Drug Master File (DMF) Submission - Overview
Proprietary and confidential information about the facilities and processes used in the manufacturing, processing, packaging, and excipients are included in a Drug Master File (DMF) and submitted to the United States Food and Drug Administration (US FDA) in support of the applications and other DMFs. A DMF submission is not mandatory. However, manufacturers submit the DMF to maintain the holder's proprietary information confidentiality.
During DMF filing, the information on the Active Pharmaceutical Ingredients (APIs)/intermediates, packaging materials, excipients, and facilities can be submitted to the US FDA under Type II, Type III, Type IV, and Type V DMFs respectively.
The Generic Drug User Fee Act (GDUFA II) is applicable for Type II DMF filing, which is intended for the submission of information for APIs. The Type II DMFs are assessed through a Letter of Access (LoA) to the applicants, so they can refer to the information in their applications (ANDA/NDA/IND/DMF) after the US FDA completes the Initial Completeness Assessment (ICA). Subsequently, a technical review of the DMF is performed by the US FDA in connection with the other applications. Any queries raised by the US FDA on the DMF content will delay the approval of the application filed by the applicant.
Freyr has a Regulatory team with a deep understanding and experience in DMF filing that includes gap analysis, authoring and submission in the eCTD format, and managing & updating the DMFs per the latest guidelines by the FDA.
Drug Master File (DMF) Submission - Expertise
- Regulatory submission strategy for different types of DMFs for drug substance (Type II), packaging materials (Type III) and Excipients (Type IV).
- Identifying the Regulatory starting material.
- Guidance on selection of route of synthesis for Drug Substance in line with US FDA expectations.
- Support in designing the limits for impurities in starting materials, intermediates, and their carry-over to Active Pharmaceutical Ingredients (APIs).
- Designing of specifications for starting materials, in-process, intermediates and drug substance.
- Support in setting the strategy and limits for genotoxic impurities and elemental impurities in intermediates or Drug Substances.
- Review support for the finalization of the development report with Quality by Design (QbD).
- Guidance on designing the protocols for stability studies, process validation, hold time study, and forced degradation studies for Drug Master File submission.
- Review of executed batch manufacturing records for adequacy.
- Preparation and submission of Drug Master Files in line with GDUFA, Initial completeness assessment (ICA) requirements for Drug Substances.
- Guidance for GDUFA fee compliance.
- Publishing of DMFs in eCTD format as per current USFDA guidelines and requirements.
- Regulatory strategy, preparation, and submission of amendments and annual reports for already registered Drug Master Files.
- Regulatory strategy, preparation, and submission of the response to health authority queries.
