ABSTRACT
The current EMA, FDA, and WHO guidelines for biosimilar development recommend a scientifically rigorous stepwise process that is different from that for generic small-molecule drugs. This chapter highlights the key recommendations included in the guidances for biosimilar development, focusing on those related to nonclinical development. Contrary to applications for generic medicinal products, animal studies have traditionally been requested for biosimilars from early on. While reviewing historical and current regulatory thinking on nonclinical testing of biosimilars and focusing on the evolution in the recommendations in the European Union (EU) guidelines, the chapter clarifies the shift in paradigm on the need for in vivo testing. The guideline indicates that these in vitro assays can be considered paramount for the nonclinical biosimilar comparability exercise, since in vitro assays may often be more specific and sensitive to detect differences between the biosimilar and the reference product than studies in animals (or humans). biosimilar development, nonclinical development, nonclinical testing, in vitro assays,.
