Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Delivery of nucleic acids mediated by engineered protein nanoparticles - Preclinical development from a regulatory point of view

Dr. Nadine Temme (Abschlußjahr: 2017)

Summary
Language: English
Based on limitations in efficacy or observed adverse side effects, the target specific transport of therapeutic ingredients mediated by drug delivery systems still remains a remarkable challenge. Their development is of great value with respect to promising pharmaceuticals which need to be "sheltered" due to their toxicity or instability. Nucleic acids are one type of active substances falling in this category and they keep a high therapeutic potential.
In recent years, virus-like particles (VLPs) formed by major structural protein VP1 of the human polyomavirus John Cunningham (JCV) were frequently used to deliver different types of nucleic acids. An innovative drug delivery system on the basis of these JC-VLPs allows the encapsulation of different active compounds and moreover, the target specific addressing of different tissues through molecular modifications of the so-called engineered protein nanoparticles (EPN).
This thesis provides an overview of the requirements for EPN drug development with regard to file an application for "First In Man" (FIM) studies. The legal and regulatory environment for nucleic acids encapsulated by EPN is described as well as the medicinal product classification depending on the type of packaged nucleic acids. This product classification influences the quality and safety assessment for EPN medicines. Therefore, the focus is set on EPN encapsulating plasmid DNA and the data which have to be collected in order to compile the Investigational Medicinal Product Dossier (IMPD). With respect to safety issues, this thesis outlines the use of human relevant alternative methods, even though most of them are not yet approved by authorities. However, the development of those methods should be enforced as modern biopharmaceuticals are often designed species–specific and animal "models" are increasingly considered as inadequate. Finally, critical issues are discussed possibly arising with a view to the clinical development of EPN medicines in human beings.
Pages: 60
Annex pages: 3