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设计强大的单克隆抗体药物产品:稳定性预测简单方法的陷

Kelvin B Rembert¹, Yatin R Gokarn¹, Atul Saluja¹

¹Biologics Drug Product Development & Manufacturing, Global CMC, Sanofi, One Mountain Road, Framingham, MA 01701, USA.

Journal of pharmaceutical sciences

|March 31, 2024

概括

像T_m这样的热稳定性测量通常用于单克隆抗体 (mAb) 开发. 然而,这项研究表明T_m是长期聚合的不充分预测因素,特别是在典型的储存条件下.

科学领域:

生物制药开发生物制药开发
蛋白质的稳定性蛋白质的稳定性
抗体工程抗体工程

背景情况:

热稳定性参数,如T_onset和T_m,经常用于单克隆抗体 (mAb) 开发用于选择和配方.
常见的方法假定热和运动物理稳定性之间存在直接的相关性,这得到了一些文献的支持,但有已知的例外.

研究的目的:

系统地分析不同条件下mAbs的热稳定性 (T_m) 和运动稳定性 (聚合率) 之间的相关性.
评估T_m在相关产品储存和加速条件下对mAb聚合的预测效用.

主要方法:

对一组具有不同热稳定性和运动稳定性配置的mAbs进行分析,包括工程低变体.
在不同的溶液条件下制备mAbs,并使用各种辅助剂来调节T_m.
在加速和长期储存条件下 (冷藏,室温) 评估聚合率.

主要成果:

在加速条件下观察到高T_m和低聚合率之间的一般相关性.
在冷藏和室温下,T_m被证明是长期聚合率的不充分预测.
在加速条件下,当储存温度超过15°C时,T_m是聚合的糟糕预测指标.

结论:

热稳定性 (T_m) 和mAbs的动力稳定性 (聚合) 之间的直接相关性并不普遍适用,特别是对于长期存储.
仅仅依靠T_m来预测mAb聚合可能会在生物制药产品开发中产生误导作用.
对T_m的预测限制进行批判性评估是强大的mAb开发工作流程所必需的.

关键词:

在Fc工程师设计的.配方开发配方开发的选择的选择长期稳定性的长期稳定性单克隆抗体是一种单克隆抗体.保质期货架上使用期限储存的稳定性储存的稳定性热稳定性热稳定性开发能力开发能力

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