15/04/2015
Recommendations of the EMA for the risk assessment of metallic impurities in approved drugs
EMA关于已上市药品中金属杂质的风险评估的建议
Recently, with the inclusion of the Guideline ICH Q3D in the collection of "Scientific Guidelines", the EMA established the deadlines for its entry into force (see our news "The CHMP adopts the Guideline ICH Q3D as a 'Scientific Guideline'" of 21 January 2015). For drug producers, there is a relatively short transition period of 20 months to implement the requirements of the ICH Q3D; as of December 2017, the provisions for approved medicines will be mandatory. 近日，随着指南ICH Q3D被包括在“科学指南”里，EMA指定了其生效的最后期限（参见我们2015年1月21日的新闻“CHMP采购ICH Q3D指南作为“科学指南””。对于药品生产者，有一个相对较短的过渡时间，约为20个月来实施ICH Q3D的要求，最后实施日期为2017年12月，已上市药品的条件将成为法定。
On 27 March 2015, the EMA published a document entitled "Elemental impurities in marketed products. Recommendations for implementation". The targeted audience of these recommendations are pharmaceutical companies and the national regulatory authorities; the latter are to conform their activities to these recommendations in order to ensure a uniform approach. This should also reduce the workload in the processing of variations, which will then be evaluated according to the same criteria. 在2015年3月27日，EMA公布了题为“上市药品中的元素杂质：实施建议”。该建议的目标读者是制药公司和国家法规药监人员，后者需要确认药品生产商符合这些建议的活动，以保证方法的一致性。这还可以降低变更处理中的工作量，这些变更需要根据相同的标准进行评估。
The main points of the "recommendations" are as follows:
建议的要点如下：
- Each national authority should officially inform the drug companies (manufacturing authorisation holders; MAH) in their country of the application of the provisions of Guideline ICH Q3D.
- 每个国家药监机构应正式通知其国家的制药公司（生产许可持有人，MAH）关于ICH Q3D指南中的条件的申报
- Within the transition period, the drug manufacturer should perform a risk assessment of his products in terms of elemental impurities. In doing so, all potential sources, such as starting materials for active substances, excipients, reagents, catalysts, process water, equipment, container closure systems, etc. are to be taken into account. This risk assessment should provide the basis for a control strategy that ensures that the respective permitted daily exposure limits (PDEs) specified in the guideline are adhered to.
- 在过渡期间，药品生产商应对其产品在元素杂质方面实施风险评估。在做这些时，所有潜在的来源，如活性物质的起始物料、辅料、试剂、催化剂、工艺用水、设备、容器密闭系统等，均要考虑进去。该风险评估应提供控制策略的制订基本，用以保证能符合指南中指定的相应的允许日暴露限度（PDE）。
- In all cases, a thorough risk assessment is to be conducted, which should be available to be presented during an inspection upon request.
- 在所有情况下，都要实施完整的风险评估，在检查期间，如果检查员要求查看应能提供这些资料
- The application for a variation at the regulatory authority is not required if a risk analysis has shown that
- 如果风险分析显示符合以下要求，则不需要向法规机构提交的变更申报
- -no further monitoring for elemental impurities in starting materials, intermediates, active ingredients, excipients and finished products is required, and that these do not have to be replaced or exchanged for others,
- 不需要对起始物料、中间体、活性成分、辅料和制剂中的元素杂质进行监测，这些物料不必要采用其它来替代
- no change in the manufacturing process is necessary. In all other cases, proceed as described in the variations regulation and the corresponding variation guidelines.
- 不需要对生产工艺进行变更。在所有其它情形下，在按照变更管理和相应的变更指南处理
- For the analyses of elemental impurities, specific procedures are to be used. Non-specific pharmacopoeia methods will not be accepted.
- 对于元素杂质的分析，要使用专属性方法。非专属性药典方法将不被接受。
It remains to be seen whether these recommendations will result in a standardised approach of the authorities of the EU Member States and how the pharmaceutical manufacturers will be supported in their efforts of a timely implementation of the requirements of the Guideline ICH Q3D. An article by the "Industry Coalition" in the March issue of the magazine "Pharmaceutical Technology Europe" which provides practical suggestions for conducting risk assessments is also very helpful in this context. 这些建议是否会导致欧盟成员国药监机构制订一个标准化的方法，药品生产商要如何才能努力地及时实施ICH Q3D指南中的要求现在还在观望中。3月份在杂志“欧洲药物技术”上有一篇“行业联盟”发的文章，给出了关于实施风险评估的可行建议，在此情形下也是非常有用的。
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