Optimizing drug discovery by Investigative Toxicology: Current and future trends

Investigative toxicology describes the de-risking and mechanistic elucidation of toxicities, supporting early safety decisions in the pharmaceutical industry. Recently, investigative toxicology has contributed to a shift in pharmaceutical toxicology, from a descriptive to an evidence-based, mechanistic discipline. This was triggered by high costs and low throughput of Good Laboratory Practice in vivo studies, and increasing demands for adherence to the 3R (Replacement, Reduction, and Refinement) principles of animal welfare. Outside the boundaries of regulatory toxicology, investigative toxicology has the flexibility to embrace new technologies, enhancing translational steps from in silico, in vitro to in vivo mechanistic understanding to eventually predict human response. One major goal of investigative toxicology is to improve preclinical decisions, which coincides with the concept of animal-free safety testing. Currently, compounds under preclinical development are being discarded owing to the use of inappropriate animal models. Progress in investigative toxicology could lead to humanized in vitro test systems and the development of medicines less reliant on animal tests. To advance this field, a group of 14 European-based leaders from the pharmaceutical industry founded the Investigative Toxicology Leaders Forum (ITLF), an open, non-exclusive, and pre-competitive group that shares knowledge and experience. The ITLF collaborated with the Centre for Alternatives to Animal Testing Europe (CAAT-Europe) to organize an “Investigative Toxicology Think Tank”, which aimed to enhance interaction with experts from academia and regulatory bodies in the field. Summarizing the topics and discussion of the workshop, this article highlights investigative toxicology’s position by identifying key challenges and perspectives.

BEILMANN M.;  BOONEN Harrie;  CZICH Andreas;  DEAR Gordon;  HEWITT Philip;  MOW Thomas;  NEWHAM Peter;  OINONEN Teija;  POGNAN Francois;  ROTH Adrian;  VALENTIN Jean-Pierre;  VAN GOETHEM Freddy;  WEAVER R. J.;  BIRK Barbara;  BOYER Scott;  CALONI Francesca;  CHEN Alice;  CORVI Raffaella;  CRONIN Mark;  DANESHIAN Mardas;  EWART Lorna C.;  FITZGERALD Rex;  HAMILTON Geraldine;  HARTUNG T.;  KANGAS Joshua D.;  KRAMER Nynke;  LEIST Marcel;  MARX Uwe;  POLAK Sebastian;  ROVIDA Costanza;  TESTAI Emanuela;  VAN DE WATER Bob;  VULTO Paul;  STEGER-HARTMANN Thomas; 

2021-06-30

SPEKTRUM AKADEMISCHER VERLAG-SPRINGER-VERLAG GMBH

JRC112900

1868-596X (online),   

https://www.altex.org/index.php/altex/article/view/1163,    https://publications.jrc.ec.europa.eu/repository/handle/JRC112900,   

10.14573/altex.1808181 (online),