EU GMP问答-3：制剂第5章 供应商确认3问

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European Union (EU) GMP guide part I: Basic requirements for medicinal products: Chapter 5: Qualification of suppliers

EU GMP指南第一部分：药品的基本要求：第五章：供应商确认

1. Is anaudit performed by a third party acceptable? H+V July 2006  由第三方实施的检查是否能被接受？H+V 2006年7月

The document 'guidance on the occasions when it is appropriate for competent authorities to conduct inspections at the premises of manufacturers of active substances used as starting materials', published aspart of theCommunity procedures, states that it is expected that manufacturing-authorisation holders will gain assurance that the active substances they use are manufactured in accordance with GMP through audit of the active-substance suppliers. Small manufacturers may not have the necessary expertise or resource to conduct their own audits.

作为欧盟程序的一部分发布的《药监机构对用作起始物料的原料药生产商设施实施检查情形指南》中提到：期望生产许可持有人通过对原料药供应商的审计确保其所使用的原料药符合GMP。小型制造商自己可能没有必需的技能或资源来自己进行审计。

Section 5.25 of the GMP guideline requires starting materials to be purchased from approved suppliers and about whom the manufacturer has a particular and thorough knowledge.

EU GMP指南第5.25部分要求从批准的供应商处购买起始物料，生产商应对批准的供应商其有具体和详尽的了解。

An audit conducted by the manufacturing-authorisation holder itself should be integral to the manufacturer's quality-assurance system and subject to the basic GMP requirements, i.e. conducted by properly qualified and trained staff, in accordance with approved procedures. It should be properly documented. These aspects can be inspected as necessary by the competent authorities.

由生产许可持有人自己进行的审计，应该整合为其质量保证体系的一部分并且符合基本的GMP规范，即由适当的、有资质、经培训的人员按照批准的程序进行审计。应妥善做好记录。必要药监机构会检查此类文件。

If a third party is involved, the arrangements should besubject to chapter 7 of the GMP guideline. There should be evidence that the contract-giver has evaluated the contract-acceptor with respect to the aspects described above.

如果第三方参与这些工作，应按照EUGMP指南第7章的要求执行。应有证据证明委托方对受托方进行了评估。确认受托方是否满足上面的要求。

All parties involved should be aware that audit reports and other documentation relating to the audit will be made available for inspection by the competent authorities if requested. This should normally provide sufficient assurance that the results of an audit carried by the thirdparty are credible, thus waiving the need for an audit conducted by the manufacturing-authorisation holder itself. However, it must also be satisfactorily demonstrated that there are no conflicts of interests. Conflicts of interests could arise for example from:

所有涉事方应知道，如主管当局提出检查要求，审计报告以及与审计有关的其他记录应可以提供以备检查。一般应充分确保由第三方所做审计的结果是可信的，如此即可使得生产许可持有人免于亲自进行审计。无论如何，还必须充分证明没有利益冲突。利益冲突可能包含如下几种情况：

l a commercial relationship between the organisation performing the audit and the organisation being audited;

l 进行审计的机构和被审计的机构之间有商业合作关系

l a personal conflict on the part of the auditor where he / she has been employed by the organisation being audited in the recent past (i.e. within the lastthree years) or has a financial interest in it.

l 如审计员曾在被审计的机构工作（即过去3年之内）或与其有经济利益关系，则审计员个人存在利益冲突

This topic should also be addressed in the technical contractual arrangements. Any measures taken by the contract-giver should be documented, e.g. signed undertakings by the auditors.

技术委托协议亦应包括这些内容。应记录合同委托方所采取的所有措施，如审计员签署的承诺函。

Similarly, the principles outlined above could be used to allow sharing of audit reports between different manufacturing-authorisation holders using the same active substance supplier, provided that the scope ofthe audits can be shown to be applicable to the active substances of mutual interest.

类似地，如审计范围显示审计适用于具有共同利益的原料药，那么上述原则用于判定相同原料药生产商的不同生产许可持有人是否可共用审计报告。

2. Is it possibleto use multiple batch numbers in packaging of medicinal products? H+V January 2005

药品包装上可否使用多个批号？H+V 2005年1月

GMP inspectors have discussed the desirability of more than one batch number appearing on the packaging of medicinal products.

GMP检查员已就药品 包装中出现多个批号进行了必要性讨论。

It is normal practice for companies to use a bulk batch number that is different from the finished product batch when the bulk is packaged as several sub-batches. There is normally an element in the numbering format common to the bulk batch and finished product batches that clearly tiesthese together. The difference normally takes the form of a suffix, prefix orboth.

通常，在将散装药品包装为几个亚批时，公司会使用与散装批号不同的包装后成品批号。一般在散装批与成品批的批号中会有一个元素将两者清楚联系起来，使用前缀或后缀或前后缀加以区别。

A matter of concern for the inspectors is when the bulk and finished product batch numbers are completely different and there is no obvious connection between the two. Even though the manufacturer has a system of traceability, the inspectors agree that this is an undesirable practice and should be avoided. The main reasons for this are:

检查员关切点是散装和成品批号完全不同的情形，这时两者之间没有任何明显的联系。即使生产商有追溯系统，检查员一致认为这样不方便，应该避免。主要原因有：

l patients and healthcare professionals may mistakenly believe that there has been a packaging error;

l 患者和医疗专业人员可能会误认为包装错误；

l hospitals often remove products from the outer packaging and traceability may therefore be lost;

l 医院经常将药品从外包装中拿出来，可能因此失去可追溯性；

l confusion may occur in the case of recall, rendering such action potentially ineffective.

l 召回时可能出现混淆，可能导致召回低效。

It is accepted that there may be exceptional cases where multiple batch numbers are displayed on a pack, such as in combination product packages. In addition, products that require relabelling following parallel distribution are expected to display the original manufacturer's batch number. Manufacturers are recommended to discuss individual cases with the relevant supervisory authority. In all cases, traceability must be maintained.

有些例外情况下在一个包装中显示多个批号，例如组合产品包装，是可以接受的。此外，平行销售之后需要重新包装的产品，需要标示原始生产商的批号。建议生产商与有关药监机构就个案进行探讨。在任何情况下必须保持可追溯性。

3. What are the expectations with regard to documentation and verification of the supply chain for active substances (ref. Paragraph 5.29, Chapter 5 EU GMP Guide)? H+VAugust 2015  活性物质供应链的文件记录和核查方面有什么要求（参见EU GMP指南第5章第5.29段）？H+V 2015年8月

The supply chain for each active substance must be established back to the manufacture of the active substance starting materials. This should be documented and must be kept current. The risks associated with this supply chain should be formally documented. Control of each incoming consignment of active substance should include verification thatit has been received from the approved supplier and approved manufacturer. The entire supply chain should be verified for a supplied batch periodically to establish a documented trail for the batch back to the manufacturer(s) of the active substance starting materials. The frequency of this verification should bebased on risk.

每个活性物质的供应链必须追溯回活性物质起始物料的生产。此类信息必须记录并保持更新。与此供应链有关的风险应正式记录。活性物质的每次进厂货物的控制应包括核对是否来自已批准的供应商和已批准的生产商。应定期对收到的批次进行整个供应链核查，以建立回溯至活性物质起始物料的书面追踪。此核查的频次应基于风险确定。

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