2022 Volume 12 Issue 2 Pages 125-141
It is essential during new drug development to assess the effects of food on oral drug products. The effects of food on absorption have been evaluated in the early clinical stages and a food-effect (FE) study using the final formulation has also been conducted, based on the basic principles of the regulatory document. This study systematically evaluated FE studies conducted when developing oral dose formulations containing new active pharmaceutical ingredients (APIs) that were approved in Japan between 2010 and 2019, in order to consider the designs and practical aspects of FE studies for new drug development. Most FE studies were conducted with healthy subjects in a cross-over design using a single clinical dose under a high-fat meal versus fasting conditions. We summarized cases in which FE studies were not necessary or FE studies outside the standard study design were acceptable. The FE study using the final formulation should be basically essential in the development of drug substances with properties of low-solubility and/or-permeability, other types of formulations such as extended-release, and changes in excipients with which effects on gastrointestinal absorption are expected. FE studies results under multiple test meals are useful, depending on API characteristics and indications to be developed. While, for high-solubility and -permeability APIs in immediate-release formulation, early FE studies are considered informative for product labeling because the effects of food on bioavailability is not considered to be clinically significant. The findings of this study provide specific and practical points to consider in the planning, implementation, and evaluation of FE studies in new drug development.
