转自：Julia法规翻译

延伸阅读：

缬沙坦事件后，雷尼替丁标准拟增加NDMA杂质控制

2019年12月5日，FDA发文，在非美国糖尿病药品中发现杂质NDMA。

12月6日，EMA发文，关于二甲双胍糖尿病药物的更新也是关于NDMA。

一、FDA：非美国糖尿病药品中发现杂质

Statementfrom Janet Woodcock, M.D., director of FDA’s Center for Drug Evaluation andResearch, on impurities found in diabetes drugs outside the U.S.

非美国糖尿病药品中发现杂质

For Immediate Release:

December 05, 2019

Statement From:

Director - Center for Drug Evaluation and Research

Janet Woodcock M.D.

The U.S. Food and Drug Administration has been investigating the presence of genotoxic impurities, called nitrosamines, in some types of drugs. Over the past year and a half, several drug products including angiotensin II receptor blockers (ARBs) and ranitidine, commonly known as Zantac, have been found to contain small amounts of nitrosamines such as N-Nitrosodimethylamine (NDMA). During this time, there has been an ongoing investigation into the presence of nitrosamines in other drug products. This effort is focused on ensuring the drugs used by Americans continue to meet strict quality standards.

美国FDA还在继续调查某些类别药品中出现称为亚硝胺的基因毒性杂质。在过去的一年半时间内，有几种药品，包括ARB和雷尼替丁（善胃得）均发现含有少量亚硝胺如NDMA。在此期间，我们持续调查了其它药品中亚硝胺杂质情况。此工作主要集中在确保美国公众所用药品持续符合严格质量标准方面。

The FDA is aware that some metformin diabetes medicines in other countries were reported to have low levels of NDMA. Based onthe information we have available, the levels of NDMA seen outside the U.S. are within the range that is naturally occurring in some foods and in water. While we are aware that some regulatory agencies outside the U.S. may be recalling some metformin drugs, there are no metformin recalls affecting the U.S. marketat this time. The FDA is investigating whether metformin in the U.S. market contains NDMA, and whether it is above the acceptable daily intake limit of 96 nanograms. The agency will also work with companies to test samples of metformin sold in the U.S. and will recommend recalls as appropriate if high levels of NDMA are found. If as part of our investigation, metformin drugs are recalled, the FDA will provide timely updates to patients and health care professionals.

FDA了解到其它国家报告在一些二甲双胍糖尿病药品含有低水平NDMA。根据我们所获得的信息，在非美国区域发现的NDMA水平处于一些食物和水中自然存在的范围内。虽然我们了解到美国以外的一些药监机构可能会召回一些二甲双胍药品，但目前暂无二甲双胍召回影响到美国市场。FDA正在调查美国市场的二甲双胍是否含有NDMA，以及其水平是否超出可接受日摄入限度96ng。FDA也将与公司合作对在美销售的二甲双胍样品进行检测，如果发现其中NDMA水平较高将在必要时建议召回。如果调查后召回二甲双胍，FDA将及时为患者和医护专业人员提供更新信息。

Metformin is a prescription drug used to control high blood sugar in patients with type 2 diabetes. Patients should continue taking metformin to keep their diabetes under control. It could be dangerous for patients with this serious condition to stop taking their metformin without first talking to their health care professional. The FDA recommends prescribers continue to use metformin when clinically appropriate, as the FDA investigation is still ongoing, and there are no alternative medications that treat this condition in the same way.

二甲双胍是一种用于控制2类糖尿病患者高血糖的处方药。患者应继续服用二甲双胍保持其糖尿病受控。症状严重的患者如不与其医护专业人员沟通即停止服用二甲双胍可能会很危险。在调查期间，FDA建议处方医生在临床适合时继续使用二甲双胍，目前并无替代药品以相同方式治疗该症状。

NDMA is a common contaminant found in water and foods including cured and grilled meats, dairy products and vegetables. Everyone is exposed to some level of NDMA. The FDA and the international scientific community do not expect it to cause harm when ingested at low levels. The acceptable daily intake limit for NDMA in the U.S. is 96 nanograms. Genotoxic substances such as NDMA may increase the risk of cancer if people are exposed to them above acceptable levels and over long periods of time, but a person taking a drug that contains NDMA at-or-below the acceptable daily intake limit every day for 70 years is not expected to have an increased risk of cancer.

