Main goals of safety evaluation are:
(1) to identify an initial safe starting dose, (2) to identify potential target organ toxicity and their reversibility and (3) to identify safety parameters for clinical monitoring.
Development plans need to be adapted
According, at least, to ICH S6 (biotechnology products), and ICH S9 (for oncology products) as well as EMA (FIH trials, 2007). Main specificities include species selection (toxicology studies should be conducted in a pharmacology relevant species, as such only one species could be accepted), study design and duration, immunogenicity (ADA), reproductive toxicity and carcinogenicity.
Starting dose selection for First in human
Various approaches could be elaborated based on NOAEL, HED, MRSD (as per FDA 2005) or MABEL (EMA, 2007).
