初始聚合水平对不同缓冲系统中单克隆抗体聚合潜力的影响
Anuj Shrivastava1, Anurag S Rathore2
1Department of Chemical Engineering, Centre of Excellence for Biopharmaceutical Technology, Indian Institute of Technology Delhi, Hauz Khas, New Delhi, 110016, India.
Pharmaceutical research
|June 6, 2025
概括
甘氨酸缓冲剂为单克隆抗体 (mAb) 中介产物提供了最佳的稳定性,显著优于酸盐和酸盐缓冲剂. 最佳的储存条件对于保持生物治疗产品的质量至关重要.
科学领域:
- 生物制药制造业 生物制药制造业
- 蛋白质的稳定性 蛋白质的稳定性
- 过程开发 过程开发
背景情况:
- 单克隆抗体 (mAbs) 是重要的生物治疗药物.
- 工艺中间体需要稳定的储存条件.
- 蛋白A化缓冲器对mAb的稳定性产生影响.
研究的目的:
- 在常见的蛋白质A化缓冲器中研究mAb过程的中间稳定性.
- 在不同的聚合物水平和温度下评估降解动力学.
- 确定mAb制造的最佳缓冲和储存条件.
主要方法:
- 将mAb样本置于热应力下,以创建不同的聚合物水平.
- 在酸盐,酸盐和甘氨酸缓冲器中在4°C和30°C时化样品.
- 使用动态光散射 (DLS) 与机器学习 (ML) 的量化聚合物.
主要成果:
- 甘氨酸缓冲剂表现出卓越的稳定性,特别是在4°C,初始聚合物低 (129天半衰期).
- 酸盐缓冲物表现出最不稳定性,特别是在30°C高聚合物 (3.5天半衰期) 的温度下.
- 降解动力学从二级转移到一级,随着总体水平的增加.
结论:
- 缓冲区的选择和储存温度极大地影响了mAb的中间稳定性.
- 建议使用甘氨酸缓冲剂和受控温度,以实现强大的mAb制造.
- 优化的储存条件确保生产安全有效的生物治疗药物.
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