When Is FDA Form 3864 Required? (w/Examples) + FAQs

Yes, FDA Form 3864 is required whenever a person or company wants to legally market a designated medical gas in the United States for human or animal use. This form is the official certification request that triggers a 60-day FDA review period. If FDA does not deny the request within 60 days, the certification is automatically granted.

Section 576 of the Federal Food, Drug, and Cosmetic Act (FD&C Act) creates this requirement. Without certification, selling a medical gas for therapeutic purposes makes it an “unapproved new drug.” This can trigger FDA enforcement actions including warning letters, seizures, and injunctions. Between 1996 and 2011, the FDA received reports of at least 8 deaths and 18 serious injuries from medical gas mix-ups—incidents that proper certification and compliance help prevent.

Here is what you will learn in this article:

• 🏭 Who must file Form 3864 and who is exempt from filing (initial manufacturers vs. downstream distributors)
• 📋 Line-by-line walkthrough of every section on Form 3864 and what each field requires
• ⚠️ Common mistakes that cause FDA to deny certification requests and how to avoid them
• 📊 Real-world scenarios showing when certification is needed vs. when it is not
• 🕐 Processing timelines, annual reporting duties, and adverse event obligations after certification

What Is FDA Form 3864?

FDA Form 3864 is the official document used to request certification of a designated medical gas under 21 CFR Part 230. The Food and Drug Administration Safety and Innovation Act (FDASIA) created this streamlined certification process in 2012. Before FDASIA, medical gas manufacturers faced a regulatory paradox. They had to comply with drug regulations but could not submit traditional drug applications for gases that had been in medical use since before World War II.

The certification process solves this problem. When FDA grants a certification, the designated medical gas is deemed to have an approved New Drug Application (NDA) for human use, a New Animal Drug Application (NADA) for animal use, or both.

The Seven Designated Medical Gases

Only seven specific gases qualify as “designated medical gases” under Section 575 of the FD&C Act. Each must meet compendial standards set by the United States Pharmacopeia (USP) or National Formulary (NF).

Important distinction: “Oxygen 93 Percent” (90-96% O₂) is a different USP monograph from “Oxygen” (≥99.0% O₂). Only products meeting the “Oxygen” monograph qualify as designated medical gases. The same applies to “Nitrogen” versus “Nitrogen 97 Percent.”

Who Must File FDA Form 3864?

Initial Manufacturers and Original Marketers

The person or entity that first introduces a designated medical gas into interstate commerce must file Form 3864. In most cases, this is the original manufacturer—the company that produces the gas through chemical reaction, physical separation, compression of atmospheric air, or other methods.

Consider this scenario: A large industrial gas company produces oxygen solely for welding and manufacturing applications. That company does not need certification because its product is not intended for medical use. However, if a downstream company purchases that industrial gas, re-processes it to meet USP standards, and markets it as medical-grade oxygen—that downstream company becomes the “original marketer” and must obtain certification.

Downstream Distributors and Transfillers

Companies that receive already-certified designated medical gases and redistribute them do not need to file Form 3864. This includes wholesale distributors, transfillers, and home healthcare equipment providers.

These downstream entities have different obligations:

• Verify and document that incoming gases come from certified sources
• Maintain records including the original manufacturer’s name and NDA/NADA number
• Comply with current Good Manufacturing Practices (cGMP) under 21 CFR Part 213 for their operations
• Register with FDA as drug establishments and report distribution data

Transfillers—companies that transfer medical gases from large bulk containers to smaller cylinders—must register with FDA and comply with cGMP but do not need separate certification if the gas they receive is already certified.

Complete Walkthrough: Every Section of Form 3864

Form FDA 3864 contains seven main sections. Each section collects specific information that FDA uses to determine whether certification should be granted. Missing or incomplete information can cause FDA to deny the request or delay the review.

Section 1: Applicant Information

This section captures the legal identity of the person or company requesting certification.

Required fields include:

• Applicant Name (legal business name)
• Address 1 and Address 2 (if applicable)
• City, State/Province/Region, ZIP or Postal Code
• Country
• Contact Information (name, title, phone, email, fax)

For non-U.S. applicants: You must provide contact information for an authorized U.S. agent—a person who resides or maintains a place of business within the United States and is authorized to represent the applicant. The U.S. agent receives communications from FDA on your behalf and must be able to respond to questions.

