Studiengang „Master of Drug Regulatory Affairs"

Master-Thesis

EU Enlargement on 1 May 2004: Implications on Existing Marketing Authorizations in the Candidate Countries: Practical Aspects

Dr. Isabel Schemainda (Abschlußjahr: 2003)

As of 1 May 2004 the European Union (EU) will have ten new member states which are Cyprus, Czech Republic, Estonia, Hungary, Latvia, Lithuania, Malta, Poland, Slovakia and Slovenia. Focussing on the implications of the EU enlargement on medicinal products for human use and regulatory affairs items, the required compliance of the candidate countries (CCs) with the "acquis communautaire" upon accession has the major impact. In particular, competent authorities of the CCs as well as marketing authorisation holders (MAHs) and manufacturers operating in these countries are obliged to follow the requirements of Art. 6 (1) of Directive 2001/83/EC upon accession, which reads:

"No medicinal product may be placed on the market of a Member State unless a marketing authorisation has been issued by the competent authorities of that Member State in accordance with this Directive or an authorisation has been granted in accordance with Regulation (EEC) No. 2309/93."

Among a number of bodies, organised within agreements, initiatives, or projects, the Collaboration Agreement between Drug Regulatory Authorities in European Union Associated Countries (CADREAC) and the Pan European Regulatory Forum on Pharmaceuticals (PERF) are the key players involved in the facilitation of the EU enlargement with regard to medicinal products and regulatory affairs activities. The outcome of their discussions has a considerable influence on the fate of marketing authorisations (MAs) in the CCs. Particularly, the CADREAC initiative has developed the simplified procedures for granting of MAs in their member countries for products authorised in the EU through the centralised or mutual recognition procedure (CP or MRP) to achieve harmonisation with corresponding EU products already in the pre-accession phase. The PERF initiative is providing practical advice on the implementation of the European pharmaceutical legislation and their interpretation in the CCs.

In the present thesis the implications of the required compliance with the "acquis communautaire" upon EU accession on existing MAs in the CCs granted either through the common simplified CADREAC procedures or other national procedures are analysed and described. In a further step the results are discussed in regard to practical and strategic aspects.

The PERF Acquis Working Group has agreed on the principle that "there are no minimum requirements for the Acquis below the standard set out in the hard law". Consequently, nearly all "old" dossiers have to be "upgraded" (to adjust the dossiers to the current EU standards and requirements) and Commission decisions on certain medicinal products have to be "phased-in" (to apply Commission decisions on mutually recognised, ex-concertation, referral, and centrally authorised products (CAPs) to the corresponding products in the CCs) until accession, unless transition periods for derogation have been agreed in the Accession Treaty. The implications of this exercise on existing MAs in the CCs can be summarised as follows:

Irrespective whether a medicinal product was authorised in a CC by a simplified CADREAC procedure for CAPs or by an other national procedure, a central MA for the "same" product (i.e. same qualitative and quantitative composition of active substance, same pharmaceutical form, same strength, legal or economic link between the companies which are the respective MAHs) will take precedence and the Commission decision will be applicable for all new member states upon accession. Consequently, the dossiers of those products do not need to be upgraded and their SmPCs will be harmonised on a mandatory basis upon accession. Nationally authorised "generic" MAs of CAPs are illegal and have to be withdrawn at the day of accession.

Irrespective whether a medicinal product was authorised in a CC by a simplified CADREAC procedure for products approved through MRP in the EU or by another national procedure, the MA retains its national status in the CC upon accession, even if MAs (national or MRP) for the "same" product exist in the current EU. Harmonisation of the SmPCs of those products in the CCs with the SmPCs of the corresponding products in the EU or inclusion into an existing MRP, if applicable, is not mandatory. If the product is authorised by the simplified procedure for MRP products, no dossier upgrade is necessary.

The Commission expects the CCs to take over the Commission decisions following a referral procedure according to Art. 29, 30 or 31 of Directive 2001/83/EC.

All product dossiers not complying with the "acquis" have to be upgraded according to their legal basis until accession, otherwise the MAs have to be withdrawn or suspended by the respective competent authority at that time.

Conclusively, important steps have been made towards the identification of regulatory issues and implementation of EU standards connected to achieving compliance with the "acquis". Therefore, it is advisable for companies holding MAs in the future member states

to harmonise the national MAs in the CCs corresponding to central MAs with the EU status in the pre-accession phase by the use of the respective CADREAC procedure, to consider the harmonisation of the national MAs in the CCs with the corresponding MRP MAs in the pre-accession phase by the use of the respective CADREAC procedure and to consider their inclusion into the MRP after accession, to use generally the simplified CADREAC procedures for new applications, to implement the Commission decisions into the national MAs in the CCs by means of variations, and to upgrade adequately the dossiers concerned and to observe carefully the timelines specified in the guidelines published by the CCs.

Pages: 38, 1 Annex : pages 6