@ARTICLE{10.3389/fmed.2020.00237, AUTHOR={Rouanet, Alice and Bolca, Selin and Bru, Audrey and Claes, Ingmar and Cvejic, Helene and Girgis, Haymen and Harper, Ashton and Lavergne, Sidonie N. and Mathys, Sophie and Pane, Marco and Pot, Bruno and Shortt, Colette and Alkema, Wynand and Bezulowsky, Constance and Blanquet-Diot, Stephanie and Chassard, Christophe and Claus, Sandrine P. and Hadida, Benjamin and Hemmingsen, Charlotte and Jeune, Cyrille and Lindman, Björn and Midzi, Garikai and Mogna, Luca and Movitz, Charlotta and Nasir, Nail and Oberreither, Manfred and Seegers, Jos F. M. L. and Sterkman, Luc and Valo, Audrey and Vieville, Frédérique and Cordaillat-Simmons, Magali}, TITLE={Live Biotherapeutic Products, A Road Map for Safety Assessment}, JOURNAL={Frontiers in Medicine}, VOLUME={7}, YEAR={2020}, URL={https://www.frontiersin.org/articles/10.3389/fmed.2020.00237}, DOI={10.3389/fmed.2020.00237}, ISSN={2296-858X}, ABSTRACT={Recent developments in the understanding of the relationship between the microbiota and its host have provided evidence regarding the therapeutic potential of selected microorganisms to prevent or treat disease. According to Directive 2001/83/EC, in the European Union (EU), any product intended to prevent or treat disease is defined as a medicinal product and requires a marketing authorization by competent authorities prior to commercialization. Even if the pharmaceutical regulatory framework is harmonized at the EU level, obtaining marketing authorisations for medicinal products remains very challenging for Live Biotherapeutic Products (LBPs). Compared to other medicinal products currently on the market, safety assessment of LBPs represents a real challenge because of their specific characteristics and mode of action. Indeed, LBPs are not intended to reach the systemic circulation targeting distant organs, tissues, or receptors, but rather exert their effect through direct interactions with the complex native microbiota and/or the modulation of complex host-microbiota relation, indirectly leading to distant biological effects within the host. Hence, developers must rely on a thorough risk analysis, and pharmaceutical guidelines for other biological products should be taken into account in order to design relevant non-clinical and clinical development programmes. Here we aim at providing a roadmap for a risk analysis that takes into account the specificities of LBPs. We describe the different risks associated with these products and their interactions with the patient. Then, from that risk assessment, we propose solutions to design non-clinical programmes and First in Human (FIH) early clinical trials appropriate to assess LBP safety.} }