Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Review of the European variation regulation and the impact on changes in manufacturing and control of medicinal products ***

Dr. Ulrike Bodesheim (Abschlußjahr: 2002)

At the beginning of February 2002 the European Commission published the proposals for revisions to Regulations (EC) 541/95 and 542/95. The revision of the variation regulation is intended to meet the purpose of the ongoing process of continuous improvement in the pharmaceutical regulatory framework in Europe. Variations represent a significant workload for both industry and regulators. This workload is going to continue increasing with the approval of new products and the complexity will increase with the accession of further countries to the European Union.

As within the results of the review 2001 the view on a revision of the variation regulation should be towards simplification, rationalisation and overall improvement and transparency of procedures. The EU regulatory system, pre- and postapproval, should develop towards global best practice standards of time, quality and resource utilisation due to the fact the marketing authorisation holder act more and more in a global environment and have to consider different regulations for marketing authorisation applications. The increasingly rapid spread of new technologies in research and development requires a flexible regulatory environment based on stable, well-defined principles, which correspond to international dimension. This "global" dimension of regulatory requirements is one of the main changes since the beginning of the 1990s, when the current processes for marketing authorisations in Europe were established.

Most of the postapproval changes are in the manufacturing and control of the medicinal products. Marketing authorisation holder have to plan changes in manufacturing and control within a complex frame work of regulatory requirements, adaptation to the evolving scientific knowledge, technical conditions in the factory, logistic aspects and desire of the marketing department. The marketing authorisation holder has to establish a close contact to the experts of the health authorities and to the board control responsible for the inspection of Good Manufacturing Practice. The process of manufacturing has to comply completely with GMP requirements and the manufacturing licence.

The complex regulatory system of post approval changes is binding resources in the pharmaceutical industry. The different times of the approval process and the following implementation of the planned changes lead some times to a logistic challenge for the marketing authorisation holder to be in regulatory compliance with the product, which is marketed in different regions. Furthermore the documentation to be submitted with the variation has to filed individually for each region. Both industry in Europe and US feel that significant further down regulation of manufacturing changes could be possible, which has the potential to simultaneously speed industry implementation of changes, enhance quality and allow the health authorities reviewers to focus on more significant matters.

This paper will discuss the advantages and disadvantages of the proposed revision of the European variation regulation on the maintenance activities of the pharmaceutical industry and provide a comprehensive overview about the changes to be expected on the basis of the latest available proposal. Taking into consideration FDA's guidance on post-approval changes for drugs, issued in November 1999, which was called one of the agency's most significant regulations in recent years, it will be discussed if the revision of the variation regulations (EC) 541/95 and 542/95 could be considered as a further step towards international dimension of the regulatory environment also in the area of post-approval activities.

Pages: 36