结合
药品
电流(流体)
抗体
化学
制药工业
色谱法
药理学
风险分析(工程)
业务
组合化学
医学
生化工程
免疫学
工程类
数学
数学分析
电气工程
作者
Paul G. Bulger,Michael T. Jones,J. Gair Ford,Kate Schrier,Kevin P. Cole,Frank Bernardoni,Olivier Dirat,Qunying Zhang,Osama Chahrour,J. Richard Miller,Llorente V. R. Boñaga,Andrew T. Parsons,Lan Yang
标识
DOI:10.1021/acs.oprd.4c00254
摘要
Antibody–drug conjugates (ADCs) and N-nitrosamines are two topics that have seen a surge of interest in recent years. ADCs are increasingly prevalent as oncology therapeutics in clinical development and on the market. Concerns about the potential presence of N-nitrosamines in pharmaceutical products have led to increased regulatory scrutiny and implementation of robust control strategies by the industry. This article, the first in a two-part series, provides visibility into current industry practices for risk assessment and control of N-nitrosamines in ADCs with results and analysis from a benchmarking survey of member companies of the IQ Consortium. Items covered include assessment methodology, identification and characterization of risks, control limits at the drug-linker intermediate and drug substance, and specific factors related to the ADC modality that can be considered. Simpler N-nitrosamines (e.g., NDMA) and more complex N-nitrosamine drug-linker-related impurities (NDLRIs) are discussed. Areas where there are greater or lesser degrees of consistency across companies are highlighted. The second paper builds on these survey results by presenting a comprehensive set of recommendations for the risk evaluation and control strategy of N-nitrosamine impurities in drug-linkers and ADCs. Taken together, these papers provide a perspective on the current state and encourage further development of scientifically sound approaches in this field.
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