419-35 We do not believe that such Suggested specific recommendations replacement text: for log-drops and specific on the current infections or levels” body of evidence, it “burden are supported by adequate is not possible to data for all drugs and all broadly specify models of infection such levels of bacterial that specific thresholds killing in in vitro and would be stated in the in animal models of guidance. infection that relate Suggest replacement of to efficacy at text in 419-35 with the specific sites of following points for infections or consideration: indications in patients. A drug’s Sponsor should justify the mechanism(s) of selection of the target action and based on the totality of the resistance, inoculum data, which includes size, and duration of consideration of: therapy in the Mode of action and model are among drug class several factors that Resistance development preclude generalized Endpoint and timing recommendations. (e.g., rapidity of clinical and microbiological However, there may response) be instances where Linkage (where one can use possible) to other previously derived
419-35 We do not believe that such specific recommendations for log-drops and specific infections or “burden levels” are supported by adequate data for all drugs and all models of infection such that specific thresholds would be stated in the guidance. Suggest replacement of text in 419-35 with the following points for consideration: Sponsor should justify the selection of the target based on the totality of the data, which includes consideration of: Mode of action and drug class Resistance development Endpoint and timing (e.g., rapidity of clinical and microbiological response) Linkage (where possible) to other Suggested replacement text: on the current body of evidence, it is not possible to broadly specify levels of bacterial killing in in vitro and in animal models of infection that relate to efficacy at specific sites of infections or indications in patients. A drug’s mechanism(s) of action and resistance, inoculum size, and duration of therapy in the model are among several factors that preclude generalized recommendations. However, there may be instances where one can use previously derived