354 360 If a drug is not highly Change to: – “The protein and there is no degree of binding of in vitro evidence of the test agent to concentration-dependent human plasma binding, further study is not proteins in the needed. Non-linear binding presence of clinically may need to be addressed relevant by measuring free concentrations concentration in a study or should be assessed. using a model-based Initially, this is approach [e.g., Singh et al. typically done in CP&T 2014; vitro. For drugs with 95(suppl.1):S87]. non-linear binding, Technical difficulties in if technically measuring protein binding feasible, further may be an issue. assessment may be necessary during drug development.”
354 – 360 If a drug is not highly protein and there is no in vitro evidence of concentration-dependent binding, further study is not needed. Non-linear binding may need to be addressed by measuring free concentration in a study or using a model-based approach [e.g., Singh et al. CP&T 2014; 95(suppl.1):S87]. Technical difficulties in measuring protein binding may be an issue. Change to: “The degree of binding of the test agent to human plasma proteins in the presence of clinically relevant concentrations should be assessed. Initially, this is typically done in vitro. For drugs with non-linear binding, if technically feasible, further assessment may be necessary during drug development.”
efpia_comments_draft_guideline_ema_pk-pd_antibacterial_final.docx