EMA关于在EU内实施ICH Q3D指南的新指南

EMA's new Guideline on the Implementation of the ICH Q3D Guideline in the EU

EMA关于在EU内实施ICH Q3D指南的新指南

On 8 March 2017, the EMA published the guideline entitled "Implementation strategy of ICH Q3D guideline" (EMA/CHMP/QWP/115498/2017). This document is the final version of the draft (EMA/404489/2016) of the same name from July 2016 which had been open for comment 4 weeks long. We reported in "Practical Implementation of the Control of Elemental Impurities: EMA's new Guideline Draft" in July 2016.

2017年3月8日，EMA发布了题为“ICH Q3D指南实施策略（EMA/CHMP/QWP/115498/2017）”的指南。该文件是2016年7月同一题目指南EMA/404489/2016草案的最终版本，该草案于四周前开始征求意见。我们曾在2016年7月有过报道。

The objective of the guideline is to provide medicinal product manufacturers with support regarding the implementation of the ICH Q3D "Guideline on Elemental Impurities".

该指南的目的是为药品生产商提供关于ICH Q3D“元素杂质指南”实施的支持。

Compared to the draft version, the final guideline which has been published now contains notable changes. Those are:

相比于草案，现已发布的最终版指南包括重大变化。变化如下：

• Analytical methods for the determination of elemental impurities have to be validated for the intended purpose.
• 元素杂质检测方法必须验证其适用于既定用途。
• A summary of the risk assessment with regard to the elemental impurities has to be submitted in the marketing authorisation dossier in Module 3 and in the Quality Overall Summary in Module 2 of the CTD.
• 元素杂质的风险评估总结必须在上市许可文档模块3以及CTD模块2质量综述里提交。
• The guideline concedes that the observation of the requirements laid down in ICH Q3D is also possible with limited knowledge of the possible sources of elemental impurities by means of a risk assessment - based on some process and product understanding. If one waives such an assessment, routine testing of the medicinal product for all elements listed in ICH Q3D has to be performed.
• 指南承认根据一些工艺和药品理解，采用风险评估对元素杂质可能来源知识有限情况下，ICH Q3D里给出的指南可能会有缺陷。如果免于进行此评估，则必须检验药品中ICH Q3D里列出的所有元素。
• The procedure for both approaches "Drug Product Approach" and "Component Approach" is described more clearly. In the "Drug Product Approach" for example it is pointed out that analytical data alone are not sufficient to justify the omission of a specification for an element whereas in the "Component Approach" the contribution of elemental impurities from each potential source along the manufacturing process is identified, evaluated and summarized.
• 更清楚地描述了“药品方法”和“组分方法”两种方法流程。在“药品方法”中，例如，文件指出单单只有分析数据是不充分的，不能论证在质量标准里不包括元素检测，而在“组分方法”里，每个潜在来源与生产工艺对元素杂质的影响均要进行识别、评估和总结。
  

When the supplier of a component - e.g. an excipient - has no information about where and how the medicinal product manufacturer uses the component in question, it is almost impossible to set a specification for the impurities. One possibility is to use Option 1 from ICH Q3D setting limits for elements with a daily administration of 10 grams.

如果组分的供应商，例如辅料，没有关于药品生产商在何处以及如何使用所讨论的组分，要建立杂质的标准几乎是不可能的。一个可能性是对日摄入剂量为10g的元素使用ICH Q3D设定限度方法一。

One requirement of evidence has been included unchanged: all elements intentionally added, like for example metal catalysts used in the last step of the synthesis, have to be below the control threshold of 30% of the PDE in the final API product. This is different from the requirement laid down in the ICH Q3D Guideline according to which this limit has to be complied with for the finished product but not for the API.

有一个对证据的要求仍保留着没有变：所有有意加入的元素，如用于合成最后步骤的金属催化剂，在最终API产品中必须保持在PDE的30%控制阈以下。这与ICH Q3D指南中的要求是不同的。在ICH Q3D中，这个限度是制剂必须达到，但对API并没有这个要求。

感谢楼主分享，辛苦