FDA Form 3938 is required for all Drug Master File (DMF) submissions to the FDA. This form must accompany every new DMF, amendment, annual report, and Letter of Authorization submitted in the electronic Common Technical Document (eCTD) format. According to 21 CFR 314.420, a Drug Master File allows a company to share confidential manufacturing and quality information with the FDA without disclosing it directly to other pharmaceutical applicants.
In Q1 2025, Drug Master File submissions surged by 44% compared to the previous year, with 339 Type II DMFs submitted — a record high for any first quarter. Failure to properly complete Form 3938 can result in your submission being rejected, delaying drug approvals by months or even years.
In this article, you will learn:
📋 Exactly when Form 3938 is required and who must submit it
🔍 How to complete each field of the form step-by-step with real examples
⚠️ Common mistakes that cause FDA rejection and how to avoid them
💰 Fee requirements and timelines for DMF processing
✅ Do’s and don’ts that experienced regulatory professionals follow
What Is FDA Form 3938?
FDA Form 3938 is a standardized, fillable electronic form designed for Drug Master File submissions. The FDA created this form to replace the older, inconsistent methods of providing administrative information. Before Form 3938, companies submitted administrative details in various formats, which made it difficult for the FDA to process submissions efficiently.
The form serves three primary purposes. First, it provides a standardized way to capture all relevant DMF submission information. Second, it allows for automated data extraction into FDA databases. Third, it ensures that submissions comply with the eCTD format requirements that became mandatory in May 2018.
Form 3938 is used for both CDER (Center for Drug Evaluation and Research) DMF submissions and CBER (Center for Biologics Evaluation and Research) Master File submissions. The form supports application types including Investigational New Drug applications (INDs), New Drug Applications (NDAs), Biologics License Applications (BLAs), and Abbreviated New Drug Applications (ANDAs).
Who Must Use FDA Form 3938?
Three types of parties may complete and submit Form 3938. Understanding which category you fall into determines how you fill out certain fields on the form.
DMF Holders are the companies or individuals who own the Drug Master File. The holder is typically the manufacturer of the drug substance, packaging material, or excipient. Only one entity can be the DMF holder for any given file. If the holder is not the actual manufacturer, they must include a signed statement assuming responsibility for the manufacturing of the material covered by the DMF.
DMF Agents are persons or companies appointed by foreign DMF holders to serve as their representative in the United States. While not legally required, the FDA strongly recommends that DMF holders located outside the U.S. appoint an agent. Agents can sign Form 3938 on behalf of the holder, but the agent appointment must be documented with a separate letter.
Third-Party Contractors may prepare and submit DMF documents on behalf of the holder, but they cannot sign Form 3938. The signature must come from either the DMF holder’s Responsible Official or an appointed agent.
When Is Form 3938 Required?
Form 3938 must accompany all DMF submissions submitted in eCTD format. The table below shows exactly when the form is needed:
| Submission Type | Form 3938 Required? | Notes |
|---|---|---|
| Original (New) DMF | Yes | For establishing a new Drug Master File |
| Administrative Amendment | Yes | Changes to holder name, address, agent, or subject |
| Quality Amendment | Yes | Changes to manufacturing, controls, or technical information |
| Annual Report | Yes | Required annually to maintain “Active” status |
| Letter of Authorization | Yes | Grants another party permission to reference the DMF |
| Withdrawal of Letter of Authorization | Yes | Removes a party’s permission to reference the DMF |
| Response to Deficiency Letter | Yes | Answers FDA questions or concerns about the DMF |
| Meeting Request | Yes | Formal request for a meeting with FDA reviewers |
| DMF Closure | Yes | Request to close or inactivate the DMF |
Important Exception: Type III DMFs (Packaging Materials) are exempt from mandatory eCTD requirements. They can be submitted in eCTD format through the Electronic Submissions Gateway (ESG) or in non-eCTD format through the CDER NextGen Portal. However, if you choose to submit a Type III DMF in eCTD format, Form 3938 is still required.
