Masterstudiengang "Drug Regulatory Affairs"


Comparison and assessment of the current EU-Variation Regulations 541/95 and 542/95 and the revised new EU-Variation Regulations 1084/2003 and 1085/2003 ***

Birgit Moetamedi (Abschlußjahr: 2003)

The practical experience in the application of Commission Regulation 541/95 and 542/95 has shown that it is necessary to simplify and speed up the variation procedures. The execution of variations represents an eminent workload for both industry and competent authorities. Especially the increasing number of minor variations is binding human resources with administrative burden. This is disproportionate in many cases to public health issues and leaves inadequate time to focus sufficiently upon important variations.
Moreover this workload will further increase due to the approval of new medicinal products and as a result of Enlargement of the EU.

That is why the European Commission adopted the revised Variation Regulations 1084/2003 and 1085/2003 which shall apply from 1 October 2003. It had to be considered that the revised Variation Regulations has to fit into the existing legal framework as Directive 2001/83 and Council Regulation 2734/98.
Since Directive 2001/83, Article 35 (1) determines that the concept of a minor variation is to be defined precisely this basic principle had to be preserved for the revised Regulations.

But, two subcategories of minor changes are created, type IA and type IB listed in a common Annex I. The former is a new type of variation intended for changes, which do not affect the approved quality, safety or efficacy of the product and thus are suitable for a rapid "tell and do" notification procedure. For the latter variations it is necessary to maintain the evaluation of the submitted documentation; the procedure to be followed is similar to the one applicable for the current type I.
It means an immense progress that the RMS should evaluate the file on behalf of all CMS for both types of minor variations in order to avoid duplication of work.

With regard to the procedure concerning major variations some modifications are introduced regarding the evaluation period within the RMS has to prepare the assessment report and the draft decision. Variations concerning safety issues could be accelerated by following reduced time scale for which the MRFG recommends a period of 30 days whereas variations requiring a more comprehensive assessment as to be managed in the regular 60-day time scale could be extended to 90 days. This prolonged time sale is intended for variations concerning a change to or addition of a therapeutic indication.

Another important improvement is that the concept of 'extension' is officially introduced and defined as change to an existing marketing authorisation which fulfils the conditions set out in Annex II. It is favourable that the documentation to be submitted for an extension according to Annex II is of reduced volume in comparison with a full new application.

All in all the revision of both Variation Regulations represents a considerable improvement in the pharmaceutical regulatory framework. It is reasonable to assume that the implementation of the revised legislation will actually achieve reduction of workload by facilitation and acceleration of the variation procedures. The revised variation system seems to be a suitable basis for the accession of further countries to the EU.

Pages: 35, 1 Annex (p. 25)