Optimizing drug discovery by investigative toxicology: Current and future trends

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 DaneshianLorna C. Ewart, Rex E. FitzGerald, Geraldine A. Hamilton, Thomas Hartung, Joshua D. Kangas, Nynke I. Kramer, Marcel Leist, Uwe Marx, Sebastian Polak, Costanza Rovida, Emanuela Testai, Bob Van de Water, Paul Vulto, Thomas Steger-Hartmann

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)289-313
Number of pages25
JournalALTEX
Volume36
Issue number2
DOIs
StatePublished - 2019

ASJC Scopus subject areas

  • Pharmacology
  • Medical Laboratory Technology

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  • Cite this

    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. J., Birk, B., Boyer, S., Caloni, F., Chen, A. E., Corvi, R., Cronin, M. T. D., ... Steger-Hartmann, T. (2019). Optimizing drug discovery by investigative toxicology: Current and future trends. ALTEX, 36(2), 289-313. https://doi.org/10.14573/altex.1808181