NDMA是一种常见污染物，在水中和食物中，包括熏肉和烤肉、奶制品和蔬菜中均有发现。所有人均会暴露于一定水平的NDMA。FDA和国际科学团体并不认为摄入低水平会导致伤害。NDMA在美国的可接受摄入限度为96ng。长期暴露于高出可接受水平的基因毒性物质如NMDA可能会增加患癌风险，但持续70年每天服用含有等于或低于可接受水平NDMA的药品的人并不会增加患癌风险。

Today, we have better testing methods than everbefore, and we know what to look for in products’ chemical structure and manufacturing processes that may increase the risk of forming low levels of nitrosamines. Improved technology enables us to detect even trace amounts of impurities in drug products and may be the reason why more products have been found to have low levels of NDMA. The agency has strict standards for safety, effectiveness and quality, and our staff makes every effort to help keep the U.S. drug supply as safe as possible. We also work closely with international drug regulatory agencies so that we leverage resources and testing done outside the U.S. which can help inform testing of the U.S. drug supply. As our investigations and testing continues, along with the investigations done by other drug regulatory agencies, we may find low levels of nitrosamines in additional drugs.

我们现在已具备比以前更好的检测方法，并且我们知晓在药品化学结构和生产工艺中要找寻哪些可能增加形成低水平亚硝胺风险的因素。技术改进使得我们可以检出药品中甚至痕量的杂质，这也可能是为什么越来越多药品中被检出NDMA的原因。FDA具有严格的安全性、有效性和质量标准，并且我位的员工正尽其最大努力帮助保护美国药品供应尽可能安全。我们亦与国际药品监管当局紧密合作，使得我们可利用美国以外的资源和所做的检测，这些都可以帮助我们通知对美国药品供应进行检测。在我们持续调查和检测时，结合其它药监机构所做的调查工作，我们可能会在更多药品中发现低水平亚硝胺。

The FDA will continue to investigate the source of these impurities, but it is important to note that there are multiple reasons why NDMA can be present in drugs. Previously, we found the source of NDMA canbe related to the drug’s manufacturing process or its chemical structure or even the conditions in which they are stored or packaged. As food and drugs are processed in the body, nitrosamines, including NDMA, can be formed. The FDA continues to test and research possible sources for the several drugs found to contain NDMA.

FDA将继续调查这些杂质来源，但要注意药品中出现NDMA有很多原因。之前我们已发现NDMA的来源可能与药品生产工艺或其化学结构甚至是基存贮或包装条件有关。由于食品和药品在体内会进行处理，此时亦可能形成亚硝胺包括NDMA。FDA会继续检测和研究含有NDMA的几种药品中NDMA的可能来源。

We are taking a systematic approach to identify medicines with nitrosamines above acceptable daily intake limits and remove them from the market. For example, yesterday we announced expanded testing requirements for ranitidine manufacturers to help give consumers confidence that the drugs on the market do not have NDMA above the acceptable daily intake limit.

在识别含有高于可接受水平摄入限度的药品并将其清除出市场时，我们采用的是一种系统性方法。例如，昨天我们宣布要求雷尼替丁生产商扩大检测，帮助消费者确信在售药品不含有高于可接受水平的NDMA。

Our investigations, including our current investigation of metformin, take into account the medical necessity of thedrug, how many Americans may take it, and whether there may be alternative treatments available. The American public can expect that we will act quickly to address any issue as soon as we find out about it.

我们的调查，包括当前对二甲双胍的调查均考虑了对药品的需求、美国公众可能服用该药的人数，以及是否有其它可替代治疗方式。美国公众可以相信我们会快速行动，解决所有发现的问题。

These investigations take time. We understand that these issues affect patients’ health and well-being in many ways, and the FDA’s goal is to provide patients and health care providers as much clarity and as many answers as possible to inform their health care decisions. The FDA will communicate any information we have scientifically confirmed to ensure the public knows as much as possible as soon as possible.

这些调查会需要一些时间。我们了解这些问题会在许多方面影响患者健康和福利，而FDA的目标是为患者和医护人员提供尽可能多的透明度和尽可能回复告知其医疗决定。FDA将在第一时间向公众发布经过科学确认的资料，以确保公众及时了解相关信息。

Protecting patients is the FDA’s highest priority,and Americans can be confident in the quality of the products the agency approves. We are patients too, and we’re committed to maintaining our high standards for quality, safety and efficacy for all drugs we, our families, friends, colleagues and millions of fellow Americans rely on for their health.

