[3S06a] 16. Cell and Tissue Engineering for Biomedical Process Innovation - Part 2

2:00 PM - 2:40 PM JST(5:00 AM - 5:40 AM UTC)

[3CTBP-06-KL] Latest Technologies in Cell Manufacturing

○Masahiro Kino-oka¹ (1. The University of Osaka (Japan))

Keywords:

cell manufacturability,process stability,Stem cells,scaling technology,automation

The clinical success of regenerative medicine is increasingly dependent on the transition from bench-top discovery to global commercial implementation. This necessitates a profound paradigm shift in how we approach the large-scale production of human therapeutic cells. This presentation delineates the critical engineering and biological frontiers required to achieve the robust, reproducible, and industrial-scale fabrication of high-potency cellular products. As the industry matures, the integration of bioprocess engineering with fundamental cell biology becomes the primary driver for therapeutic and economic success. Central to this discourse is the imperative of cell manufacturability. Unlike conventional small-molecule or protein-based biopharmaceuticals, living cell products—specifically iPS cells and their differentiated cells, as well as MSCs —exhibit inherent biological complexity and extreme sensitivity to culture microenvironments. These cells act as the "process" itself; every physical and chemical stimulus can alter the final therapeutic phenotype. Consequently, achieving rigorous process stability is the paramount challenge. We propose that such stability cannot be reached through traditional, manual expansion. Instead, it requires a comprehensive process development framework rooted in moumentum, transport phenomena, and cell kinetics. A pivotal component of this framework is the application of scale-up by scale-down techniques. To ensure successful industrialization, it is essential to characterize the large-scale bioreactor environment—including shear stress, oxygen mass transfer gradients, and nutrient distribution—within representative small-scale models. By simulating large-scale stressors at the bench scale, we can identify critical process parameters (CPPs) and optimize culture conditions before significant capital is invested in large-scale production. This methodology allows for a predictable transition from laboratory curiosity to high-volume manufacturing while maintaining the integrity of the cellular product.Furthermore, the integration of sophisticated automation within the cell manufacturing workflow is no longer merely a matter of labor reduction; it is a fundamental requirement for minimizing human-induced contamination and ensuring physiological consistency. The systems facilitate the transition from "operator-dependent" cell culture to a data-driven, reproducible industrial process that meets global Good Manufacturing Practice (GMP) standards.In addition, we will discuss the role of multivariate analysis and predictive modeling in characterizing the developmental trajectory of undifferentiated iPS cells toward specific lineages. By quantifying the relationship between process parameters and cellular potency through a Quality by Design (QbD) approach, we can enhance the predictability of outcomes for complex therapies. In conclusion, the future of regenerative medicine hinges on our ability to harmonize biological insights with advanced engineering solutions. By prioritizing cell manufacturability and leveraging both automation and robust scaling technologies, the field can secure a stable, scalable, and economically viable supply of life-saving cellular therapeutics.