361 363 We agree with the Change to: – “As importance of obtaining relevant to the test drug concentration data at agent and its bodily sites more relevant intended clinical to the site of infection in uses, test agent both preclinical animal concentration-time efficacy studies and in data should be humans. But, we remain presented for concerned about the specific body fluids limitations and use of data and related to obtained at body sites plasma/serum levels outside of plasma and using would offer two points for compartmental PK consideration. modeling.” First, we would not specify (line 361) as free “free” drug is not always specifically assayed for (e.g., ELF). Second, and using ELF as an example, limitations of the data (BAL collection methodology, sampling limitations, drug/urea assay quality) and the influence of these limitations on measurement variability are
361 – 363 We agree with the importance of obtaining drug concentration data at bodily sites more relevant to the site of infection in both preclinical animal efficacy studies and in humans. But, we remain concerned about the limitations and use of data obtained at body sites outside of plasma and would offer two points for consideration. First, we would not specify “free” (line 361) as free drug is not always specifically assayed for (e.g., ELF). Second, and using ELF as an example, limitations of the data (BAL collection methodology, sampling limitations, drug/urea assay quality) and the influence of these limitations on measurement variability are Change to: “As relevant to the test agent and its intended clinical uses, test agent concentration-time data should be presented for specific body fluids and related to plasma/serum levels using compartmental PK modeling.”
efpia_comments_draft_guideline_ema_pk-pd_antibacterial_final.docx