Section 2: Type of Submission

You must check one box indicating what type of submission you are making.

For original certification requests, you also specify whether you want an NDA (for human drug use), NADA (for animal drug use), or both. Most medical gas companies request both because the same gas often serves both human patients and veterinary applications.

Section 3: Description of Medical Gas

This section is straightforward but critical. You select only one gas from the list of seven designated medical gases. By checking the box, you certify that your gas meets the applicable compendial standard.

The form provides checkboxes for:

• Oxygen, USP
• Medical Air, USP
• Nitrogen, NF
• Helium, USP
• Nitrous Oxide, USP
• Carbon Dioxide, USP
• Carbon Monoxide (no current monograph)

Important: If you manufacture multiple designated medical gases, you must submit separate Form 3864 requests for each gas. You cannot combine oxygen and nitrogen certification into a single form.

Section 4: Facility Information

FDA needs to know where the designated medical gas will be initially produced. This section requires:

• Facility Name
• Complete Address
• D-U-N-S Number (Data Universal Numbering System)
• FDA Establishment Identifier (FEI) number, if one exists
• Brief description of manufacturing activities (e.g., “production of oxygen by physical separation” or “production of nitrogen by purification”)

Getting Your Identifiers:

The D-U-N-S number is a unique nine-digit identifier assigned by Dun & Bradstreet. You can obtain one for free at their website. FDA requires this number because it helps track facilities across different regulatory programs.

The FEI number is assigned by FDA after you register your establishment. You cannot directly request an FEI number—it is generated automatically when FDA processes your facility registration. If your facility does not have an FEI number yet, do not delay your Form 3864 submission. Submit the form and obtain your FEI number as soon as possible.

Multiple Facilities: If the designated medical gas is produced at more than one facility, click the Add Continuation Page button to add fields for additional locations.

Section 5: Certification of Adequate Manufacturing

This section contains a single checkbox, but it carries significant legal weight. By checking this box, you affirm that your methods, facilities, and controls for manufacturing, processing, packaging, and holding the designated medical gas are adequate to preserve the safety, identity, strength, quality, and purity of the gas.

This certification means you are stating your compliance with current Good Manufacturing Practice requirements under 21 CFR Part 213. Making a false statement here is a federal crime under 18 U.S.C. § 1001.

Section 6: Additional Information

This is a free-text field where you can provide any other information you believe FDA needs. Common uses include:

• Explaining unusual manufacturing arrangements
• Describing medically appropriate combinations of designated medical gases
• Providing context about your quality systems
• Addressing questions from previous FDA communications

If FDA later determines it needs additional information to decide whether your gas qualifies as a designated medical gas, they may request it through this section.

Section 7: Signature(s)

The form must be signed and dated by the requestor or their authorized representative (attorney, agent, or other authorized official). Ordinarily, only one person should sign.

Exception for non-U.S. applicants: If the person signing does not reside or have a place of business in the United States, the form must be countersigned by an attorney, agent, or other authorized official who does reside or maintain a U.S. business presence.

How to Submit Form 3864

FDA strongly encourages electronic submission through the CDER NextGen Portal. The portal offers several advantages:

• Faster processing than paper submissions
• Ability to track submission status online
• Secure communication with FDA
• Automatic assignment of tracking numbers

To access the portal, you must create an account. The account creation process typically takes less than 30 minutes. Once enrolled, navigate to “FDA Alternate Submission” and select “Medical Gas” as the submission type.

Paper submissions are still accepted. If you prefer this method, send two copies of the completed, signed Form FDA 3864 to:

Central Document Room
5901B Ammendale Road
Beltsville, MD 20705

The 60-Day Review Period

Once FDA receives your Form 3864, a 60-calendar-day review period begins. This is not a typical approval process—it operates by default approval.

How Review Works

If FDA does not notify you of a denial within 60 days of filing, your certification is automatically granted. You will receive a letter from FDA confirming the grant and providing your NDA and/or NADA number.

Three Reasons FDA Can Deny Certification

FDA may deny your certification request only if it makes one of three specific findings under Section 576(a)(2):

1. The gas is not a designated medical gas. This happens if the gas does not meet the applicable USP or NF compendial standards, or if you are seeking certification for a gas not on the statutory list (e.g., argon, xenon).
2. The request lacks required information. Missing facility details, unsigned forms, or failure to affirm cGMP compliance can trigger this denial.
3. Denial is necessary to protect public health. FDA can deny certification based on inspection findings, reports from state officials, or other evidence of quality or safety concerns.

