Prediction of active human dose: learnings from 20 years of Merck KGaA experience, illustrated by case studies.

•A retrospective analysis of active human dose predictions for 15 drugs is reported.•Case studies illustrate the value of adhering to translational best practices.•Underestimation of active dose in 5 drugs is due to pharmacology rather than exposure.•Identified weaknesses are generic to the industry.•Predicted active dose range should reflect translational and exposure uncertainties.