Opportunities for use of one species for longer-term toxicology testing during drug development: A cross-industry evaluation
| Autor: | Keith Jones, Michael K. Pugsley, Helen Booler, Wendy Roosen, Aidan McGuire, Jacques Richard, David Jones, Noel Downes, Ruth A. Roberts, Ankie Schoenmakers, Mark Holbrook, Andreas Rothfuss, Julia Hui, Paul Brown, Marjorie A. Peraza, S.G. Moesgaard, Helen Prior, Sonja Beken, Meghan Flaherty, Leigh Ann Burns-Naas, Ian Kimber, Melissa Chapman, Lolke de Haan, Olaf Doehr, Richard J. Weaver, Paul Brooker, Nichola Gellatly, Brian Burlinson, Elisabeth Mortimer-Cassen, Hilla Kedar, Nancy Bower, Lucinda Weir, Andreas Mahl, Alison Wolfreys, Jennifer Harris, Alli Manninen, David W. Clarke, Warren Casey, Paul Baldrick, Fiona Sewell |
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| Rok vydání: | 2020 |
| Předmět: |
Drug
Databases Factual media_common.quotation_subject Drug Evaluation Preclinical Computational biology 010501 environmental sciences Toxicology Risk Assessment 030226 pharmacology & pharmacy 01 natural sciences Toxicology studies 03 medical and health sciences 0302 clinical medicine Drug Development Toxicity Tests Animals Humans 0105 earth and related environmental sciences media_common Toxicology testing Modalities Modality (human–computer interaction) General Medicine Guideline Data sharing Drug development Business |
| Zdroj: | Regulatory Toxicology and Pharmacology. 113:104624 |
| ISSN: | 0273-2300 |
| Popis: | An international expert working group representing 37 organisations (pharmaceutical/biotechnology companies, contract research organisations, academic institutions and regulatory bodies) collaborated in a data sharing exercise to evaluate the utility of two species within regulatory general toxicology studies. Anonymised data on 172 drug candidates (92 small molecules, 46 monoclonal antibodies, 15 recombinant proteins, 13 synthetic peptides and 6 antibody-drug conjugates) were submitted by 18 organisations. The use of one or two species across molecule types, the frequency for reduction to a single species within the package of general toxicology studies, and a comparison of target organ toxicities identified in each species in both short and longer-term studies were determined. Reduction to a single species for longer-term toxicity studies, as used for the development of biologicals (ICHS6(R1) guideline) was only applied for 8/133 drug candidates, but might have been possible for more, regardless of drug modality, as similar target organ toxicity profiles were identified in the short-term studies. However, definition and harmonisation around the criteria for similarity of toxicity profiles is needed to enable wider consideration of these principles. Analysis of a more robust dataset would be required to provide clear, evidence-based recommendations for expansion of these principles to small molecules or other modalities where two species toxicity testing is currently recommended. |
| Databáze: | OpenAIRE |
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