对于来自内药制品中的杂质的允许每日暴露限值的考虑和推导
Yi Yu Rice1, David G Dolan1, Suren B Bandara1
1Amgen Inc., Thousand Oaks, CA, 93010, USA.
Regulatory toxicology and pharmacology : RTP
|November 24, 2024
概括
对于眼部药物安全来说,确定注射室内 (IVT) 注射的允许每日暴露 (PDE) 限值至关重要. 本研究提出了一种新的方法来推导这些极限,考虑眼部和全身毒性,以更好地保护患者.
科学领域:
- 制药科学 制药科学
- 眼部药物输送 眼部药物输送
- 毒理学 毒理学 毒理学
背景情况:
- 静脉内注射 (IVT) 对于治疗诸如黄斑变性等眼部疾病至关重要.
- 目前的监管指南缺乏具体方法来确定IVT产品中杂质的允许每日暴露 (PDE) 限值.
- 关于玻璃体 (VH) 代谢和清除的有限数据使PDE导出IVT给药变得复杂.
研究的目的:
- 提出一种全面的方法来推导IVT制药产品中杂质和残留工艺试剂的PDE限值.
- 为了解决IVT PDE建立的具体监管准则的缺失.
- 推进对IVT PDE限制进行协调,基于科学的方法.
主要方法:
- 开发一个可行的框架,用于PDE极限导出.
- 考虑局部眼部和全身毒性终点.
- 使用五个不同杂质概况和数据可用性的案例研究 (无机元素,酸,聚乙烯糖醇,酸,罗拉克塔姆) 的方法论的示例.
主要成果:
- 描述了一种用于导出IVT PDE极限的实用方法.
- 案例研究展示了该框架在各种化学类型和数据场景中的应用.
- 拟议的方法考虑了IVT管理和眼组织脆弱性的独特挑战.
结论:
- 提出的方法提供了一种可靠的方法,用于建立基于科学的PDE限制,用于IVT药物产品.
- 这一框架支持监管合规,并提高通过IVT注射给眼部药物的安全性.
- 该方法的进一步应用和验证可以导致IVT杂质控制的协调全球标准.
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