose when using a Circuit without an Adaptive Sensor

This section describes how to set a Nitric Oxide dose when an Adaptive Sensor is not used in the patient circuit, such as when initiating a dose when using a Console as Back-up (Section 5.5). Refer to Section 3.2 for recommended set up diagrams. In the absence of an Adaptive Sensor, the GENOSYL DS will properly deliver and control Nitric Oxide dose. However, the user will have to manually select a Total Flow Range.

5.2 Adjusting the Dose

To adjust the dose of Nitric Oxide administered per hospital protocol or physician order, follow the instructions listed below.

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

5.2.2 Adjust the Dose and Flow Range when using a Circuit without an Adaptive Sensor

5.3 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 if a secondary Cassette is properly inserted and preheated. After transition, the depleted Cassette is automatically ejected.

5.4 Manual Mode

5.4.1 Manual Ventilation Use (Bagging)

This section will describe NO administration when manual ventilation is required.

5.4.2 Preset Manual Mode Flow Rate (OPTIONAL)

User has the option to preset a Manual Mode Flow rate. This can be completed during set up or at any time.

5.4.3 Resuming Primary Dosing

This section describes the process for resuming primary dosing from Manual Mode.

5.5 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.

GENOSYL® DS

SECTION 6
CONSOLE SHUTDOWN

6. CONSOLE SHUTDOWN AND CASSETTE DISPOSAL

6.1 Console Shutdown

If the administration of NO must be stopped, then the dose level must be set to "0". The following procedure describes how to remove the Cassette and the following section will describe how to shut down the Console.

6.2 Cassette Disposal

Following dosing use, any remaining Cassette liquid contents in a dosing Cassette 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.

GENOSYL® DS

SECTION 7
USING THE SYSTEM IN THE MR SCANNER ROOM

7. USING THE SYSTEM IN THE MR SCANNER ROOM

7.1 Connection to the Ventilator Breathing Circuit

To connect the GENOSYL DS to an MR Conditional ventilator, see Section 3.2 for example breathing circuits. When using the GENOSYL DS in the MR environment, a Sample Line Extension may be required. See Section 3.5.2 for steps to install the Sample Line Extension.

7.2 Transferring to and from the MR Scanner Room

1. Verify that both gauss alarms are installed on the GENOSYL DS Cart.

2. Move the patient, MR conditional ventilator circuit, and GENOSYL DS into the MR scanner room.

3. Position the GENOSYL DS outside of the MR exclusion zone, as shown in Figure 22.

4. Engage the locks on wheels and confirm caster lock function. Attaching a facility supplied tether to the System Cart handle may be utilized as a redundant means to limit the distance the Cart can move.

5. Move the patient, MR conditional ventilator, and GENOSYL DS outside of the MR scanner room.

6. Verify ventilator and GENOSYL DS function following transition from the MR scanner room.

GENOSYL® DS

SECTION 8
ALARMS, ALERTS, AND TROUBLESHOOTING

8. ALARMS, ALERTS, AND TROUBLESHOOTING

8.1 Alarms, Alerts, and Troubleshooting

This section contains the System alarms and messageS in order of High (red), Medium (yellow), and Low Priority (cyan) 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. 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 the table below for descriptions of each alarm status:

The alarm order, color, and audio signal will follow the highest priority alarm.

Some alarms may be adjusted within the Alarms Tab. See Table 5 below for adjustment characteristics. The System will always resort to the original default alarm settings upon reboot or complete power failure.

In addition, the System has a fallback safety dose interruption feature which will temporarily interrupt delivery of NO when the sensors detect a sampled value of ≥ 100 ppm NO and/or ≥ 3 ppm NO2. The System will resume NO dosing after dissipation of high gases without operator input.

Review Table 5 for complete details about the alarm adjustment ranges, defaults, alarm activation timing and interruption conditions.

Alarms are legible for a person with 20/20 vision at a distance of 1 meter when viewed directly on the screen.

