腺病毒载体类治疗产品的药学评价考虑

Considerations on pharmaceutical evaluation of adenovirus-based vector therapeutic products

腺病毒(adenovirus,Adv)载体与其他病毒载体类型相比,具有组织细胞感染类型广、可感染分裂或非分裂细胞、非基因组整合、基因转导效率高、外源基因表达水平高等优点,已成为基因治疗和溶瘤病毒类药物载体的主要类型之一。目前,国内外已有多个Adv载体相关的产品获批上市,同时还有百余个候选药物正在开展临床试验。但是,当前业界在开发应用于临床的Adv载体时,仍面临较多的挑战,药品监管部门对此类产品的药学评价经验也较为有限,监管技术指南尚不完善。本文总结了Adv载体的特点和最新的研究进展,围绕原材料、生产工艺、质量控制和稳定性研究等方面提出现阶段的审评考虑,供业界和监管机构探讨交流,以期能促进此类产品的临床转化和应用。

Compared with other viral vector types,adenovirus(Adv)-based vector has shown great promise for human gene therapy and tumor oncolytic therapy,due to its advantage in the variety of cell infection tropism,infection ability to both dividing and non-dividing cells,non-genomic integration,effective gene transduction and expression.It has become one of the main vector types of gene therapy and oncolytic viral drugs.To date,several Adv-based products have been authorized to enter the market at home and abroad,and more than 100 Adv-based candidates are in the process of clinic trails.Nevertheless,domestic industry is facing the challenge of manufacturing clinical grade Adv vectors,and regulatory agency is gaining information and experience on the review of these products,the regulatory technical guidelines are not perfect.Herein,this paper summarized the characteristics of Adv-based products and discussed some quality assessment concerns in raw materials,manufacturing process,quality control and stability,expecting to promote their clinical transformation and application.