通过设计使用分析质量来改善疫苗质量控制中的分析方法开发:应用到优化的定量高性能阴离子交换色谱方法
Isabelle Moineau1, Véronique Chambon2, Céline Perret2
1AKTEHOM, Berges du Rhône, 64 avenue Leclerc, 69007 Lyon, France.
概括
通过设计分析质量 (AQbD) 优化了一种用于量化疫苗中脱聚合多糖的方法. 这种方法为关键参数建立了强大的操作范围,确保方法可靠性并支持监管文件.
科学领域:
- 药品分析 药品分析
- 分析化学 分析化学
- 生物技术是生物技术.
背景情况:
- 通过设计分析质量 (AQbD) 正在获得分析方法开发的引力,新出现的指导方针草案.
- 精确量化复杂疫苗中的特定成分对于产品质量和患者安全至关重要.
研究的目的:
- 应用AQbD原则来开发和验证一种分析方法,以量化六价液体疫苗中非吸附的聚基酸 (PRP) 和非聚合的PRP.
- 为开发的方法建立一个强大的分析控制策略 (ACS).
主要方法:
- 采用高性能离子交换色谱 (HPAEC),在超离心后进行脉冲电流检测,用于样品制备.
- 开发了一个分析目标配置文件 (ATP) 来定义测量目标和范围.
- 采用风险评估和多变量设计实验 (DOE) 来识别关键方法变量 (CMV) 并建立方法操作设计区域 (MODR).
主要成果:
- 定义了七个CMV的强大的MODR,包括超离心参数 (速度,温度,持续时间,保持时间) 和色谱参数 (移动相压力,移动相存储,样品存储).
- 已建立的设计空间确保了脱聚合多糖控制的定义精度标准内的方法性能.
- 确定了关键参数的特定范围:超离心 [483,000-520,000] g, [11-19]°C, [29-34] 分钟;染色学 [2-6] psi,移动阶段储存 [0-7] 天,样品储存 [0-3] 天.
结论:
- 在AQbD方法成功建立了可靠的分析方法和控制策略,用于疫苗成分量化.
- 定义的MODR为关键参数提供了科学证明的范围,确保了方法的一致性.
- 这种方法通过为分析方法参数和生命周期管理提供强有力的理由来加强监管提交.
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