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.

Animal Study and Pre-clinical Trials of Biomaterials

“…: (1) Medical research involving human subjects must conform to generally accepted scientific principles, be based on a thorough knowledge of the scientific literature, other relevant sources of information, and on adequate laboratory and, where appropriate, animal experimentation; (2) Appropriate caution must be exercised in the conduct of research which may affect the environment, and the welfare of animals used for research must be respected. The ethical use of animals in doing research should follow the instruction and recommendations of international standards (Grimm 2014;Guhad 2005; Törnqvist et al 2014). Russell and Burch (1959) were the first people that stated the idea of the use of animals in doing research which was expected to follow the rules of 3 R (The "three R principle").…”

Multi-omics analysis of ten carbon nanomaterials effects highlights cell type specific patterns of molecular regulation and adaptation

“…However, responding to the constant pressure in developing reliable and efficient alternative screening methods, many studies tried to predict the potential ENMs effects in vivo by analyzing their effects in vitro (Drasler et al, 2017;Braakhuis, 2015;Törnqvist et al, 2014;Bachler et al, 2015). We recently demonstrated that carbon based nanomaterials have distinct transcriptional MOA between in vivo and in vitro experimental settings and that commonalities are to be found by using comprehensive gene network models (Kinaret et al, 2017b).…”

Hepatotoxicity prediction by systems biology modeling of disturbed metabolic pathways using gene expression data

“…Growing pressures from major initiatives currently under way such as the European regulation REACH (Gleeson et al, 2012) and the widely-accepted adoption of the 3Rs principles (Replacement, Reduction and Refinement) for toxicity testing (Törnqvist et al, 2014) urge their replacement.…”