STREAMLINING FOOD EFFECT ASSESSMENT – ARE REPEAT FOOD EFFECT STUDIES NEEDED? AN IQ ANALYSIS

Current regulatory guidelines on drug-food interactions recommend an early assessment of food effect to inform clinical dosing instructions, as well as conducting a pivotal food effect study on the to-be-marketed formulation if different from that used in pivotal trials. Study waivers are currently only granted for BCS Class 1 drugs. Thus, repeated food effect studies are very common in clinical development, with the initial evaluation conducted as early as the first-in-human studies. Information on such repeated food effect studies is not common in the public domain. The goal of the work presented in this manuscript from the Food Effect PBPK IQ Working Group was to compile a dataset with experience on these studies across pharmaceutical companies and provide recommendations on their conduct. Based on 53 studies collected, we report here that the majority of the repeat food effect studies do not result in meaningful differences in the assessment of food effect. Seldom changes observed were more than 2-fold. There was no clear relationship between the change in food effect and the formulation change, indicating that in the majority of cases the food effect is primarily driven by inherent compound properties, and not formulation,. Representative examples of PBPK models demonstrate that following appropriate validation of the model with the initial food effect study, the models can be applied to future formulations. We recommend that repeat food effect studies should be approached on a case-by-case basis taking into account the totality of evidence including use of PBPK modeling as appropriate