An alarm history indicating the date, time, and type of alarm can be viewed by selecting the Alarms Tab and then selecting the alarms history button. The alarm history can be cleared by pressing the "Clear Alarm Button". If the alarm history reaches capacity, the oldest alarms will begin rolling off and become non-visible to the user. Upon Console shut down or power loss, the alarm log is cleared. If the alarm log is cleared, or reaches capacity, history of alarms will still be recorded in permanent memory accessible when logged in as admin. The operator of the equipment should be physically in front of the Console while interacting with the System. During NO delivery, the operator should remain within visual and auditory distance of the System.

The alarm system is automatically tested during the initial power-on self-test with an audible beep to confirm successful completion. Should there be an issue with communication to the alarms System electronics, a Hardware Failure error message will appear at the end of the self-test.

8.2 High Priority Alarms and Messages

High priority alarms and messages will have a red background and be accompanied by an audible alarm. These alarms and messages require immediate operator response.

8.3 Medium Priority Alarms and Messages

Medium priority alarms and messages will have a yellow background. Medium priority alarms and messages require a prompt response from the operator.

8.4 Low Priority Alarms and Messages

A low priority message will have a turquoise background. A low priority message will require that the operator is aware of the condition.

8.5 Informational Messages

Informational messages will have a green background. These messages require that the user is notified of the condition.

8.6 GaussAlert™ Alarm

The gauss alarm will sound if the GENOSYL DS is too close to the MR Scanner. If the gauss alarm sounds, move the GENOSYL DS away from the MR scanner until the gauss alarm stops sounding.

8.7 Troubleshooting

The table below provides resolutions to issues that may be encountered with the GENOSYL DS.

GENOSYL® DS

SECTION 9
SYSTEM MAINTENANCE

9. SYSTEM MAINTENANCE

9.1 Calibration

This section describes the process for performing high and low calibration for NO, NO2, and O2. Calibration of the GENOSYL DS should be performed every 14 days to ensure the accuracy of NO, NO2, and O2 measurements. All calibrations can be performed at any time the Console is powered on, including while actively dosing. Air calibrates the low range for the NO and NO2 sensors. The high range of the NO and NO2 sensors are calibrated by using calibration gas tanks. The software will notify the user when calibration is due.

The display within the calibration tab provides the status and the calibration due date of the different types of sensors. Air calibration provides the time of the last calibration since the System automatically performs this calibration every 4 hours while actively dosing or every 24 hours while powered on. A green check under status indicates that sensor has successfully been executed within the calibration period. A red X under status indicates that the sensor has not successfully been executed within the calibration period.

During calibration, the display will provide measured readings from each sensor. Note, there are two redundant NO sensors which are used to verify and ensure accuracy of the dosage provided by the System. During calibration, the display will provide a real-time status of the test with colored boxes to the right of the displayed sensor output. A yellow box indicates that the sensor is being calibrated. A green box indicates that calibration was successful for that sensor. A red box indicates that calibration for that sensor failed.

9.1.1 Air Calibration

9.1.2 NO Calibration

9.1.3 NO2 Calibration

9.2 Maintenance Schedule

The Console components require the following maintenance:

The Console requires yearly factory service. The System will display an Information Message to remind the operator when service is required. Call Technical Support at 877-337-4118 for support or to schedule service.

9.3 Testing the GaussAlert™ Function

To use the GaussAlert™ test magnet tool to test alarm function, follow the steps listed below.

1.

Place the test magnet tool on the GaussAlert™ alarm bracket in the area identified in Figure 23.

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™.

9.4 Water Trap Maintenance

The following section will describe the emptying of the Water Trap. The Water Trap should be emptied when the liquid contents reach the horizontal black line marked on the Water Trap.

Prior to emptying the Water Trap, ensure the Gas Sample Line is removed and reattached after emptying the Water Trap.

9.4.1 Emptying the Water Trap

9.4.2 Water Trap Replacement

If the Water Trap / Sample Line Leak Test fails, and Sample Gas Line integrity is confirmed with blue stopcock in place, replace the Water Trap.