Types of Drug Master Files
Before completing Form 3938, you must understand which DMF type applies to your submission. The FDA recognizes four active types of DMFs (Type I was discontinued).
| DMF Type | Description | eCTD Required? | User Fee? |
|---|---|---|---|
| Type I | Manufacturing Site, Facilities (No longer accepted) | N/A | N/A |
| Type II | Drug Substance, Intermediate, or Drug Product | Yes | Yes ($95,084 in FY 2025) |
| Type III | Packaging Material | Optional | No |
| Type IV | Excipient, Colorant, Flavor, Essence | Yes | No |
| Type V | FDA Accepted Reference Information, REMS | Yes | No |
Type II DMFs
Type II DMFs are the most common and contain information about Active Pharmaceutical Ingredients (APIs), drug substance intermediates, or finished drug products. Since May 2018, all Type II DMF submissions must use eCTD format. This type is the only one subject to the GDUFA (Generic Drug User Fee Amendments) fee.
The user fee for FY 2025 is $95,084 and increases to $102,584 in FY 2026. This fee is a one-time charge, triggered when an ANDA first references your DMF or when you request an initial completeness assessment.
Type III DMFs
Type III DMFs contain information about packaging materials such as bottles, vials, caps, closures, and blister packs. These materials come into direct contact with drug products. Information typically included covers composition, manufacturing processes, specifications, and compatibility data.
Type III DMFs do not require eCTD format and do not incur user fees. However, the FDA encourages electronic submission to improve processing efficiency.
Type IV DMFs
Type IV DMFs cover excipients, colorants, flavors, essences, and related materials. These are inactive ingredients used in drug formulation. Since May 2018, Type IV DMFs must be submitted in eCTD format.
While no user fee applies to Type IV DMFs, they still require Form 3938 and must meet all technical standards for electronic submission.
Type V DMFs
Type V DMFs are reserved for FDA-accepted reference information that does not fit into other categories. The most common use is for shared system Risk Evaluation and Mitigation Strategies (REMS). Before submitting a Type V DMF, you must obtain FDA approval through a letter of intent.
How to Complete FDA Form 3938: Line-by-Line Instructions
The following section explains every field on Form 3938. Completing each field correctly the first time prevents delays and rejections.
Field 1: Date
Enter the date you are submitting the form using the format mm/dd/yyyy. For example, if you are submitting on February 1, 2026, enter “02/01/2026.” Do not use any other date format, as this can cause processing errors.
Field 2: DMF Number
Provide your six-digit DMF number. If your DMF number has fewer than six digits, add leading zeros to make it six digits. For example, DMF 12345 should be entered as “012345.”
If you are submitting a new (original) DMF, you must first request a pre-assigned DMF number through the CDER NextGen Portal or by email to [email protected]. The FDA typically issues pre-assigned numbers within three business days.
Field 3: DMF Subject
Enter the subject (title) of your DMF. This information is publicly available on the FDA’s DMF list. Choose your title carefully — it should accurately describe the material covered without revealing proprietary information.
For an API, a typical subject might be: “Metformin Hydrochloride USP.” For packaging, it might be: “High Density Polyethylene (HDPE) Bottles for Pharmaceutical Use.”
Field 4: DMF Type
Select one applicable DMF type from the options:
- Type II: Drug Substance, Drug Substance Intermediate, Material Used in Their Preparation, or Drug Product
- Type III: Packaging Material
- Type IV: Excipient, Colorant, Flavor, Essence, or Material Used in Their Preparation
- Type V: FDA Accepted Reference Information, REMS
You cannot select multiple types. Each DMF should cover only one type of material or information.
Field 5: DMF Holder Information
This field requires several pieces of information about the DMF holder:
Company Name: The legal name of the entity that owns the DMF.
DUNS Number: The nine-digit Data Universal Numbering System identifier. If you do not have a DUNS number, enter nine nines: “999999999”.
Address: Complete mailing address including street, city, state/province, country, and postal code.
Contact Person: Name, telephone number, email address, and fax number of the person who handles DMF correspondence. The fax field should not be left blank — if you do not have a fax number, enter “not available.”
