Cell-based therapies could revolutionize treatments of unsolved and chronic medical conditions, thus making a transformative impact on global health and economy. Despite numerous clinical trials and growing industry commitment, no concerted effort has been made to enable scalable manufacturing of therapeutic cells as an effective, safe, reproducible, and affordable product with standardized characterization, and quality control. This has hindered broad translation of cell therapies into clinical and industrial practice. To overcome this, the engineering community must develop new tools and technologies to reproducibly manufacture high-quality cells at large-scale and low-cost; enable robust supply-chain, storage, and distribution logistics; and train a diverse cell-manufacturing workforce. The proposed ERC for Cell Manufacturing Technologies (CMaT) is a national, comprehensive, convergence-science effort where engineers will work closely with industry partners, clinicians, biologists, workforce experts, as well as standards and regulatory agencies to transform the production of therapeutic cells into a large-scale, low-cost, reproducible, and high-quality engineered manufacturing process. Georgia Tech is the lead university of CMaT. The University of Georgia, University of Wisconsin ? Madison, and University of Puerto Rico ? Mayaguez are major partners, alongside several affiliate institutions. CMaT will have broad and lasting societal impact: producing new fundamental knowledge and transformative technologies, building an inclusive workforce, nurturing a nascent industry, and improving healthcare. It will be an internationally recognized exemplar center with state-of-the-art facilities and equipment, an embedded culture of innovation and inclusion, and will engage deeply and broadly in education and workforce development through a comprehensive program involving under-represented students and teachers from high schools, students with disabilities, veterans, technical and community college students, as well as undergraduate and graduate students.
The CMaT team recently led the development of an industry-driven, 10-year national roadmap for cell manufacturing that provides a prioritized pathway for critical technology development. CMaT will be a natural venue for implementing this roadmap. Scalable manufacturing of high-quality therapeutic cells poses complex challenges, different from those currently experienced by industry. First, the product is a "living" entity whose properties can change with every manipulation requiring a whole new paradigm for large-scale manufacturing and quality-control. Second, little is known about the Critical Quality Attributes (CQA) of therapeutic cells, i.e. measurable biomarkers that render them safe and effective for specific disease indications in patients and how to measure them. Third, little standardization exists across the field. Thus, Quality-by-Design (QbD), a fundamental premise of current manufacturing practice, has not been implemented in cell manufacturing. To enable these, CMaT will innovate transformative tools, technologies, and methods using three Engineered Systems (Test-Beds): (a) Mesenchymal Stem/stromal Cells for immune-modulation and musculoskeletal regeneration, (b) T cell immunotherapies for cancer, and (c) induced Pluripotent Stem Cell-derived cardiac cells to treat heart diseases. In each of these systems CMaT will develop (a) new omics-based tools that couple big-data analytics and modeling to identify CQAs for safety and efficacy prediction; (b) novel cell-process sensors to measure quality attributes, both at the initial starting point and throughout the manufacturing process, and ensure well-defined, reproducible and high quality cells for therapy; (c) new scale-up and scale-out technologies with integrated quality control; (d) efficient cell purification and separation technologies that maintain cell purity, yield, and quality; (e) high throughput methods for rapidly validating function, potency and safety of manufactured cells; and (f) critical industrial-design principles, automated closed-system manufacturing, and supply-chain modeling to lower cost, ensure reproducibility, and enable scalable production.
