Bristol Myers Squibb, 100 Binney Street, Cambridge, Massachusetts, 02143, USA.
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, 46285, USA.
AAPS J. 2023 Jun 2;25(4):55. doi: 10.1208/s12248-023-00820-7.
A survey conducted by the Therapeutic Product Immunogenicity (TPI) community within the American Association of Pharmaceutical Scientists (AAPS) posed questions to the participants on their immunogenicity risk assessment strategies prior to clinical development. The survey was conducted in 2 phases spanning 5 years, and queried information about in silico algorithms and in vitro assay formats for immunogenicity risk assessments and how the data were used to inform early developability effort in discovery, chemistry, manufacturing and control (CMC), and non-clinical stages of development. The key findings representing the trends from a majority of the participants included the use of high throughput in silico algorithms, human immune cell-based assays, and proteomics based outputs, as well as specialized assays when therapeutic mechanism of action could impact risk assessment. Additional insights into the CMC-related risks could also be gathered with the same tools to inform future process development and de-risk critical quality attributes with uncertain and unknown risks. The use of the outputs beyond supporting early development activities was also noted with participants utilizing the risk assessments to drive their clinical strategy and streamline bioanalysis.
美国药物科学家协会(AAPS)治疗性产品免疫原性(TPI)分会对参与者进行了一项调查,询问他们在临床开发前的免疫原性风险评估策略。该调查分两个阶段进行,历时 5 年,调查了免疫原性风险评估的计算算法和体外检测方法,以及如何利用这些数据为发现、化学、制造和控制(CMC)以及非临床开发阶段的早期可开发性提供信息。代表大多数参与者趋势的主要发现包括使用高通量计算算法、基于人免疫细胞的检测方法和基于蛋白质组学的检测方法,以及在治疗作用机制可能影响风险评估时使用专门的检测方法。同样的工具还可以深入了解与 CMC 相关的风险,以便为未来的工艺开发提供信息,并降低具有不确定和未知风险的关键质量属性的风险。参与者还指出,除了支持早期开发活动外,还可以利用这些检测结果来指导临床策略和简化生物分析。
J Immunotoxicol. 2006-9-1
Cochrane Database Syst Rev. 2022-2-1
Pharm Res. 2025-3-24
Biomedicines. 2025-1-26
Clin Pharmacol Ther. 2025-6
Nat Rev Drug Discov. 2024-12
Comput Struct Biotechnol J. 2020-12-29