USFDA Guidance: Certification Process for Designated Medical Gases

Medical gases such as oxygen, nitrous oxide, and medical air are essential components of modern healthcare. Although they are widely used and often considered routine clinical supplies, these gases are regulated as drugs under the Federal Food, Drug, and Cosmetic Act (FD&C Act). Recognising the unique nature of these products, Congress created a dedicated certification pathway for Designated Medical Gases (DMGs) under sections 575 and 576 of the FD&C Act.

On 11 February 2026, the Food and Drug Administration issued a revised draft guidance titled “Certification Process for Designated Medical Gases – Guidance for Industry (Revision 2)” to reflect the implementation of new regulatory requirements codified in 21 CFR Part 230 

What Are Designated Medical Gases?

Under section 575 of the FD&C Act, the following gases are defined as Designated Medical Gases (DMGs) if they meet official compendial standards:

• Oxygen

• Nitrogen

• Nitrous oxide

• Carbon dioxide

• Helium

• Medical air

• Carbon monoxide

To qualify as a DMG, the gas must conform to the standards set forth in an official compendium, specifically the United States Pharmacopeia–National Formulary (USP-NF).

The statute also specifies the approved indications for which certification may be sought. For example:

• Oxygen for treatment or prevention of hypoxemia or hypoxia

• Nitrous oxide for analgesia

• Carbon dioxide for respiratory stimulation or ECMO therapy

• Helium for upper airway obstruction

• Medical air to reduce the risk of hyperoxia

These indications are limited to those listed in section 576(a)(3)(A)(i) of the FD&C Act. Any use beyond those specified indications requires a different approval pathway, such as a traditional New Drug Application (NDA).

Carbon Monoxide – A Special Consideration

Although carbon monoxide is listed statutorily as a DMG, the USP-NF currently does not contain a monograph for carbon monoxide. Therefore, FDA does not presently plan to grant certification requests for carbon monoxide. However, FDA has stated it does not intend to object to the marketing of carbon monoxide for lung diffusion testing if it conforms to the European Pharmacopoeia monograph. Once a USP monograph is established, manufacturers will be required to submit certification requests consistent with the updated compendial standard.

Certification Equals Deemed Approval

A key feature of the DMG pathway is that once a certification request is granted, the DMG is deemed to have an approved application under section 505 (for human use) or section 512 (for animal use) of the FD&C Act, depending on the scope of the submission. Until certification is granted, marketing a DMG for medical use without approval may be considered distribution of an unapproved new drug and could result in enforcement action.

Who Must Submit a Certification Request?

Any person who initially introduces or delivers a DMG into interstate commerce must request certification. In most cases, this will be the original manufacturer of the gas. However, if a downstream entity reprocesses an industrial gas into a medical gas for human or animal use, that entity must seek certification.

Downstream distributors who are neither the original manufacturer nor the first marketer of the DMG should not submit certification requests. Instead, they must verify that their source holds an active certification and comply with registration, listing, labeling, and CGMP obligations.

What Must Be Submitted?

FDA has created Form FDA 3864 to standardise certification requests. The submission must include:

• Applicant name and contact information

• Type of submission (original, amendment, resubmission, supplement, etc.)

• Description of the medical gas and certification that it meets compendial standards

• Facility information, including FDA Establishment Identifier and Unique Facility Identifier (e.g., DUNS number)

• Affirmation that manufacturing methods, facilities, and controls are adequate to ensure identity, strength, quality, and purity

FDA encourages electronic submission through the CDER NextGen Portal.

FDA Review and the 60-Day Rule

Under section 576(a)(2) of the FD&C Act, a certification request is deemed granted within 60 calendar days unless FDA identifies grounds for denial.

FDA may deny certification if:

1. The gas does not qualify as a DMG,

2. Required information is missing,

3. Manufacturing methods and controls are inadequate, or

4. Denial is necessary to protect public health.

If additional information is requested during review, the 60-day clock restarts upon submission of amendments.

Post-Certification Requirements

Certification approval triggers ongoing responsibilities, including:

Annual Reporting

Each applicant must submit an annual report within 60 calendar days of the new calendar year using Form FDA 5025. The report must include:

• Summary of significant safety or effectiveness updates

• Distribution data (including NDC numbers and domestic/foreign quantities)

• Administrative changes

• List of current and former manufacturing facilities

Supplements

Changes to previously submitted information—such as adding a facility, updating contact details, or corporate restructuring—must be submitted as supplements within 30 days of the change.

Change in Ownership

In case of mergers or acquisitions, both former and new owners must submit documentation transferring certification rights.

Withdrawal or Revocation

FDA may withdraw approval under certain conditions, including failure to maintain compliance or public health concerns. Certification may also be revoked if FDA determines that the original submission contained material omissions or falsifications.

Applicants are afforded notice and opportunity for hearing before such actions, except in voluntary withdrawal cases.

By establishing a streamlined certification pathway under 21 CFR Part 230, FDA balances efficiency with oversight—ensuring that medical gases meet compendial standards, are manufactured under appropriate controls, and remain subject to ongoing monitoring.

For manufacturers, early understanding of eligibility criteria, submission requirements, and post-approval obligations is essential to ensure uninterrupted compliance and lawful market entry.