NOxBOXi Nitric Oxide Delivery System

K171696 · Praxair Distribution, Inc. · MRN · Oct 2, 2018 · Anesthesiology

Device Facts

• Record ID: K171696
• Device Name: NOxBOXi Nitric Oxide Delivery System
• Applicant: Praxair Distribution, Inc.
• Product Code: MRN · Anesthesiology
• Decision Date: Oct 2, 2018
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 868.5165
• Device Class: Class 2
• Attributes: Therapeutic, Pediatric

Intended Use

The NOxBOXi Nitric Oxide Delivery System is intended for use by healthcare professionals for the delivery and monitoring of a constant (user set) concentration of nitric oxide (NO) and the monitoring of NO2 and O2 in the inspiratory ventilator lines of a patient undergoing nitric oxide therapy (iNO). The NOxBOXi Nitric Oxide Delivery System Includes: - The NOxBOXi head unit, which delivers NO gas while in the intelligent delivery mode. - Continuous monitoring and alarms for NO, O2, and NO2. - The integrated NOxMixer, which provides a backup NO delivery capability that is intended to deliver a continuous flow of NO, mixed with O2, for iNO therapy and provides a continuous treatment option during transit and transfer conditions within hospitals. The NOxBOXi Nitric Oxide Delivery System must only be used in accordance with the indications, warnings and precautions described in the nitric oxide drug packaging (currently neonates). Refer to this material prior to use.

Device Story

NOxBOXi delivers nitric oxide (NO) gas to patients undergoing iNO therapy; inputs include NO gas source and ventilator waveform data. Device uses intelligent delivery mode for synchronous NO administration; integrated NOxMixer provides backup continuous flow NO/O2 delivery for manual bagging or transit. Used in hospital settings (NICU, transport) by healthcare professionals. System monitors NO, O2, and NO2 levels in inspiratory limb; provides alarms for safety. Output allows clinicians to maintain precise NO concentrations; helps manage respiratory status in neonates. Device includes head unit, sample lines, regulators, and power supply.

Clinical Evidence

No clinical data. Substantial equivalence supported by non-clinical bench testing, including biocompatibility (ISO 10993), electrical safety/EMC (ISO 60601), gas monitoring accuracy (ISO 80601-2-55), software verification/validation (ISO 62304), and usability testing (ISO 62366).

Technological Characteristics

Class II device. Components: head unit, NOxMixer, NOxFLOW sample line, regulators. Sensing: NO, O2, NO2 electrochemical/gas sensors. Connectivity: standalone. Sterilization: not specified. Software: Major level of concern. Complies with ISO 10993-1, ISO 60601-1, ISO 60601-1-2, ISO 80601-2-55.

Indications for Use

Indicated for neonates undergoing inhaled nitric oxide (iNO) therapy. Used by healthcare professionals for delivery and monitoring of constant NO concentrations and monitoring of NO2 and O2 in inspiratory ventilator lines.

Regulatory Classification

Identification

The nitric oxide administration apparatus is a device used to add nitric oxide to gases that are to be breathed by a patient. The nitric oxide administration apparatus is to be used in conjunction with a ventilator or other breathing gas administration system.

Special Controls

The special control for this device is FDA's “Guidance Document for Premarket Notification Submissions for Nitric Oxide Administration Apparatus, Nitric Oxide Analyzer, and Nitrogen Dioxide Analyzer.”

Predicate Devices

• INO Therapeutics' INOmax DS Delivery System (K092545)
• INO Therapeutics' INOblender Nitric Oxide Administration Back-up system (K122689)

Submission Summary (Full Text)

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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

Praxair Distribution, Inc Michael Skrjanc Executive Director, Quality, Regulatory Compliance and Product Safety 10 Riverview Drive Danbury, Connecticut 06810

Re: K171696

Trade/Device Name: NOxBOXi Nitric Oxide Delivery System Regulation Number: 21 CFR 868.5165 Regulation Name: Nitric Oxide Administration Apparatus Regulatory Class: Class II Product Code: MRN, MRP, MRQ, CCL, MRO Dated: October 1, 2018 Received: October 1, 2018

# Dear Michael Skrjanc:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part

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801); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.htm); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice

(https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email ([e-mail]) or phone [phone] or 301-796-7100).

