NOxBOXi Nitric Oxide Delivery System
Device Facts
| Record ID | K220898 |
|---|---|
| Device Name | NOxBOXi Nitric Oxide Delivery System |
| Applicant | Linde Gas & Equipment, Inc. |
| Product Code | MRN · Anesthesiology |
| Decision Date | Apr 27, 2022 |
| Decision | SESE |
| Submission Type | Special |
| Regulation | 21 CFR 868.5165 |
| Device Class | Class 2 |
| Attributes | Therapeutic, Pediatric |
Indications for Use
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 inspirator 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
The NOxBOXi is a nitric oxide (NO) delivery and monitoring system for patients undergoing iNO therapy. It takes NO gas from cylinders and O2 from a hospital supply as inputs. The head unit delivers NO in an intelligent, synchronous manner to the patient's inspiratory ventilator line. It features an integrated NOxMixer for backup continuous flow delivery of NO mixed with O2, useful during manual bagging or patient transit. The device continuously monitors NO, NO2, and O2 levels, providing alarms to ensure patient safety. Used in hospital settings by healthcare professionals, the system provides real-time gas concentration data to clinicians, allowing for precise titration of therapy. The device benefits patients by maintaining constant, controlled NO concentrations, reducing the risk of hypoxia or toxic NO2 exposure. This submission adds compatibility with additional ventilators and introduces a modified sample line accessory.
Clinical Evidence
No clinical data was required to support substantial equivalence. Evidence is based on bench testing, including verification of functional performance, gas delivery accuracy, and compatibility testing with additional ventilators.
Technological Characteristics
System includes head unit, NOxMixer, NOxFLOW sample line, feed hoses, regulators, and monitors. Delivers NO (0-80 ppm) and monitors NO, NO2, O2. Battery backup provides 4 hours of operation. Connectivity includes integration with various ventilators. Complies with IEC 60601-1, IEC 60601-1-2, ISO 80601-2-55, and ISO 14971. Software lifecycle follows IEC 62304.
Indications for Use
Indicated for healthcare professional use for delivery and monitoring of nitric oxide (NO) therapy in patients (currently neonates) undergoing inhaled nitric oxide therapy (iNO).
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.”
The special control developed by the agency is a guidance document, entitled Guidance Document for Premarket Notification Submissions for Nitric Oxide Delivery Apparatus, Nitric Oxide Analyzer and Nitrogen Dioxide Analyzer. This guidance document identifies the risks associated with these types of devices and contains information that will help manufacturers address those risks. This document is available on FDA's website at http://www.fda.gov/cdrh/ode/1157.pdf.
Predicate Devices
Submission Summary (Full Text)
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April 27, 2022
Linde Gas & Equipment Inc. % Olga Lewis Consultant, Quality and Regulatory Affairs Emergo Global Consulting, LLC 2500 Bee Cave Road, Building 1, Suite 300 Austin, Texas 78746
Re: K220898
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, MRO, MRP, MRQ, CCL Dated: March 28, 2022 Received: March 28, 2022
Dear Olga Lewis:
We have reviewed vour 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
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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 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/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) 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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). 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 (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Todd Courtney Assistant Director DHT1C: Division of Sleep Disordered Breathing, Respiratory and Anesthesia Devices OHT1: Office of Ophthalmic, Anesthesia, Respiratory, ENT and Dental Devices Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
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# Indications for Use
510(k) Number (if known) K220898
Device Name NOxBOXi Nitric Oxide Delivery System
### Indications for Use (Describe)
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 inspirator 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) | |
|----------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------|
| <span style="font-family: DejaVu Sans, sans-serif">❌</span> Prescription Use (Part 21 CFR 801 Subpart D) | <span style="font-family: DejaVu Sans, sans-serif">□</span> Over-The-Counter Use (21 CFR 801 Subpart C) |
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## Special 510(k) Summary
## NOxBOXi Nitric Oxide Delivery System
### 1. Submission Sponsor
Linde Gas & Equipment Inc. (LG&E) 175 E Park Drive Tonawanda, NY 14150 USA Phone: (412) 874.3315 Dave Loflin Director of Quality and FDA Regulations
### 2. Submission Correspondent
Emergo Global Consulting, LLC 2500 Bee Cave Road Building 1, Suite 300 Austin, TX 78746 Office Phone: (512) 327.9997 Olga Lewis; Consultant, Quality and Regulatory Affairs
## 3. Date
March 25, 2022
#### Device Identification 4.
| Trade/Proprietary Name: | NOxBOXi Nitric Oxide Delivery System |
|---------------------------------------------|------------------------------------------------------------------|
| Classification Names: | Nitric Oxide administration apparatus, back-up and gas analyzers |
| Common/Usual Name: | Nitric Oxide administration apparatus - primary |
| | Nitric Oxide administration apparatus - backup |
| | Nitric Oxide Analyzer |
| | Nitrogen Dioxide Analyzer |
| | Oxygen Gas Analyzer |
| Classification Regulation and Product Code: | 21 CFR 868.5165 - primary delivery system MRN |
| Additional Regulations and Product Codes: | 21 CFR 868.5165 - backup delivery system MRO |
| | 21 CFR 868.2380 – Nitric Oxide Analyzer MRP |
| | 21 CFR 868.2385 - Nitrogen Dioxide Analyzer MRQ |
| | 21 CFR 868.1720 - Oxygen Gas Analyzer CCL |
| Device Class: | Class II |
| Classification Panel: | Anesthesiology |
### 5. Legally Marketed Predicate Device
Primary Predicate Device: NOxBOXi Nitric Oxide Delivery System K201339 Additional Predicate Device: NOxBOXi Nitric Oxide Delivery System K171696
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#### 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 inspiratorylimb 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 NOxBOXiwill 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, O3 & 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).