Field 6: DMF Agent or Holder Representative
Complete this field if the DMF holder has appointed an agent or has a representative at a different address. Include the company name, address, and full contact information.
If the Responsible Official (the person signing in Field 17) is employed by the agent company, this must be specified in the Agent Appointment Letter. Remember: “appoint” is the correct term for agent appointments. Do not use “authorize,” as this term is reserved for Letters of Authorization.
Field 7: Submission Type
Select all applicable submission types. A single submission can contain more than one type. The options include:
| Submission Type | When to Use |
|---|---|
| Original (new) | Establishing a brand new DMF |
| Administrative Amendment | Changing holder name, address, agent, or subject |
| Annual Report | Yearly submission to keep DMF active |
| Letter of Authorization | Granting reference permission to another party |
| Withdrawal of Letter of Authorization | Removing reference permission |
| Meeting | Requesting or supporting a meeting with FDA |
| Quality Amendment | Changing manufacturing or technical information |
| Response to Administrative Filing Issue | Responding to administrative concerns |
| Response to Deficiency Letter | Answering technical deficiencies |
| REMS | Shared system REMS submissions |
| Other | Anything not covered above (e.g., closure) |
Scenario Example: A pharmaceutical company submits an amendment that changes their agent’s contact information (administrative) and also updates their manufacturing process (technical). On Form 3938, they would select both “Administrative Amendment” and “Quality Amendment.”
Field 8: Amendment Type
When submitting an amendment, select all applicable categories. Common options include:
- Change of agent/address/contact person
- Change of holder/address/contact person
- Change of DMF Subject (title)
- Controls Information
- Facility Information
- Manufacture Information
- Stability Information
- New Item (primarily for Type III and IV DMFs)
- Agent Appointment
Field 9: Establishment Information
This field is critical for Type II DMFs and certain Type III and V DMFs. You must provide information about every facility involved in manufacturing, testing, and packaging.
For each establishment, include:
- Establishment name and complete address (P.O. Box is NOT acceptable)
- DUNS number (enter “999999999” if unknown)
- FEI number — the FDA Establishment Identifier (enter “9999999999” — ten digits — if unknown)
- Whether the establishment is new to this DMF
- Establishment role (e.g., “drug substance manufacturing,” “release testing,” “packaging”)
- Whether the establishment is ready for FDA inspection
- Contact person information
Important: Do not enter establishment information for Type IV excipient manufacturers or Type III packaging material manufacturers in this field. Leave it blank for those DMF types.
Field 10: Referenced DMFs
If your DMF references another DMF (for example, an API DMF that references a starting material DMF), list all referenced DMFs here. Include the DMF number, subject (title), and holder name.
If your DMF does not reference any other DMFs, skip this field entirely. Do not enter “none” or “not applicable.”
Fields 11-17: Certification
Field 11: Enter the name and title of the Responsible Official — the person with authority to sign on behalf of the DMF holder or appointed agent.
Field 12: Enter the date of signature in mm/dd/yyyy format.
Fields 13-15: Enter the Responsible Official’s telephone number, fax number, and email address.
Field 16: Enter the Responsible Official’s business address.
Field 17: The Responsible Official must sign the form. The FDA accepts scanned signatures, digital signatures, or flattened digital signatures. Use the Adobe Acrobat Self-Sign plug-in for electronic signatures on fillable PDF forms.
Three Real-World Scenarios
Understanding when and how Form 3938 is used becomes clearer with practical examples.
Scenario 1: New API Drug Master File Submission
Situation: A pharmaceutical manufacturer in India develops a generic version of a diabetes medication API. They want to allow U.S. generic drug companies to reference their manufacturing information without disclosing trade secrets.
| Step | Action |
|---|---|
| 1 | Request pre-assigned DMF number via CDER NextGen Portal |
| 2 | Appoint U.S.-based DMF agent and submit Agent Appointment Letter |
| 3 | Prepare complete technical dossier in eCTD format |
| 4 | Complete Form 3938 selecting “Original (new)” and “Type II” |
| 5 | Submit via FDA Electronic Submissions Gateway (ESG) |
| 6 | Await acknowledgment letter with DMF number confirmation |
Consequence of Error: If the manufacturer submits without a pre-assigned number, the entire submission will be rejected. If the Agent Appointment Letter is missing, the agent cannot sign Form 3938 on behalf of the holder.
