Bioreactor Design and Bioprocess Controls for Industrialized Cell Processing Bioengineering Strategies and Platform Technologies

level: interMediate I t’s official: The “Age of Cell Therapy” has arrived. A robust pipeline of cell therapies, with increasing numbers of both earlyand late-stage clinical trials as well as FDA-approved commercial products that have entered the market already, strongly indicates that the cell therapy industry is poised to emerge as a distinct healthcare sector (1). Renewed investor interest and recent activity among major pharmaceutical companies suggest that this industry will rapidly develop the capability and capacity to be a highly competitive, sustainable, multibillion-dollar enterprise. But when commercialization comes, will companies be ready to meet the enormous demand for viable cells? The maturing field of automated cell cultivation using highly specialized bioreactor designs and stringent bioprocess controls will be crucial for the development of biomanufacturing technologies suitable for clinical-grade production of future cytotherapeutics. However, unlike well-established therapeutic modalities (pharmaceuticals, biopharmaceuticals, and medical devices), the broad spectrum of highly diverse cell therapies in development requires a customizable manufacturing platform that is flexible enough to accommodate bespoke cellular designs yet rigorous enough to consistently produce a complex, viable product: living cells. As for those widely integrated pillars of medicine, however, the unique core competencies and underlying scientific principles of platform technologies used in manufacturing cell-based products will ultimately define their potency, purity, stability, efficacy, safety, and quality. In addition to other special challenges (e.g., constraining the innate protean nature of polymorphically active cells, assessing the variableness of their multipotencies, and tracking highly personalized medicines), creatively addressing manufacturingrelated issues is key for successful bioengineering of cell products at an industrial scale. As in other biotechnology applications such as the mass production of therapeutic antibodies or live-attenuated virus vaccines, bioengineered cell therapies will critically depend on bioreactor-based manufacturing systems (2). Intended as a means to create and maintain a controlled physiochemical culture environment, bioreactors represent a key element for the automated, standardized, traceable, cost-effective, safe, and regulatory-compliant manufacture of cell-based products for clinical applications. The realization that industrializing the cell therapy industry will require pioneering manufacturing systems has promoted interactions among scientists, engineers, clinicians, and business professionals to create devices that will facilitate the transfer of academic-level, cell-based processes into clinically and commercially viable solutions. Companies need to translate highly individualized culture protocols developed by research laboratories into validated, streamlined bioprocesses that can guarantee reproducibility, scalability, standardization, robustness, and safety. It has become increasingly apparent that success will rely on the Human embryonic stem cell colonies are stained for alkaline phosphatase (red) to show pluripotency. They are growing on a layer of mouse embryonic fibroblasts that help sustain their growth and pluripotency.