Considerations Regarding the Future Use of Nonhuman Primates to Support the Clinical Development of Biopharmaceuticals

Preclinical safety evaluation aims to support clinical trial initiation and subsequent progress through studies according to guidelines provided by The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (International Conference on Harmonisation, ICH). For biopharmaceuticals, the ICH S6 guideline (1996) was unique in primarily recommending a basic framework for preclinical safety evaluation rather than prescribing study design set(s). Although preceding establishment of the “3Rs” (replace, reduce, refine), the guidance was consistent with those principles. Despite stressing the importance of selecting relevant animal species for toxicity assessment, it omitted the term most relevant to avoid nonhuman primate (NHP) species as the systematic first choice. Over the years, accumulated knowledge of specific products, product classes, and across various product classes led to improved preclinical developments, but NHP use increased rather than decreased, in large part to be more consistent with the practices used for pharmaceuticals (ICH M3). Therefore, the addendum (ICH S6 (R1), 2012) reinforced the importance of an alternative approach based on product attributes explicitly addressing the “3R” principles, and it expanded topics especially relevant to NHP use (species selection, study design, immunogenicity, reproductive toxicity). In vitro alternative methods for safety evaluation are also referred and encouraged. This chapter addresses the use and usefulness of NHP research, particularly for biopharmaceutical safety assessment, and discusses its future effect by emerging scientific and technological advances, including in vitro, human-based systems.