Virtual Bioequivalence Assessment of Ritlecitinib Capsules with Incorporation of Observed Clinical Variability Using a Physiologically Based Pharmacokinetic Model

The study developed and applied a physiologically based pharmacokinetic (PBPK) model to assess the bioequivalence of ritlecitinib capsules, a treatment for alopecia areata. Despite slower in vitro dissolution of 100-mg capsules compared to proposed 50-mg capsules, virtual bioequivalence (VBE) trials incorporating clinically observed intra-subject variability (ICV) demonstrated that the 50-mg capsules are bioequivalent to the 100-mg capsules with over 90% probability of success. This suggests a PBPK model-based biowaiver for clinical bioequivalence studies, offering a novel approach to integrate clinical ICV into VBE trials.