此前，EMA发布了一份标题为《EMA建议药企采取步骤避免人用药物中的亚硝胺（EMA / 511347/2019）》的文件。要求对所有化学合成药物的亚硝胺的潜在污染的进行风险评估。
现在，EMA更新了EMA / 428592/2019《有关“提供上市许可持有人使用的亚硝胺信息”的问答》，新增问答12，包含了目前确定的亚硝胺污染的可能原因，以帮助药企对所生产药品的亚硝胺污染进行评估。
12. New! What are the currently identified root causes for presence of nitrosamines?
12.（新增！）目前确定的亚硝胺存在的根本原因是什么？
Potential sources of nitrosamine impurities currently identified are listed below:
下面列出了目前确定的亚硝胺杂质的潜在来源：
1. Use of sodium nitrite (NaNO2), or other nitrosating agents, in the presence of secondary, tertiary amines or quaternary ammonium salts within the same or different process steps (if carry over can occur).
在仲，叔胺或季铵盐存在的条件下，在同一加工步骤或不同加工步骤（如果可能发生残留）中使用亚硝酸钠（NaNO2）或其他亚硝化剂。
2. Use of sodium nitrite (NaNO2), or other nitrosating agents, in combination with reagents, solvents and catalysts, which are susceptible to degradation to secondary or tertiary amines, within the same or different process steps (if carry over can occur).
在同一加工步骤或不同加工步骤（如果可能发生残留）中，将亚硝酸钠（NaNO2）或其他亚硝化剂与易降解为仲胺或叔胺的试剂，溶剂和催化剂结合使用。
3. Use of contaminated raw materials in the API manufacturing process (e.g. solvents, reagents and catalysts).
在API生产过程中使用受污染的原材料（例如溶剂，试剂和催化剂）。
4. Use of recovered materials (e.g. solvents, reagents and catalysts), including recovery outsourced to third parties who are not aware of the content of the materials they are processing and routine recovery processes carried out in non-dedicated equipment.
使用回收的物料（例如溶剂，试剂和催化剂），包括外包给第三方回收，这些第三方不知道他们正在处理的物料的内容，并在非专用设备中进行的常规回收过程。
5. Use of contaminated starting materials and intermediates supplied by vendors that use processes or raw materials which may allow nitrosamine formation.
使用供应商提供的受污染的起始物料和中间体，这些物料和中间体的使用可能会导致亚硝胺形成。
6. Cross-contaminations due to different processes run on the same line and due to operator-related errors such as inadequate phase separations.
在同一条生产线上进行不同工艺并且由于与操作员相关的错误（例如相分离不充分）而造成的交叉污染。
7. Degradation processes of starting materials, intermediates and drug substances, including those induced by inherent reactivity in combination with carry-over of sodium nitrite (NaNO2), or other nitrosating agents. This could potentially occur also during finished product formulation or storage.
起始物料，中间体和药物的降解过程，包括固有反应以及亚硝酸钠（NaNO2）或其他亚硝化剂的残留而引起的降解过程。在成品配制或存储过程中也可能发生这种情况。
8. Use of certain packaging materials. Nitrosamine contamination has been observed by one MAH in a finished product stored in blister. The MAH has hypothesised that the lidding foil containing nitrocellulose printing primer may react with amines in printing ink to generate nitrosamines, which would be transferred to the product under certain packaging process conditions.
使用某些包装材料。一些MAH已在泡罩中存储的成品中发现了到亚硝胺污染。MAH认为包含硝化纤维印刷底漆的盖箔可能会与印刷油墨中的胺反应生成亚硝胺，在某些包装工艺条件下，亚硝胺会转移到产品中。
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