Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Forced degradation studies - comparison between ICH, EMA, FDA and WHO guidelines and ANVISA's resolution RDC 53/2015 ***

Helene Janzen (Abschlußjahr: 2016)

Summary
Language: English
The stability of drug substances or drug products is a critical parameter and a matter of great concern as it may affect the quality of drug product - its safety, potency and efficacy. Forced degradation studies help to identify the chemical behavior of the drug substance and provide data to support identification of possible degradants (impurities) and degradation pathways. Further, forced degradation studies are crucial for the development of stability-indicating methods.
Currently, several guidelines emphasize the importance of forced degradation studies, but none of the guidelines yields a clear and complete strategy for the execution of these studies or provides detailed instructions regarding the individual aspects e.g. exact stress conditions or exposure times. This leads to uncertainty and disagreement between pharmaceutical companies and results in different approaches when conducting forced degradation studies. This master thesis provides a general overview on the current available regulatory guidance (ICH including EMA, FDA and WHO) with regard to forced degradation. In addition, the recently published new requirements by ANVISA, the National Health Surveillance Agency of Brazil, for conducting of forced degradation studies and for the development of stability-indicating analytical methods, are presented (RDC 53 from December 2015). The thesis includes a comparison between the available regulatory standards and the new requirements by ANVISA and assesses the similarities and differences. Additionally, the challenges and critical points for the pharmaceutical companies are pointed out and the content of a degradation profile protocol of a drug product, requested by ANVISA for future submissions, is discussed. The introduction of ANVISA’s resolution RDC 53/ 2015 includes several changes and challenges for pharmaceutical companies, but also chances and opportunities. The new requirements will lead to an extension of work for forced degradation studies for new and for already registered drug substances and drug products. The development and achievement of meaningful forced degradation studies will require a great deal of effort and additional resources, but will also lead to a better knowledge of risks and stability of drug products. The provision of a degradation profile protocol, which provides an assessment of the suitability of proposed analytical method and confirms the chosen formulation, recommended packaging and storage conditions, will further create a great value towards safety of drug products.
Pages: 51