Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Revision of the Variation Regulations Commission Regulation (EC) No. 1084/2003 and No. 1085/2003 - Industry-Proposals and Consultation Paper from the European Commission, Impact on Industry and Health Authorities ***

Ellen Frey-Stanislawski (Abschlußjahr: 2007)

The current revision of the Variation Regulations has a great potential to contribute to the EU Commissions objective in strengthening Europes economic power insuring high quality medicinal products and being still affordable, their availability and continuous improvement, as well as putting the pharmaceutical industry into a position to develop new products for a growing population of the elderly. This applies to every single EU state and citizen.

The attempts to streamline the change system in the past were not able to reduce the overall number of variations. On the contrary they kept rising. The main reasons are that every change is subject to a separate variation, the same change is reviewed multiple times by many authorities (e.g. CEP changes), grouped variations are not accepted and the inflexible system of defined minor change lists which are fixed by the Variation Regulations. The national change systems (procedures, timelines and assessment criteria) were not included in the former revision. (Chapter 2.1 and 2.2)
At present the Competent Authorities are unable to meet the procedural timelines (EFPIA survey from 2005) since they are obviously working above capacity.
The current revision of the Variation Regulations is influenced by

  • The German and Austrian change systems, defining major changes and allowing grouped variations (Chapter 3.1),
  • The concepts of ICH Q8 Pharmaceutical Development, Q9 Quality Risk Management and Q10 Pharmaceutical Quality Management providing tools and potential to further save resources and costs (Chapter 2.4) and
  • The US approach showing how minor changes can be dealt with in a more efficient way by a do-and-tell-procedure and how the ICH Q8, 9 and 10 concepts can be implemented in respect to the variation system (Chapter 3.2).
The trigger of the revision of the Variation Regulations was the EU initiative “Better regulation” commission policy, which is aiming to reduce bureaucracy in order to strengthen the European industry.
The industry proposals with the key document from EFPIA/EVM/EBE introduce a radical change of the European variation system whereas the Consultation Paper of the EU Commission follows a more moderate approach. The main changes are the harmonisation of the EU variation systems and the worksharing procedures between EU Member States, an annually reportable notification system, the shift from defining minor to major changes and immediate notifications, the introduction of the Design Space concept, Comparability Protocols and Regulatory Agreements (Chapter 4). The standpoints from industry, EU Commission and national health authorities currently show some essential differences. These issues should be further discussed and the impacts of each on all stakeholders carefully worked out in order to meet the set objectives.
The discussion in chapter 4.9 shows the impact on industry and health authorities.
The major challenges are:
  • To harmonise the EU change systems (national, MR and CP) and introduce the mandatory participation in the worksharing procedure of all national Competent Authorities concerning assessment criteria, procedures, timelines including the national phase in cases where a change of the product information is involved
  • To define immediate notifications and major changes
  • To introduce group and related variations
  • To establish appropriate national fee systems
  • The implication of ICH Q8 Pharmaceutical Development, Q9 Quality Risk Management and Q10 Pharmaceutical Quality System concepts
Discussions on the details how Q8, Q9, Q10 can be used to streamline the variation processes seem necessary.
To adjust the variation system to new innovative medicinal products and processes in the future the regulatory framework should be set by regulations and the details by guidelines which can be adapted more easily.
Besides the overall number of variations the publication of review times by the Competent Authorities themselves could be an indicator for the efficiency of the variation system.
The challenging objectives can be achieved by overcoming a typical EU problem where many Member States have to cooperate and give up their individuality to a certain extent. Common assessment criteria, procedures and timelines including another authorities assessment would have to be accepted also for the nationally approved products.
The revision of the Variation Regulations facilitates the switch from a huge amount of single variations of minor changes leading to authorities operating above their capacities towards focusing on continuous improvement of medicinal products and major changes in the context of the implementation of ICH Q8, Q9 and Q10.

Pages: 84, Annex pages : 92
Download Master-Thesis (PDF, 1 MB)
zurück zur Übersicht