在IgG1单克隆抗体配方中,低分子量杂质形成的机制
Pinaki Basu1, Nidhi Verma2, Sigireddi Indra Kumar1
1Formulation and Drug Product Development, Biologics, Dr. Reddy's Laboratories, Hyderabad, India.
Journal of pharmaceutical sciences
|January 18, 2025
概括
配方的pH值和酸盐水平会影响生物类似单克隆抗体 (IgG1) 的稳定性,可能导致杂质. 特定的辅助剂度和低pH值增加了低分子量杂质形成的风险.
科学领域:
- 生物制药配方开发发展
- 蛋白质化学和降解途径
背景情况:
- 生物类似单克隆抗体 (mAbs) 需要强大的配方才能稳定.
- 了解杂质形成对于产品质量和监管合规性至关重要.
研究的目的:
- 为了评估生物类似IgG1.1的配方稳定性.
- 为了确定影响杂质生成的关键配方参数.
主要方法:
- 在IgG1配方中,pH和辅助剂度 (酸盐) 的系统变化.
- 使用质谱学分析低分子量杂质.
- 在分析中使用盲码对接来预测降解机制.
主要成果:
- 低pH值和高酸盐度使IgG1配方易受低分子量杂质的影响.
- 质谱测量确定了高质酸盐物种和重链碎片化 (-DKTH-序列).
- 在Cys224附近的酸盐与素222的结合与IgG1碎片化有关.
结论:
- 配方pH和酸盐度是IgG1生物相似稳定性的关键属性.
- 酸盐诱导的碎片化是这种mAb的潜在降解途径.
- 这些发现为开发稳定的mAb配方的策略提供了信息.
关键词:
降解产品 (s) 降解产品 (s)配方 配方 配方 是一个质谱法 (MS) 是一种质谱法.单克隆抗体 (monoclonal antibody) 是一种单克隆的抗体.蛋白质配方 (s) 蛋白质配方更多相关视频
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