Minimising non-human primate use in drug development

The NC3Rs has a long history of projects that have identified opportunities to minimise the use of non-human primates (NHPs) in toxicology programmes. This page provides an overview of all our activities and recommendations in this area.

Optimal duration of mAb chronic studies

The NC3Rs was involved in a project funded and supported by the European Partnership for Alternative Approaches to Animal Testing (EPAA) including 14 pharmaceutical companies and the Netherlands Medicines Evaluation Board (MEB) to evaluate whether a 6-month toxicity study is still necessary to assess the long-term safety of mAbs.

The project led to the development of a weight-of-evidence (WoE) model to suggest when three-month toxicity studies are likely sufficient to support late-stage clinical development and registration for some mAbs.

The data collected for the project also enabled a review of study designs and current practices on animal use during mAb development and identification of opportunities to minimise the use of NHPs.

You can read more about this project on our project page: Re-evaluating the need for mAb chronic toxicity studies.

Study design recommendations

• Group sizes (main test): use 3M+3F for all pivotal studies (short-term and longer term studies).
• Number of groups: control + 2 dose levels.
• Number of studies: no more than two pivotal repeat dose studies (one short-term and one long-term study).

Species relevance

Rodents are a pharmacologically-relevant species for many mAbs. It is critical to maximise the information derived from the rat or mouse, to further minimise the use of NHPs and avoid the risk of a two species approach becoming common practice for safety studies.

Biosimilars

Testing requirements for approval of biosimilars differ widely from one country to another with some requiring extensive animal testing. We identified widespread opportunities for waiving NHP studies and encouraging in vitro testing for biosimilars.

You can read more about all these projects on our project page: Reducing animal use in monoclonal antibody development.

There are opportunities to reduce to a single species for longer term toxicity studies, when similar toxicities are identified in earlier studies in two species. This is currently permitted for biologics, but we have shown that it could also be applicable for small molecules and other drug modalities.

You can read more about this project on our project page: Review of the use of two species in regulatory toxicology studies.

Recovery animals should only be included for scientific reasons and in later (rather than earlier) studies, once the toxicological profile is known. If required, group size should be 2M+2F for control + one dose group only.

You can read more about this project on our project page: Reducing the use of recovery animals.