FDA Issues Early Alert on NOxBOX Nitric Oxide Delivery System (August 19, 2026)

Key Takeaways

The U.S. FDA Center for Devices and Radiological Health (CDRH) has issued an Early Alert stating that the NOxBOXi Nitric Oxide Delivery System, including the NOxMixer module, presents a risk of oxygen leakage. An oxygen leak may result in an increased nitric oxide dose or in treatment interruption; in severe cases it may cause hypoxemia, increased pulmonary artery pressure and methemoglobinemia.

• The manufacturer has advised updating pre-use check instructions and implementing preventive maintenance part replacement.
• Affected product: NOxBOXi Nitric Oxide Delivery System (including NOxMixer module).
• UDI: 05060541640016. A complete list of affected serial numbers has been published by FDA.
• Companies concerned should verify UDI and serial numbers and assess the impact on registrations, labelling, technical documentation and post-market surveillance.

Source and Applicability

• Source organisation: FDA CDRH News & Updates
• Original publication date: August 21, 2026
• Original alert date referenced in the article: August 19, 2026
• Source link: https://www.fda.gov/medical-devices/medical-device-recalls-and-early-alerts/early-alert-nitric-oxide-delivery-system-issue-noxbox

This article has been compiled and translated from publicly available information published by FDA CDRH News & Updates. Specific requirements are subject to the latest official publications of the regulatory authority.

Full Translation of the Original Content

CDRH has issued this Early Alert to inform the public about a potentially high-risk device issue. FDA will keep the public informed and will update this page as significant new information becomes available.

Affected Product

FDA has learned that NOxBOX has sent a letter to affected customers recommending that the instructions for use of certain nitric oxide delivery systems be updated.

Affected device:

• Product name: NOxBOXi Nitric Oxide Delivery System (including NOxMixer module)
• Unique Device Identifier (UDI): 05060541640016
• Complete list of affected serial numbers: published by FDA on the alert page

Actions to Be Taken

These devices are used in critical and emergency situations. Users should review and follow the updated pre-use check instructions. Before continued use, users should confirm that the NOxBOXi device functions correctly during the pre-use system check.

On August 19, NOxBOX issued a letter to all affected customers recommending the following actions:

• NOxBOXi devices affected by this issue do not need to be removed from use unless the device fails the pre-use system checks and setup checks described below.
• To avoid leakage at the NOxMixer oxygen inlet, ensure that the connection between the oxygen supply line and the NOxMixer is firm and tight.
• Complete all NOxBOXi pre-use system checks. Ensure that the device functions correctly in emergency mode or manual bag ventilation mode, as described in Chapter 8 of the Technical Guide.
• Check the flow meter to ensure that the flow indicator ball rises appropriately as the oxygen flow setting on the NOxMixer control knob is increased.
• Ensure that at least one backup device is available so that a rapid device change can be made if an oxygen leak is detected within the NOxMixer module of the NOxBOXi device.
• Ensure that all personnel using the device receive a copy of these recommendations and that the manufacturer's notice is posted near the device.

Please check this page periodically for updates. FDA is reviewing information about this potentially high-risk device issue and will inform the public promptly as significant new information becomes available.

How to Identify the Affected Product

The images in the original FDA alert show the location of the serial number on the NOxBOXi delivery system (left) and the NOxMixer module (right).

Reason for the Alert

NOxBOX has reported complaints of oxygen leakage caused by a failure of the oxygen tubing or tubing connection within the NOxMixer module of the NOxBOXi device. The issue affects only the oxygen tubing or tubing connection at the elbow fitting upstream of the O2 flow meter. A different tubing is used downstream of the flow meter, and downstream tubing is not affected by this issue.

In some cases, an oxygen leak may lead to an increased nitric oxide dose or to treatment interruption. Potential health consequences of treatment interruption include decreased oxygen saturation and increased pulmonary artery pressure and related complications. An increased nitric oxide dose may cause methemoglobinemia and related complications. Neonates with congenital heart disease are at higher risk of health complications than other patients.

NOxBOX has stated that alternative tubing and tubing connections have been developed and that it will work with distributors to repair all affected devices. Further details will be provided to distributors to ensure that all upgrades are completed successfully.

NOxBOX has also stated that it is updating the NOxBOXi + NOxMixer service manual to incorporate inspection and replacement of the internal NOxMixer oxygen tubing and tubing connections into the preventive maintenance (PM) programme. Further details will be provided to distributors once these updates are available.

As of August 12, 2026, NOxBOX has not reported any serious injury or death related to this issue.

Device Intended Use

The NOxBOXi Nitric Oxide Delivery System is intended to continuously deliver and monitor a constant concentration of nitric oxide to the inspiratory breathing circuit of patients receiving inhaled nitric oxide therapy, while also monitoring nitrogen dioxide and oxygen. The NOxMixer module is intended for emergency applications and manual ventilation, where it continuously delivers nitric oxide blended inline with oxygen.

Contact Information

Customers in the United States who experience adverse reactions or quality problems, or who have questions about this issue, should contact NOXBOX at: NOxBOX_qatech@linde.com.

Unique Device Identification (UDI)

The Unique Device Identification (UDI) system helps identify individual medical devices sold in the United States from distribution through to use. UDI supports more accurate reporting, review and analysis of adverse event reports, enabling devices to be identified more quickly and problems to be resolved more rapidly.

