Drugdu.com expert's response:

The registration of a Drug Master File (DMF) for pharmaceuticals in the United States is a complex process involving multiple steps and requirements. Below are the main procedures and key points for registration:

I. Determine the DMF Type

Select the appropriate DMF type based on the product characteristics. Common types include:

Type II: Manufacturing and control information for Active Pharmaceutical Ingredients (APIs) and intermediates, which is the most common type.

Type III: Packaging materials.

Type IV: Excipients.

Type V: Information specifically requested by the FDA.

II. Prepare Required Documents

Cover Letter: Introduce the content and purpose of the DMF, including the DMF type.

DMF Holder Information: Company name, address, contact person, etc.

Letter of Authorization (LOA): If another company will reference this DMF, provide an LOA.

Manufacturing Process Description: Detailed description of the production process and key process parameters.

Quality Standards: Include specifications, impurities, and physicochemical properties, etc.

Analytical Methods and Validation: Provide testing methods and validation data.

Stability Study Data: Include long-term and accelerated stability study results.

Facility Description: Provide detailed information about the production facilities and confirm compliance with Good Manufacturing Practices (GMP) requirements.

GMP Statement: Confirm that the production complies with FDA's GMP requirements.

Environmental Impact Statement or Exemption Statement: Assess in accordance with the National Environmental Policy Act (NEPA) of the United States.

III. Register for an ESG Account and Submit Documents

Register for an ESG Account: Visit the FDA's Electronic Submissions Gateway (ESG) website and register for an account.

System Testing: Conduct system testing to ensure the ability to submit documents normally.

Document Preparation: All documents must be prepared in the electronic Common Technical Document (eCTD) format, ensuring that the document structure and format comply with FDA requirements.

Submit Documents: Use the registered ESG account to submit the DMF documents.

IV. Receive FDA Confirmation and Follow-up Maintenance

Receive Confirmation: After submission, the FDA will confirm receipt and assign a DMF number, usually completed within a few days to a few weeks.

Annual Update: Submit an update once a year to confirm the validity of the information.

Change Report: If there are significant changes in the manufacturing process, facilities, or quality control, update the DMF in a timely manner.

Respond to FDA Inquiries: If the FDA has questions about the information in the DMF during the review process, they will contact the DMF holder to request supplementary information or modifications. Timely responses are necessary to avoid delays.

V. Payment of Fees

Initial Application Fee: According to FDA regulations, the fee for the initial application (new DMF registration) may be relatively high. The specific amount should be referred to the latest information on the FDA's official website.

Annual Update Fee: An annual fee may be required when updating the DMF each year.

Other Fees: If external consultants or consulting firms are hired to assist in preparing the DMF application, the fees may vary depending on the scope and complexity of the services provided.