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Selecting a pharmacologically relevant animal species for testing the safety and toxicity of novel monoclonal antibody (mAb) therapies to support clinical testing can be challenging. Frequently, the species of choice is the primate. With the increased number of mAbs in the pharmaceutical pipeline, this has significant implications for primate use, and so raises several important scientific, ethical and economic issues. Here, following a recent international workshop held to debate this topic, we discuss issues in the preclinical testing of mAbs, with a particular focus on species relevance and primate use, and provide suggestions for how these issues might be addressed. [ABSTRACT FROM AUTHOR]

The current animal-based paradigm for safety assessment must change. In September 2016, the UK National Centre for Replacement, Refinement and Reduction of Animals in Research (NC3Rs) brought together scientists from regulatory authorities, academia and industry to review progress in bringing new methodology into regulatory use, and to identify ways to expedite progress. Progress has been slow. Science is advancing to make this possible but changes are necessary. The new paradigm should allow new methodology to be adopted once it is developed rather than being based on a fixed set of studies. Regulatory authorities can help by developing Performance-Based Standards. The most pressing need is in repeat dose toxicology, although setting standards will be more complex than in areas such as sensitization. Performance standards should be aimed directly at human safety, not at reproducing the results of animal studies. Regulatory authorities can also aid progress towards the acceptance of non-animal based methodology by promoting “safe-haven” trials where traditional and new methodology data can be submitted in parallel to build up experience in the new methods. Industry can play its part in the acceptance of new methodology, by contributing to the setting of performance standards and by actively contributing to “safe-haven” trials. [ABSTRACT FROM AUTHOR]

It has been predicted that the use of non-human primates (NHPs) is going to increase considerably in the development of monoclonal antibodies (mAbs). Opportunities exist to focus on a rigorous, science-based approach to drug development, however, which will minimize this increase. In this article, the authors review current and future NHP use in mAb development based on surveys, experience and expert opinion and propose a framework that will minimize future NHP use and continue to support science and innovation. [Copyright &y& Elsevier]