During document submission to regulatory agencies, the Drug Master File (DMF) plays an important role in pharmaceuticals in protecting confidential information. If your company is a manufacturer of active pharmaceutical ingredients (APIs), intermediate products, excipients, or packaging material then it is required to know that how to properly prepare and submit a drug master file to regulatory authorities.
In this post, we'll understand the process to submit a DMF to the FDA, including its types, components, regulatory requirements and best practices to ensure a drug master file is submitted successfully.
1. Type I – The information about manufacturing site, facilities, operating procedures, and personnel are included.
2. Type II – Information about drug substances, drug substance intermediates, and materials used in preparation of drugs, or drug products are included in this DMF.
3. Type III – It includes packaging materials used for drug products
4. Type IV – Excipient, Colorant, Flavor, Essence, or Material Used in their Preparation and included in Type IV DMF.
5. Type V – FDA Accepted Reference Information
Module 1: Regional administrative information (specific to the country)
Module 2: Quality overall summary (a summary of Module 3)
Module 3: Detailed information about the drug substance or product (this is the core of DMF)
Module 4: Nonclinical study reports (not always applicable)
Module 5: Clinical study reports (not always applicable)
A drug master file should contain:
You will be required to submit:
Ensure that the XML backbone in the eCTD file is correct and contains no broken hyperlinks. All required files should be in the correct folders. Any technical issues can lead to rejection before the FDA begins reviewing the DMF.
This letter of authorization must be included by referencing the applicant in their application.
2. Use Clear and Concise Language: Ensure the language of the documentation is understandable to FDA reviewers.
3. Follow FDA Guidance Documents: Read the latest FDA guidelines on DMF submission before creating and submitting a drug master file.
4. Establish Document Control Systems: Maintain version history of DMF, track amendments and use a quality management system to control the DMF life cycle.
5. Maintain Confidentiality: The Drug master file is a confidential document, so don’t share your full DMF with customers and only provide the letter of authorization to protect confidential information.
Drug master file submission is an essential part of pharmaceutical compliance. A perfectly prepared DMF can help in the regulatory approvals, protect confidential information and streamline collaboration with suppliers. DMF is not just a regulatory requirement but it provides a competitive advantage to the companies producing pharmaceutical products.
In this post, we'll understand the process to submit a DMF to the FDA, including its types, components, regulatory requirements and best practices to ensure a drug master file is submitted successfully.
What Is a Drug Master File (DMF)?
DMF is a confidential document submitted to FDA containing detailed information about facility, processes materials used in manufacturing, processing, packaging and storing of pharmaceutical products. Drug master file is not a substitute for new drug application (NDA) or abbreviating new drug application (ANDA) while it supports these replications by providing important data that can provide references.Types of Drug Master Files
Drug master files are classified into five main types by FDA.1. Type I – The information about manufacturing site, facilities, operating procedures, and personnel are included.
2. Type II – Information about drug substances, drug substance intermediates, and materials used in preparation of drugs, or drug products are included in this DMF.
3. Type III – It includes packaging materials used for drug products
4. Type IV – Excipient, Colorant, Flavor, Essence, or Material Used in their Preparation and included in Type IV DMF.
5. Type V – FDA Accepted Reference Information
Why Submit a DMF?
DMF protects the intellectual property rights of the manufacturers when they share technical details with regulatory agencies. For example,- By submitting DMF an API manufacturer can share process data and synthesis with finished dosage form manufacturers with disclosing trade secrets.
- Excipients and packaging material suppliers can confidentially disclose product specifications.
Step-by-Step Process for DMF Submission
Step 1: Determine the Type and Purpose of the DMF
Before you start, identify that- The type of DMF is based on your product (e.g., API, excipient, packaging)
- The goal of DMF whether it will support an ANDA, NDA, IND, or export application
Step 2: Prepare the DMF in CTD Format
It is an FDA requirement to submit DMF in eCTD (electronic Common Technical Document) format. CTD is divided into 5 modules.Module 1: Regional administrative information (specific to the country)
Module 2: Quality overall summary (a summary of Module 3)
Module 3: Detailed information about the drug substance or product (this is the core of DMF)
Module 4: Nonclinical study reports (not always applicable)
Module 5: Clinical study reports (not always applicable)
A drug master file should contain:
- Manufacturing process flowcharts
- Controls for materials and intermediates
- Specifications and test methods
- Stability data
- Validation studies
- Environmental controls (for sterile APIs or packaging)
Step 3: Obtain a Pre-Assigned DMF Number
Before starting the submission of DMF, it is required to request a DMF pre-assignment number using FDA’s Electronic Submissions Gateway (ESG).You will be required to submit:
- Form FDA 3938
- A letter of intent
- Company information
Step 4: Compile and Validate the Submission
After preparation of DMF in eCTD format, you have to validate it using an eCTD validation tool like Lorenz docuBridge, eCTDmanager, or GlobalSubmit.Ensure that the XML backbone in the eCTD file is correct and contains no broken hyperlinks. All required files should be in the correct folders. Any technical issues can lead to rejection before the FDA begins reviewing the DMF.
Step 5: Submit via Electronic Submissions Gateway (ESG)
After validation, upload the eCTD file to the FDA’s ESG portal using your active ESG credentials. After a successful submission, you will receive a Receipt of Acknowledgement and Technical Acceptance Notification from the FDA. DMF enters the review queue only after the technical acceptance.Letter of Authorization (LOA)
Issue a letter of authorization to allow another party to reference your DMF. A letter of authorization includes DMF number, DMF holder name and address, authorized party name, description of information being referenced and signature and contact information.This letter of authorization must be included by referencing the applicant in their application.
Maintaining and Updating Your DMF
Submitting a DMF is not a one-time activity. You must submit updates to keep DMF active and notify FDA and authorized parties for any change in manufacturing site or process improvements. If updates of DMF are not submitted, then it will be considered inactive.Tips for a Successful DMF Submission
1. Ensure Data Integrity: Data submitted in DMF must be accurate, traceable and complete. Do not copy data from other documents without verification.2. Use Clear and Concise Language: Ensure the language of the documentation is understandable to FDA reviewers.
3. Follow FDA Guidance Documents: Read the latest FDA guidelines on DMF submission before creating and submitting a drug master file.
4. Establish Document Control Systems: Maintain version history of DMF, track amendments and use a quality management system to control the DMF life cycle.
5. Maintain Confidentiality: The Drug master file is a confidential document, so don’t share your full DMF with customers and only provide the letter of authorization to protect confidential information.
Drug master file submission is an essential part of pharmaceutical compliance. A perfectly prepared DMF can help in the regulatory approvals, protect confidential information and streamline collaboration with suppliers. DMF is not just a regulatory requirement but it provides a competitive advantage to the companies producing pharmaceutical products.
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