Active Substance Master Files (ASMFs) contain detailed information on the manufacture and properties of active substance and is therefore valuable and confidential. The ASMF procedure ensures protection of the manufacturer’s intellectual property and allows applicants and Marketing Authorization Holders (MAHs) to undertake responsibility for the medicinal product and the quality control of the active substance.
Active Substance Master Files should be presented in CTD format and are usually divided into two separate parts based on the confidentiality of the content. Information that is considered by the ASMF holder to be non-confidential to the Applicant/MAH is contained in the Applicant’s Part (AP), and information considered to be confidential is included in the Restricted Part (RP). The EMA guideline on the Active Substance Master File procedure must be followed in order to submit ASMFs in compliance with health authority requirements. The submissions must be accompanied by other documentation as specified in the guideline (e.g., Quality Overall Summary (QOS) and Letter of Access).
Manufacturers of substances that are described in the European Pharmacopoeia (Ph.Eur.) can apply for a Certificate of Suitability (CEP). The EDQM provides guidance on the process to follow when applying for a CEP, which includes the submission of a CTD formatted dossier and a QOS. If a Certificate of Suitability is available for an active substance, companies can use this document in place of an ASMF, thus simplifying the active substance documentation required for medicinal product applications. This can also streamline some active substance-related post-approval changes that can arise during the Life-cycle of the product.
Freyr’s Regulatory expertise in compilation, review and submission of Active Substance Master Files (ASMF) and knowledge of the CEP process in line with EU and national submission procedures, makes it a preferred Regulatory partner for API and medicinal product manufacturers.
Identifying starting materials
Designing limits for impurities in starting materials, intermediates and their potential carry over to drug substance
Designing specifications and in-process limits for starting materials, intermediates and drug substance
Setting strategy and limits for genotoxic impurities and elemental impurities in intermediates or drug substances
Guidance on designing the protocols for stability studies, process validation, hold time studies and forced degradation studies
Gap analysis of source documents/data generated for ASMF submission in line with current guidelines
Preparation and submission of ASMFs and CEP applications (including support for the CEP sister file procedure)
Publishing of ASMFs and EU CEP applications in the eCTD format as per the current guidelines and requirements
Life-cycle management and maintenance of existing ASMFs and CEPs
Regulatory strategy support, including preparation and submission of responses to health authority queries