PDF(Pubmed)
Abstract：
Pharmaceutical companies have recently focused on accelerating the timeline for initiating first-in-human (FIH) trials to allow quick assessment of biologic drugs. For example, a stable cell pool can be used to produce materials for the toxicology (Tox) study, reducing time to the clinic by 4-5 months. During the coronavirus disease 2019 (COVID-19) pandemic, the anti-COVID drugs timeline from DNA transfection to the clinical stage was decreased to 6 months using a stable pool to generate a clinical drug substrate (DS) with limited stability, virus clearance, and Tox study package. However, a lean chemistry, manufacturing, and controls (CMC) package raises safety and comparability risks and may leave extra work in the late-stage development and commercialization phase. In addition, whether these accelerated COVID-19 drug development strategies can be applied to non-COVID projects and established as a standard practice in biologics development is uncertain. Here, we present a case study of a novel anti-tumor drug in which application of \"fast-to-FIH\" approaches in combination with BeiGene\'s de-risk strategy achieved successful delivery of a complete CMC package within 10 months. A comprehensive comparability study demonstrated that the DS generated from a stable pool and a single-cell-derived master cell bank were highly comparable with regards to process performance, product quality, and potency. This accomplishment can be a blueprint for non-COVID drug programs that approach the pace of drug development during the pandemic, with no adverse impact on the safety, quality, and late-stage development of biologics.
摘要：
制药公司最近专注于加快启动首次在人（FIH）试验的时间表，以便快速评估生物药物。例如,稳定的细胞池可用于生产用于毒理学（Tox）研究的材料，减少4-5个月到诊所的时间。在2019年冠状病毒病（COVID-19）大流行期间，抗COVID药物从DNA转染到临床阶段的时间表缩短到6个月，使用稳定的池产生稳定性有限的临床药物底物(DS)，病毒清除,和毒性研究包。然而,精益化学，制造,和控制（CMC）包装会增加安全性和可比性风险，并可能在后期开发和商业化阶段留下额外的工作。此外,这些加速的COVID-19药物开发策略是否可以应用于非COVID项目并被确立为生物制剂开发的标准实践尚不确定.这里,我们介绍了一种新型抗肿瘤药物的案例研究，其中“快速至FIH”方法的应用与BeiGene的去风险策略相结合，在10个月内成功交付了完整的CMC包装。一项全面的可比性研究表明，从稳定池和单细胞衍生的主细胞库产生的DS在工艺性能方面具有高度可比性。产品质量,和效力。这一成就可以成为非COVID药物计划的蓝图，这些计划在大流行期间接近药物开发的步伐，对安全没有不利影响，质量,和生物制品的后期发展。