This submission is for the addition of compatibility claims for specific ventilators and is not related to product changes. It also introduces a new accessory, a modified sample line. There are no changes to the indications for use of the product and there are no significant design changes.
#### 7. Indication for Use Statement
NOxBOXi Nitric Oxide DeliverySystem 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.
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| | Subject: NOxBOXi Nitric Oxide<br>Delivery System | Predicate: NOxBOXi Nitric Oxide<br>Delivery System | Comparison | |
|-----------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------|--|
| 510(k) Number | K220898 | K201339 | N/A<br>No Change | |
| Manufacturer | NOxBOX Ltd. | | No Change | |
| | Regulatory & Indications for Use | | | |
| Product Code | MRN, MRO, MRP, MRQ, CCL | | No Change | |
| Regulation Numbers | 21 CFR 868.5165, .2380, .2385, .1720 | | No Change | |
| Regulation Name | Nitric Oxide administration apparatus, back-up and gas analyzers | | No Change | |
| Indications for Use | NOxBOXi Nitric Oxide Delivery System is intended for use by healthcare<br>professionals for the delivery and monitoring of a constant (user set)<br>concentration of nitric oxide (NO) and the monitoring of NO2 and O2 in the<br>inspiratory ventilator lines of a patient undergoing nitric oxide therapy (iNO).<br><br>The NOxBOXi Nitric Oxide Delivery System includes:<br>The NOxBOXi head unit, which delivers NO gas while in the intelligent<br>delivery mode.Continuous monitoring and alarms for NO, O2 and NO2.The integrated NOxMixer which provides a backup NO delivery<br>capability that is intended to deliver a continuous flow of NO, mixed<br>with O2, for iNO therapy and provides a continuous treatment option<br>during transit and transfer conditions within hospitals.<br>The NOxBOXi Nitric Oxide Delivery System must only be used in accordance<br>with the indications, contraindications, warnings and precautions described<br>in the nitric oxide drug packaging inserts and labeling (currently neonates).<br>Refer to this material prior to use. | | No Change | |
| | Technical | | | |
| NO administration | NO blended with O₂ in the patient's inhalation circuit | | No Change | |
| NO flow rate (sample flow<br>rate) | 225 ml/min | | No Change | |
| NO concentration<br>provided | 0.0 TO 80ppm | | No Change | |
| NO monitor | Yes | | No Change | |
| O2 monitor | Yes | | No Change | |
| Monitoring accuracy | NO & NO2-+/-2% or 0.2ppm | | No Change | |
| NO2 monitor & alarm | Yes | | No Change | |
| Battery Backup capability | 4 hours without AC power | | No Change | |
| Manual bagging & back<br>up system | NOxMIXER® | | No Change | |
| NO dosing range in<br>manual mode | 0 - 185ppm on 800ppm cylinders | | No Change | |
| NO dosing Accuracy in<br>manual mode | ± 20% or 2 ppm, whichever is the greater for NO doses from 5 - 80 ppm (800 ppm drug cylinder) and O2 flow rates of 5 - 14 L/min | | No Change | |
| | Subject: NOxBOXi Nitric Oxide<br>Delivery System | Predicate: NOxBOXi Nitric Oxide<br>Delivery System | Comparison | |
| | * +/-40% or 4 ppm, whichever is the greater; for NO doses from 0 to < 5 ppm<br>or > 80 to 185 ppm (800 ppm drug cylinder) and O2 flow rates of 2 to < 5<br>L/min or > 14 to 25 L/min | | | |
| NO flow in manual mode | Adjustable 50 – 600 mL/min of NO/N2 | | No Change | |
| O2 flow range in manual<br>bagging mode | 2 to 25 L/min of O2 | | No Change | |
| Oxygen inlet pressure | 3.5 – 4.5 bar | | No Change | |
| NO delivery pressure | 1.65bar from manual control valve | | No Change | |
| Manual bagging & back<br>up system | NOxMIXER® | | No Change | |
| Dimensions | 65 mm (W) X 185 mm (H) x 60.8 mm (D) | | No Change | |
| Pre-use set up time | Instant set-up | | No Change | |
| Monitoring during manual<br>bagging | Yes | | No Change | |
| Alarms active during<br>bagging | Yes | | No Change | |
| Stand alone vs Built-in | Built-in | | No Change | |
| Can be used as a back-up<br>function | Yes | | No Change | |
| Back-up accuracy | ± 20% or 2 ppm, whichever is the greater for NO doses from 5 - 80 ppm (800 ppm drug cylinder), * +/-40% or 4 ppm, whichever is the greater; for NO<br>doses from 0 to < 5 ppm or > 80 to 185 ppm (800 ppm drug cylinder) | | No Change | |
| | Ventilator Compatibility | | | |
