The RETHINK project on minipigs in the toxicity testing of new medicines and chemicals: conclusions and recommendations.

The objective of the RETHINK project was to evaluate the potential impact of toxicity testing in the minipig as an alternative approach in regulatory toxicity testing that can contribute to the replacement, refinement and reduction of animal testing (3Rs). Expert study groups (Working Groups) were assembled to review five different areas relating to the use of minipigs in regulatory safety testing: ethical issues, welfare and animal care, development of new medicines and chemicals, safety testing issues and emerging technologies in safety testing. The conclusions and recommendations of the projects are presented in this article. It is concluded that there are no specific areas where restrictions to the use of minipigs in toxicology are required for welfare reasons. The minipig model is generally acceptable to regulatory authorities, provided it is adequately justified. The minipig is an interesting model for safety testing since there are numerous anatomical, physiological, genetic and biochemical similarities to humans. In addition many features of the minipig make it a practical and flexible model for safety testing. The use of the minipig in development of products does not bring any financial penalty in terms of the cost of testing. Benefits in terms of 3Rs can be identified in terms of life-cycle analysis of the use of minipigs compared to dogs and non-human primates. Finally the minipig (unlike the dog) is well positioned to take advantage of genomics and gene manipulation technologies. Specific recommendations for further research are made, which could bring 3Rs benefits. To deploy the minipig to the best advantage, clear information is needed about the predictivity of the minipig for human toxicities, and focussed action to define the potential role of the minipig in testing of biologics.