title: Strategic focus on 3R principles reveals major reductions in the use of animals in pharmaceutical toxicity testing.
abstract: The principles of the 3Rs, Replacement, Reduction and Refinement, are being increasingly incorporated into legislations, guidelines and practice of animal experiments in order to safeguard animal welfare. In the present study we have studied the systematic application of 3R principles to toxicological research in the pharmaceutical industry, with particular focus on achieving reductions in animal numbers used in regulatory and investigatory in vivo studies. The work also details major factors influencing these reductions including the conception of ideas, cross-departmental working and acceptance into the work process. Data from 36 reduction projects were collected retrospectively from work between 2006 and 2010. Substantial reduction in animal use was achieved by different strategies, including improved study design, method development and project coordination. Major animal savings were shown in both regulatory and investigative safety studies. If a similar (i.e. 53%) reduction had been achieved simultaneously within the twelve largest pharmaceutical companies, the equivalent reduction world-wide would be about 150,000 rats annually. The results point at the importance of a strong 3R culture, with scientific engagement, collaboration and a responsive management being vital components. A strong commitment in leadership for the 3R is recommended to be translated into cross-department and inter-profession involvement in projects for innovation, validation and implementation. Synergies between all the three Rs are observed and conclude that in silico-, in vitro- and in vivo-methods all hold the potential for applying the reduction R and should be consequently coordinated at a strategic level.
authors: Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Former AstraZeneca R&D, Södertälje, Sweden.
authors: Elin
authors: E
authors: Törnqvist
authors: Former AstraZeneca R&D, Södertälje, Sweden.
authors: Anita
authors: A
authors: Annas
authors: Former AstraZeneca R&D, Södertälje, Sweden; Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors: Britta
authors: B
authors: Granath
authors: Former AstraZeneca R&D, Södertälje, Sweden; Karolinska University Hospital, Stockholm, Sweden.
authors: Elisabeth
authors: E
authors: Jalkesten
authors: Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Former AstraZeneca R&D, Södertälje, Sweden; Swedish Toxicology Sciences Research Center, Södertälje, Sweden.
authors: Ian
authors: I
authors: Cotgreave
authors: Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Swedish Toxicology Sciences Research Center, Södertälje, Sweden.
authors: Mattias
authors: M
authors: Öberg
mesh_terms: D032761:Animal Experimentation / Q000592:standards; D000826:Animal Testing Alternatives / Q000379:methods*; D000827:Animal Welfare / Q000592:standards; D000818:Animals; D035843:Biomedical Research / Q000379:methods / Q000639:trends; D003299:Cooperative Behavior; D004285:Dogs; D004353:Drug Evaluation, Preclinical / Q000379:methods* / Q000639:trends; D004345:Drug Industry / Q000379:methods* / Q000639:trends; D006801:Humans; D051379:Mice; D011817:Rabbits; D051381:Rats; D015203:Reproducibility of Results; D012107:Research Design; D018675:Toxicity Tests / Q000379:methods* / Q000639:trends