An Active Substance Master File (ASMF) submission is not a mandatory requirement from the European Union (EU) Health Authorities as it would be reviewed only in connection with a Marketing Authorization Application (MAA). Active substance (Active Pharmaceutical Ingredient (API)) manufacturers/Active Substance Master File holders can directly submit the ASMFs to the EU Health Authorities as per the submission procedure identified by the MAA holder.
To avoid administrative comments/rejection of MAA due to non-availability of the ASMF and to receive timely MAA approval, submission of the ASMF as per the EU specific requirements (ASMF guidelines) is critical. The ASMF holder can provide a Letter of Authorization (LoA) to multiple MAA holders as a reference in multiple applications. Freyr’s expertise in handling the ASMF submissions and its life cycle management includes:
- Support in identifying the Regulatory starting material and intermediates.
- Guidance on selecting the route of synthesis for APIs.
- Support in designing the limits for impurities in starting materials, intermediates, and their carry-over to APIs.
- Designing specifications for starting materials, in-process, intermediates, and active substance.
- Support in setting the control strategy and limits for genotoxic impurities, and elemental impurities in intermediates or in the active substance.
- Guidance on designing the protocols for stability studies, process validation, hold time study, and forced degradation studies for ASMF submission.
- Review of manufacturing details of starting materials for adequacy in ASMF.
- Preparation, review, and submission of ASMF to avoid any delays.
- Publishing ASMFs in the eCTD format as per the current EU guidelines.
- Regulatory strategy, preparation, and submission of variations and renewals for already registered ASMFs.
- Regulatory strategy, preparation, and submission of responses to Health Authority queries.