Advanced Biomanufacturing: A Radical Manufacturing Paradigm Shift from Conventional, Centralized, Off-the-Shelf Production to On-Demand, Decentralized, Plug-and-Play Production of Cell- and Tissue-Based Products

Production of Cell-and Tissue-Based Products C urrent biomanufacturing, where pharmaceutical produc- tion dominates the entire bioindustry, focuses on the mass production of small molecules and therapeutic agents, such as proteins and vaccines.With the rise of regenerative therapies that utilize cell-based products, new manufacturing technologies are required to realize their full translational potential.In particular, regenerative therapies that use human stem cells pose novel challenges in developing robust and scalable cell manufacturing technologies that ensure consistent product quality.Closed system operations, automated processing of cells, and reliable testing and tracking of biological products must be addressed in order to manufacture cell therapeutics in a reproducible fashion at a medically relevant scale.Biomanufacturing of tissues from human cells presents additional challenges.The creation of highly organized multicellular constructs enables the production of functional organoids and large grafts for transplantation, disease modeling, and predictive screening of new drugs for toxicity and efficacy.Because individual patients respond to therapeutic interventions differently as a result of genetic differences and the state of disease, cellular treatments need to be better tailored to individual needs.This concept of precision medicine shifts the emphasis from massive production of uniform biomedical products to high throughput parallel production of customized tissue products, each at a small scale, that have a short shelf life.Precision medicine presents significant challenges to existing biomanufacturing technologies, including product formulation preservation, testing and tracking, quality control, regulatory pathways, and supply chains.These challenges necessitate a radical manufacturing paradigm shift from conventional, centralized, off-the-shelf medicinal products to a new class of cell-based products for precision medicine.The ultimate realization of new manufacturing practices for human cell and tissue clinical application demands more basic research and technology innovations.Advanced Biomanufacturing is an emerging cross-disciplinary field that focuses on studying the use of cells or cellular products, usually in combination with natural or synthetic biomaterials, to generate biofunctional materials, devices and tissue and organ constructs.It is built upon the groundbreaking discoveries in 3D additive manufacturing, genome editing, cell programming, systems and synthetic biology, stem cell biology, computational modeling, micro-and nanofabrication, material genomes, tissue engineering, and regenerative medicine.This emerging field offers tremendous opportunities to spur research, education, and industry growth and innovation.