The recent discovery of nitrosamines within marketed drugs, such as Valsartan, has led to changes within the regulatory landscape. Most notably, the requirement for a risk evaluation of the presence of nitrosamines within the drug product has been extended from sartan-type tetrazole containing drugs to all marketed products. The largest inherent risks associated with a drug substance will generally arise from impurity formation and carryover in the synthetic manufacturing process. Despite the classification of nitrosamines within the cohort of concern, the understanding of their behavior based on physicochemical properties is unaffected by this status, and as such all control options laid out in ICH M7 should be considered acceptable. This communication aims to show how the use of purge calculations, utilizing the Mirabilis software, fully de-risked nitrosamine concerns related to the development of Candesartan cilexetil. Aligned to the principles of impurity control in the ICH M7 guideline, this provided a suitable strategy to determine, and subsequently demonstrate control of, the nitrosamine risk.

中文翻译：

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控制队列：使用基于Mirabilis的清除计算方法来了解亚硝胺相关的风险和控制策略选项

最近在市售药物（如Valsartan）中发现亚硝胺，导致监管环境发生变化。最值得注意的是，对药物产品中亚硝胺的存在进行风险评估的要求已从含沙坦型四唑的药物扩展到所有市售产品。与原料药相关的最大固有风险通常将来自合成制造过程中的杂质形成和残留。尽管在关注的人群中对亚硝胺进行了分类，但基于理化性质对其亚硝胺的行为的理解不受此状态的影响，因此应认为ICH M7中列出的所有控制选项均可接受。本通讯旨在说明如何使用Mirabilis软件使用清除计算，与Candesartan cilexetil的发展有关的完全脱险的亚硝胺问题。符合ICH M7指南中的杂质控制原则，这为确定亚硝胺风险提供了合适的策略，并随后证明了对亚硝胺风险的控制。