A group of more than 40 industry, government and academic experts from all over Europe has reported that minipigs have many advantages for drug and chemical safety testing and could improve drug safety for humans.
The conclusions of the group’s RETHINK report, published today, deal with the impact and animal welfare implications of minipigs in safety testing of new medicines and other products. It was funded by the European Union. Minipigs are miniature pig breeds, easier to handle and better suited to a laboratory environment than farmyard pigs. The “Göttingen minipig”, developed at the University of Göttingen in Germany, and bred commercially in Denmark, is the leading breed in Europe.
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).
Minipigs are strains of domestic pigs that are markedly smaller than farmyard varieties, and thus better adapted to laboratory housing. The pig closely resembles man in many features of its anatomy, physiology, biochemistry and lifestyle.
In particular, the cardio-vascular system, skin and digestive tract are considered to be very good models for man. Because of these similarities the toxic effects of chemicals and drugs in pigs may resemble the effects in man more closely than do some other commonly used laboratory animals. The pig also has some features that make it a very practical model for laboratory studies.
Finally, being a food animal, testing in the minipig may be more acceptable to the public than animals such as dogs or monkeys. 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 RETHINK report includes 20 concrete proposals for actions or research to optimize the way in which minipigs are deployed in safety testing.
“The RETHINK report looks at minipigs from all angles,” said Dr Roy Forster, coordinator of the RETHINK project and Chief Scientific Officer at CIT, a non-clinical contract research organization in France. “The ethical issues of using minipigs were carefully addressed and we did not identify major differences compared to other non-rodent species.
"We reviewed handling and housing to be sure that their welfare is guaranteed during testing. We studied legal and technical guidance documents and found that minipig testing is fully accepted by regulatory authorities. On the scientific side, we assembled information on the minipig as a safety testing model and found close physiological and anatomical similarity to man. We also looked at the suitability of the minipig with powerful new technologies such as gene manipulation and genomics.
“All that we saw convinced us that the minipig has a very useful role to play in safety testing and it probably provides better prediction of drug safety for patients than traditional models such as rats and dogs. And in terms of animal welfare, we were able to show significant 3Rs (Reduction, Replacement, Refinement) benefits in comparison with the use of other large animal species.”
“We welcome this initiative to improve drug safety evaluation,” said Professor Beatriz Silva Lima, Chairperson of the Safety Working Party of the European Medicines Agency. “This report fills a gap in our knowledge on the usefulness of animals in safety testing and provides additional scientific basis for the selection of the best animal model.”
The RETHINK steering committee consists of the coordinator Roy Forster, Gerd Bode, pharmaceutical industry veteran, Lars Ellegaard, founder of the Ellegaard Minipigs breeding company, and Jan Willem van der Laan, senior assessor for pharmaceuticals with the Dutch Authorities. It is sending copies of the report to government agencies and committees around Europe within an invitation to comment on the report and on whether sufficient is being done to obtain its potential patient safety benefits.
The report is published as a special dedicated issue of the high-impact “Journal of Pharmacological and Toxicological Methods” and copies are by request at http://www.rethink-eu.dk
RETHINK
