Optimizing drug discovery by investigative toxicology: Current and future trends

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Mario Beilmann
Harrie Boonen
Andreas Czich
Gordon Dear
Philip Hewitt
Tomas Mow
Peter Newham
Teija Oinonen
Francois Pognan
Adrian Roth
Jean-Pierre Valentin
Freddy Van Goethem
Richard J. Weaver
Barbara Birk
Scott Boyer
Francesca Caloni
Alice E. Chen
Raffaella Corvi
Mark T. D. Cronin
Mardas Daneshian
Lorna C. Ewart
Rex E. Fitzgerald
Geraldine A. Hamilton
Thomas Hartung
http://orcid.org/0000-0003-1359-7689
Joshua D. Kangas
Nynke I. Kramer
Marcel Leist
http://orcid.org/0000-0002-3778-8693
Uwe Marx
Sebastian Polak
Costanza Rovida
Emanuela Testai
Bob van der Water
Paul Vulto
Thomas Steger-Hartmann

Abstract

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.

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How to Cite
Beilmann, M., Boonen, H., Czich, A., Dear, G., Hewitt, P., Mow, T., Newham, P., Oinonen, T., Pognan, F., Roth, A., Valentin, J.-P., Van Goethem, F., Weaver, R., Birk, B., Boyer, S., Caloni, F., Chen, A., Corvi, R., Cronin, M., Daneshian, M., Ewart, L., Fitzgerald, R., Hamilton, G., Hartung, T., Kangas, J., Kramer, N., Leist, M., Marx, U., Polak, S., Rovida, C., Testai, E., van der Water, B., Vulto, P. and Steger-Hartmann, T. (2019) “Optimizing drug discovery by investigative toxicology: Current and future trends”, ALTEX - Alternatives to animal experimentation, 36(2), pp. 289-313. doi: 10.14573/altex.1808181.
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