Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

New challenges in biosimilar development in the context of current regulatory guidance ***

Dr. Kendra Schafti (Abschlußjahr: 2020)

Summary
Language: English
The first biosimilar has been approved in the EU in 2006. Since then not only the number of biosimilars applying for marketing authorisation has increased but also the (reference) medicinal products for which biosimilars are being developed. Nowadays, with the development and approval of complex molecules such as monoclonal antibodies new challenges in biosimilar development have evolved. Although the current European regulatory framework is well established there appears to be a lack of specific guidance for newly advancing challenges in this field resulting from an increase in knowledge, advancing technologies and a rapidly changing landscape.
The first part of this master thesis highlights the variability of the clinical comparability exercise in biosimilar development. Based on data obtained from the publicly available assessment reports on the EMA website the clinical development programs for biosimilars of two EU-approved medicinal products containing the active substances trastuzumab and rituximab have been compared. Differences in the choice of the clinical setting are discussed including the relevance of the patient population, the endpoints and the equivalence margin and their impact on study results as well as the comparability exercise in general.
The second part addresses specific aspects related to biosimilars that are considered challenging for both regulators and pharmaceutical companies currently and potentially in the near future. An outlook on upcoming patent and market protection expiries is provided followed by an overview of commonly used terminology to highlight differences to the term biosimilar including an analysis of aspects related to biobetters. Subsequently, the impact of specific regulatory procedures – such as duplicates, autobiologicals and the change of marketing authorisation of the reference medicinal product – on the availability, development and principal concept of biosimilars is highlighted. Moreover, the general need for Phase 3 trials in the development of biosimilars is explored along with the implication of extensions of the biosimilar marketing authorisation on the alignment and harmonisation of the product information of other medicinal products with the same active substance.
Finally, the thesis outlines which of the illustrated challenges are adequately addressed by the available regulatory framework and where the regulation is partly insufficient, thereby highlighting the need for additional and more specific regulatory guidance.
Pages: 60