TY - JOUR
T1 - Live biotherapeutic products, a roadmap for safety assessment
AU - Rouanet, Alice
AU - Bolca, Selin
AU - Bru, Audrey
AU - Claes, Ingmar
AU - Cvejic, Helene
AU - Girgis, Haymen
AU - Harper, Ashton
AU - Lavergne, Sidonie N
AU - Mathys, Sophie
AU - Pane, Marco
AU - Pot, Bruno
AU - Shortt, Colette
AU - Alkema, Wynand
AU - Bezulowsky, Constance
AU - Blanquet-Diot, Stephanie
AU - Chassard, Christophe
AU - Claus, Sandrine P
AU - Hadida, Benjamin
AU - Hemmingsen, Charlotte
AU - Jeune, Cyrille
AU - Lindman, Björn
AU - Midzi, Garikai
AU - Mogna, Luca
AU - Movitz, Charlotta
AU - Nasir, Nail
AU - Oberreither, Manfred
AU - Seegers, Jos F M L
AU - Sterkman, Luc
AU - Valo, Audrey
AU - Vieville, Frédérique
AU - Cordaillat-Simmons, Magali
N1 - Copyright © 2020 Rouanet, Bolca, Bru, Claes, Cvejic, Girgis, Harper, Lavergne, Mathys, Pane, Pot, Shortt, Alkema, Bezulowsky, Blanquet-Diot, Chassard, Claus, Hadida, Hemmingsen, Jeune, Lindman, Midzi, Mogna, Movitz, Nasir, Oberreither, Seegers, Sterkman, Valo, Vieville and Cordaillat-Simmons.
PY - 2020
Y1 - 2020
N2 - Recent developments in the understanding of the relationship between the microbiotica 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.
AB - Recent developments in the understanding of the relationship between the microbiotica 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.
KW - Probiotics
KW - nutrition
KW - bacteria
KW - toxicity
KW - probiotica
KW - bacteriën
KW - voeding
KW - toxiciteit
UR - https://www.mendeley.com/catalogue/61e50ebd-5ff6-363b-ac65-633ec5d14516/
U2 - 10.3389/fmed.2020.00237
DO - 10.3389/fmed.2020.00237
M3 - Article
C2 - 32637416
VL - 7
JO - Frontiers in Medicine
JF - Frontiers in Medicine
SN - 2296-858X
M1 - 237
ER -