9.5 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 (see Section 11.1.5 for additional information).

9.6 Cleaning

9.6.1 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 as specified in Section 6.1 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 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%).

9.6.2 Display Screen

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

9.6.3 Cleaning the Gauss Alarms Mount

Use a soft cloth dampened with water to clean the enclosure. Use an aqueous solution of up to 75% isopropyl alcohol for more efficient cleaning. Disinfection may be accomplished with the use of denatured alcohol.

9.7 Storage

9.7.1 Cart / Console Storage

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

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 (see Section 11.1.5 for additional information).

9.7.2 Cassette / Accessory Storage

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).

GENOSYL® DS

SECTION 10
MECHANICAL VENTILATION

10. MECHANICAL VENTILATION

10.1 Mechanical Ventilation

There are two main effects of connecting the GENOSYL DS to a ventilator breathing circuit:

• The System injects up to 0.9 LPM of NO/air (21% Oxygen) into the inspiratory output of the ventilator.
• The System samples up to 0.3LPM from the ventilator circuit as a measurement to the built-in gas analyzers

The results of adding and subtracting gas into the ventilator circuit are described in sections 10.1.1 to 10.1.4:

10.1.1 Oxygen Dilution

The ventilator typically is flowing gas to the patient with enhanced oxygen content from room air at 21% to pure oxygen at 100%. The DS is injecting the NO in air with a concentration of oxygen at nominally 21%. Thus, except for the case where the ventilator is supplying gas to the patient at 21% oxygen, there is some dilution of the oxygen to the patient. This dilution is given by the following equation:

Percent O2 to Patient = [{%O2/100 + (Flowinj/Flowvent)×0.21}/{1 + (Flowinj/Flowvent)}]×100

Where:

 

Flowinj = Injection flow in same units as ventilator flow

 

Flowvent = Ventilator flow in same units as injection flow

 

%O2 = Percent oxygen out of ventilator

 

0.21 = Fraction of oxygen in injection flow (21%)

The table below shows the effect on the actual concentration of oxygen supplied to the patient for set ventilator flow settings with a nominal flow of 0.6 LPM of NO/air (21% Oxygen) into the inspiratory output of the ventilator.

10.1.2 Minute Volume

When using volume ventilation with the GENOSYL DS, the tidal volume delivered to the patient may show small changes due to the addition and subtraction of gases by the Delivery System. Some minor ventilator adjustments to the minute volume may be required. Maximum total flow added to the ventilator circuit is 0.9 LPM of concentrated NO gas and the maximum total flow removed from the ventilator circuit is 0.3 LPM of sampled gas.

10.1.3 Trigger Sensitivity

The addition and subtraction of gases by the GENOSYL DS may affect the trigger sensitivity of the ventilator when using synchronized modes of ventilation. This may cause the ventilator to auto-trigger in ventilators which have flow trigger modes, especially where the trigger flow is less than the total flow added to the System.

10.1.4 Maximum NO Delivery

The maximum combination of dose (ppm) and flow (LPM) is 800. ppm x 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 x LPM (e.g., 1 ppm at 1 LPM). See the graph below for the minimum and maximum dose ranges for the System, based on ventilator circuit total minute volume.

10.2 Ventilator Compatibility

The GENOSYL DS is compatible with the following equipment and accessories.

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 Breath 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 10.1.1, "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. The following ventilators and non-invasive gas delivery systems in Table 9 have been validated for use with the GENOSYL DS. See Section 3.2 for use configurations.

Use of a Mixer is recommended when delivering in specific tidal volume ranges on various ventilation devices. Refer to Table 10 for when a Mixer is and is not recommended.

See Section 3.4 for assembly instructions for Injection Assembly with Adaptive Sensor and Mixer Assembly with Adaptive Sensor.

