CGMP Compliant Closed Cell Culture System for culturing iPSC derived lung epithelial cells to COVID19 Therapy

CGMP合规封闭细胞培养系统用于生产用于COVID-19的iPSC衍生细胞 临床试验 摘要 新型冠状病毒是现代历史上最大的流行病之一，达到约100 据报道，全世界有200万例病例和200万例死亡。肺泡细胞、内皮细胞和肺结构 在感染阶段受到严重破坏。肺泡修复不充分可能增加肺脆弱性 吸入的微生物和物质或导致肺纤维化。因此，在全球范围内，医疗保健行业使用几种 抑制病毒造成的威胁的方法，包括使用活性疗法， 杀伤细胞、T细胞、干细胞组合疗法和外来体。目前，间充质干细胞是 已经显示出治疗COVID-19的有趣潜力，但尚未发现 可检测到肺上皮再生的潜力。2型复合肺泡上皮细胞的生成 细胞（AEC 2），即来自诱导多能干细胞（iPSC）的肺泡的兼性祖细胞， 最近，使用iPSC和定向分化，肺上皮祖细胞和 产生AEC 2用于潜在的再生基因或细胞疗法。这些iPSC的进步- 能够有效修复肺上皮的基于个性化细胞疗法目前受到以下因素的阻碍： 生物制造的挑战。尽管有一些方法使衍生、生长和分化 iPSC的效率更高，但在重编程功效，基因组完整性， 和源自患者组织样品的iPSC的发育潜力。这些变量包括： 依赖或技术人员依赖的分化效率、细菌或真菌污染风险、CO2或 电池维护期间的O2浓度水平压力、高成本或交叉污染风险 集中式生物制造设施，以及cGMP标准或法规合规性要求。进一步 基于iPSC的个性化COVID-19治疗的进展目前受到难以生成和 以可承受的成本为大量人群区分iPSC。因此，Biopico Systems Inc将解决此类问题， 通过开发符合cGMP要求的自动化封闭式细胞培养系统， 基于iPSC衍生细胞的临床试验，用于再生COVID-19损伤的肺上皮。到 商业化Biopico的放大“CellsMX”系统，优化封闭的培养基交换系统， 将在本研究中进行修改的泵送算法和GMP生产方案的验证。 research.此外，即使大量患者需要基于iPSC的个性化细胞疗法， 系统可以部署在护理点，避免与运输，物流，跟踪， 和录音。Biopico将向FDA提交CellsMX系统的监管文件， 发布给客户用于IND前申请。

CGMP Compliant Closed Cell Culture System for Manufacturing iPSC Derived Cells for COVID-19 Clinical Trials Abstract The novel Coronavirus represents one of the largest pandemics in modern history, reaching around 100 million cases and two million deaths reported worldwide. Alveolar cells, endothelial cells, and lung structure are severely damaged during the infection stage. Insufficient alveolar repair may increase lung vulnerability to inhaled microbes and substances or lead to lung fibrosis. So globally, the healthcare industry uses several methods to suppress the threat caused by the virus, including the use of living therapies such as natural killer cells, T-cells, stem cells combination therapies, and exosomes. Currently, mesenchymal stem cells are already showing intriguing potential for the treatment of COVID-19 but have not been found to have detectable potential to regenerate lung epithelium. Though generation of complex alveolar epithelial type 2 cells (AEC2s), the facultative progenitors of lung alveoli from induced pluripotent stem cells (iPSCs) have been challenging, recently, using iPSCs and directed differentiation, lung epithelial progenitor cells and AEC2s were generated for potential regenerative gene or cell therapies. The advancement of these iPSC- based personalized cell therapies, capable of effectively repairing lung epithelium, is currently hindered by biomanufacturing challenges. 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 further advance of iPSC-based personalized COVID-19 therapy is currently limited by the difficulty to generate and differentiate iPSCs for large populations at an affordable cost. Therefore Biopico Systems Inc will solve such challenges by developing an automated cGMP Compliant Closed Cell Culture System for manufacturing iPSC derived cells based clinical trials for regenerating lung epithelium damaged by COVID-19. To commercialize Biopico's scaled up “CellsMX” system, optimization of closed media exchange system with modified pumping algorithm and validation of GMP manufacturing protocols will be performed in this research. Further, even if a large number of patients need iPSC-based personalized cell therapies, the system can be deployed at the point of care avoiding risks associated with transportation, logistics, tracking, and recording. Biopico will submit regulatory documents with FDA for the CellsMX system that will be released to the customers for their pre-IND applications.