Manufacturing and Quality of Advanced Therapeutics: Cellular Therapies, CAR-T and Gene Therapies

Advanced therapeutics include cellular and gene therapies, fields originally distinct but now sometimes converging as exemplified by CAR-T approaches. Common to all facets of advanced therapies is that the active pharmaceutical ingredients are vastly more complex than those of common biologics such as antibodies and hence pose elevated challenges regarding their manufacture and quality control. We discuss prominent examples of advanced therapies and their technology platforms, delineate their historic and technological origin as well as possible paths forward so as to understand the evolution of manufacturing processes seen today. Importantly, using this approach we draw lessons from past experiences with the intent to steer the current and future manufacturing and quality control professional away from potentially problematic and towards likely successful approaches. Given the complexity of advanced therapeutics, regulatory guidelines evolved accordingly and we discuss the current state; it is with a degree of pride to see that many of the experiences we and others in the field shared with authorities eventually contributed to regulatory guidelines such as the EU ATMP guide. Finally, we hope to share the profound satisfaction we experience by working in a field at the intersection of cutting-edge science and production technology, thereby providing crucial medicinal products, most recently in the context of the Covid19 pandemic, at a pace previously unimaginable.