Sincerely,

Todd D. Courtney -

Tina Kiang, Ph.D. for Acting Director Division of Anesthesiology, General Hospital, Respiratory, Infection Control, and Dental Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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# Indications for Use

510(k) Number (if known) K171696

Device Name NOxBOXi Nitric Oxide Delivery System

#### Indications for Use (Describe)

The NOxBOXi Nitric Oxide Delivery System is intended for use by healthcare professionals for the delivery and monitoring of a constant (user set) concentration of nitric oxide (NO) and the monitoring of NO2 and O2 in the inspiratory ventilator lines of a patient undergoing nitric oxide therapy (iNO).

The NOxBOXi Nitric Oxide Delivery System Includes:

- · The NOxBOXi head unit, which delivers NO gas while in the intelligent delivery mode.
- · Continuous monitoring and alarms for NO, O2, and NO2.
- The integrated NOxMixer, which provides a backup NO delivery capability that is intended to deliver a continuous flow of NO, mixed with O2, for iNO therapy and provides a continuous treatment option during transit and transfer conditions within hospitals.

The NOxBOXi Nitric Oxide Delivery System must only be used in accordance with the indications, warnings and precautions described in the nitric oxide drug packaging (currently neonates). Refer to this material prior to use.

| Type of Use (Select one or both, as applicable) | |
|-------------------------------------------------|---------------------------------------------|
| > Prescription Use (Part 21 CFR 801 Subpart D) | Over-The-Counter Use (21 CFR 801 Subpart C) |

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# 510(k) Summary NOxBOXi Nitric Oxide Delivery System K171696

#### 1. Submission Sponsor

Praxair Distribution, Inc. (PDI) 10 Riverview Dr. Danbury, CT 06810 Phone: [phone] Contact: Mike Skrjanc, Executive Director, Quality, Regulatory Compliance and Product Safety

### 2. Submission Correspondent

Michael E. Skrjanc Executive Director, Quality, Regulatory Compliance and Product Safety Praxair Distribution, Inc. 10 Riverview Drive Danbury, CT 06810

### 3. Date Revised

September 23, 2018

### 4. Device Identification

| Trade/Proprietary Name: | NOxBOXi Nitric Oxide Delivery System | |
|------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------|
| Classification Names: | Nitric Oxide administration apparatus, back-up and gas<br>analyzers | |
| Common/Usual Name: | Nitric Oxide administration apparatus – primary<br>Nitric Oxide administration apparatus – backup<br>Nitric Oxide Analyzer<br>Nitrogen Dioxide Analyzer<br>Oxygen Gas Analyzer | |
| Classification Regulation<br>and Product Code: | 21 CFR 868.5165 - primary | MRN |
| Additional Product Codes: | 21 CFR 868.5165 – backup<br>21 CFR 868.2380 – Nitric Oxide Analyzer<br>21 CFR 868.2385 - Nitrogen Dioxide Analyzer<br>21 CFR 868.1720 – Oxygen Gas Analyzer | MRC<br>MRP<br>MRC<br>CCL |
| Device Class:<br>Classification Panel: | Class II<br>Anesthesiology | |

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# 5. Legally Marketed Predicate Device(s)

There are two predicate devices chosen for this submission.

- 1. K092545 INO Therapeutics' INOmax DS Delivery System
- 2. K122689 INO Therapeutics' INOblender Nitric Oxide Administration Back-up system.

Note that both the functionality of the INOmax DS Delivery System and INOblender NO administration backup unit are integrated into the NOxBOXi Nitric Oxide Delivery System.

# 6. Device Description

The NOxBOXi Nitric Oxide Delivery System (NOxBOXi) simultaneously delivers Nitric Oxide (NO) medical gas, while monitoring Nitric Oxide, Nitrogen Dioxide and Oxygen levels in the inspiratory limb of a ventilator for patients undergoing inhaled Nitric Oxide Therapy.

The system is designed for use by healthcare professionals to administer treatment to patients undergoing inhaled Nitric Oxide (iNO) therapy. The NOxBOXi will deliver nitric oxide in a synchronous manner to a single patient.

An integrated component to the NOxBOXi, the NOxMixer is intended to deliver a continuous flow of Nitric Oxide from the NOxBOXi, mixed in line with Oxygen (O₂) for use in iNO therapy. The NOxMixer will be used in conjunction with manually bagging a patient.

The NOxBOXi includes the NOxBOXi Head Unit, a NOxFLOW sample line, two NO feed hoses, two regulators (connector type dependent on the gas supplier), a test circuit, NO, O₂ & NO2 monitors, power supply, drainage syringe, Operating Manual & Technical Guide.

