NSF Engineering Research Center for Cell Manufacturing Technologies (CMaT)

细胞疗法可以彻底改变未解决和慢性疾病的治疗方法，从而对全球健康和经济产生变革性影响。尽管有大量的临床试验和不断增长的行业承诺，但没有一致的努力使治疗细胞作为一种有效、安全、可重复和负担得起的产品进行规模化生产，并具有标准化的特性和质量控制。这阻碍了细胞疗法广泛转化为临床和工业实践。为了克服这个问题，工程界必须开发新的工具和技术，以大规模、低成本地生产高质量的电池；建立健全的供应链、仓储和配送物流；培训多样化的电池制造劳动力。拟议的细胞制造技术ERC （CMaT）是一项全国性、综合性、融合科学的努力，工程师将与行业合作伙伴、临床医生、生物学家、劳动力专家以及标准和监管机构密切合作，将治疗细胞的生产转变为大规模、低成本、可重复和高质量的工程制造过程。佐治亚理工学院是CMaT的领头大学。佐治亚大学，威斯康辛大学？麦迪逊大学和波多黎各大学？Mayaguez是主要合作伙伴，还有几个附属机构。CMaT将产生广泛而持久的社会影响：产生新的基础知识和变革性技术，建立包容性的劳动力队伍，培育新兴产业，改善医疗保健。它将成为一个国际公认的示范中心，拥有最先进的设施和设备，嵌入创新和包容的文化，并将通过一个全面的项目，深入和广泛地参与教育和劳动力发展，包括来自高中的弱势学生和教师，残疾学生，退伍军人，技术和社区大学生，以及本科生和研究生。CMaT团队最近领导制定了一个行业驱动的10年国家电池制造路线图，为关键技术开发提供了优先途径。CMaT将是实施这一路线图的自然场所。高质量治疗细胞的规模化生产面临着复杂的挑战，与目前业界所经历的不同。首先，产品是一个“有生命的”实体，其属性可以随着每一次操作而改变，这需要一种全新的大规模制造和质量控制模式。其次，对治疗细胞的关键质量属性（CQA）知之甚少，即可测量的生物标志物，使其对患者的特定疾病适应症安全有效，以及如何测量它们。第三，整个领域几乎没有标准化。因此，设计质量（QbD）作为当前制造实践的一个基本前提，并没有在单元制造中得到实施。为了实现这些目标，CMaT将利用三种工程系统（试验台）创新变革性的工具、技术和方法：(a)用于免疫调节和肌肉骨骼再生的间充质干细胞/基质细胞，(b)用于癌症的T细胞免疫疗法，以及(c)用于治疗心脏病的诱导多能干细胞衍生的心脏细胞。在这些系统中，CMaT将开发(a)新的基于组学的工具，将大数据分析和建模结合起来，以识别用于安全性和有效性预测的cqa；(b)新型细胞过程传感器，用于在初始起点和整个制造过程中测量质量属性，并确保用于治疗的定义明确、可重复和高质量的细胞；(c)具有综合质量控制的新扩大和扩大技术；(d)保持细胞纯度、产量和质量的高效细胞纯化和分离技术；(e)用于快速验证制造细胞的功能、效力和安全性的高通量方法；关键的工业设计原则、自动化封闭系统制造和供应链建模，以降低成本，确保可重复性，并实现可扩展的生产。

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.