Innovation Showcase

KEY REQUIREMENTS FOR EFFICIENT AND LINEAR SCALE-UP OF SHEAR SENSITIVE CELL THERAPY PRODUCTS USING THE VERTICAL-WHEEL BIOREACTOR

Pluripotent stem cells (PSCs) offer promising potential for life-saving therapies, but their clinical adoption faces challenges due to inadequate scalable production processes. Key process hurdles include understanding bioreactor mixing, medium exchange, gas transfer, and cell harvest. Developing reliable methods to scale up manufacturing processes is crucial for robust and reproducible production of clinically relevant lot sizes. Our systematic process development has identified the following key requirements to overcome these challenges: versatile bioreactors with well-characterized hydrodynamics, efficient and scalable MX methods, well characterized gas transfer in large-scale bioreactors, and scalable, low-shear methods for cell harvest, wash, and concentration. The Vertical-Wheel bioreactor-based platform enables scalable production of shear-sensitive PSCs and PSC derived products through planar seed train expansion and scalable 3D expansion/differentiation phases. We successfully scale production from 0.1L to 15L, generating clinically relevant quantities of various cell types (PSCs, PSC derivatives, MSCs, and other primary cells) and growth modalities (microcarriers, aggregates, and single cells). By proactively addressing scale-dependent challenges, we have established reliable large-scale processes for shear-sensitive cell therapy production, facilitating their transition from research to clinical use and enabling widespread access for the population.