Three Real-World Scenarios

Scenario 1: Initial Manufacturer Seeking First Certification

Situation: AirMed Corp produces medical-grade oxygen at its facility in Houston, Texas, through cryogenic air separation. The company has never sold medical gases before and wants to enter the hospital supply market.

Result: AirMed can legally market its oxygen as a designated medical gas for treatment or prevention of hypoxemia or hypoxia.

Scenario 2: Downstream Transfiller

Situation: HomeCare Oxygen LLC purchases bulk medical oxygen from AirMed Corp (which has a granted certification). HomeCare transfills the oxygen into portable cylinders for home healthcare patients.

Result: HomeCare can legally distribute the certified oxygen without filing its own Form 3864.

Scenario 3: Industrial Gas Converter

Situation: Industrial Gases Inc. produces nitrogen for manufacturing applications. A hospital approaches them about purchasing nitrogen for hypoxic challenge testing. The company wants to convert its industrial nitrogen into medical-grade nitrogen.

Result: The company must complete the full certification process before selling to medical customers.

After Certification: Ongoing Obligations

A granted certification is not the end of your regulatory journey. 21 CFR Part 230 imposes ongoing requirements.

Annual Report (Form FDA 5025)

Every holder of a granted certification must submit an annual report within 60 calendar days of the new calendar year. This means reports for calendar year 2025 are due by March 1, 2026.

The annual report (Form FDA 5025) requires:

• Summary of significant new information that might affect safety, effectiveness, or labeling
• Distribution data including NDC numbers and quantities distributed domestically and internationally
• Administrative changes such as updates to applicant name or contact information
• Facility updates listing all facilities where the gas was initially produced, noting any additions or removals

Adverse Event Reporting

Holders of granted certifications must report serious adverse events to FDA. Individual Case Safety Reports (ICSRs) for serious adverse events must be submitted within 15 calendar days of receipt.

A “serious adverse event” includes any event that results in:

• Death
• Life-threatening condition
• Hospitalization or prolonged hospitalization
• Persistent or significant disability
• Congenital anomaly or birth defect

The final rule on medical gases exempted designated medical gases from periodic safety reporting requirements (quarterly and annual safety summaries) because new safety issues for these well-established gases are unlikely. However, serious events still require prompt individual reporting.

cGMP Compliance Under 21 CFR Part 213

As of December 18, 2025, all medical gas manufacturers must comply with the new cGMP requirements in 21 CFR Part 213. This regulation replaces the previous approach of applying general drug cGMP rules (21 CFR Parts 210-211) to medical gases.

Key requirements include:

• Quality unit review of batch production records
• Certificate of Analysis (COA) verification for incoming designated medical gases
• Complaint investigation for leaking containers and closures
• Container and closure controls specific to medical gas cylinders
• Labeling controls including new warning requirements

New Labeling Requirements (June 2024 Final Rule)

The June 2024 FDA Final Rule added important labeling requirements for medical gas containers.

Updated Oxygen Warning Language

Oxygen labels must include a hyperoxia warning—alerting users to dangers of uninterrupted high-concentration oxygen without medical oversight. The label must state that oxygen should only be administered by properly trained personnel in emergencies involving oxygen deficiency or resuscitation. For non-emergency uses, the label must indicate a prescription is required.

No Smoking, No Vaping Requirement

All medical gas labels must now include a “No Smoking, No Vaping” warning and a graphic symbol indicating No Smoking, No Vaping, and No Open Flames. This can be a single combined pictogram or three separate pictograms.

Rx Only for Non-Oxygen Gases

Medical air, nitrous oxide, carbon dioxide, and other non-oxygen gases must bear the “Rx Only” symbol to underscore their classification as prescription drugs.

Mistakes to Avoid

Filing Form 3864 incorrectly can result in certification denial or significant delays. Here are the most common errors and their consequences.

Do’s and Don’ts

Do’s

Don’ts

State-Level Requirements

While FDA Form 3864 is a federal requirement, many states impose additional licensing obligations for medical gas activities.

