344 350 We agree that an early read Break these lines – of the PK in patients is into 2 parts and important so that the change to: population PK model data should be “PK generated with healthy obtained from volunteer data can be patients typical of updated with patient the intended target specific data and used to population in terms confirm the dose/exposure of site of infection for larger clinical studies. and severity of infection (but We do not agree with regardless of specifying the sample pathogen design. The guidance susceptibility) as should point to the need for early as possible in a sample design that allows development and development of a robust should be used to model and accurate/precise update the POPPK PK parameter estimates to model based on be obtained. healthy volunteer data. The updated model can support repeat PK-PD analyses and simulation to confirm or reject the likely sufficiency of the dose regimen before proceeding
344 – 350 We agree that an early read of the PK in patients is important so that the population PK model generated with healthy volunteer data can be updated with patient specific data and used to confirm the dose/exposure for larger clinical studies. We do not agree with specifying the sample design. The guidance should point to the need for a sample design that allows development of a robust model and accurate/precise PK parameter estimates to be obtained. Break these lines into 2 parts and change to: “PK data should be obtained from patients typical of the intended target population in terms of site of infection and severity of infection (but regardless of pathogen susceptibility) as early as possible in development and should be used to update the POPPK model based on healthy volunteer data. The updated model can support repeat PK-PD analyses and simulation to confirm or reject the likely sufficiency of the dose regimen before proceeding
efpia_comments_draft_guideline_ema_pk-pd_antibacterial_final.docx