Scenario 2: Annual Report Submission
Situation: A DMF holder in Germany has an active Type II DMF that was established three years ago. They must submit an annual report to maintain active status.
| Step | Action |
|---|---|
| 1 | Prepare list of all amendments submitted in past 12 months |
| 2 | Compile list of all parties with active Letters of Authorization |
| 3 | Include signed Statement of Commitment from DMF holder |
| 4 | Complete Form 3938 selecting “Annual Report” |
| 5 | Submit on or before the anniversary date of original DMF submission |
Consequence of Error: Failure to submit annual reports for three consecutive years results in the FDA issuing an Overdue Notice Letter. If no response is received within 90 days, the DMF status changes to “Closed” and becomes unavailable for reference.
Scenario 3: Letter of Authorization for ANDA Application
Situation: A generic drug company in the United States wants to file an ANDA that references an API DMF held by a Chinese manufacturer. The Chinese company must grant authorization.
| Step | Action |
|---|---|
| 1 | Generic company contacts DMF holder to request authorization |
| 2 | DMF holder prepares Letter of Authorization naming specific authorized party |
| 3 | DMF holder includes Statement of Commitment in LOA or eCTD section 1.2 |
| 4 | DMF holder completes Form 3938 selecting “Letter of Authorization” |
| 5 | DMF holder submits LOA to FDA; copies authorized party |
| 6 | Generic company includes copy of LOA in their ANDA submission |
Consequence of Error: If the LOA is not submitted to the DMF before the ANDA references it, the ANDA may receive a filing deficiency. The generic company’s application timeline could be delayed significantly.
Common Mistakes to Avoid
Approximately 98% of Type II DMFs are found inadequate after first-cycle review. Many issues stem from Form 3938 errors or related administrative problems.
Mistake 1: Missing or Incorrect DMF Number Format
DMF numbers must be exactly six digits. Entering “DMF 12345” or “12345” instead of “012345” triggers validation errors. The FDA’s automated systems cannot process improperly formatted numbers.
Mistake 2: Leaving Required Fields Blank
The form requires entries in specific fields. If you do not have a DUNS number, you must enter “999999999” — not leave the field blank. If you do not have a fax number, enter “not available.” Blank required fields cause the form to generate errors.
Mistake 3: Agent Signing Without Proper Appointment Letter
A DMF agent cannot sign Form 3938 unless a valid Agent Appointment Letter has been submitted to the FDA. The letter must be on the DMF holder’s letterhead and signed by the holder. If the agent signs without this documentation, the submission may be rejected.
Mistake 4: Confusing “Appoint” and “Authorize”
The term “appoint” is used for agents. The term “authorize” is used for Letters of Authorization granting reference permission. Using “authorize” in an Agent Appointment Letter causes confusion and may be rejected.
Mistake 5: Not Submitting Form 3938 with Every Submission
Each submission to a DMF requires a new Form 3938. Some holders mistakenly believe the original form covers subsequent amendments. This is incorrect. Even annual reports require a fresh Form 3938.
Mistake 6: Missing Statement of Commitment
Every DMF submission should include a signed Statement of Commitment from the DMF holder. This statement certifies that the DMF is current and that the holder will notify FDA and authorized parties of any changes. Missing this statement delays processing.
Mistake 7: Incorrect Establishment Information
For Type II DMFs, all manufacturing, testing, and packaging facilities must be listed with accurate FEI and DUNS numbers. Providing a P.O. Box instead of a physical address, or omitting facilities entirely, results in deficiency letters.
