Generic dry powder inhalers bioequivalence: Batch–to-batch variability insights. Issue 11 (November 2022)

• Record Type: Journal Article
• Authors: Salama, Rania; Choi, Hong Jun; Almazi, Juhura; Traini, Daniela; Young, Paul
• Is Part Of: Drug discovery today. Volume 27:Issue 11(2022)
• Publication Date: 2022-11
• Subjects: Batch-to-batch variability -- Dry powder inhalers -- DPIs -- Bioequivalence -- Orally inhaled products -- Regulatory guidelines; Drugs -- Design -- Periodicals; Drugs -- Research -- Periodicals; 615.1
• DOI: 10.1016/j.drudis.2022.103350
• Languages: English
• ISSNs: 1359-6446

Abstract

Highlights: Batch-to-batch bioinequivalence has negligible clinical downsides. Choice of Reference batch for generic bioequivalence testing is significant. To date, different regulations do not address the batch-to-batch variability issue. Respiratory specific and reliable in vitro dissolution tests and IVIVC are needed. Inherent factors in DPI formulations contribute to the batch-to-batch variability. Abstract : 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.