Masterarbeit

Contained Use or Deliberate Release? - National regulatory requirements for clinical trials with gene therapy medicinal products containing or consisting of GMOs in Europe ***

Dr. Eleni Karakasili (2019)

Summary
Language: English
Gene therapy has the potential to treat a disease by targeting a defect in specific gene(s) which cause the disease and, therefore, provides innovative treatment options for a broad range of medical conditions for which conventional approaches have been proven inadequate. In Europe, a gene therapy medicinal product (GTMP) is defined as a product that is of biological origin and contains recombinant nucleic acid(s) which are directly involved in the mechanism of action and hence in the therapeutic action of the product. Moreover, based on the regulatory definitions set out in EU legislation, most GMTPs will be categorized as products containing or consisting of Genetically Modified Organisms (GMOs) whether delivered by in-vivo or by ex-vivo methods.
The approval of the first ever gene therapy product in 2012 was in Europe and this created a boost to the field with the development of gene therapies increasing constantly since then. From a regulatory point of view, GTMPs are heterogeneous biopharmaceuticals that are often targeting rare or orphan diseases or in some cases common diseases but with unmet medical needs. This translates to a lack of solid knowledge of the disease mechanisms as well as to a limited pool of available patients. Moreover, there is a difficulty in determining the appropriate dose and regimen. Due to this scientific and technical complexity their clinical development is uniquely challenging from a regulatory perspective.
Additionally to these challenges, sponsors also need to tackle many differences between the GMO regulatory frameworks of each region and the specific national and regional requirements for the clinical development of GTMPs containing or consisting of GMOs.
This thesis presents and analyzes the specific national GMO regulatory requirements which the pharmaceutical companies need to observe when developing their products in Europe namely the differential interpretation and adoption of two EU Directives in the European countries; the Contained Use and the Deliberate Release directives. Simply by these specific national regulatory differences, clinical development of GMTPs containing or consisting of GMOs in Europe is elongated, challenged and in some occasions avoided by the pharmaceutical companies. The challenges arising from the national requirements are presented and what can be done in order to overcome the challenges. Harmonizing the national requirements across all of the European countries will facilitate GTMP development in Europe and will improve patient access to such innovative treatments.
Pages: 84