Optional accessories include 4 separate NOxKITs (22mm, 12 mm, & 10mm), one way valve for HFOV (High Frequency Oscillatory Ventilation), bagging kits (hyperinflation & selfinflating) and circuit reducers (22f – 15m).

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# 7. Indication for Use Statement

NOxBOXi Nitric Oxide Delivery System is intended for use by healthcare professionals for the delivery and monitoring of a constant (user set) concentration of nitric oxide (NO) and the monitoring of NO2 and O2 in the inspiratory ventilator lines of a patient undergoing nitric oxide therapy (iNO).

# The NOxBOXi Nitric Oxide Delivery System includes:

- The NOxBOXi head unit, which delivers NO gas while in the intelligent delivery mode. ●
- Continuous monitoring and alarms for NO, O2 and NO2.
- . The integrated NOxMixer which provides a backup NO delivery capability that is intended to deliver a continuous flow of NO, mixed with O2, for iNO therapy and provides a continuous treatment option during transit and transfer conditions within hospitals.

The NOxBOXi Nitric Oxide Delivery System must only be used in accordance with the indications, contraindications, warnings and precautions described in the nitric oxide drug packaging inserts and labeling (currently neonates). Refer to this material prior to use.

# 8. Substantial Equivalence Discussion

The following table compares the NOxBOXi to the predicate device with respect to intended use, technological characteristics and principles of operation.