保护患者是FDA的最高宗旨，美国人民尽可相信FDA已批准药品的质量。我们亦是患者，我们承诺将保持我们、我们家庭、友人、同事和成千上万美国人民健康所依赖的所有药品的最高质量、安全和有效性标准。

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

FDA作为美国卫生福利部内的机构，其职责是确保人药和兽药、人用疫苗和其它生物制品，和医疗器械的安全性、有效性和安保工作，从而保护公众健康。FDA亦负责我们国家食品供应、化妆品、膳食补充剂、电子辐射产品和受监管烟草产品的安全和安保。

二、EMA关于二甲双胍糖尿病药物的更新

EMA update on metformin diabetes medicines

EMA关于二甲双胍糖尿病药物的更新

Pressrelease 06/12/2019

新闻稿 06/12/2019

EMA is aware that trace amounts of an impurity, N-nitrosodimethylamine (NDMA), have been found in a small number of metformin diabetes medicines outside the EU.

EMA了解到在欧盟以外的少数二甲双胍糖尿病药物中发现了痕量的杂质N-亚硝基二甲胺（NDMA）。

The levels of NDMA inthe affected non-EU metformin medicines are very low and appear to be within or even below the range that people can be exposed to from other sources, including certain foods and water.

受影响的非欧盟二甲双胍药物中的NDMA含量很低，似乎在人们可能从其他来源（包括某些食物和水）接触的范围内，甚至低于该水平。

At this point, there are no data indicating that EU metformin medicines are affected. Authorities in theEU are in the process of working with companies to test EU medicines and will provide further updates as more information becomes available.

目前，尚无数据表明欧盟二甲双胍药物受到影响。欧盟当局正在与公司合作测试欧盟药品，并将在有更多信息时提供进一步的更新。

Patients in the EU should continue taking their metformin medicines as normal. The risk from not having adequate diabetes treatment far outweighs possible effects of the low levels of NDMA seen in tests. Healthcare professionals should remind patients of the importance of keeping their diabetes under control.

欧盟地区的患者应继续正常服用二甲双胍药物。得不到足够的糖尿病治疗的风险远远超过测试中发现的低水平NDMA可能产生的影响。医护人员应提醒患者控制糖尿病的重要性。

Metformin is widely used alone or in combination with other medicines to treat type 2 diabetes. It is usually the first-line treatment, and it works by reducing the production of glucose in the body and reducing its absorption from the gut.

二甲双胍被广泛单独使用或与其他药物联合用于治疗2型糖尿病。该药通常用于一线治疗，其作用原理为减少体内葡萄糖的产生并减少其从肠道的吸收。

NDMA is classified as a probable human carcinogen (a substance that could cause cancer) on the basis of animal studies. It is present in some foods and in water supplies, but it is not expected to cause harm when ingested in very low levels.

根据动物研究，NDMA被归类为可能的人类致癌物（一种可能导致癌症的物质）。它存在于某些食品和水供应中，但是如果摄入非常低的水平，则不会造成伤害。

Last year, NDMA and other impurities of the same class (nitrosamines) were found in some blood pressure medicines known as sartans. Subsequently, EMA started a review of ranitidinemedicines and launched a procedure to request companies to take specific measures to avoid the presence of nitrosamines in human medicines, including metformin.

去年，在一些沙坦类降压药中发现了NDMA和其他同类杂质（亚硝胺）。随后，EMA开始对雷尼替丁药物进行审查，并启动了一项程序，要求公司采取具体措施避免人用药物（包括二甲双胍）中亚硝胺的存在。

This procedure, known as an Article 5 (3) procedure, is still ongoing and will be used to provide guidance to companies and support the evaluation of data on nitrosamines. The expedited testing of metformin medicines in the EU is part of this procedure.

该程序被称为第5条第3款程序，目前仍在进行中，将用于为公司提供指导并支持对亚硝胺数据的评估。欧盟对二甲双胍药品的快速检测是该程序的一部分。

EMA and national authorities together with international partners and the European Directorate for the Quality of Medicines & HealthCare (EDQM) are continuously sharing information about impurities such as NDMA and are taking action to protect patients and reassure them about the quality of their medicines.

EMA和国家主管部门与国际合作伙伴以及欧洲药品和医疗质量局（EDQM）持续分享有关NDMA等杂质的信息，并正在采取行动保护患者并向他们保证其药物质量。