Obligations regarding updates of Active Substance Master Files (ASMF/DMF)

Updated 16 September 2021

We often experience difficulties concerning updates of active substance master files (ASMF/DMF). Therefore, we have made a list of the obligations involved in such updates.

Marketing authorisation holders (MAH) are obligated to update the documentation in module 3 / part IIC.1 in relation to the newest version of an ASMF by applying for variations. This applies to changes in both the Applicants’ Part (AP) and the Restricted Part (RP) of the ASMF.

In our experience, the MAH frequently applies for changes to the AP and refrains from applying for changes introduced in the RP (or is not informed about them). The active substance manufacturer (ASM) is required to inform the MAH when changes are made to the AP and/or RP, and the MAH is responsible for applying for these changes in order for them to be implemented in the marketing authorisation.

Changes or updates of an ASMF should be applied for in accordance with the rules in Commission Regulation No. 1234/2008 (the Variation Regulation) and related guidelines.

We recommend MAHs to apply for changes to an ASMF as a single type II variation, e.g. update from version 01 to version 02. This allows for all changes to both AP and RP to be applied for simultaneously in one single application, thus avoiding any unnecessary discussion about categorisation of changes. Furthermore, it ensures that all changes are included in the application, which makes submission of subsequent follow-up variations unnecessary. In addition, situations are avoided in which the AP and RP within the same version of the ASMF are not approved at the same time.

Although all changes can be applied for as one single type II variation, the MAH in cooperation with the ASM are of course responsible for distinctly describing in the application scheme the changes made between two versions of an ASMF. PRESENT/PROPOSED in the application scheme should include information about version numbers of AP and RP together with an overall description of the present and proposed changes to the AP and RP.

In cases with no amendment of the RP, the MAH is recommended to clearly state it in the application scheme and identify/verify which version of the RP the proposed AP belongs to. To facilitate the processing of the variation, please include the Danish DMF file number (2215-XXXX) in the application scheme. The ASM must send a detailed description of the changes made between the two versions of an ASMF directly to the Danish Medicines Agency.

Spørgsmål og svar om dokumentation i eCTD format for råvare- og færdigvarefremstillere

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