Risk assessment report of potential impurities in cetirizine dihydrochloride.
Risk assessment report of potential impurities in cetirizine dihydrochloride.
复制标题
二盐酸西替利嗪潜在杂质的风险评估报告。
DOI：
10.1016/j.jpba.2020.113425
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发表时间：
2020
影响因子：
3.4
通讯作者：
U. Holzgrabe
中科院分区：
文献类型：
--
作者：
A. Leistner;Stephan Haerling;Joerg;Ivonne Becker;Dirk Jung;U. Holzgrabe
最近，欧洲药品管理局(EMA)和美国食品和药物管理局(FDA)报告了几种沙坦、雷尼替丁和二甲双胍中“意想不到的”杂质。这些事件引发了关于生产过程本身的风险评估的大量讨论。这些讨论大多只涉及亚硝胺杂质领域，但这是过于短视的。我们应该扩大这一范围。合成一种对所有活性药物成分(原料药)都适用的100%纯化合物是不可能的。不同的合成路线会产生不同的杂质分布。因此，药典试图将来自不同药物合成路线的所有可能的杂质考虑在一本用于杂质评估的专著中。然而，原料药制造商不能简单地依赖药典中报告的杂质情况来生产高质量的产品。他们必须实施全面的风险评估，以评估原料药中是否存在杂质。在此，在一份详细的风险评估报告的框架内，展示了一种评估和最小化药物盐酸西替利嗪制造过程中的潜在的杂质风险负荷的策略。
Recently, the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA) had reported on “unexpected” impurities in a couple of sartans, ranitidine, and metformin. These events led to a lot of discussion with regard to the risk assessment for the production process itself. Most of these discussions covered the field of nitrosamine impurities only, but that would be too short-sighted. One should expand that scope. It is impossible to synthesize a 100 % pure compound which holds true for all active pharmaceutical ingredients (APIs). Different synthetic routes result in different impurity profiles. Therefore, pharmacopoeias try to consider all possible impurities that can arise from different drug synthesis routes in one a single monograph for impurity assessment. However, API manufacturers cannot simply rely on the impurity profile reported in pharmacopoeias for the production of a high-quality product. They have to implement a whole risk assessment to rate the presence of impurities in the API. Here, a strategy to evaluate and minimize the load of potential risks of impurities during the manufacturing process of the drug substance cetirizine dihydrochloride within the frame of a detailed risk assessment report is demonstrated.