DGRA e.V. - STUDIENARBEITEN / MASTER-THESIS

This thesis describes plasma protein therapeutics which is a distinct subgroup of biological medicinal products. They are characterized by their common and unique starting material human blood and plasma, their mostly relative long presence on the market and their use in life threatening often orphan indications.

The focus of the analysis has been put on scientific background and the EU/German regulatory legislation regarding biological medicinal products in general and specifically the plasma protein therapeutics (PPTs). Relevant regulatory requirements are described which are essential for the life cycle management of these products. An overview is given on PPTs currently authorized in Germany on a purely national basis, via mutual recognition (MRP) or centralized procedures.

The organizational set-up of a RA department dealing with PPTs is discussed along with the specific life cycle aspects for these products, including format of dossiers, new marketing authorizations, experience with MRPs, sunset clause, paediatric regulations, article 126a authorizations, orphan drug issues, labeling aspects, regulatory obstacles for commercialization (ASMF, remuneration), plasma master file (PMF) procedure and routine maintenance activities such as variations, extensions, renewals and periodic safety update submissions. Practical examples and comments on different regulatory requirements are provided, as appropriate.

In this context also the new variation legislation, a flagship of ECs “Better Regulation” initiative is critically discussed, also in comparison to the German legislation. Unfortunately Regulation (EC) no. 1234/2008 is quite complicated and provides no real improvement for biologicals. On the contrary, substantial issues are encountered for PMF/grouped variations and the PMF second step, i.e. a drastic increase in fees and workload, respectively. One aspect which could be of significant help in regulatory daily life, namely worksharing, cannot be exploited because purely national marketing authorizations have not yet been embraced and curiously it appears that EC is currently not pushing this forward, so that the promised harmonized system might be only available in 2013.