Exposure Robustness by Design: a translational framework for oral drug product development

Oral drug product development has traditionally been optimized around maximizing mean bioavailability in healthy volunteers, yet clinically relevant exposure liabilities including food effects, pH sensitivity, transit dependence and drug-drug interactions often emerge only after first-in-human (FIH) studies, driving label restrictions or reformulation. We introduce Exposure Robustness by Design (ERbD) - a prospective framework that reframes formulation development from maximizing mean bioavailability toward achieving exposure robustness across the physiological variability of the intended patient population. Supported by biopredictive dissolution, physiologically based biopharmaceutics modeling and model-informed drug development, ERbD guides pre-FIH formulation decisions to support predictable, clinically translatable oral drug products.