Biopharmaceutics Meets Inhaled Drug Delivery – Introducing the iBCS Grid
Jayne E. Hastedt1, Per Bäckman2 Antonio Cabal3, Andy Clark4, Carsten Ehrhardt5, Ben Forbes6, Anthony J. Hickey7, Guenther Hochhaus8, Wenlei Jiang9, Stavros Kassinos10, Philip Kuehl11, David Prime12, Yoen-Ju Son13, Simon Teague14, Ulrika Tehler15, & Jen Wylie16
1JDP Pharma Consulting, California, USA
2Emmace Consulting, Lund, Sweden
3Eisai, Woodcliff Lake, NJ, USA
4Aerogen Pharma, California, USA
5Trinity College Dublin, Dublin, Ireland
6King’s College London, London, UK
7University of North Carolina, North Carolina, USA
8University of Florida, Florida, USA
9FDA Office of Generic Drugs, Maryland, USA
10University of Cyprus, Cyprus
11Lovelace Biomedical, New Mexico, USA
12Pulmonary Drug Delivery Consultant, Ware, UK
13Genentech, South San Francisco, CA, USA
14GlaxoSmithKline, Stevenage, UK
15AstraZeneca, Gothenburg, Sweden
16Merck & Co., Rahway, NJ USA
The delivery of an inhaled drug is influenced by several factors including its physicochemical properties, lung deposition and disposition. Each of these properties is influenced by underlying factors such as the formulation, the delivery device, and the physiology, anatomy and pulmonary function of the patient. The assessment of an inhalation-based classification system (iBCS) has progressed since the concept was first introduced at an AAPS workshop in 2014 [[i]]. The principles of the proposed iBCS are based on those used for the classification of oral immediate release drugs (giBCS) and therefore are well established [[ii]]. On the other hand, the framework of the iBCS needs to be altered from that used in the giBCS providing a route-specific framework encompassing the intricacies of pulmonary physiology. The premise for the proposed classification system is that it is desirable from a drug discovery, development, and regulatory perspective to anticipate the behavior of inhaled drugs. Our proposal is that a qualitative classification of a drug based on a classification system constructed from critical drug attributes will aid in understanding how to reduce the risk and overall complexity of inhaled drug product development, scale-up, and post-approval changes.
Classification of an inhaled drug using the proposed iBCS will provide an understanding of development, clinical, and regulatory risks and inform mitigation strategies that can be used by drug discovery and development scientists and engineers to reduce the risk associated with the development of inhaled drug products.
[[i]] Hastedt, J. E.; Bäckman, P.; Clark, A. R.; Doub, W.; Hickey, A.; Hochhaus, G.; Kuehl, P. J.; Lehr, C.-M.; Mauser, P.; McConville, J.; Niven, R.; Sakagami, M.; Weers, J. G. Scope and Relevance of a Pulmonary Biopharmaceutical Classification System AAPS/FDA/USP Workshop March 16-17th, 2015 in Baltimore, MD. AAPS Open 2016, 2 (1), 1. https://doi.org/10.1186/s41120-015-0002-x (online only).
[[ii]] Amidon, G. L.; Lennernas, H.; Shah, V. P.; Crison, J. R. A Theoretical Basis for a Biopharmaceutic Drug Classification: The Correlation of in Vitro Drug Product Dissolution and in Vivo Bioavailability. Pharm. Res. 1995, 12 (3), 413–420.