The factors that influence inhaled first-in-human (FIH) device and formulation selection often differ significantly from the factors that have influenced the preceding preclinical experiments and inhalation toxicology work. In order to minimize the risk of delivery issues negatively impacting a respiratory pipeline program, the preclinical and FIH delivery systems must be considered holistically. This topic will be covered in more detail in this paper. Several examples will be presented that highlight how appropriate scientific strategy can help bridge the gap between delivering to preclinical species and human. Considerations for the FIH device selection (metered dose inhaler, dry powder inhaler and nebulizer) and formulation optimization for small molecules will be discussed in context with the preclinical delivery systems.
Keywords: aerodynamic diameter; deposited fraction (DF); dry powder inhaler (DPI); in vitro/in vivo correlation (IVIVC); insufflation; intratracheal (IT) dosing; metered dose inhaler (MDI); nebulizer; pharmacodynamics (PD); pharmacokinetics (PK).