• How to identify the UDI on a label
• AccessGUDID database – identify your medical device
• Benefits of the UDI system

How to Report a Problem

Healthcare professionals and consumers can report adverse reactions or quality problems experienced with the use of these devices through MedWatch, the FDA Safety Information and Adverse Event Reporting Program.

AIMEILI Regulatory Interpretation and Business Impact

Information of this kind published by FDA CDRH News & Updates should first be incorporated by companies into their regulatory intelligence and post-market surveillance activities, rather than being treated merely as general news. Companies need to determine whether the update relates to a guidance document, a recall or safety communication, a product approval, digital health, a quality system matter or post-market regulatory information, and to confirm whether it affects existing registration projects or products under development.

Where the content concerns a specific product, test performance, risk warning or regulatory measure, companies should further assess whether it affects product classification, the 510(k), De Novo or PMA pathway, technical documentation, labelling and instructions for use, quality system records or post-market reporting obligations. Companies pursuing U.S. market registration should record the original source link, publication date, scope of applicability and internal conclusions in their project register.

What This Means for Medical Device Companies

This Early Alert is a clear signal for manufacturers of respiratory therapy, gas mixing and gas delivery devices. Although it is not a formal recall, FDA has published it as a “potentially high-risk device issue” involving nitric oxide delivery systems and NOxMixer modules used in emergency settings. Chinese manufacturers exporting to the United States or holding U.S. clearances should pay close attention to safety communications of this type and should not treat them as isolated cases.

• Registration and market access: Nitric oxide delivery systems are medium- to high-risk devices subject to close FDA oversight. Companies should confirm whether their own products use a comparable oxygen tubing and upstream flow meter fitting design, and evaluate whether the scope of substantial equivalence of any existing 510(k) still covers the current design. If leakage issues of this kind are deemed to affect safety and effectiveness, FDA may subsequently issue more binding recall orders or require design changes; cleared device holders should proactively assess whether a supplement or a 30-day notice is required.
• Technical documentation and performance verification: Companies should review the design verification and risk management files covering oxygen tubing, elbow fittings and upstream flow meter connections, and should strengthen leakage-related failure mode analysis, misuse scenario testing, and reliability verification in emergency and manual ventilation modes. NOxBOX has incorporated inspection of internal oxygen tubing and connections into its preventive maintenance programme; Chinese manufacturers should also assess whether their own service manuals cover periodic replacement requirements for comparable critical components, in order to avoid similar problems arising from maintenance gaps.
• Labelling and instructions for use: FDA emphasises that users should review the updated pre-use check instructions and re-verify that the device passes its system self-check. Exporting manufacturers should correspondingly update the IFU, technical manuals, service guides and manufacturer notices posted near the device so that users receive complete, actionable safety information. The accuracy of UDI labelling and serial number lists is also particularly important: FDA expressly publishes the UDI number and requires verification of the serial number location, which shows that companies must maintain UDI data traceability well after market launch.
• Post-market surveillance and complaint handling: NOxBOX addressed the issue through customer letters, distributor-coordinated repairs and service manual updates, and Chinese manufacturers should establish comparable emergency response mechanisms for product quality problems. Where a high-risk malfunction has occurred or is suspected, companies must assess whether reporting is required under FDA Medical Device Reporting (MDR) requirements and should consider implementing a Field Safety Corrective Action (FSCA). Companies should also initiate Corrective and Preventive Action (CAPA) under an ISO 13485 quality management system, identifying root causes across the supply chain, raw materials, assembly processes and after-sales feedback, so that similar problems do not jeopardise U.S. market access or maintenance of CE marking.

Overall, when tracking FDA Early Alerts, Chinese medical device companies should not limit their attention to a single product model but should convert each official alert into an input for their own risk assessment, design improvement and registration maintenance work. Companies are advised to review whether they have already submitted, or intend to submit, comparable gas delivery devices for U.S. marketing authorisation, and to share information promptly with their U.S. agent, distributors and clinical or after-sales teams in order to prepare contingency plans.

Documentation to Review

It is recommended that companies check their basis for product classification, applicable regulatory provisions, predicate device or equivalence determination, performance testing, software and cybersecurity documentation, risk management, clinical evidence, labelling and instructions for use, and quality system readiness.

Common Risks

Common risks include misjudging the applicable FDA pathway, overlooking changes in guidance documents, insufficiently robust performance test design, over-broad labelling claims, unclear post-market reporting obligations, and applying documentation developed for other markets directly to a U.S. registration.

Frequently Asked Questions

Does an update to an FDA public page always represent a regulatory change?

No. An update to an FDA public page does not necessarily represent a change in regulation. It is necessary to distinguish between news items, guidance documents, database pages, recall information and formal regulatory documents; for matters of significance, companies should refer back to the original FDA source and the applicable regulations.

What should a company do after seeing an FDA update?

A company should first determine whether the update affects product classification, the registration pathway, technical documentation or post-market obligations, and then decide whether the project plan needs to be updated.

Content Review and Scope of Application

• Author: AIMEILI Regulatory Editorial Team
• Professional review: AIMEILI Medical Device International Registration Project Team
• Source principle: Priority is given to official regulatory authorities, international organisations, standards bodies and publicly available regulatory materials; industry media and project experience are used only as supporting references.
• Scope of application: This article is intended for preliminary understanding, documentation preparation and project planning. It does not replace the formal requirements of the target country's regulatory authority, test conclusions or legal advice.

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