An Expert's View on the Application of TIM Technology in the Development of Oral Drug Products

The TIM models tiny-TIM and TIM-1 enable a physiologically relevant in vitro simulation of drug product performance in the upper human gastrointestinal tract under various intake conditions. These systems are considered to be among the most biorelevant oral in vitro models commercially available on the market. This White Paper has been written by a group of experienced users of the TIM systems and shall provide an independent and comprehensive review of the various applications of these systems in the field of pharmaceutical development, as well as current limitations of the systems and how to address them. Recent improvements in the function of the TIM systems, as well as in the use of the data generated, have expanded the application of TIM systems beyond the prediction of food effects and the support of formulation development. For instance, the incorporation of intraluminal concentration and bioaccessibility profiles into in silico models can significantly improve clinical PK predictions and thereby inform decision-making in drug product development in many ways. This work provides an overview of the TIM systems in preclinical and clinical drug product development, supported by selected case studies of various applications. Furthermore, regulatory aspects, the contribution to reducing animal experimentation (3R), and options for future improvement of the TIM systems are highlighted.