Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Assessment of the new EU variation regulation No 1234/2008/EC on the practicality aspects for post-approval changes of human medicinal products

Ridwan Sarwin (Abschlußjahr: 2010)

Currently, the new regulation No 1234/2008 provides the basis of the regulatory framework for variations for European marketing authorisations maintained by a European procedure (Centralised, Mutual Recognition, and Decentralised). By 20 January 2011 at the latest, through Directive 2009/53/EC amending Directives 2001/82/EC and 2001/83/EC and its implementation into national legislation, the rules of the new variations regulation are also applicable for purely national authorizations. This represents a significant change to the legal basis of the Variations Regulations, so that virtually all authorised medicinal products, including those authorised at a purely national level, are subject to the same criteria for the evaluation, approval and administrative handling of changes, regardless of the procedure under which those medicines were initially authorised.

The introduction of the new regulation allows a much more flexible approach. Previously, a simple type IA variation was first reported and could only be implemented following approval. Instead of “tell and do”, this has now become “do and tell”; changes can be implemented immediately and reported afterwards. The new regulation also breaks the link between the modification of the marketing authorisation and the moment at which the MAH may implement the change for larger variations. This means that the MAH no longer has to wait until the authorities in charge of authorisation have administratively processed a variation, but can already implement these changes following approval. Theoretically it is possible for an amended package leaflet to be placed in the package by the company before the national authority has placed the new package leaflet on its website.

With respect to new features "grouping and worksharing" of the Variation regulation EC No. 1234/2008, the following positive aspects can offer to MAH:

  • Reduction of administrative burden, at least as it goes in one step for several variations and several MAs, i.e. One submission and one data package.
  • Predictable time lines for implementation, at least when the procedure gets started.
  • Harmonised regulatory outcome, at least when worksharing is applied. One assessment by a Reference Authority on behalf of other NCAs is guaranteed.


A few drawbacks to the above aspects may include like increased bureaucracy, at least in the pre-submission step (ie. Justification for Worksharing and discussion at CMD and working groups). The latter can demand up to 3-6 months of consultation timeline.

In sum, to get maximum out of the new variation regulation the MAH can determine the way forward dependent on the company strategy. Of paramount importance is the choice of strategic Projects along the implementation and launch timetable. With this plan MAH can define:

  • Timeline: to group variations with one single notification
  • Cost: to determine which RMS with "low variation fee structure", at least in the first wave of MR procedure and go at the later stage for the second wave once the big changes have been approved.


The master thesis offers an up-to-date practical aspects of the new variation regulation to be considered for daily tasks and for a strategic decisions when variations of existing marketing authorizations are planned well and consequently submitted to NCA.

An assessment of the guidelines, best practices and Questions & Answers issued to describe the practical aspects of the new variation regulation EC 1234/2008 is made. The impact of cost and timing for Regulatory Affairs department within a company is analysed. Key aspects of the data necessary for submission are highlighted under consideration of the grouping and worksharing setting. Special emphasis is laid on already existing guidelines and respective examples are given.

In conclusion, an individual assessment for each variation type is required to decide upon the Variation application for existing Marketing Authorisations as it could be an interesting opportunity for both the company and the regulatory agency due to the flexible, simple regulatory framework of the new variation regulation.

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