评估降低粘度的辅助剂对高度单克隆抗体溶液液体液相分离的影响
Chelsea R Thorn1, Deep Bhattacharya1, Lindsey Crawford1
1BioTherapeutics Pharmaceutical Sciences, Pharmaceutical Research and Development, Pfizer, Andover, MA, USA.
Journal of pharmaceutical sciences
|May 4, 2025
概括
高度单克隆抗体配方需要仔细控制辅助剂,如L-氨酸化,以防止液态液相分离 (LLPS). 严格控制pH和离子含量对于稳定性和防止抗体药物产品中的LLPS至关重要.
科学领域:
- 生物制药配方开发发展
- 蛋白质化学和生物物理学
背景情况:
- 高度单克隆抗体 (mAb) 制药对于皮下注射至关重要.
- 挑战包括管理蛋白质-蛋白质相互作用,粘度和稳定性问题,如聚合和粒子形成.
- L-氨酸化物是减少mAb配方粘度的常见辅助剂.
研究的目的:
- 调查液态液态相分离 (LLPS) 在高度mAb配方中具有不同L-氨酸化物度的潜力.
- 确定辅助剂和pH控制在预防LLPS中的关键作用.
- 展示用于评估LLPS和指导配方优化的生物物理工具包.
主要方法:
- 利用生物物理工具包进行基于结构和分子相互作用的评估.
- 评估了L-氨酸化物度,pH值和离子含量对配方特性的影响.
- 评估了LLPS的可逆性及其对蛋白质折叠和结构的影响.
主要成果:
- 在特定的pH值和辅助剂条件下,L-氨酸化物度的轻微变化可以诱导LLPS,这与现有的文献相反.
- 增加的离子含量显著改变了度平衡,促进了LLPS.
- 观察到的LLPS是可逆的,并没有影响固有的蛋白质折叠和结构.
结论:
- 精心控制辅助剂度和pH值对于防止高度mAb配方中的意外LLPS至关重要.
- 离子含量和度是影响LLPS发生的关键因素.
- 多样化的生物物理工具箱对于在mAb配方开发中做出明智决策至关重要,以确保产品的稳定性和有效性.
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