Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Submission-relevant Illustration of Risk Management in Pharmaceutical Development

Dr. Christoph Brenner (Abschlußjahr: 2013)

Summary

Language: English

The initial idea of a risk-based pharmaceutical development was formulated about 10 to 15 years ago. Regulatory guidance by the FDA and from the ICH further elaborated a framework describing the principles of quality risk management during development. The combination of ICH guidelines Q8, Q9, and Q10 together with FDAs PAT Framework for Innovative Pharmaceutical Development, Manufacturing, and Quality Assurance defines the current requirements for quality risk management. Although the implementation of these principles is not mandatory yet their application can be seen as strongly recommended by the authorities.

A typical risk management process as described by ICH Q9 consists of multiple steps from initiating the process, risk assessment, control, communication and review. The application of such a process in the setting of pharmaceutical development is briefly described and an overview of some risk assessment methodologies and tools is provided.

Some known case studies and examples that make use of risk management principles are discussed. The description of the pharmaceutical development has its place in section 3.2.P.2 of the CTD structure. Elements needed to describe a risk based development include a Quality Target Product Profile (QTPP) and the identification of Critical Quality Attributes (CQA). Possibilities for the inclusion of risk management activities during development into the marketing authorization application are illustrated in the thesis.

The methodology to describe risk assessments may vary, but tables were found to be very useful not only to give an overview of the assessed risks but also to guide the reviewer through the dossier. Initial risk assessment tables often reveal chances for further experimental development activities, which lead to improved process understanding and knowledge gain. The thereby indentified risks can normally either be experimentally ruled out resulting in risk acceptance or further measures for risk mitigation should be taken. Risk mitigation can also be achieved by the inclusion of Critical Material Attributes (CMA) and Critical Process Parameters (CPP) into a control strategy.

Benefits of using risk management in the pharmaceutical development include a better product and process understanding, which is hoped to result in faster development and subsequent production of high quality products for patients. Obstacles on the way for making broader use by applicants are fears of additional efforts and costs. It is further not fully clear to which extent opportunities for flexible regulatory approaches are really meaningful.

In the future rising expectations by the authorities but also increasing use of quality risk management during pharmaceutical development in the companies is expected.

Total Pages: 68