CGMP Compliant Closed Cell Culture System for Reproducible De-differentiation of human somatic cells into iPSCs

符合cGMP的闭合细胞培养系统用于可复制的人去分化 体细胞转化为iPSCs 摘要 基于IPSC的个性化细胞疗法的进展目前受到以下挑战的阻碍 治疗性细胞的生物制造。尽管这些方法已经使派生、增长和 IPSC的分化更有效，在重新编程效率方面仍然存在显著的变异性， 来自患者组织样本的IPSCs的基因组完整性和发育潜力。这些 变量包括取决于批次或技术人员的分化效率、细菌或真菌 污染风险、电池维护过程中的二氧化碳或氧气浓度水平压力、高成本或交叉 集中式生物制造设施的污染风险以及cGMP标准或法规的要求 合规性。同一标本来源的IPSCs体外生长特性的差异 而他们无法重新分化为所需的组织类型，将在治疗中造成严重问题。这个 基于IPSC的个性化医疗的进一步发展目前受到产生IPSC的困难的限制 以负担得起的成本为大量人口提供服务。因此，Biopico Systems Inc将通过以下方式解决这些挑战 可重复脱分化的cGMP全自动封闭细胞培养系统的研制 将人类体细胞转化为ipscs。Biopico“CellsMX”系统商业化，封闭式优化 媒体交换系统和定制的mRNA/媒体配方前端的集成 在这项第二阶段的研究中将进行重新编程。CellsMX系统将提供高质量 根据cGMP指导方针向客户提供批量生产的保证，因为已向 生物实体以及细胞是如何产生、测试和释放用于治疗的。更进一步，甚至， 如果大量患者需要基于IPSC的个性化细胞治疗，在CellsMX封闭系统下， 患者细胞没有交叉污染，该系统可以在护理点部署，避免高 与运输、物流、跟踪和记录相关的成本和风险。同时针对特定患者 IPSC战略减少免疫刺激将推动CellsMX的初始细分市场 系统，Biopico将为几个这样的治疗培养过程开发一套产品。

CGMP Compliant Closed Cell Culture System for Reproducible De-differentiation of human somatic cells into iPSCs Abstract The advancement of iPSC-based personalized cell therapies is currently hindered by the challenges in the biomanufacturing of therapeutic cells. Despite approaches that have made the derivation, growth and differentiation of iPSCs more efficient, there remains significant variability in reprogramming efficacy, genomic integrity and developmental potential of iPSCs derived from patient tissue samples. These variabilities include lot-dependent or technician-dependent differentiation efficiency, bacterial or fungal contamination risks, CO2 or O2 concentration level stresses during cell maintenance, high costs or cross- contamination risks with centralized biomanufacturing facility and requirement of cGMP criteria or regulatory compliance. The difference of iPSCs derived from the same sample in their in-vitro growth characteristics and their inability to re-differentiate into the desired tissue type will cause serious problems in therapy. The further advance of iPSC-based personalized medicine is currently limited by the difficulty to generate iPSCs for large populations and at an affordable cost. Therefore Biopico Systems Inc will solve such challenges by developing an automated cGMP Compliant Closed Cell Culture System for reproducible de-differentiation of human somatic cells into iPSCs. To commercialize Biopico's “CellsMX” system, optimization of closed media exchange system and integration of customized mRNA/ media formulation front-end for reprogramming will be performed in this Phase II research. The CellsMX system will provide quality assurance to the customers for mass production under cGMP guidelines, as operating license are issued to biological entities along with how cells are produced, tested, and released for therapeutic use. Further, even, if a large number of patients need iPSC-based personalized cell therapies, under CellsMX closed system, patient cells are not cross-contaminated and the system can be deployed at the point of care avoiding high costs and risks associated with the transportation, logistics, tracking, and recording. While patient-specific iPSC strategy's reduction of immunologic stimulus will drive the initial market segment for the CellsMX system, Biopico will develop a suite of products for several of such therapeutic culture processes.