Mistake 8: Submitting Quality Information in Annual Reports
Annual reports should only contain administrative information: lists of amendments, authorized parties, and the statement of commitment. If you include quality or technical changes in an annual report, FDA will recategorize the submission, potentially affecting review timelines for applications referencing your DMF.
Do’s and Don’ts for Form 3938
Do’s
| Do | Why |
|---|---|
| Request a pre-assigned DMF number before submission | The FDA will not accept submissions without a valid number |
| Submit Form 3938 with every DMF submission | Each submission requires its own form |
| Use Adobe Acrobat Self-Sign for electronic signatures | FDA accepts this format without issues |
| Include leading zeros in DMF numbers | The system requires exactly six digits |
| Verify all establishment FEI numbers before submission | Incorrect numbers delay processing |
| Submit annual reports on the anniversary date | Late reports risk DMF closure |
| Keep copies of all submissions | You may need to reference them for deficiency responses |
| Notify authorized parties of any DMF changes | Required by 21 CFR 314.420(c) |
Don’ts
| Don’t | Why |
|---|---|
| Leave required fields blank | Use placeholder values like “999999999” if data is unavailable |
| Use “authorize” when appointing an agent | This term is reserved for Letters of Authorization |
| Allow third-party contractors to sign Form 3938 | Only the DMF holder or appointed agent can sign |
| Submit non-eCTD format for Type II or IV DMFs | Electronic format is mandatory since May 2018 |
| Include quality amendments in annual reports | This causes recategorization and delays |
| Wait until the last minute to respond to deficiency letters | Late responses delay applications referencing your DMF |
| Assume one Form 3938 covers all future submissions | A new form is required for every submission |
Pros and Cons of Drug Master Files
Pros
| Advantage | Explanation |
|---|---|
| Protects proprietary information | Manufacturers share data with FDA without disclosing it to customers |
| Simplifies regulatory submissions | ANDA applicants reference DMFs instead of duplicating information |
| Supports multiple applications | One DMF can be referenced by unlimited authorized parties |
| Streamlines FDA review | FDA reviews technical information once, not repeatedly for each application |
| Enables global market access | U.S. DMFs can support applications for multiple generic products |
Cons
| Disadvantage | Explanation |
|---|---|
| User fees for Type II DMFs | The $95,084 fee (FY 2025) can be prohibitive for smaller companies |
| Annual maintenance required | Failure to submit annual reports results in closure |
| Complex formatting requirements | eCTD compliance requires specialized software and expertise |
| Long review timelines | 98% of first-time DMFs require multiple review cycles |
| Dependent relationships | Application approvals depend on timely DMF updates and responses |
FDA DMF Review Process and Timelines
Understanding the FDA’s review timeline helps you plan your submissions effectively.
Initial Administrative Review
When the FDA receives a DMF submission, the Office of Business Informatics (OBI) conducts an administrative review. They check for completeness: Is Form 3938 included? Is the fee paid (for Type II)? Is the eCTD format correct?
If administratively complete, the FDA sends an acknowledgment letter and assigns the DMF an “Active” status. This process typically takes two to three weeks.
Completeness Assessment (Type II API DMFs)
For Type II API DMFs referenced in ANDAs, the FDA performs a completeness assessment. This assessment determines whether the DMF contains sufficient information to support review. If the DMF passes, it appears on FDA’s public list of DMFs available for reference.
The FDA aims to complete initial completeness assessments within 60 days of fee payment or DMF submission, whichever is later.
Scientific Review
Scientific review occurs when an application (such as an ANDA) references the DMF. FDA reviewers examine the technical content to determine if it supports approval. If deficiencies are found, the FDA issues a deficiency letter.
Deficiency Response Timelines
When you receive a deficiency letter, respond within 30 days to keep your DMF on track. The FDA can complete a second review within 60 days of receiving a timely response. However, data shows that less than 10% of DMF holders respond within 30 days, and 91% take two and a half years to provide complete responses.
Late or incomplete responses trigger deferrals. If your response arrives in the last third of an ANDA review cycle, the FDA may defer your DMF review to the next cycle.
