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

用于制造新冠肺炎IPSC来源细胞的符合CGMP的闭合细胞培养系统 临床试验 摘要 新的冠状病毒代表了现代历史上最大的流行病之一，达到了大约100 据报道，全球有100万病例和200万人死亡。肺泡细胞、内皮细胞和肺结构 在感染阶段受到严重破坏。肺泡修复不足可能会增加肺的脆弱性 以吸入微生物和物质或导致肺纤维化。因此，在全球范围内，医疗行业使用了几种 抑制病毒造成的威胁的方法，包括使用自然疗法等生活疗法 杀伤细胞、T细胞、干细胞联合疗法和外切体。目前，间充质干细胞是 已经显示出治疗新冠肺炎的耐人寻味的潜力，但尚未被发现有 可检测到再生肺上皮的潜力。复杂肺泡上皮2型的发生 诱导多能干细胞(IPSCs)诱导的肺泡兼性祖细胞(AEC2s) 最近，使用IPSCs和定向分化，肺上皮祖细胞和 AEC2是为潜在的再生基因或细胞治疗而产生的。这些IPSC的进步- 基于个性化细胞疗法，能够有效地修复肺上皮，目前受到以下因素的阻碍 生物制造挑战。尽管方法已经使派生、增长和差异化 在IPSC效率更高的情况下，在重新编程效率、基因组完整性、 以及从患者组织样本中提取的IPSCs的发展潜力。这些变量包括LOT- 取决于或取决于技术人员的分化效率、细菌或真菌污染风险、二氧化碳或 电池维护期间O2浓度水平压力大、成本高或存在交叉污染风险 集中式生物制造设施，以及cGMP标准或法规遵从性的要求。越远 目前，基于IPSC的个性化新冠肺炎治疗的进展受到难以生成和 以实惠的成本为广大用户提供差异化的IPSC。因此，Biopico Systems Inc将解决这样的问题 为制造业开发符合cGMP标准的自动化闭合细胞培养系统面临的挑战 以IPSC来源细胞为基础的新冠肺炎损伤肺上皮再生的临床试验。至 将Biopico的规模化“CellsMX”系统商业化，优化封闭媒体交换系统 将在此执行改进的泵送算法和GMP制造方案的验证 研究。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地点，以避免与运输、物流、跟踪、 和录音。Biopico将向FDA提交CellsMX系统的监管文件，该文件将 发布给客户，用于他们的预IND应用程序。

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.