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.

Toxicity studies of drugs and chemicals in animals: an overview

“…Nonsigmoidal model should be used with caution as it may underestimate the risk (Oberg et al, 2014a). Therefore, there is need for revision of the current doseresponse model selection paradigm, e. g. as expressed in the expert opinion from European Food Safety Agency (EFSA) and in the current modelling software in which dose-response/effect models are selected based on principle of Ocham's razor (Oberg et al, 2014b). In the European Union, under REACH regulation, companies are faced with the need to phase out chemicals of very high concern and are challenged to identify and demonstrate the safety of chemical alternatives.…”

Optimization of Zebrafish Larvae Sectioning for Mass Spectrometry Imaging

“…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 [ 1 ]. Among the many methods that lead the way towards a more humane situation in animal testing, the use of zebrafish larvae follows the principle of the 3Rs as required by national and international regulatory bodies.…”