201502 EMA: 关于GMP的问答(5)---Julia翻译

巴西木

EU GMP guide annexes: Supplementary requirements: Annex 8: Sampling of starting and packaging materials: Glycerol

EU GMP指南附录：附加要求：附录8：起始物料和包材取样：甘油

1. What is the background regarding international incidents of glycerol contamination? H+V December 2007

关于甘油污染的国际事件有什么背景？H+V 2007年12月

There is a history of sporadic reports from around the world of supplies of glycerol contaminated with diethylene glycol (DEG) resulting in mortality and serious morbidity in patients receiving contaminated products.

全球范围内有一些历史零星报告，关于甘油受到二甘醇污染导致使用受污染产品的患者死亡和重症的事件。

In late 2006, DEG-contaminated glycerol in cough syrup was the cause of about 50 deaths in Panama. DEG-contaminated glycerol in paracetamol syrup was also attributed to at least 80 deaths in a similar incident in Haiti in 1995-1996. Other incidents have been reported in Argentina, Bangladesh, India and Nigeria and attributed to the deaths of hundreds of children. DEG was also responsible for a poisoning incident resulting in the death of 107 people in the United States in 1937, following ingestion of contaminated sulphanilamide elixir.

在2006年底，止咳糖浆中含有被二甘醇污染的甘油导致帕拉马约50人死亡。1995-1996年在海地，与此类似的，扑热息痛糖浆中含有被二甘醇污染的甘油引起至少80人死亡。在阿根廷、巴格达、印度和尼日利亚，也有一些其它事件被报导，同样的污染造成了成百儿童死亡。二甘醇还引起1937年美国107人由于摄入受污染的对氨基苯磺酰胺中毒死亡。

（译者注：1937年秋天，美国田纳西州的一家制药公司生产和销售以二甘醇作为溶剂的磺胺口服液，命名为Elixir Sulfanilamide（磺胺酏剂），在2 个多月时间里导致107 人死亡，大部分都是儿童。该制药公司的首席化学家在事故发生后也自缢身亡。）

These incidents were related to both accidental cross-contamination of glycerol with industrial grade materials and, in some cases, to intentional substitution.

这些事故与甘油和工业级原料的交叉污染有关，在某些案例中，与有意替换相关。

Recent cases show the following similarities:

最近的案例显示出以下相似性：

l  pharmaceutical manufacturers of products containing contaminated glycerol did not perform full identity testing or tests to determine DEG on the glycerol raw material;

l  含有被污染的甘油的药物生产商没有进行全部的鉴别测试，或测定甘油原料中的DEG

l  pharmaceutical manufacturers of contaminated products relied on certificates of analysis (COAs) provided by the supplier;

l  被污染的药品的生产商依赖于供应商提供的COA

l  the origin of glycerine was not apparent from the COA. The COA provided with the glycerol raw material may have been a copy of the original on a distributor letterhead. The supply chain for glycerol was not readily known by the medicinal-product manufacturer because the glycerol may have been sold several times between its manufacture and the medicinal-product manufacturer.

l  甘油的来源显然与COA不同。所提供的COA可能由分销商台头签发，但内容是原始生产商的。药品生产商其实并不知道甘油的供应链，因为甘油从其原始生产商开始到药品生产商之间可能已经过了数次倒卖。

2. How is the EU patient protected from similar contamination occurring in EU products? H+V December 2007

EU患者怎么能受到保护，不让类似的污染在欧盟药品中发生呢？H+V 2007年12月

EU GMP requires all manufacturing companies to confirm that all its raw materials are checked on receipt to confirm their identity and quality. Competent authorities expect product manufacturers to routinely ensure that incoming samples of glycerol are tested according to the European Pharmacopoeia  monograph.

EU GMP要求所有生产公司要确认其所有原料在接收时检查确认其正确性和质量。药监机构期望药品生产商保证进厂甘油样品根据欧洲药典进行常规检测。

The European Pharmacopoeia monograph for glycerol includes a specific limit test for diethylene glycol (0.1%).

欧洲药典甘油各论包括二甘醇的特定限度。

3. Annex 8 of the GMP provides for derogations from the requirement for identity testing of every container where there is a validated supply chain. Can I use this derogation for the glycerol I purchase? H+V December 2007

GMP附录8说，如果有一个经过验证的供应链，可以对每个容器识别其厂方标记来进行检查的要求，我在采购甘油时是否可以使用该标记？H+V 2007年12月

It is correct that annex 8 does provide for a relaxation of identity testing of every container, but it also states that this would not normally be possible if brokers or intermediates were involved in the chain of supply.

的确，在附录8中说了可以对每个容器进行标记号检查作为放松的验收条款，但它也说了，如果供应链中牵涉到中间商时，一般情况下这是不可能的。

Glycerol is a commercial article that is widely used in the food and other industries. Generally speaking, the supply chain for glycerol tends to be complex and lengthy. The involvement of brokers is common in the supply chain.

