Have Population PK analyses been conducted and have all important covariates been explored to explain interindividual or intra-individual variability in PK? Do exposure-response or PK/PD analyses together with clinical data suggest that unexplained or explained variability in PK may change the benefit-risk profile of the medicine in certain clinical scenarios and thus specific risk minimisation measures should be included in the RMP such as restrictions/precautions/dose adjustments in special populations or therapeutic drug monitoring or a post- safety or efficacy study. Interactions Critical presentation of study results. Comments on drug-drug interactions should be provided if data are available (the presentation of data should be similar to preceding sections and should preferably be included in a summary table). • In vitro Data from CTD module 5.3.2 in-vitro studies using human biomaterials. Assessor’s comment • In Silico Populate with data from various eCTD modules depending on the question being answered. Discuss the role of PBPK models. How do simulated data compare to the in vivo data. Discuss confidence in in–silico predictions based on submitted or literature data and the impact on dosing recommendations. Is the in house or commercial PBPK platform qualified for the intended purpose? Assessor’s comment • In vivo Data from CTD module 5.3.3.4 Extrinsic factor PK study reports.
Have Population PK analyses been conducted and have all important covariates been explored to explain interindividual or intra-individual variability in PK? Do exposure-response or PK/PD analyses together with clinical data suggest that unexplained or explained variability in PK may change the benefit-risk profile of the medicine in certain clinical scenarios and thus specific risk minimisation measures should be included in the RMP such as restrictions/precautions/dose adjustments in special populations or therapeutic drug monitoring or a safety or efficacy study. Interactions Critical presentation of study results. Comments on drug-drug interactions should be provided if data are available (the presentation of data should be similar to preceding sections and should preferably be included in a summary table). • In vitro Data from CTD module 5.3.2 in-vitro studies using human biomaterials. Assessor’s comment • In Silico Populate with data from various eCTD modules depending on the question being answered. Discuss the role of PBPK models. How do simulated data compare to the in vivo data. Discuss confidence in in–silico predictions based on submitted or literature data and the impact on dosing recommendations. Is the in house or commercial PBPK platform qualified for the intended purpose? Assessor’s comment • In vivo Data from CTD module 5.3.3.4 Extrinsic factor PK study reports. post-
WC500187042.docx