Tan Kee Wee, Ji Pengfei, Qian Zichen, Gao Qiao, Wang Shuai, Li Qin, Gu Mingzhu, Zhang Qi, Hou Chengjian, Huang Yang, Lian Dujuan, Wang Junghao, Zhang Zheng, Zhang Sam, Wu Jiansheng, Zhou Weichang
WuXi Biologics, Waigaoqiao Free Trade Zone, Shanghai, China.
Biotechnol Bioeng. 2022 Dec 8. doi: 10.1002/bit.28302.
Since the Coronavirus Disease 2019 (COVID-19) outbreak, unconventional cell line development (CLD) strategies have been taken to enable development of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-neutralizing antibodies at expedited speed. We previously reported a novel chemistry, manufacturing, and control (CMC) workflow and demonstrated a much-shortened timeline of 3-6 months from DNA to investigational new drug (IND) application. Hereafter, we have incorporated this CMC strategy for many SARS-CoV-2-neutralizing antibody programs at WuXi Biologics. In this paper, we summarize the accelerated development of a total of seven antibody programs, some of which have received emergency use authorization approval in less than 2 years. Stable pools generated under good manufacturing practice (GMP) conditions consistently exhibited similar productivity and product quality at different scales and batches, enabling rapid initiation of phase I clinical trials. Clones with comparable product quality as parental pools were subsequently screened and selected for late-stage development and manufacturing. Moreover, a preliminary stability study plan was devised to greatly reduce the time required for final clone determination and next-generation sequencing-based viral testing was implemented to support rapid conditional release of the master cell bank for GMP production. The successful execution of these COVID-19 programs relies on our robust, fit for purpose, and continuously improving CLD platform. The speed achieved for pandemic-related biologics development may innovate typical biologics development timelines and become a new standard in the industry.
自2019年冠状病毒病(COVID-19)爆发以来,已采取非常规的细胞系开发(CLD)策略,以加快开发严重急性呼吸综合征冠状病毒2(SARS-CoV-2)中和抗体。我们之前报道了一种新颖的化学、制造和控制(CMC)工作流程,并展示了从DNA到研究性新药(IND)申请的时间大幅缩短至3至6个月。此后,我们在药明生物将这种CMC策略应用于多个SARS-CoV-2中和抗体项目。在本文中,我们总结了总共七个抗体项目的加速开发情况,其中一些项目在不到2年的时间内就获得了紧急使用授权批准。在良好生产规范(GMP)条件下产生的稳定细胞库在不同规模和批次下始终表现出相似的生产力和产品质量,从而能够快速启动I期临床试验。随后筛选并选择了与亲本细胞库产品质量相当的克隆用于后期开发和生产。此外,还制定了初步稳定性研究计划,以大幅减少确定最终克隆所需的时间,并实施基于下一代测序的病毒检测,以支持主细胞库快速有条件释放用于GMP生产。这些COVID-19项目的成功实施依赖于我们强大、适用且不断改进的CLD平台。大流行相关生物制品开发所实现的速度可能会革新典型生物制品的开发时间表,并成为该行业的新标准。