EDQM元素杂质状态更新

11 January 2017, Strasbourg, France

UPDATE ON THE PH. EUR. POLICY ON ELEMENTAL IMPURITIES

With the implementation of the ICH Q3D guideline on elemental impurities, the control of elemental impurities is undergoing a shift in paradigm, moving away from pure substance-based testing towards a holistic control strategy in the finished product. While these approaches are not contradictory, this change has triggered the revision of numerous texts in the European Pharmacopoeia (Ph. Eur.).

随着ICH Q3D元素杂质指南的实施，元素杂质的控制正在经历模式变化，从纯粹的基于物质的检测朝向制剂全面控制策略发展。虽然这些方法相互并不冲突，但该变化已经引发了EP中大量内容修订。

The Ph. Eur. Commission has already communicated its plan for the implementation of this important guideline via a number of press releases (see hyperlinks below). The implementation schedule in the Ph. Eur. has been aligned as closely as possible with the application timelines decided by the Committee for Medicinal Products for Human use (CHMP), i.e. June 2016 for new marketing authorisation applications and December 2017 for all authorised products on the market of the European Economic Area.

EP委员会已经通过大量的信息发布方式（参见以下超链接）将些重要指南实施计划进行了沟通。EP的实施计划安排是尽量接近CHMP确定的应用时间表，即新的上市许可申报2016年6月1日开始，欧洲境内市场上所有已批准药品自2017年12月开始。

Therefore, at its 156th Session in last November, the Ph. Eur. Commission adopted several general texts integrating the new approaches and requirements of the ICH Q3D guideline for elemental impurities into the Ph. Eur. and, in broader terms, into the global regulatory framework. These texts are to be published in Supplement 9.3 with an implementation date of 1st January 2018. The revision plan for general texts was broken down as follows:

因此，在2016年11月第156次会议上，EP委员会采纳了几个通论，将ICH Q3D元素杂质指南中新的方法和要求整合到了EP和全球法规框架中。这些内容将在EP9.3发布，实施日期为2018年1月1日。通论修订计划分列如下：

?      General chapter 5.20 Elemental impurities: reproduces parts of the Scope and the Introduction sections of the ICH Q3D guideline and refers to the guideline which can be found in full on the ICH website;

?      通论5.20《元素杂质》：复制了ICH Q3D的范围和介绍部分，引用了ICH官网中的指南。

?      General monograph on Pharmaceutical preparations (2619): refers to chapter 5.20, rendering it —and by extension the ICH Q3D guideline — legally binding;

?      通论2619《制剂药品》：引用了第5.20章，通过将ICH Q3D指南延伸使得其具有强制约束力。

?      General monograph on Substances for pharmaceutical use (2034): introduces requirements for the control of elemental impurities intentionally added during production and explains the absence of a test for elemental impurities from individual monographs except for special cases (see paragraph on specific tests below);

?      通论2034《药用物质》：引入了对生产过程中有意加入的元素杂质的控制要求，解释了为什么除了特殊情况外，单个各论中没有元素杂质检测方法（参见以下专用检测段落）。

?      General method 2.4.20 Determination of elemental impurities: provides guidance for aspects of method development such as sample preparation and method validation for the determination of elemental impurities. In addition to this recent revision, this text remains a priority on the work program of the Pharmacopoeial Discussion Group (PDG), the aim being to harmonise the respective general chapters on elemental impurities in the different regions.

?      通用方法2.4.20《元素杂质检测》：提供了元素杂质检测方法开发指南，例如样品制备和方法验证。除了此最近修订外，此章节还在PDG工作计划的优先工作中，目的是要与不同地区的元素杂质相应的通则协调。

The Ph. Eur. Commission has also discussed the fate of specific elemental impurities (individual metal) tests (about 500 of these tests for various elemental impurities are described). Feedback gathered from stakeholders during workshops and conferences held over the past year has been used to help define the best approach to these tests. Consequently, the Ph. Eur. Commission has decided to keep the published specific elemental impurities tests in monographs on substances of natural origin only. Given the intrinsic nature of elemental impurities in these substances, they are amongst the major potential sources of elemental contamination in medicinal products. The Ph. Eur. Commission has also recommended keeping in particular the different tests for elements for which no Permitted Daily Exposure limits have been established, i.e. those identified as “other elements” in the ICH Q3D guideline (such as aluminium and iron), in individual monographs.

EP委员会还讨论了具体元素杂质（单个金属）检测（约描述了500个此类元素杂质检测）。过去几年里在研讨会和会议中从相关方所收集的反馈已经用来帮助确定这些检测的最好方法。因此，EP委员会已决定在只有自然来源的物质各论中保留已发布的专有元素杂质检测。由于这些物质中元素杂质的固有特性，它们成为药品中元素污染的主要潜在来源。EP委员会也建议特别保留物质各论中对还没有建立PDE限度的元素的不同检测，即在ICH Q3D指南中被作为“其它元素”（例如铝和铁）对待的元素。

Conversely, specific elemental impurities tests will be deleted from monographs on other substances (i.e. not from natural origin), unless otherwise justified. In particular, the Ph. Eur. Commission decided that, unless otherwise justified, specific tests for elemental contaminants originating from the production process will be deleted. As these elemental impurities are specific to the production process, they will remain the responsibility of the substance manufacturer; this is reflected in the new sentence added to the Production section of the general monograph on Substances for Pharmaceutical Use (2034).

相反，除有其它论证者以外，其它物质各论（即不是自然来源的物质）中的特定元素杂质检测将会删除。尤其是EP委员会决定除有其它论证者外，来自于生产工艺的元素污染物的特定检测将被删除。因为这些元素杂质是特定于生产工艺的，对其进行检测是物质生产商的责任。这在EP2034《药用物质》中生产部分所新加的一句话中有所反映。

The Ph. Eur. Commission and the corresponding groups of experts will continue their work on clearly defining on a case by case basis which monographs are concerned and to what extent they are impacted by the rationale developed above. The list of concerned monographs will be published in Pharmeuropa for public consultation in due time.

EP委员会和相关的专家组将继续其工作，对个案进行分析清楚说明哪篇通论是相关的，受到上述理论影响的程度有多大。相关各论清单将会发布在药典在线，指定期限征求公众意见。

As new data become available, the groups of experts intend to examine opportunities for revision of the set of individual metal tests in monographs in order to align them with newer standards and/or to reflect more closely the actual quality of substances available on the European market. Support from stakeholders will be crucial for the success of this initiative.

在获得新的数据之后，专家组将会查看是否要修订各论中的单个金属检测方法，以使其与新的标准保持一致，并/或更真实地反映欧洲市场药用物质的实际质量。

For your convenience, previous communications on the Ph. Eur. implementation strategy of the ICH Q3D guideline on elemental impurities can be accessed by clicking on the following links:

为方便起见，之前关于ICH Q3D元素杂质指南的EP实施策略相关信息可点击以下链接获取：

Press release from April 2015

2015年4月的信息

Press release from August 2015

2015年8月的信息

Contact: Caroline Larsen Le Tarnec, Public Relations Division, EDQM, Council of Europe

Tel.: +33 (0) 3 88 41 28 15 - E-mail: caroline.letarnec@edqm.eu

Note for the Editor: Further information is available on the internet site www.edqm.eu

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