了解从工艺流中超过/透过过程中元素液的清除行为
Noemí Dorival-García1, Anna Mulligan2, Ronan Hayes3
1Characterisation and Comparability Laboratory, The National Institute for Bioprocessing Research and Training (NIBRT), Foster Avenue, Mount Merrion, A94 X099, Co. Dublin, Ireland.
Journal of pharmaceutical and biomedical analysis
|May 17, 2025
概括
从一次性使用技术中产生的微量元素杂质对生物制药品构成风险. 超过/透过 (UF/DF) 有效地去除这些杂质,清除取决于工艺参数和元素特性.
科学领域:
- 生物制药制造业 生物制药制造业
- 分析化学 分析化学
- 工艺工程是过程工程.
背景情况:
- 微量元素杂质,称为工艺设备相关漏物 (PERLs),是使用一次性使用技术 (SUTs) 的生物制药制造中的一个问题.
- 现有的PERLs监管指南 (ICH Q3A) 没有充分涵盖像单克隆抗体 (mAbs) 这样的生物药物.
- 缺乏对生物制品中的PERLs进行标准化,基于风险的测试策略,影响产品质量和患者安全.
研究的目的:
- 调查超过和透过 (UF/DF) 过程对元素杂质的清除能力.
- 通过描述 UF/DF.期间的 PERL 行为来为可提取和可漏 (E&L) 评估提供信息.
- 开发UF/DF过程中元素杂质去除的预测模型.
主要方法:
- 通过使用缩蛋白样本,研究了UF/DF期间22个尖元素的清除.
- 根据ICH Q2 (R1) 准则开发并验证了一种感应合等离子体质谱法 (ICP-MS) 方法.
- 采用直角局部最小平方 (OPLS) 回归和选系数来开发用于清除预测的数学模型.
主要成果:
- 大多数元素 (22种中的18种) 的有效清除 (>97%) 在10个方体后实现,这代表了2个日志的减少或更高.
- 元素清除受UF/DF过程参数,特别是pH和元素的物理化学性质的影响.
- 经过验证的数学模型成功地描述和预测了UF/DF过程中的元素杂质清除.
结论:
- UF/DF 工艺显示出大量的能力去除基本的可浸物,为生物制造提供了显著的风险降低.
- 珀尔清除建模为开发强大,基于风险的测试策略提供了有价值的工具,提高了产品安全性和监管合规性.
- 这些发现支持使用UF/DF作为管理单克隆抗体和其他生物疗法的元素杂质的关键步骤.
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