Optimizing drug discovery by Investigative Toxicology: Current and future trends.

Autor:	Beilmann M; Nonclinical Drug Safety, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany., Boonen H; H. Lundbeck A/S, Valby, Denmark., Czich A; Sanofi Deutschland GmbH, Frankfurt, Germany., Dear G; Platform Technology & Science, David Jack Centre for R&D, GSK, Hertfordshire, UK., Hewitt P; Non Clinical Safety, Merck KGaA, Darmstadt, Germany., Mow T; Global Discovery and Development Sciences, Novo Nordisk A/S, Maaloev, Denmark., Newham P; Drug Safety and Metabolism, Astra Zeneca, Cambridge, UK., Oinonen T; Investigative Toxicology and ADME, Orion Pharma, Espoo, Finland., Pognan F; PreClinical Safety, Novartis Pharma, Basel, Switzerland., Roth A; Pharma Research and Early Development, Hoffmann-La Roche Ltd, Basel, Switzerland., Valentin JP; Development Science, UCB Biopharma SPRL, Braine-l'Alleud, Belgium., Van Goethem F; Mechanistic & Investigative Toxicology, Discovery Sciences, Janssen Research & Development, Beerse, Belgium., Weaver RJ; Research & Biopharmacy, Servier, Suresnes Cedex, France., Birk B; Experimental Toxicology and Ecology, BASF, Ludwigshafen, Germany., Boyer S; Computational Toxicology, Swedish Toxicological Sciences Research Center, Södertäljje, Sweden., Caloni F; Department of Veterinary Medicine (DIMEVET), Università degli Studi di Milano, Milan, Italy., Chen AE; Organovo, Inc., San Diego, CA, USA., Corvi R; EURL-ECVAM, Joint Research Center, European Commission, Ispra (VA), Italy., Cronin MTD; School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, England., Daneshian M; Center for Alternatives to Animal Testing (CAAT)-Europe, University of Konstanz, Konstanz, Germany., Ewart LC; Drug Safety and Metabolism, Astra Zeneca, Cambridge, UK., Fitzgerald RE; Swiss Centre for Applied Human Toxicology, SCAHT / University of Basel, Basel, Switzerland., Hamilton GA; Emulate Inc., Boston, MA, USA., Hartung T; Johns Hopkins University, CAAT, Baltimore, MD, USA.; Center for Alternatives to Animal Testing (CAAT)-Europe, University of Konstanz, Konstanz, Germany., Kangas JD; Computational Biology Department, Carnegie Mellon University, Pittsburgh, PA, USA., Kramer NI; Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands., Leist M; Center for Alternatives to Animal Testing (CAAT)-Europe, University of Konstanz, Konstanz, Germany., Marx U; TissUse, GmbH, Berlin Germany., Polak S; Certara UK (Simcyp), Sheffield, United Kingdom.; Jagiellonian University Medical College, Kraków, Poland., Rovida C; Center for Alternatives to Animal Testing (CAAT)-Europe, University of Konstanz, Konstanz, Germany., Testai E; Istituto Superiore di Sanità, Rome, Italy., Van der Water B; Division of Drug Discovery and Safety, Leiden Academic Centre for Drug Research (LACDR), Leiden University, RA Leiden, The Netherlands., Vulto P; Mimetas, Leiden, The Netherlands., Steger-Hartmann T; Research & Development, Pharmaceuticals, Investigational Toxicology, Bayer AG, Berlin, Germany.
Jazyk:	angličtina
Zdroj:	ALTEX [ALTEX] 2019; Vol. 36 (2), pp. 289-313. Date of Electronic Publication: 2018 Dec 20.
DOI:	10.14573/altex.1808181
Abstrakt:	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 adhering 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 improving preclinical decisions, which coincides with the concept of animal-free safety testing. Currently, compounds under preclinical development are being discarded due 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 the 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.
Databáze:	MEDLINE
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