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

Summary

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.

Key Message

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.