State Pharmacy Board Licenses

Most states require medical gas wholesalers, distributors, and sellers to obtain permits from the state Board of Pharmacy. For example, Mississippi requires a “medical gas wholesaler permit” for any business that maintains, buys, sells, or distributes medical gases. Permit holders must:

• Distribute only to persons authorized by state law to receive medical gases
• Not distribute directly to patients
• Maintain acquisition and sales records for two years
• Register with FDA if transfilling

New Mexico requires separate licensing for medical gas repackagers, distributors, and sellers. Pharmacies licensed by the Board may provide medical gas without a separate medical gas license, but standalone distributors need specific licensure.

Texas requires drug wholesale distributor licenses for most drug distribution activities but exempts compressed medical gas distribution from separate licensing in some circumstances.

Multi-State Operations

Companies operating in multiple states face compounded compliance obligations. Each state where you sell or distribute medical gases may require:

• Foreign qualification of your business entity with the Secretary of State
• Medical gas distributor or wholesaler license
• Controlled substance registration (for nitrous oxide in some states)
• Corporate income tax registration

The Safety Imperative: Why This Matters

Between 1996 and 2011, the FDA documented at least 8 deaths and 18 serious injuries from medical gas mix-ups. These incidents reveal disturbing patterns.

In one case, a delivery person connected a cryogenic vessel of industrial nitrogen to a hospital’s oxygen supply system. When the fitting did not match, the delivery person used a wrench to remove the nitrogen fitting and replace it with an oxygen fitting. Two patients died.

In another incident, a hospital discovered that argon—an industrial gas—had been connected to the oxygen system. Again, the delivery person had bypassed the built-in safety incompatibility by swapping fittings. A patient undergoing minor surgery died.

These tragedies occurred because:

• Personnel did not understand that connection incompatibility is a built-in safeguard
• Personnel did not examine drug labels before connecting vessels
• Large cryogenic vessels often lack permanently brazed connections that cannot be removed
• Medical gas vessels sometimes lacked adequate 360-degree wraparound labels

The Form 3864 certification process and the associated cGMP requirements exist to prevent these outcomes. Certification ensures that manufacturers have adequate quality controls. Labeling requirements ensure that containers are clearly identified. And the documentation requirements ensure traceability throughout the supply chain.

FAQs

Does a transfiller need to file Form 3864?
No. Transfillers transfer gas from certified sources into smaller containers. They must register with FDA and follow cGMP but do not need their own certification because the upstream source is already certified.

Can I certify oxygen and nitrogen on the same Form 3864?
No. You must submit separate Form 3864 requests for each designated medical gas. One form covers one gas, but can include multiple manufacturing facilities for that single gas.

Is there a fee for Form 3864 certification?
No. FDA does not charge a user fee for designated medical gas certification requests. However, export certificates have separate fees ranging from $40 to $175 depending on the FDA center.

What happens if FDA doesn’t respond within 60 days?
Certification is granted automatically. Under Section 576(a)(2), the certification is deemed granted if FDA does not deny it within 60 calendar days of filing.

Does “Oxygen 93 Percent” qualify as a designated medical gas?
No. Only products meeting the USP monograph titled “Oxygen” (≥99.0% O₂) qualify. The “Oxygen 93 Percent” monograph covers a different product (90-96% O₂) that is not a designated medical gas.

Can FDA revoke a granted certification?
Yes. FDA may revoke a certification if the request contained any material omission or falsification. FDA may also withdraw approval based on safety or effectiveness concerns.

Do I need state licenses in addition to FDA certification?
Yes, usually. Most states require medical gas wholesalers and distributors to obtain permits from the state Board of Pharmacy. Requirements vary by state.

How do I update FDA about facility changes?
File a supplement. Submit a “Supplement to Granted Certification” through Form 3864. For new manufacturing facilities specifically, file a “changes being effected” supplement under 21 CFR 314.70(c).

What is the deadline for annual reports?
March 1 (60 days after New Year). Annual reports for the prior calendar year must be submitted within 60 calendar days of the new calendar year using Form FDA 5025.

Can carbon monoxide be certified right now?
No. There is no USP or NF monograph for carbon monoxide. FDA does not plan to grant certifications until a monograph is added, but does not object to marketing for lung diffusion testing if the product meets an acceptable alternative compendial standard.