Review of the use of a second species in regulatory studies

Current regulatory guidelines usually require safety and tolerability data from two species, a rodent (rat or mouse) and a non-rodent (dog, minipig or non-human primate), before administration of potential new medicines to humans in the first clinical trials. In the UK in 2015, animals used for repeat dose toxicity testing purposes (just one of the safety tests conducted) amounted to 9,636 experimental procedures using mice, 29,597 experimental procedures using rats, 2,454 experimental procedures using dogs and 1,330 experimental procedures using non-human primates (data from 2015 Home Office statistics). Obviously the UK is only one of the countries performing these tests and it is impossible to estimate how many animals are used by the industry as a whole worldwide. Many of these regulatory toxicology tests were introduced 30 or 40 years ago - the pharmaceutical industry has changed considerably in the intervening years with new drug targets, new types of compounds and new in vitro and in silico technologies available to evaluate safety. Where appropriate, regulatory requirements have evolved and been updated to adopt in vitro tests, refine in vivo tests and reduce the numbers of animals used. This project is a further opportunity to review whether the standard testing paradigm can be modified, to provide an evidence base to propose updates with regards to the need for two species.

The scope of this ABPI-funded project will encompass a number of different questions and aspects within the regulatory toxicology package, as outlined in the figure below. Some of these areas are already being investigated by other international industry consortia and we will interact and collaborate wherever possible to reduce duplication in effort whilst maximising opportunities to leverage change. Initially, we intend to focus on whether data from one relevant species could be sufficient for the progression of a potential new drug in human clinical trials (the light green box in the figure below).

We are convening a steering group of expert industry and regulatory scientists to oversee this project, which will involve data sharing of published and unpublished data. We encourage questions and offers for participation from biopharmaceutical companies and contract research organisations worldwide. Please contact Dr Helen Prior for more information.  

Prior H et al. (2018). Reviewing the Utility of Two Species in General Toxicology Related to Drug Development. International Journal of Toxicology 37(2): 121-124. doi:10.1177/1091581818760564

Back to top