欧盟CHMP发布亚硝胺评估的最终报告！
CHMP's Assessment Report on Nitrosamines published
CHMP发布关于亚硝胺的评估报告
On 9 July 2020,the final report on nitrosamine contamination was published onthe EMA website. This final statement of the CHMP entitled 'Assessment report - Nitrosamineimpurities in human medicinal products' EMA/369136/2020represents the end of the procedure under Article 5(3) of Regulation 726/2004,which started on 10 September 2019. The 90-page document contains the currentstate of science and knowledge regarding nitrosamine impurities in human medicinalproducts and provides recommendations for manufacturers of medicinal productsbased on chemically defined APIs and biological medicinal products.
2020年7月9日，EMA发布了关于亚硝胺污染的最终报告。CHMP题为'评估报告 - 人用药物产品中亚硝胺杂质'EMA/369136/2020的最终声明代表2019年9月10日开始的第726/2004号条例第5（3）条程序的结束。这份90页的文件载有人用药物产品中亚硝胺杂质的当前科学和知识，并为原料药和生物医药产品的药品制造商提供建议。
These recommendations are listed in the last section of the report (5.'Recommendations') and constitute an orientation framework for the manufacturers or marketing authorisation holders of the above-mentioned medicinal products. Below is a brief summary of the central points covered bythese recommendations:
这些建议在报告的最后一节（5.'建议'）列出，并构成上述药品的制造商或上市许可持有人的基本目标。以下是这些建议所涵盖的主要要点的简要概况：
The content of nitrosamines in medicinal products for human use must be kept to a minimum and must not exceed the limits laid down in the ICH M7(R1) guideline. The daily exposure over a lifetime must be taken into account.
人用药物产品中的亚硝胺含量应保持在最低水平，并且不得超过 ICH M7（R1）指南规定的限制。应考虑一生每天的暴露。
Risk assessments shall be carried out to evaluate the risk for the presence of nitrosamines. If risks are identified, confirmatory tests must be carried out on the finished medicinal product. The potential sources of this type of contamination known so far shall be taken into account.
应进行风险评估，以评估亚硝胺存在的风险。如果发现风险，必须对成品进行确认性测试。应考虑到迄今已知的这类污染的潜在来源。
If nitrosamines are present, limit values according to ICH M7(R1) must be established taking lifetime exposure into account.
如果存在亚硝胺，则必须根据 ICH M7（R1）确定限制值，并考虑终生暴露。
If contamination with several distinct nitrosamines is present, the total risk must not exceed 1:100,000 of lifetime risk. An alternative approach may be to limit the overall risk below the level of the highest risk nitrosamine species.
如果存在多种不同亚硝胺的污染，则总风险不得超过 1：100，000 的终生风险。另一种方法可能是将总风险控制在最高风险亚硝胺种类的限制水平以下。
For new applications for authorisation, a risk assessment on the presence of nitrosamines must be submitted with the application.
对于新的许可申请，必须随申请一起提交亚硝胺的风险评估。
The risk assessment should include manufacturing processes of active substances and finished products, taking into account the root-causes, and subsequent confirmatory tests on the finished product, if a risk exists.
风险评估应包括活性物质和成品的制造过程，并考虑根本原因，以及随后对成品的确认测试（如果存在风险）。
For biological medicinal products the general risk of nitrosamine formation is very low, but the following cases should be considered: Biological medicinal products containing chemically synthesised fragments where risk factors similar to chemically synthesised active substances exist, biological medicinal products to which nitrosating reagents are deliberately added during the manufacturing process, biological medicinal products packaged in primary packaging such as blisters made of nitrocellulose
对于生物医药产品，亚硝胺形成一般风险非常低，但应考虑以下情况：含有化学合成片段的生物医药产品，其中存在类似于化学合成活性物质的危险因素；在制造过程中故意添加亚硝基试剂的生物医药产品；在内包装中包装的生物医药产品，如硝基纤维素泡罩。
The list of recommendations contains some more detailed guidance on how to proceed in special cases, e.g. when substance-specific lifetime exposure cannotbe calculated due to insufficient data or for preparations with genotoxic APIs.
建议的清单包含关于在特殊情况下的更详细的指导，例如，当由于数据不足或基因毒性 API 的制剂无法计算特定物质的终生暴露时。
One of the central statements in this section states that marketing authorisation holders must have implemented a control strategy thatis suitable for minimising or completely preventing the risk of contaminationwith nitrosamines.
本节中的一项核心声明指出，上市许可持有人必须实施一项控制策略以将亚硝胺污染的风险降到最低或完全防止。
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