药学学报, 2018, 53(10): 1637-1644
引用本文:
刘伯宁, 曹越, 卢加琪, 罗建辉. 关于嵌合抗原受体修饰T细胞产品药学评价的思考[J]. 药学学报, 2018, 53(10): 1637-1644.
LIU Bo-ning, CAO Yue, LU Jia-qi, LUO Jian-hui. Regulatory perspective for chemistry manufacturing and controls considerations in chimeric antigen receptor-modified T cell therapy[J]. Acta Pharmaceutica Sinica, 2018, 53(10): 1637-1644.

关于嵌合抗原受体修饰T细胞产品药学评价的思考
刘伯宁, 曹越, 卢加琪, 罗建辉
国家食品药品监督管理总局药品审评中心, 北京 100038
摘要:
CAR-T细胞作为一种活的个体化治疗药物,其药学研究与评价显著区别于小分子化学药和大分子重组蛋白。CAR-T产品的药学研究表现出原材料的“多样性”、制备工艺的“差异化”和质控策略的“互补性”等特点。申报临床阶段的药学评价重在识别重大风险点,在保证临床用药安全性的前提下,兼顾细胞制品的产品特殊性。本文结合近期国内CAR-T产品药学审评实践,提出此类产品药学评价的一般考虑与评价要点,并就行业共性问题与发补原因展开讨论,以期促进此类产品尽快进入临床,在临床实践中不断改进完善,最终转化成可实际应用的药品。
关键词:    嵌合抗原受体修饰T细胞      基因修饰T细胞      逆转录病毒载体      慢病毒载体      生产工艺      质量控制     
Regulatory perspective for chemistry manufacturing and controls considerations in chimeric antigen receptor-modified T cell therapy
LIU Bo-ning, CAO Yue, LU Jia-qi, LUO Jian-hui
Center for Drug Evaluation, China Food and Drug Administration, Beijing 100038, China
Abstract:
As a living cell product, chimeric antigen receptor (CAR)-T cell therapy displays multiple characteristics including the diversity of raw materials, the complexity of manufacturing process and the complementarity of quality control set. Pharmaceutical research and evaluation of CAR-T cell therapy are fundamentally different from small molecule and macromolecular recombinant proteins. Chemistry manufacturing and controls (CMC) review of investigational new drug (IND) submission for CAR-T therapy should especially pay attention to above unique characteristics and focus on potential risks to ensure clinical safety. Based on questions and concerns from recent CMC review practice and workshop on CAR-T cell therapy IND application, the critical points to consider for CMC study is proposed, and questions related to supplementation are also discussed in this review to accelerate the clinic translation of CAR-T therapy.
Key words:    chimeric antigen receptor-modified T cell    gene modified T cell    lentiviral vector    retrovirus vector    manufacturing process    quality control   
收稿日期: 2018-05-29
DOI: 10.16438/j.0513-4870.2018-0505
基金项目: 国家科技重大专项“重大新药创制”课题资助项目(2015ZX09501008).
通讯作者: 罗建辉,Tel:86-10-68586655,E-mail:Luojh@cde.org.cn
Email: Luojh@cde.org.cn
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