基于干细胞的再生医学产品研究进展与监管现状

Research progress and regulatory perspectives for stem cell-based regenerative medicine products

随着干细胞基础研究与临床应用的快速发展,近年来针对重大及难治疾病治疗的再生医学产品不断涌现.干细胞具有自我增殖与分化的特性,再生医学产品复杂、多样,细胞性质与风险各异,其研究制备及临床试验中存在较高的变异性和不确定性(如细胞生存、分化、迁移、定植等过程中培养、诱导条件或个体化方面的差异).因此,基于干细胞的再生医学产品按照药物监管极具挑战性.文章总结了国际上已上市干细胞药物的研究进展,比较了再生医学监管领域美国FDA、欧盟EMA、日本PMDA的监管法规和技术指导原则,重点探讨了干细胞产品药学审评的一般考虑,以期为国内干细胞药物的研发与评价提供参考.

Advances in stem cell therapy have led to the surge of regenerative medicine products for treating severe diseases worldwide in the recent years. Stem cells are capable of self-renewal and differentiation, and regenerative medicine products are remarkably complex and varied in their manufacturing processes including methods for cell culture, induction of differentiation and engraftment. The outcomes of the clinical trials of stem cell products also bear uncertainty partly due to the disparities among patients. Therefore it is challenging for the drug administrative agencies to regulate stem cell products. In this article, we review the research progress of the licensed stem cell-based products in the USA, Europe and Japan, along with the regulations and guidance documents of FDA, EMA and PMDA. We also summarize the considerations in evaluating the Chemistry, Manufacture and Control section of stem cell product applications. We hope our effort would contribute to the establishment of science-based regulatory policy in China, and provide the insights for the development and evaluation of regenerative medicine products.