Addressing Manufacturing Challenges for Commercialization of iPSC-Based Therapies
Addressing Manufacturing Challenges for Commercialization of iPSC-Based Therapies
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DOI：
10.1007/7651_2020_288
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发表时间：
2021-01-01
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影响因子：
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通讯作者：
Baghbaderani, Behnam Ahmadian
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文献类型：
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作者：
Dashtban, Mehdi;Panchalingam, Krishna Morgan;Baghbaderani, Behnam Ahmadian
用于产生人类诱导多能干细胞（iPSC）的重编程技术的发展极大地影响了再生医学和临床治疗领域，其中治愈性细胞替代疗法可用于治疗帕金森病（PD）和糖尿病等毁灭性疾病。为了将这些疗法商业化以治疗大量个体，重要的是要证明这些疗法的安全性和有效性，并确保 iPSC 衍生的功能细胞的制造过程能够以可承受的成本实现工业化。然而，为了实现这一愿景，需要解决许多制造障碍。值得注意的是，生成 iPSC 衍生的特化细胞的制造过程相对较长且相当复杂，需要以受控方式将高质量 iPSC 分化为特化细胞。在本章中，我们总结了我们为解决 iPSC 衍生细胞治疗产品工业化中存在的主要挑战所做的努力，重点是开发当前符合良好生产规范 (cGMP) 的 iPSC 制造工艺、全面的 iPSC 表征平台、符合 cGMP 的 iPSC 的长期稳定性，以及解决在 3D 计算机控制生物反应器中建立 iPSC 加工过程中遇到的一些放大挑战的创新技术。
The development of reprogramming technology to generate human induced pluripotent stem cells (iPSCs) has tremendously influenced the field of regenerative medicine and clinical therapeutics where curative cell replacement therapies can be used in the treatment of devastating diseases such as Parkinson's disease (PD) and diabetes. In order to commercialize these therapies to treat a large number of individuals, it is important to demonstrate the safety and efficacy of these therapies and ensure that the manufacturing process for iPSC-derived functional cells can be industrialized at an affordable cost. However, there are a number of manufacturing obstacles that need to be addressed in order to meet this vision. It is important to note that the manufacturing process for generation of iPSC-derived specialized cells is relatively long and fairly complex and requires differentiation of high-quality iPSCs into specialized cells in a controlled manner. In this chapter, we have summarized our efforts to address the main challenges present in the industrialization of iPSC-derived cell therapy products with focus on the development of a current Good Manufacturing Practice (cGMP)-compliant iPSC manufacturing process, a comprehensive iPSC characterization platform, long-term stability of cGMP compliant iPSCs, and innovative technologies to address some of the scale-up challenges in establishment of iPSC processing in 3D computer-controlled bioreactors.