Masterarbeit

Potential impact of optimisation proposals for the revision of the regulatory framework for variations

Sarah Gieseler (2025)

Summary

Language: English

The life cycle management (LCM) of medicinal products is a time-consuming and cost-intensive process for the regulatory authorities and the industry. As the number of variations has increased in recent years, a revision of the regulatory framework was needed to make the LCM more efficient. The revision of the Variations Regulation by Commission Delegated Regulation (EU) 2024/1701 has resulted in several changes such as the mandatory annual update for type IA variations or the obligatory use of the worksharing procedure. Before the actual revision of the variation framework for medicines, the European Commission conducted a call for evidence to gather feedback from stakeholders.

In this thesis the changes introduced with Commission Delegated Regulation (EU) 2024/1701 are explained and the feedback received from stakeholders during the call for evidence is summarised. In a gap analysis, the key proposals for the revision of the Variations Regulation are compared with the changes introduced with Commission Delegated Regulation (EU) 2024/1701 and the entire applicable legislation for variations, respectively. In addition, this thesis focuses on the impacts and benefits of optimisation proposals for the next revision of the variation framework.

Most of the proposals from the call for evidence were only partially implemented or were not implemented at all. Some proposals could not yet be implemented as the legal basis for this is lacking. These include, for example, the further use of databases for the notification of changes or the full implementation of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Q12 guideline. The further use of databases like SPOR has a high potential to make the LCM of medicinal products more efficient. It reduces the administrative burden connected with the preparation and assessment of variations and saves time and human resources for regulatory authorities and MAHs. By implementing the regulatory tools described in the ICH Q12 guideline in countries worldwide, a globally harmonised management of post-approval chemistry, manufacturing and control (CMC) changes could be achieved. The concepts of Established Conditions (ECs) and Product Lifecycle Management (PLCM) document provide additional flexibility, lead to fewer submissions of post-approval CMC changes and thus reduce the associated regulatory burden. Furthermore, there is also a need for further optimisation in the handling of Certificates of suitability of monographs of the European Pharmacopoeia (CEPs). The total number of valid CEPs has increased in the last years. Since one CEP is often used by several different MAHs, a CEP revision can cause a multiple number of variations. 

The current revision of the variation framework is only a short-term solution under the existing legislation and a further comprehensive revision will take place after the revision of the general pharmaceutical legislation. 

Pages: 65

Annexes: 1, Pages: 1