甘油是一种商业化物品，广泛用于食品和其它行业。一般来说，甘油的供应链较长较复杂，其中通常会牵涉到中间商。

4. What steps are expected of manufacturers based in the EU when purchasing glycerol or of manufacturers based in third countries supplying glycerol-containing medicines? H+V December 2007

在向EU境内的生产商采购甘油时，或向第三国供应含药品的甘油生产商采购甘油时，一般要有哪些步骤？H+V 2007年12月

When designing supplier-assurance and incoming-goods-control programmes, companies should consider glycerol a higher-risk material.

在设计供应保证和进厂货物控制程序时，公司要将甘油作为高风险物料进行考虑。

Companies should be able to exhibit a good knowledge of starting material supply chains and apply this knowledge and principles of quality risk management to their programmes for supply-chain management. Inspectors will look to ensure that the basis for qualification of the supply chain is demonstrably robust for higher-risk materials such as glycerol. It is expected that identity testing and the European Pharmacopoeia limit test for DEG will be performed on each container as a matter of routine.

公司应可以获得对起始物料供应链的很深入了解，在供应链管理程序中应用该知识和质量风险管理原则。检查人员要进行检查以保证供应链的确认基础可以证明对高风险物料，如甘油，的稳定供应。期望作为常规检查对每个容器的甘油进行鉴别，并测试欧洲药典所要求的DEG限度测试。

5. The European Pharmacopoeia limit test for DEG involves a gas chromatographic method, which may be difficult to perform on a large number of containers. H+V December 2007

欧洲药典中DEG限 度测试涉及到使用气相色谱法，有很多容器时可能会比较难做。 H+V 2007年12月

This point is acknowledged and currently, alternative tests are under consideration with a view to work up a possible change to the identity tests in the monograph. The European Pharmacopoeia DEG limit test remains the official method for confirmation of compliance with the monograph.

这个问题大家都已知道了，也是目前确实存在的，目前正在考虑采用替代性测试，看看有没有可能对各论中的鉴别测试进行变更。欧洲药典的DEG限度测试仍是用于确认各论符合性的官方方法。

6. Are there any considerations applicable to the pharmaceutical assessment of marketing-authorisation applications? H+V July 2008

是否有任何考虑适用于上市许可申报的品评估中？H+V 2008年7月

In application dossiers for new marketing authorisations (MAs), or in case of relevant variations for existing MAs (for example, replacement of an excipient with glycerol) for medicinal products containing glycerol, confirmation of the tests applied on receipt of batches of glycerol to control the risk from potential DEG contamination in relation to the specific intended use of the product should be provided. A test for DEG content should be conducted in addition to identity testing for glycerol. A suitable control for DEG is included in the European Pharmacopoeia monograph for glycerol.

在新的上市许可（MA）申报文件中，或如有对已有含有甘油的药品MA的相关变更（例如，采用甘油替代一种辅料），需要提交对应用于每批甘油接受测试以控制潜在DEG污染风险，使其适用于其用途的确认。除甘油鉴别检测外，要进行DEG含量测试。对DEG进行适当的控制包括在欧洲药典甘油各论中。

Sufficient information regarding satisfactory control of this risk will be required in the dossier before approval of the MA application or variation.

在批准MA申报或变更前，要求将关于该充分控制该风险的足够的信息包括在申报文件中。

For existing approved medicinal products, no variation application is required, except for those few specific types of variations referred to in the first paragraph. However, as a minimum, the specific European Pharmacopoeia control for DEG should be conducted along with the identity test at receipt of each batch of glycerol. The excipient is required to comply with the current European Pharmacopoeia glycerol monograph, and as the specification approved in the dossier will have been that of the European Pharmacopoeia , the risk of DEG contamination will have been appropriately controlled. Compliance with this requirement will be verified during GMP inspections.

对于已有的批准的药品，除少数第一段中提及的特定变更类型外，不需要提交变更。但是，作为最低要求，在接收每一批甘油时，欧洲药典中对DEG的特定要求应与鉴别试验一起实施。辅料要求符合现行的欧洲药典甘油各论，在申报文件中批准的甘油质量标准应与欧洲药典一致，DEG污染风险要进行适当控制。对本要求的符合性将在GMP检查中进行核实。

7. My company manufactures products for external use. Does this guidance apply? H+V July 2008

我公司生产外用产品。该指南是否适用？H+V 2008年8月

Where a company manufactures products for external use, and when it has justified that the presence of DEG in these products poses a low risk, the omission of the test for DEG on each container may be accepted by the supervisory authority.

如果公司生产的药品为外用药，且已论证有DEG存在时该产品风险为低，则不在每个容器样品中检测DEG是可以被监管机构所接受的。

航行

顶一下

土豆王

感谢楼主分享！

Whats

谢谢分享。

清风化雨

谢谢分享!!!

赤道雪

谢谢分享!顶

彩虹

二甘醇污染导致使用受污染产品的患者死亡和重症的事件

发生的不少，危害也不小啊

yihaoli035

谢谢分享，受教了

一沙一叶

了解一下。   

tianhe

谢谢分享！

yanzhengren

谢谢，学习了