Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Experiences with the New Decentralised Procedure –Changes, Limits, Perspectives ***

Mariela Becker (Abschlußjahr: 2008)

Language: English

During the last decade European procedures for marketing authorisation have increasingly gained importance over national licensing systems. Since 01 January 1998, parallel national applications for drug approvals in EU Member States (MSs) have disappeared and now marketing a new drug in more than one Member State is only possible via European procedures.

Until 2005, the Mutual Recognition Procedure (MRP) was the only marketing authorisation route to obtain several national marketing authorisations in the EU at the same time. This changed when the new Decentralised Procedure (DCP) was introduced on 30 April 2004 as a result of the Review, in which the pharmaceutical legislation had been scrutinised. This new legislative package among others includes Directive 2004/27/EC, amending Directive 2001/83/EC. It had to be implemented in all European Member States 18 months after its publication, i.e. by 31 October 2005, and contains many new provisions for obtaining marketing authorisations in the EU via decentralised procedures. As a result, the former MRP was essentially changed and became legally split into a MRP and a DCP, now the two possibilities of obtaining national marketing authorisations in more than one EU Member State.

According to Article 28(3) of Directive 2001/83/EC as amended, the DCP applies when a medicinal product has not previously been granted a marketing authorisation at the time of application. Thus, it offers an alternative to the MRP. Under the DCP, the Reference Member State (RMS) prepares, in consultation with the Concerned Member States (CMSs), a Draft Assessment Report (DAR) within 120 days. Within the following 90 days, RMS and CMSs agree on the terms of the authorisation.

The DCP is supposed to be a straightforward, but flexible procedure. On the one hand it is competitive to the Centralised Procedure (CP), and on the other hand superior to the MRP. To achieve this goal, the new procedure combines general principles of both MRP and CP. The timetables of CP and DCP are comparable and the decision on a dossier is a joint process with input from all Member States. This contrasts to the MRP where one Member State has already decided on the approval of the dossier, Summary of Product Characteristics (SmPC) and Package leaflet (PL). Similar to the MRP, DCP applications are handled at the level of national agencies where they share the same legal types of applications; in both procedures flexibility is maintained, as the applicant can choose the RMS and the number of concerned Member States.

The start of the new European procedure experienced some delay when implemented into national law. In 2005, only nine DCPs were started, five with Germany and the remaining four with The Netherlands as Reference Member State (RMS). However, judging from the statistics of two full years in which the new legislation has been applied, it can be concluded that the slow start was followed by a remarkable increase in the use of the new DCP, so that by now it has already dwarfed the MRP in number of applications. It is obvious that the National Competent Authorities (NCAs) had untertaken enormous preparatory work to implement the new DCP in November 2005. The true beneficiaries of the new European procedure are manufacturers of generics: about 75 % of all DCPs are generic applications.

Two and a half years after the introduction of the DCP (and the revised MRP), it can be concluded that both procedures are functioning well. The Co-ordination Group for Mutual Recognition and Decentralised Procedures (CMD(h)), which started in November 2005 with a broad mandate given in Article 27 of Directive 2001/83/EC as amended, has fulfilled the expectations regarding its responsibility for the smooth functioning and good outcome of the DCP (and MRP). Obliged by the Heads of Medicines Agencies (HMA), the CMD(h) evaluated the DCP and the workability of the respective Standard Operating Procedures (SOP) in 2007. Regular meetings with stakeholders in 2006 and 2007 have resulted in revised guidance documents and the establishment of ad-hoc working groups. A further evaluation of the DCP will be performed in the third quarter of 2008. It is expected that at that time approximately 1000 procedures have been finalised.

As the generic industry is the main DCP customer using the procedure for the majority of applications, all changes aimed at improving the DCP are of great importance for them. However, a key issue of concern with the DCP is still unsolved. The DCP has become so popular with the pharmaceutical industry that the NCAs are faced with capacity problems. In particular the leading regulatory authorities in the EU have been heavily involved in the DCP from the beginning. In 2006 und 2007, four countries (Germany, The Netherlands, Denmark and the United Kingdom) predominantly acted as Reference Member States (RMS) in the DCP with more than 80 % of the workload. Although the major challenges of the enlargement of the EU seem to have been mastered, the larger and more established EU Member States still dominate as RMS. In the interest of all involved parties, the workload must be distributed more evenly. The industry's concerns regarding the availability of the NCAs needs further discussion, especially at the level of HMA. The CMD(h) is willing to contribute to this discussion in order to find ways of making the best use of the available resources.

Pages: 52
Annexes: pages: 16