Electronic Submission Requirements
All DMF submissions (except Type III) must be submitted through the FDA Electronic Submissions Gateway (ESG). The modernized ESG NextGen platform provides three submission methods:
- Unified Submission Portal (USP): A web-based interface for uploading submissions
- API Integration: Programmatic submissions integrated with sponsor systems
- AS2 Connections: System-to-system automated data exchange
Before your first submission, you must register for an ESG account and configure your connection method. Allow two to four weeks for account setup.
Common eCTD Rejection Reasons
The FDA identifies several common reasons for eCTD submission rejection:
- Duplicate sequence number submitted
- Mismatch between application number in us-regional.xml and the FDA form
- Submission sent to wrong Center (CDER vs. CBER)
- Corrupted or broken media
- Non-standard eCTD format
Validation errors 1306 (“No leaf element for file”) and 1323 (“No file for leaf element”) are elevated to high severity and will result in rejection. Always run validation checks before submission.
Key Contact Information
For DMF-related questions, use these FDA resources:
| Purpose | Contact |
|---|---|
| General DMF questions | [email protected] |
| Pre-assigned number requests | [email protected] or CDER NextGen Portal |
| FEI number requests | [email protected] |
| CBER Master Files | [email protected] |
| ESG technical support | [email protected] |
| User fee questions | [email protected] |
FAQs
Is Form 3938 required for all DMF submissions?
Yes. Form 3938 must accompany all DMF submissions in eCTD format, including original submissions, amendments, annual reports, and Letters of Authorization.
Can a third-party contractor sign FDA Form 3938?
No. Only the DMF holder’s Responsible Official or an officially appointed DMF agent may sign Form 3938. Third parties can prepare submissions but cannot sign.
What happens if I don’t submit an annual report?
Yes, consequences follow. If you miss three consecutive annual reports, the FDA issues an Overdue Notice Letter. Failure to respond within 90 days results in DMF closure.
Is the GDUFA user fee required for all DMF types?
No. Only Type II API DMFs that support generic drug applications incur the user fee. Types III, IV, and V DMFs have no user fee requirement.
Can I submit a Type III DMF on paper?
Yes. Type III DMFs are exempt from mandatory eCTD requirements. They can be submitted electronically or in non-eCTD format through the CDER NextGen Portal.
How long does it take to get a pre-assigned DMF number?
Yes, you will receive it promptly. The FDA typically issues pre-assigned numbers within three business days of request submission through the portal or email.
What if I don’t have an FEI number for my facility?
Yes, you can still submit. Enter “9999999999” (ten digits) in the FEI field. Request your FEI number by emailing [email protected].
Can one DMF be referenced by multiple ANDA applicants?
Yes. A single DMF can support unlimited authorized parties. Each authorization requires a separate Letter of Authorization submission.
Is a DMF agent legally required for foreign DMF holders?
No. While not legally required, the FDA strongly recommends that foreign holders appoint a U.S.-based agent to facilitate communication and submission processing.
What is the difference between “appoint” and “authorize” in DMF context?
Yes, there is an important distinction. “Appoint” is used for designating a DMF agent. “Authorize” is used for granting permission to reference DMF information via a Letter of Authorization.
How often is the FDA DMF list updated?
Yes, regularly. The FDA updates the public DMF list quarterly. The most recent update includes DMFs received by December 31, 2025.
Can I close my DMF voluntarily?
Yes. Submit a closure request with Form 3938, selecting “Other” as the submission type. Include a letter stating your intent to close the DMF.
What triggers the GDUFA user fee for Type II DMFs?
Yes, specific events trigger it. The fee is due when an ANDA first references your DMF via Letter of Authorization or when you request an initial completeness assessment — whichever occurs first.
Can FDA reject my submission for signature issues?
No, not immediately. The FDA does not validate signatures during routine processing. However, signatures may be checked during directed inspections, so maintain proper documentation.
Do I need to resubmit the entire DMF for amendments?
No. Amendments should contain only information pertaining to changes and updates. Only reactivation of a closed DMF requires submitting a complete copy.