Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Plant made pharmaceuticals (PMPs) as medicinal products for human use - a review of current regulatory issues and challenges to achieve a marketing authorisation in the EU ***

Caroline Mohr (Abschlußjahr: 2015)

Summary
Language: English
The number of patients with chronic diseases like diabetes, Alzheimer’s disease or chronic obstructive pulmonary disease (COPD) is increasing globally and various epidemic threats like Ebola, human immunodeficiency virus (HIV) or influenza result, particularly in the underdeveloped countries, in a high mortality. In correlation to this matter, the market demand for vaccines, therapeutic proteins and monoclonal antibodies is growing. On the other hand, only a few approved medicinal products against rare diseases are available. The production of recombinant, therapeutic proteins in conventional production systems such as genetically modified bacteria, yeast or mammalian cell cultures bears high costs and demonstrates other drawbacks, such as low yields or shortages and the occurrence of potential pathogens. Due to the high price of these medicinal products, many infectious diseases like Ebola, rabies, malaria mainly appearing in poor countries, cannot be reduced or eradicated, although medicinal treatment could be made available.
On the long run, transgene plants have the potential to serve as an alternative production platform for recombinant proteins. The research area plant molecular farming (PMF) is about the viable production of large biomolecule drugs; plants as biopharmaceutical factories can contribute to resolve the above mentioned problems as they offer potential advantages such as low cost of investment and low cost of goods, manufacturing scalability, speed of production and diversity of target products, coupled with related molecular engineering technologies including glyco-engineering.
Although there has been continuous research for almost 30 years, the development of plant medicinal products is still at an early stage. However, there are already a few success stories in this research area: in 2012 the first plant made pharmaceutical (PMP) for the human use was approved by the Food and Drug Administration (FDA) in the US and other candidates are currently entering clinical trial Phase II and Phase III, close to marketing approval.
This thesis reviews the development status of PMPs to date. The current challenges in the drug development and issues regarding the manufacturing process of PMPs in order to operate to current regulatory guidelines are examined. Then the current regulatory framework, applicable for PMPs in the EU, and the differences between the EU and US are introduced; both regions have well-sourced regulatory systems settled. Based on the experience gained from the research and development of the EU funded Pharma-Planta project and of the first approved PMP for the human use (Elelyso) conclusions are drawn, considering the necessity to revise the regulatory guidelines specifically for PMPs. Furthermore, ambiguities or gaps in the regulatory legislation are outlined. In the last chapter it is discussed, how these issues can be addressed in order to expedite the market availability of various PMPs in the near future.
Pages: 67