International – Advanced therapies: ‘Trip hazards’ on the development pathway

This article concerns the development of advanced therapies and the challenges and complexities of getting them through the developmental pathway, which the authors call “the trip.” The authors examine at strategic levels the importance of some of the fundamental building blocks for the development program and highlight some commonly encountered challenges (trip hazards) for cell and gene therapies and offer “bench-to-bedside” and chemistry, manufacturing, and controls (CMC) considerations and advise on nonclinical and clinical investigations. They conclude that early contact with regulators can help avoid “trip hazards.”

Introduction
The advanced therapy sector has grown rapidly, reflecting the tremendous interest for these complex biologic products with potentially curative effect. Advanced therapy products, including cell and gene therapies, as well as tissue-engineered products, have shown great promise for addressing medically unmet needs, particularly for orphan diseases and in oncology. The Alliance for Regenerative Medicine reported a 32% growth in clinical investigations of regenerative medicine products from 2014 to 2018.1 Currently, there are more than 2,000 product candidates under development. Although forecasts of compound annual growth rates and predicted market values vary among different reports, the cell and gene therapy market was valued at more than US$1 billion in 2018 and by 2015, is likely to exceed US$10 billion…