November 2008 saw the publication of Commission Regulation (EC) No. 1234/2008, which defines a new procedure for handling variations to the terms of marketing authorisations (also see GMP news from 15 January 2009). Article 4 of this regulation calls for detailed guidelines explaining the different categories of variations types as well as procedural questions on the documents to be submitted in each case. On 20 March 2009, the European Commission presented drafts for these guidelines, about which we reported in our GMP news from 22 April 2009.
After the consultation phase, which ended on 18 May, numerous comments were sent in by firms, associations and national authorities. Meanwhile the Commission has published them in the form of a compilation and a first evaluation on its home page. You can read the contributions as well as the respective summaries and evaluations by the Commission here.
On the whole, the simplification and more flexible handling of the variations procedure resulting from the new regulation is welcomed by almost all of the commentators. However, some of the statements critically mention that a large number of specific issues still have to be clarified. APIC, the association of European active pharmaceutical ingredients manufacturers, faults e.g. the fact that the holders of an Active Substance Master File (ASMF) will be placed at a disadvantage through the new regulation, even if they only intend to make a minimal change to the manufacture of an active pharmaceutical ingredient. In order to avoid this disadvantage, the APIC requests that the ASMF holders be allowed to "do and tell" according to the variations type IA (notification about the variation in the annual report within the next 12 months) or the variations type IAIN (immediate notification). In its comment, the APIC suggests practicable solutions. Here you can read APIC's complete statement.
Because of the high complexity of the new provisions, the comments are unanimous in calling for a publication of the final version of these "detailed guidelines" as early as September 2009 and not just a few weeks before the year is out. Since the regulation comes into force on 1 January 2010, the companies need more time in order to deal in detail with the subject and to prepare themselves.
As an example, an excerpt from the comment by the European Industry Federation (EFPIA) is quoted:"Industry understands that the guidelines may be issued as late as November or December 2009 and this is raising major concerns. Publication of implementing guidelines within 1 month or less of the new legislation entering into force will not allow companies to upgrade their internal processes in time. Such an exercise usually takes 3-6 months and therefore we would welcome the opportunity to meet with the Commission as soon as possible to explore possible avenues to make the text available earlier to allow sufficient time to prepare for implementation."
It remains to be seen if the European Commission will be responsive to this fully justified claim on the part of the industry.
Event recommendation: You will be informed comprehensively about the current developments of the new Variations Regulation at the GMP Education Course "Marketing Authorisation Procedures in the EU and the US" to be held in Prague on 10-12 November 2009. First-hand information from a representative of the European Commission and of the APIC will also be given to you at the "12th APIC/CEFIC European Conference on Active Pharmaceutical Ingredients" in Venice from 18 to 20 November 2009.
Dr Gerhard Becker
On behalf of the European Compliance Academy (ECA)