The design of chronic toxicology studies of monoclonal antibodies: Implications for the reduction in use of non-human primates

Alternative methods for the use of non-human primates in biomedical research

“…A data collection and registration system was proposed and NC3Rs mentioned that they are already working on this topic. NC3Rs and other groups saw additional 3Rs possibilities in the improvement of NHP safety study design (Chapman et al, 2012(Chapman et al, , 2013. Although much of this work has been published, not all companies have adapted their study designs accordingly.…”

“…Over the last years, NC3Rs have organized workshops, brought together working groups and published on their findings. Regarding NHP, NC3Rs have focused on the role of NHP in the development of monoclonal antibody (mAb)-based therapies, and on study design of chronic toxicity and reproductive toxicity studies that use NHP (Chapman et al, 2009(Chapman et al, , 2010(Chapman et al, , 2012(Chapman et al, , 2013. For mAb-studies, it should be noted that NHP are not necessarily the primary species of choice.…”

Developmental and Reproductive Toxicity Testing

“…Recent developments in regulations governing the use of primates demand social housing (either in pairs or groups) whenever possible [13]. Although it is evident that NHPs generally benefit from social housing [51] (refer also to Chapters 14 and 15 in this book), systematic studies on the effects of social housing of cynomolgus monkeys in the context of reproductive toxicity evaluation are limited.…”

“…Importantly, species selection should be based on the pharmacological relevance of the chosen species rather than a default approach (ICH S6(R1)), and it is not uncommon that NHPs represent the only relevant animal model. As a consequence of more biopharmaceuticals being developed, conducting DART studies using the NHP model is now more common, and NHPs are recognized as an important model for DART evaluation of monoclonal antibodies (mAbs) [13]. For example, in a review of the European Medicines Agency database through 2010, NHPs were used for 23 of 30 mAbs evaluated preclinically in DART studies [14].…”

Toxicity Testing in the 21st Century: Challenges and Perspectives

“…Due to the often exclusive species specificity of monoclonal antibodies, the nonhuman primate is in many cases the only relevant species for nonclinical safety assessment. Some areas for optimization have been identified [13,14] and some practical measures such as the inclusion of safety pharmacology endpoints in toxicology studies or the implementation of the so-called enhanced Pre-and Postnatal Development (ePPND) study design [15,16] in regulatory guidance documents, are already in place. Both approaches eliminate the need for stand-alone safety pharmacology or embryo-fetal development studies and thus reduce the number of animals used.…”