Drug Master File Submission (DMF submission) is not mandatory for the US FDA as U.S. DMFs are neither approved nor disapproved. However, to maintain the confidentiality and to refer in multiple DMFs, manufacturers/DMF holders practice maintaining independent DMF submissions for the drug substances/excipients/packaging materials.
To be compliant with the Generic Drug User Fee Act (GDUFA) II and Initial Completeness Assessment (ICA) requirements of the US FDA, the DMF holders must ensure that their DMF is compliant with the FDA prerequisites. It is critical to receive the acceptance to the DMF/approval of the applications referring to the DMF, which will enable the DMF holder to provide access through a Letter of Access (LoA) to multiple applications such as IND/NDA/ANDA/DMF.
Freyr has a dedicated and experienced Regulatory team that specializes in DMF filing with capabilities in submission, managing of the DMF for drug substances, excipients, and packaging materials to the US FDA.
- Regulatory submission strategy for different types of DMFs for drug substance (Type II DMF), packaging materials (Type III DMF), and excipients (Type IV DMF).
- Support in identifying the Regulatory starting material.
- Guidance on selection of route of synthesis for the drug substance.
- Support for designing the limits for impurities in starting materials, intermediates, and their carry-over to Active Pharmaceutical Ingredients.
- Support in setting the strategy and limits for genotoxic impurities and elemental impurities in intermediates or in drug substances.
- Review support for 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 DMF submission.
- Review of executed batch manufacturing records for adequacy.
- Preparation and submission of Drug Master Files in line with GDUFA, and ICA requirements for drug substances.
- Guidance for GDUFA fee compliance.
- Publishing of DMFs in the eCTD format as per the current US FDA 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 responses to Health Authority queries.