Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

The regulatory landscape of human microbiome modulation using live microorganisms in the EU and US ***

Theodor Tiko (Abschlußjahr: 2018)

Summary
Language: English
Microbiome research has grown exponentially in the last decades driven by the advancement of novel technologies. The long-held perceptions from the germ theory of disease that highlighted microorganism pathogenicity are evolving to holistically appreciate the central role that symbiotic or commensal microorganisms (microbiota) play in the development and maintenance of health. A wide range of conditions and diseases have been linked to imbalances in the normal structure and function of the human microbiota (dysbiosis) presenting opportunities for microbiome modulation in support of health.
The gastrointestinal tract being the densest and most biodiverse microbiota habitat on the human body offers most possibilities for direct modulation. One group of these modulatory approaches involves the additive administration of live microorganisms as Live Biotherapeutic Products (LBP), Faecal Microbiota Transplantations (FMT) or even food-related probiotic supplementation. These special categories of biological products represent a novel paradigm in medicine development and as such are challenging regulatory agencies and the biopharmaceutical industry alike.
This thesis presents and compares the regulatory landscapes for these approaches in the EU and US since these jurisdictions serve as benchmark models for regulatory issues. The topics discussed herein are borderline product demarcation, probiotic foodstuff regulation, LBP development as biological medicine and the regulation of FMT.
In summary, the regulation of live microorganisms as foodstuff under the disputed umbrella term probiotic is complex and characterized by lower regulatory barriers than medicines which often leads to safety concerns. It is thus arguably ill-suited for these biological products, especially when they are used to treat immune-compromised individuals. On the other hand, the scientific and regulatory standards for the regulation of LBPs as medicines have become increasingly harmonized addressing their distinct characteristics and developmental challenges. Finally, FMT regulation remains at best fragmented. It is argued that a two-pronged approach with the development of standardized, well-defined products as well as legislation adaptation is required to enable faster development of these clinically promising procedures.
In conclusion, although insights are growing fast, more research is currently required to provide a deeper understanding of how the human microbiome determines health or disease, or how it can be beneficially modulated. However, one may rightly envisage a future with recombinant live microorganisms and bacteriophages used to ameliorate the risk of disease linked to the microbiome fuelled by a comprehensive systems biology understanding. The regulatory landscape will necessarily always adapt to strike a balance between consumer safety and providing access to novel technologies while incentivizing the development of well-characterized and high-quality products.
Pages: 76 | Annexes: 3, Pages: 3