GENOSYL® DS

SECTION 11
PRODUCT SPECIFICATIONS

11 PRODUCT SPECIFICATIONS

11.1 System Performance

11.1.1System Classification

• Class I equipment
• Ordinary Equipment IPX1
• Continuous Use
• Essential Performance: The System shall continue to deliver a controlled dose, as configured by the user (e.g., 20 ppm @ 6 LPM within +/- 20%) with NO2 < 3 ppm and O2 = 21 +/- 3% in room air for the specified range of use conditions.

11.1.2 Testing

• ANSI ES 60601-1
• IEC 60601-1-2
• IEC 60601-1-8

11.1.3 Electrical

11.1.4 Power Supply

• Medical Grade Class I
• Input: 100-240 V, 50-60 Hz, 2A
• Output: 18 V DC, 8.3 A
• 150 Watts Max

11.1.5 Battery

• Fully charged Back-up battery that provides at least 1 hour of uninterrupted Nitric Oxide delivery in the absence of an external power source.
• Typical battery life is 300 charge/discharge cycles.
• The battery will be serviced during scheduled maintenance performed by the manufacturer.
• If the need arises to replace or dispose of the battery sooner than scheduled contact Technical Support to schedule a maintenance appointment.

The battery has an embedded 5 segment LCD battery indicator viewable through side panel window. The segments will display the following information:

• 5 segments filled – 81%-100% charged
• 4 segments filled – 61%-80% charged
• 3 segments filled – 41%-60% charged
• 2 segments filled – 21%-50% charged
• 1 segment filled – 1% - 20% charged
• No battery indication – below 1%
• Most significant segment flashing – charging
• Most significant segment not flashing – not charging

11.1.6 Display

• Touch screen – Resistive
• Brightness – 400 cd/m2
• Resolution – 800 × 480 pixels, color

11.2 Mechanical

11.3 Environmental

11.4 GaussAlert™ Specifications

11.5 MR Signal-to-Noise Ratio and Artifact Dimension Analysis

MR image artifact was evaluated using 1.5 T and 3 T MRI Systems. Testing was conducted using standard American College of Radiology (ACR) sequences and a standard ACR large phantom placed inside a transmit-receive head coil. Duplicate sequences were performed to acquire the same images with and without the GENOSYL DS Nitric Oxide Delivery System operating on battery power inside the MRI suite.

The GENOSYL DS compatibility test results are as follows:

The GENOSYL DS does not distort the geometric accuracy and the image intensity uniformity is not adversely affected by the presence of the GENOSYL DS at the 100 Gauss line. The SNR and SFNR are both impacted by the presence of the GENOSYL DS, to a more pronounced degree when the equipment is powered via a wall outlet inside the MRI suite versus operating on the battery.

11.6 EMI/EMC

Frequencies of portable and mobile transmitters for which the recommended separation distance is 30 cm (12 in).

GENOSYL® DS

INDEX

VERO Biotech and GENOSYL are registered trademarks of Vero Biotech Inc.
© 2023 VERO Biotech. Printed in U.S.A. LBL-602502 Rev D January 2023
Please read full prescribing information enclosed.
877.337.4118 | VERO-biotech.com

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1

NIOSH Pocket Guide to Chemical Hazards, Dept of Health & Human Services, Centers for Disease Control and Prevention, National Inst for Occupational Safety & Health. Publication 2005-149, Sept 2007.

2

Hess et al, Use of Inhaled Nitric Oxide in patients with Acute Respiratory Distress Syndrome. Respiratory Care 1996; 41(5):424-446.

3

Phillips M, Hall TA, Sekar K, Tomey JL. Assessment of Medical Personnel Exposure to Nitrogen Oxides During Inhaled Nitric Oxide Treatment of neonatal and Pediatric Patients. Pediatrics. 1999;104(5):1095-1110.

4

Qureshi MA, Shah NJ, Hemmen CW, Thill MC, Kruse JA.Exposure of Intensive Care Nurses to Nitric Oxide and Nitrogen Dioxide during Therapeutic use of Inhaled Nitric Oxide in Adults with Acute Respiratory Distress Syndrome. Am. J. Crit Care, 2003;12(2):147-153.