Generic dry powder inhalers bioequivalence: batch-to-batch variability insights

Active pharmaceutical ingredient(s) [API(s)] of dry powder inhalers (DPIs) deposition and their fate in the respiratory system are influenced by a complex matrix of formulation, device, manufacturing and physiological variations. DPIs on the market have shown bioinequivalence between batches of the same product. Despite being clinically insignificant, they affect bioequivalence studies when a generic product is compared with the originator. This review discusses implications of batch-to-batch variability on bioequivalence study outcomes and shortcomings of current regulatory requirements. Possible formulation and manufacturing factors resulting in batch-to-batch variability highlight the inherent nature of this issue. Despite scholarly investigations and official regulatory guidance, there remains a need for reliable and realistic in vitro tests that accurately guide a representative reference product batch selection.