Preclinical development of monoclonal antibodies: considerations for the use of non-human primates

Abstract

The development of mAbs remains high on the therapeutic agenda for the majority of pharmaceutical and biotechnology companies. Often, the only relevant species for preclinical safety assessment of mAbs are non-human primates (NHPs), and this raises important scientific, ethical and economic issues. To investigate evidence-based opportunities to minimize the use of NHPs, an expert working group with representatives from leading pharmaceutical and biotechnology companies, contract research organizations and institutes from Europe and the USA, has shared and analyzed data on mAbs for a range of therapeutic areas. This information has been applied to hypothetical examples to recommend scientifically appropriate development pathways and study designs for a variety of potential mAbs. The addendum of ICHS6 provides a timely opportunity for the scientific and regulatory community to embrace strategies which minimize primate use and increase efficiency of mAb development.

Figure 1

Scheme showing the studies carried out for a general mAb development program. Adapted from Chapman et al. 2007.

Figure 2

Flow diagram illustrating important considerations for determining species relevance and how these might be used to inform decisions on NHP studies.

Figure 3

Flow diagram incorporating general principles that inform decisions around NHP use, e.g., the therapeutic area and intended clinical dosing regime. Areas where there are potential to minimize NHP use are illustrated.