ABSTRACT
This chapter illustrates the challenges and opportunities for the bioequivalence concept when applied to locally acting, orally inhaled drug products (OIDPs). For OIDPs, heterogeneity of the site of application and widespread distribution of local biological targets suggest that the rate and extent of drug appearance at more than one biological location may be important. Perhaps the most substantial bioequivalence challenge for OIDPs is that there is no direct or surrogate measure of drug concentration at the site of action. For most OIDPs, there is a wide distribution of aerodynamic particle sizes, sometimes of varying composition. The pharmacokinetic bioequivalence study for OIDPs is conducted using the same design principles used for a solid oral pharmacokinetic bioequivalence study, on the basis that these design features increase sensitivity to product or formulation differences in rate and extent to which the active ingredient(s) is released from the drug product.
