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

Rania Salama; Hong Jun Choi; Juhura Almazi; Daniela Traini; Paul Young

doi:10.1016/j.drudis.2022.103350

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

Drug Discov Today. 2022 Nov;27(11):103350. doi: 10.1016/j.drudis.2022.103350. Epub 2022 Sep 9.

Authors

Rania Salama¹, Hong Jun Choi², Juhura Almazi³, Daniela Traini⁴, Paul Young⁵

Affiliations

¹ Respiratory Technology Group, Woolcock Institute of Medical Research, Glebe 2037, NSW, Australia; Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University 2109, NSW, Australia. Electronic address: rania.salama@mq.edu.au.
² Faculty of Medicine and Health, The University of Sydney, Camperdown 2007, NSW, Australia.
³ Respiratory Technology Group, Woolcock Institute of Medical Research, Glebe 2037, NSW, Australia.
⁴ Respiratory Technology Group, Woolcock Institute of Medical Research, Glebe 2037, NSW, Australia; Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University 2109, NSW, Australia.
⁵ Respiratory Technology Group, Woolcock Institute of Medical Research, Glebe 2037, NSW, Australia; Macquarie Business School, Macquarie University 2109, NSW, Australia.

PMID: 36096359
DOI: 10.1016/j.drudis.2022.103350

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.

Keywords: Batch-to-batch variability; Bioequivalence; DPIs; Dry powder inhalers; Orally inhaled products; Regulatory guidelines.

Publication types

Review