| Comparison of Characteristics | | | |
|----------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Manufacturer | Praxair Distribution, Inc. | INO Therapeutics | Comparison |
| Trade Name | <i>NOxBOXi</i> Nitric Oxide Delivery<br>System | INOmax DS | |
| 510(k) Number | K171696 | K092545<br>K122689 | N/A |
| Product Code | MRN, MRO, MRP, MRQ | MRN, MRO, MRP, MRQ | Identical |
| Regulation<br>Number | 21CFR 868.5165, .2380, .2385 | 21 CFR 868.5165, .2380, .2385 | Identical |
| Regulation Name | Nitric Oxide administration<br>apparatus, back-up and gas<br>analyzers | Nitric Oxide administration<br>apparatus, back-up and gas<br>analyzers | Identical |
| Indications for<br>Use | <i>NOxBOXi</i> Nitric Oxide<br>Delivery System is intended<br>for use by healthcare<br>professionals for the<br>delivery and monitoring of<br>a constant (user set)<br>concentration of nitric<br>oxide (NO) and the<br>monitoring of NO2 and O2<br>in the inspiratory ventilator | The INO Therapeutics INOmax<br>DS delivers INOmax (nitric<br>oxide of inhalation) therapy<br>gas into the inspiratory limb<br>of the patient breathing<br>circuit in a way that provides a<br>constant concentration of<br>nitric oxide (NO), as set by the<br>user, to the patient<br>throughout the inspired<br>breath. It uses a specially | Similar, both devices<br>provide controlled<br>concentrations of NO<br>into the inspiratory<br>ventilation circuit,<br>contain monitors and<br>alarms for NO, O2 and<br>NO2.<br><br>The <i>NOxBOXi</i> battery<br>functionality is |
| Manufacturer | Praxair Distribution, Inc. | INO Therapeutics | Comparison |
| Trade Name | <i>NOxBOXi</i> Nitric Oxide Delivery System | INOmax DS | |
| | lines of a patient undergoing nitric oxide therapy (iNO).<br><br><b>The <i>NOxBOXi</i> Nitric Oxide Delivery System includes:</b><br>The <i>NOxBOXi</i> head unit, which delivers NO gas while in the intelligent delivery mode. Continuous monitoring and alarms for NO, O₂ and NO₂. The integrated <i>NOxMixer</i> which provides a backup NO delivery capability that is intended to deliver a continuous flow of NO, mixed with O₂, for iNO therapy and provides a continuous treatment option during transit and transfer conditions within hospitals. The <i>NOxBOXi</i> Nitric Oxide Delivery System must only be used in accordance with the indications, contraindications, warnings and precautions described in the nitric oxide drug packaging inserts and labeling (currently neonates). Refer to this material prior to use. | designed injector module, which enables tracking of the ventilator waveforms and the delivery of a synchronized and proportional dose of NO. It may be used with most ventilators.<br><br>The INOmax DS provides continuous integrated monitoring of inspired O₂, NO₂ and NO, and a comprehensive alarm system.<br><br>The INOmax DS incorporates a battery that provides up to 6 hours of uninterrupted NO delivery in the absence of an external power source.<br><br>The INOmax DS includes a backup NO delivery capability that provides a fixed flow of 250ml/min of NO, which along with user supplied 10L/min of oxygen, provides 20ppm in the gas flow to a patient's breathing circuit. It may also use the INOblender for backup.<br><br>The target population is controlled by the drug labeling for INOmax and is currently neonates. The primary targeted clinical setting is the Neonatal Intensive Care Unit (NICU) and the secondary targeted clinical setting is the transport of neonates. | explained elsewhere in the labeling.<br><br>The <i>NOxBOXi</i> system allows adjustable NO gas flow rates for the backup delivery mode.<br><br>Indications for both devices follow the respective drug labeling for nitric oxide (currently indicated for use with neonates). |
| NO administration | NO blended with O₂ in the patient's inhalation circuit | NO blended with O₂ in the patient's inhalation circuit | Identical |
| NO flow rate<br>(sample flow rate) | 225 ml/min | 250 ml/min | Minor difference, The <i>NOxBOXi</i> system meets its measuring accuracy requirements with a lower sample flow rate from the |
| Manufacturer<br>Trade Name | Praxair Distribution, Inc.<br><i>NOxBOXi</i> Nitric Oxide Delivery<br>System | INO Therapeutics<br>INOmax DS | Comparison |
| | | | circuit. |
| NO concentration<br>provided | 0.0 TO 80ppm | 0-80ppm (800ppm cylinder) | Identical |
| NO monitor | Yes | Yes | Identical |
| O₂ monitor | Yes | Yes | Identical |
| Monitoring<br>accuracy | NO & NO₂ - +/- 2% or 0.2ppm | +/-20% or 2ppm (whichever is<br>greater) | Different, however,<br>substantially<br>equivalent. The<br>difference is that the<br>NOxBOXi system<br>measures with more<br>accurate specifications.<br><br>The NOxBOXi uses a<br>closed loop system<br>automatically adjusting<br>the dose to achieve a<br>set point within +/-2%<br>or 0.2 ppm (whichever<br>is greater). |
| NO₂ monitor &<br>alarm | Yes | Yes | Identical |
| Battery Backup<br>capability | 4 hours without AC power | 6 hours without AC power | Different, however,<br>acceptable for<br>emergency use<br>situations. The battery<br>is only to be used as a<br>backup in event of<br>facility power loss.<br>Most hospitals have<br>generators to provide<br>backup power. In a<br>worst case scenario,<br>the unit can be<br>switched to manual<br>override for gas<br>delivery without<br>monitoring (purely<br>mechanical). |
| Complies with ISO<br>10993-1 | Yes | Yes | Identical |
| Electrical Safety<br>Testing (ISO<br>60601-1 3rd ed)<br>Passed | Yes | Yes | Earlier versions of the<br>predicate device were<br>compliant with this<br>standard. |
| EMC Testing (ISO<br>60601-1-2) | Yes | Yes | Earlier versions of the<br>predicate device were<br>compliant with this<br>standard. |
| Manufacturer | Praxair Distribution, Inc. | INO Therapeutics | Comparison |
| Trade Name | NOX <i>BOXi</i> Nitric Oxide Delivery<br>System | INOmax DS | |
| Manual bagging &<br>back up system | NOxMIXER® | INOblender® | |
| NO dosing range in<br>manual mode | 0 - 185ppm on 800ppm cylinders | 5-80ppm on 800ppm NO; 2.5-<br>40ppm on 400ppm NO | Different, however,<br>substantially<br>equivalent. The<br>NOXBOXi has an<br>expanded user<br>selectable dose range. |
| NO dosing<br>Accuracy in<br>manual mode | ± 20% or 2 ppm, whichever is the<br>greater for NO doses from 5 - 80<br>ppm (800 ppm drug cylinder) and<br>O2 flow rates of 5 - 14 L/min<br>* +/-40% or 4 ppm, whichever is<br>the greater; for NO doses from 0<br>to < 5 ppm or > 80 to 185 ppm<br>(800 ppm drug cylinder) and O2<br>flow rates of 2 to < 5 L/min or > 14<br>to 25 L/min | +/- 20% indicated or 2 ppm,<br>whichever is greater | Different, however,<br>substantially<br>equivalent. The<br>NOxBOXi has an<br>expanded user<br>selectable dose range.<br>Similar accuracy for the<br>limited INOBlender<br>range. |
| NO flow in manual<br>mode | Adjustable 50 – 600 mL/min of<br>NO/N2…