翻译：JULIA 来源：Julia法规翻译
25.07.2018
Valsartan: what caused the contamination?
缬沙坦：什么导致了污染？
After the recent supply shortages of medicinal products containing the API ibuprofen, there are now massive problems with Valsartan products.
继最近的含API布洛芬的药品供应短缺事件之后，现在缬沙坦药品又面临大问题。
What’s known so far is that the API has been contaminated with N-nitrosodimethylamine (NDMA) during production. This concerns the deliveries by the Chinese manufacturer Zhejiang Huahai Pharmaceutical. Apress release by the German Federal Institute for Drugs and MedicalDevices (BfArM) states that the WHO’s and EU’s International Agency for Research on Cancer classified the substance as “potentially carcinogenic for humans”.
截止目前已知的是该API在生产过程中被N-二甲基亚硝胺（NDMA）污染。这与中国生产商浙江华海药业有关。德国药监发布的一份媒体声明说WHO和EU的国际癌症研究机构将该物质列为“可能对人体致癌的物质”。
But how exactly did this contamination occur, and since when does the problem exist? The authorities’ press releases don’t contain much information on that. The statements by Professor Dr Fritz Sörgel from the German “Institut für Biomedizinische und Pharmazeutische Forschung”(IBMP; engl: Institute for Biomedical and Pharmaceutical Research), which were being published in the online portal of”apotheke adhoc” (in German), are more informative. It seems like the contamination had been discovered by chance, which astonished Professor Sörgel.
但是，到底此污染是如何发生，自何时起存在此问题的呢？药监媒体发布并未包括关于此的太多信息。发布在apothekeadhoc上的德国IBMP的Dr Fritz Sörgel教授的声明（德文）提供了更多信息。看起来该污染是偶然间发现的，这让Sörgel大跌眼镜。
apotheke adhoc previouslyreported (in German) that the Chinese manufacturer had already changed their manufacturing process in 2012(!). It appears like the production of tetrazole had been altered and N,N-dimethylformamide (DMF) had been used as a new solvent. An expert’s statement to apotheke adhoc says that during the breakdown of DMF, small amounts of dimethylamine may develop. In the presence of nitrous acid, NDMA forms.
德文的apothekeadhoc之前报告说中国生产商已经于2012年（！）变更了其生产工艺。貌似四唑的生产已经发生了变更，DMF被用作新溶剂。提交给apotheke adhoc的一份专家声明说在DMF分解时，可能会形成小量的二甲胺，在有亚硝酸存在时就会形成NDMA。
Could this have been prevented?
可否防止发生此事呢？
This is tough to say. In the course of a robust supplier qualification, it should be agreed that changes must be reported and possibly approved beforehand. This however sounds easier than it actually is since API manufacturers are seldom willing to disclose complete synthesis details. Nevertheless, customers should try to gain as much information as possible, especially about changes to the synthesis process. According to Professor Sörgel, a good chemist could have known about the possibility of contamination. It has to be viewed as highly critical that there had apparently been contaminations of Valsartan since 2012.
这很难说。如果是有稳健的供应商确认程序，应该会一致同意必须提前报告变更并可能需要得到批准。这听起来挺容易的，但由于API生产商很少愿意公开其全部的合成细节，所以实际上很难。不管怎么样，客户应努力获得尽可能多的信息，尤其是关于合成工艺变更的信息。根据Sörgel教授的意见，一个优秀的化学师应该知道可能的污染。很显然，应该认为自2012年开始缬沙坦就已经受到污染，这是相当严重的。
What can quality assurance units do now? Besides the initiated recall campaigns, deliveries should also be assessed retrospectively.The assessment of other active substances by the manufacturer is just as important. According to their website, there’s a wide range of products, which are apparently distributed globally.
那现在质量部门还能干什么呢？除了启动召回程序，还要回顾性评估发货情况。对该生产商提供的其它活性物质进行评估也是很重要的。根据其网站信息，该生产商有很多产品，显然这些产品是在全球销售的。
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