Masterarbeit

Guidelines and regulations on excipients in medicinal products: an overview of developments, implications and challenges for the future ***

Dr. Carola Michielse (2018)

Summary
Language: English
Excipients represent a diverse group of components used in drug formulation in function, origin and complexity. They are used to improve drug stability and preservation, enhancing oral bioavailability, enhancing production, increasing patient acceptability or to control the release rate of APIs. Excipients used in medicinal products (MP) are predominantly produced for other markets, such as food, cosmetics or industrial applications, and only 5 to 10 % of the excipients produced are used in the pharmaceutical industry. They are classically bulk products of low value. The view on excipients in MPs changed over the years from being just inert components to components playing a profound and maybe sometimes even crucial role in stability or efficacy of MPs. Due to the increasing complexity of APIs, the development of biotechnologically derived MPs and the development of new strategies for drug delivery, the function of excipients within MP has become more than just providing body to the API. The increased importance of excipients within the formulation combined with several excipient related incidents contributed to the amendment and / or introduction of new regulations, directives and guidelines in order to better control excipient quality and its supply chain.
An intriguing question is how to balance between the regulations and guidelines to provide high quality and safe excipients to the pharmaceutical market on one hand, but also to maintain the willingness and capacity of excipient manufacturers to comply with an increasing regulated market and how to drive innovation to develop new excipients with increasing demand on formulation for new APIs and new therapeutic initiatives combined with increasing demands on novel excipient stability, non-clinical and clinical safety assessment.
In this thesis, an overview is given from the European pharmaceutical regulations, directives and guidelines having an impact on the excipient regulatory landscape combined with an overview of excipient-related information to be provided in the market authorization application (MAA) dossier. Finally, the impact of the evolving directives and guidelines on excipient manufacturers and excipient users from a GMP perspective including current regulatory challenges related to novel, atypical, co-processed, (modified) natural and nano-excipients will be discussed.
Pages: 59, Annexes: 1, Pages: 1