| Compatible Ventilators | Various models from the following<br>manufacturers:<br>● Bio-Med Devices<br>● Bunnel<br>● Carefusion<br>● Carefusion / SensorMedics<br>● Drägerwerk<br>● Fisher & Paykel Healthcare<br>● Hamilton Medical<br>● IMT Medical (Vyaire)<br>● Maquet (Getinge)<br>● Newport (Covidien)<br>● Percussionaire<br>● Philips Respironics<br>● Puritan Bennett (Covidien)<br>● Smiths Medical | Various models from the following<br>manufacturers:<br>● (N/A)<br>● Bunnel<br>● Carefusion<br>● Carefusion / SensorMedics<br>● Drägerwerk<br>● Fisher & Paykel Healthcare<br>● Hamilton Medical<br>● (N/A)<br>● Maquet<br>● Newport (Covidien)<br>● (N/A)<br>● Philips Respironics<br>● Puritan Bennett (Covidien)<br>● Smiths Medical | Equivalent;<br>testing<br>shows no<br>new<br>questions<br>raised<br>regarding<br>safety and<br>effectiveness | |
## Comparison of Characteristics With Changes From Device Cleared in K201339
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### Non-Clinical and Usability Performance Data 9.
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NOxBOXi has been verified and validated to ensure that it meets its functional, performance, and usability specifications and requirements. The device has been tested in compliance to international standards and US FDA guidance documents including the following:
- FDA guidance "Use of International Standard ISO 10993-1, "Biological evaluation of . medical devices – Part 1: Evaluation and testing within a risk management process" (K171696)
- . FDA guidance "Premarket Notification Submissions for Nitric Oxide Delivery Apparatus, Nitric Oxide Analyzer and Nitrogen Dioxide Analyzer" including accuracy of NO delivery, response of NO delivery to external perturbations and user changes, purity of NO drug delivery, acceptable / minimal production of NO2, NO analyzer accuracy, NO2 analyzer accuracy, and compatibility testing of ventilators listed in the product labeling (K171696, K201339 and subject submission)
- . FDA guidance "Content of Premarket Submissions for Software Contained in Medical Devices" (K171696)
- FDA guidance "Applying Human Factors and Usability Engineering to Medical Devices." (K171696)
- ISO 14971: Medical Devices – Application of Risk Management to Medical Devices (K171696, K201339 and subject submission)
- ISO 10993-1: Biological Evaluation of Medical Devices Part 1: Evaluation and Testing Within a Risk Management Process (K171696)
- ISO 10993-5: Biological Evaluation of Medical Devices Part 5: Tests for In Vitro Cytotoxicity (K171696)
- . ISO 10993-10: Biological Evaluation of Medical Devices Part 10: Tests for Irritation and Skin Sensitization (K171696)
- IEC 60601-1: Medical Electrical Equipment – Part 1: General Requirements for Basic Safety and Essential Performance (K171696)
- IEC 60601-1-2: Medical Electrical Equipment – Part 1-2: General Requirements for Basic Safety and Essential Performance - Collateral Standard: Electromagnetic Disturbances -Requirements and Tests (K171696)
- IEC 62366: Medical Devices - Application of Usability Engineering to Medical Devices (K171696)
- ISO 80601-2-55: Medical Electrical Equipment – Part 2-55: Particular Requirements for the Basic Safety and Essential Performance of Respiratory Gas Monitors (K171696)
- IEC 62304: Medical Device Software – Software Life Cycle Processes (K171696)
- ISO 15223-1: Medical Devices - Symbols to be Used With Medical Device Labels, Labelling, and Information to be Supplied – Part 1: General Requirements (K171696, K201339 and subject submission)
Additionally, gases delivered through the NOxBOXi system were analyzed for the presence of volatile organic compounds (VOC) and particulate matter. Measurement of the resulting VOC concentrations resulted in levels that were three orders of magnitude below OSHA permissible exposure levels. Particulate testing determined that the gas delivered by the NOxBOXi system contained particulate levels well below the EPA's maximum limits for total suspended particulates.
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Testing for this submission was limited to the aspects that could be affected by including compatibility with additional ventilators and introduction of a new accessory. No additional usability testing was conducted for this submission. No clinical testing was required to support substantial equivalency of this medical device.
### 10. Conclusions/Statement of Substantial Equivalence
This submission is for the addition of compatibility claims for specific ventilators and introduction of a new accessory. This submission is not related to product changes. There are no changes to the indications for use of the product. The above-described non-clinical data support the substantial equivalence of the device and the compatibility with additional ventilators. The NOxBOXi passed all testing and no different questions of safety or effectiveness were raised. The information provided within this premarket notification supports substantial equivalence to the predicate device.
