翻译：JULIA 来源：Julia法规翻译
27 July 2018, Strasbourg, France
EDQM’s actions to evaluate impact of impurity in active substance valsartan
EDQM评估原料药缬沙坦中的杂质影响的措施
The European Directorate for the Quality of Medicines & HealthCare (EDQM) is aware of a quality defect related to an impurity in the active substance valsartan used in medicines to treat high blood pressure marketed in Europe.Traces of the impurity N-nitrosodimethylamine (NDMA), a substance classified as probable human carcinogen, were discovered in one specific source of valsartan,manufactured by Zhejiang Huahai Pharmaceuticals, which supplies manufacturers of medicinal products worldwide. Patients are advised to speak to their doctor for further instructions and to continue their treatment.
EDQM了解在欧洲用于治疗高血压的药品中所用原料药缬沙坦里杂质有关的质量缺陷问题。在特定缬沙坦来源—浙江华海药业生产的缬沙坦中发现了痕量NDMA杂质，这是一种被归类为可能导致人体癌症的物质，而该生产商为全球药品生产商供应该API。建议患者与其医生讨论获取进一步指导并继续其治疗。
NDMA is an unexpected impurity that was not detected by routine tests carried out by the manufacturer. While the exact level of the contamination is still being investigated, competent authorities throughout the world have recalled batches of valsartan-containing medicines as a precautionary measure and have informed healthcare professionals and relevant prescribers of this action.
NDMA是一种非预期杂质，生产商日常执行的检测是无法检出的。由于目前正在调查确切的污染水平，全球药监机构已召回了含有缬沙坦药品批次作为预防性措施，并且通知了医疗专业人员和相关处方签发者所采取的措施。
Earlier this month, a pan-European alert system has been triggered by the European Medicines Agency (EMA) in order to assess the extent of this incident and to establish remedial action plans.
本月早些时候，EMA激活了泛欧警报系统以评价此事件的广泛程度，并制订弥补措施计划。
The EDQM is part of this pan-European alert system and is actively working with the EMA and national competent authorities to better understand the potential impact of this impurity and the extent of the issue.
EDQM是泛欧警报系统的一部分，正积极与EMA和国家药监机构合作，以更好地了解此杂质的潜在影响和问题的广泛程度。
With regardsto this investigation, the EDQM has taken a number of actions:
关于此次调查，EDQM采取了一系列措施：
– The immediate suspension of the Certificate of suitability held by Zhejiang Huahai Pharmaceuticals.The manufacturer and Competent Authorities in Europe and international partners have been informed of this suspension;
– 立即搁置了浙江华海的CEP，并将该搁置决定通知了该生产商和欧洲及国际伙伴的药监机构。
– Request tothe concerned manufacturer to eliminate or reduce the impurity to an acceptable level in future batches;
– 要求受影响生产商消除或减少该杂质使得今后的批次中该杂质处于可接受水平以下。
– Thorough review of manufacturing data submitted by other manufacturers of valsartan and other structurally related active substances in order to determine whether or not they have a comparable route of synthesis and whether their active substance is NDMA-free
– 彻底审核其它缬沙坦生产商所提交的生产数据，以及其它相关结构原料药以确定是否其它原料药存在有类似的合成路线，以及这些原料药是否不含有NDMA。
– Coordination of the activities of a group of Official Medicines Control Laboratories from memberstates to test NDMA in samples of active substances and medicinal products which are on the market in Europe.
– OMCL实验室组团合作，检测在欧洲销售的原料药和制剂样品中的NDMA。
The EDQM is doing its utmost to understand the root cause of this contamination and to reduce the impact of the issue on patients’ health.
EDQM正尽其所能了解此次污染的根本原因，以减少该问题对患者健康的影响。
The EDQM will communicate further, as soon as more information on the matter becomes available.
EDQM将在获得更多信息时尽快进行进一步沟通。
For more information, follow us on www.edqm.eu.
更多信息，请关注我们官网。
Background: 背景
Theso-called “Certificate of suitability” (or CEP) procedure of the EDQM is one out of three alternative options that can be used by a manufacturer to demonstrate that the quality of their active substance is suitably controlledby the respective monograph of the European Pharmacopoeia, and is in compliance with the current regulatory requirements. To obtain a certificate, the manufacturer may submit an application to the EDQM describing the manufacturing process and the methods applied for the quality control, including for the control of impurities. The data are assessed by experienced quality assessors nominated by National Competent Authorities and EDQM. Following a positive conclusionof the assessors, the EDQM grants a CEP. A copy of the CEP can then be used in any marketing authorisation application (MAA) for a medicinal product in which the active substance from this specific source is included.
EDQM的所谓“CEP”程序是三种程序之一，用于让生产商证明其原料药质量适合于由EP各论来控制，并符合当前的注册要求。为了获得证书，生产商可以提交一份申报资料给EDQM，在其中描述其生产工艺以及QC所用方法，包括杂质控制。数据将由国家药监机构和EDQM内具有经验的质量审评人员进行审评。如果审评员所得结论是有利的，则EDQM会颁发CEP。CEP的复印件可用于采用该CEP中原料药作为原料的上市许可申报（MAA）。
Alternatively, the same data can be filed either in an Active Substance Master File (ASMF), to be submitted to each competent authority, or in the active substance part of the quality dossier of the MAA.
另两种方法是将相同的数据通过ASMF提交给各药监机构，或者是放在MAA的质量文档里作为原料药部分提交。
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 forthe Editor: Furtherinformation is available on the internet site https://www.edqm.eu/
The EDQM is a leading organisation that protects public health by enabling development,supporting implementation, and monitoring the application of quality standards for safe medicines and their safe use. Our standards are recognised as ascientific benchmark worldwide. The European Pharmacopoeia is legally binding in member states1. Similarly, the EDQM develops guidance and standards in the areas of blood transfusion, organ transplantation and consumer health issues.
1There arethirty-nine members of the European Pharmacopoeia Commission: Austria, Belgium, Bosnia and Herzegovina, Bulgaria, Croatia, Cyprus, Czech Republic,Denmark, Estonia, Finland, France, Germany, Greece,
Hungary,Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Republic ofMoldova, Montenegro, Netherlands, Norway, Poland, Portugal, Romania, Serbia,Slovak Republic, Slovenia, Spain, Sweden, Switzerland, “the former YugoslavRepublic of Macedonia”, Turkey, Ukraine, United Kingdom and the European Union.
Apolitical organisation set up in 1949, the Council of Europe works to promote democracyand human rights continent-wide. It also develops common responses to social,cultural and legal challenges in its 47 member states.
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