基因治疗产品质量控制策略及面临挑战

Quality control strategies and challenges for gene therapy products

近年来基因疗法进入快速发展阶段,越来越多的产品进入临床研究阶段或获批上市,适应证涉及遗传病、恶性肿瘤、心血管疾病、感染性疾病等。体内基因治疗产品是指在体内通过对人体细胞的遗传物质进行修饰、表达外源基因、操纵细胞基因表达或调控细胞生物学特性等方式达到治疗疾病目的的药品,其结构、功能及生产工艺较传统蛋白类药物更加复杂,潜在的安全性风险更高,如病毒安全性和遗传毒性。因此,质量控制工作面临更多挑战。本文基于体内基因治疗产品的研发、生产和质量控制现状以及相关法规、技术指南,探讨了基于“质量源于设计”理念的质量控制策略以及目前生产和质量控制面临的挑战和解决方案,为相关产品的质量控制提供参考。

In recent years, gene therapy has entered a booming period, and an increasing number of products have accessed to the clinical research or been approved for marketing. The indications include genetic diseases, malignant tumors, cardiovascular diseases, infectious diseases, etc. In vivo gene therapy products refer to drugs that treat diseases by modifying the genetic material of human cells, expressing foreign genes, manipulating the expression of cell genes, or regulating the biological characteristics of cells in the body. Their structures, functions and production processes are more complicated than traditional protein drugs, and the potential safety risks are also higher, such as virus safety and genetic toxicity. Therefore, more challenges exist in the quality control. Based on the current situation of R&D, production, and quality control of in vivo gene therapy products as well as relevant regulations and technical guidelines, this review discusses the quality control strategy based on the concept of “quality by design”, as well as the challenges and solutions in the current production and quality control, providing reference for the quality control of related products.