European Active Substance Master File (ASMF) Single Assessment | APIC Position Paper

Active Substance MasterFile (ASMF) or Drug master file (DMF) or CEP is the set of series of information for an Active Pharmaceutical Ingredient (API) or Drug substance brought together in CTD format as per regulatory requirements.

ASMF and CEP provide confidential detailed information about facilities, processes, or articles used in the manufacturing, processing, packaging, and storing of one or more human drugs.

CEP is the dossier submitted to EDQM and undergoes review process for its approval before referencing in the MAA.

ASMF are submissions to European regulatory agencies across Europe in all individual countries used to provide confidential, detailed information about facilities, processes, or articles used in the manufacturing, processing, packaging, and storing of human drug products. ASMF is never approved nor disapproved, but is reviewed everytime it is referenced in the MAA application unlike CEP is approved. 

ASMF constitutes of two parts, Applicants Part (AP) and Restricted Part (RP).

• Applicant’s part has the information on chemistry manufacturing and control (CMC) information of API included in it for the customer reference for its inclusion in its Marketing Authorization Application (MAA) Dossier. Which is further submitted to various European agencies through National, Mutual Recognition Procedure (MRP) or Repeat Use Procedure (RUP) and Decentralized Procedure (DCP) procedures.
• Restricted Part also has the information on chemistry manufacturing and control (CMC) information of API.

European regulatory health authorities reviews the technical contents of ASMF in connection with the review of MAA that reference them (e.g. All MAA filed under Article 10.1, 10.3, 10.a and so on).

Active substance manufacturers often supply their active substances to multiple marketing authorisation (MA) holders for use in different medicinal products. As a result, the same ASMF may be submitted to multiple Member States as part of new MA or variation applications through any of the authorisation routes in Europe.

It is acknowledged by both industry and the National Competent Authorities (NCA) that the lifecycle of a European ASMF may be complicated and can lead to duplicated assessment, divergent decisions, frequent ASMF updates.

In a bid to address this issue, the European ASMF Work sharing Procedure was established. This is a voluntary procedure, applicable only to new ASMFs and certain authorisation routes.

The proposed solution is a Single, self-standing assessment of ASMFs in a “CEP-like” procedure, i.e., submission of the ASMF by the API manufacturer directly to one central European authority for a single, centralised assessment of the ASMF and its subsequent changes, similar to the CEP system.

APIC believes that by developing a good relationship, through communication, establishing sufficiently detailed quality / technical agreements, and building trust between the parties, the appropriate level of information to be shared can be defined to the satisfaction of all parties.