供应商确认的现行规则是什么？

20160309 ECA新闻：供应商确认的现行规则是什么？  

GMP News
09/03/2016

What are the current Rules for SupplierQualification?

供应商确认的现行规则是什么？

Supplier Qualification is more thanauditing. Supplier qualification can be seen as a risk assessment tool. Itshould provide an appropriate level of confidence that suppliers, vendors andcontractors are able to supply consistent quality of materials, components andservices in compliance with regulatory requirements. An integrated supplierqualification process should also identify and mitigate the associated risks ofmaterials, components and services. But what are the exact requirements?

供应商确认不仅仅是审计。供应商确认可以看作是一个风险评估工具。它应该提供一个适当水平的置信度，证明供应商、经销商和外包商可以供应持续品质的物料、部件和服务，符合法规要求。一个完整的供应商确认流程还应识别和降低与物料、部件和服务相关的风险。但确切的要求有哪些呢？

They are wide-ranging and complex. Thereare different directives and regulations for medicinal drug products for humanor veterinary use and for investigational medicinal drug products. Certainrequirements in different directives and the EU-GMP Guidelines defineexpectations. Here are some examples:

他们的范围很宽，很复杂。有不同的人用兽用和临床前药品指令和法规。在不同的指令和EU GMP指南中都有不同的要求。这里有一些例子：

Article 8 of EU-Directive 2001/83/EC
"The application [of a marketing authorization] shall beaccompanied […] by […] a written confirmation that the manufacturer of themedicinal product has verified compliance of the manufacturer of activesubstance with principles and guidelines of good manufacturing practice by conductingaudits."

EU 指令2001/83/EC第8条，“【上市许可的】申报资料应包括一份书面确认，声明药品生产商已经通过审计核实过原料药生产商符合GMP原则和指南。”

Article 46 of EU-Directive 2001/83/EC
"The holder of a manufacturing and/or import authorisation shall at leastbe obliged […] to use only active substances, which have been manufacturedin accordance with GMP for active substances and distributed inaccordance with GDP for active substances and … to ensure that theexcipientsare suitable for use in medicinal products by ascertaining what theappropriate GMP is."

EU指南2001/83/EC第46条，“生产和/或进口许可持有人应至少有义务只使用按原料药GMP生产的原料药，其销售应符合原料药GDP，并且……通过确认其所适用的GMP要求，确保辅料适用于其在药品中的用途。”

Article 46b of EU-Directive 2001/83/EC
"Active substances shall only be imported if they have been manufacturedin accordance with standards of good manufacturing practice at least equivalentto those laid down by the European Union". This can be shown by a writtenconfirmation, or the exporting country is included in the so called whitelist, or a waiver has been granted.

EU指令2001/83/EC第46b条，“进口原料药应根据达到或超出EU所要求的GMP标准生产”。这可以由书面证明来支持，如果出口国包括在所谓有白名单里，或颁发有豁免时，则可以免除。

EU-GMP Guidelines Chapter 5:
5.25 "The purchase of starting materials is an important operation whichshould involve staff who have a particular and thorough knowledge ofthe supplier."
5.26 "Starting materials should only be purchased from approvedsuppliers …"
5.40 "…printed packaging materials shall be accordedattention similar to that given to starting materials."

EU GMP指南第5章，

5.25条“起始物料的采购是一个重要的操作，它应由对供应商特别了解和完整知识的员工来参与”

5.26条“起始物料应只从批准的供应商处采购……”

5.40条“……印刷包材应象起始物料一样受到关注。”

【译者注：此处原文引用错误，其所引用 的第5章条款为旧条款，新的第5章已于2014年生效，原条款已作废】

The revised Chapter 7 of the EU-GMP Guidelines describethe responsibilities of the Contract Giver when it comes to contractmanufacturing and testing. He needs to assure the control of the outsourcedactivities, incorporating quality risk management principles and includingcontinuous reviews of the quality of the Contract Acceptor's performance.Audits are a helpful tool to asses the "legality, suitability and thecompetence of the Contract Acceptor". The new Chapter 7 was obviouslydesigned to intensify the control of Contract Acceptors by the Contract Giverand extend those controls to subcontractors.

在合同生产和合同检测方面，EU GMP指南第7章修订版本描述了发包方的职责。他需要确保对外包活动进行控制，结合质量风险管理原则，包括对合同接受方的表现进行质量审核。审计是一个有用的工作，有助于评估“合同接受方的合法性、适当性和资质是否胜任”。新的第7章显然设计成增加了合同给予方对合同接受方的控制，扩大了对转包的控制。

The holder of the manufacturingauthorisation is responsible for the supplier qualification by law but in factthe supplier qualification is one of the duties of the Qualified Person (whichcan be delegated) as defined in Annex 16 of the EU-GMP Guidelines. The QP ofthe marketing authorisation holder is responsible for certifying the drugproduct for the market place and is now being held accountable to ensure thatall aspects of the supply chain have been made under the appropriate GMPs.However, according to Chapter 2 of the EU-GMP Guidelines, the heads ofProduction, Quality Control and Quality Assurance share the responsibility ofapproving and monitoring suppliers of materials (2.9).

生产许可持有人有责任进行供应商确认，但实际上，供应商确认是EU GMP指南附录16里定义的QP的义务之一（可以委派）。上市许可的持有人的QP有责任对根据市场位置来认证药品，现在有义务确保供应链的所有方面均根据适当的GMP要求实施。但是，根据EU GMP指南的第2章，生产负责人、QC和QA负责人分担批准和监测物料供应商的职责（2.9）。

So how to proceed? At the beginning of asupplier qualification process, the regulatory requirements regarding the typeof material, component or service and the type of product (human/veterinarydrug product or IMP) should be identified and specified. Audits, if required,should be planned and executed. The compliance of the selected supplier(s) withthe requirements and user requirement specification should be demonstrated. Thescope of an audit should cover this. But a successful audit is not the end of thequalification process. After finalising the contract, the compliance of theselected supplier(s) with the applicable requirements should be evaluatedperiodically. Changes at the supplier?s site (for example manufacturing processetc.) that pose a particular risk to the compliance with the requirementsshould be assessed. There needs to be a mechanism in place so that any changemade by the supplier which could have an impact on the GMP status or theproduction or testing parameters have to be agreed to before any such changesare implemented. A supplier must also notify the contract giver immediatelyupon discovery of any deviation/non-conformance/complaint that may havean impact on the services provided. Those need to be assessed andrespective actions need to be defined.

那么要怎么做呢？在供应商确认流程开始时，关于物料、部件或服务的类型的，以及产品（人药兽药或IMP）类型的法规要求应进行识别并说明。必要时，应计划并实施审计。要证明所选择的供应商的符合要求和用户需求标准。审计的范围应包括这些。但是一个成功的审计并不是确认流程的结束。在合同签订后，所选供应商的符合适用要求的情况要进行定期评估。供应商场所的变更（例如，生产工艺等），如果对符合这些要求具有特定的风险，则应进行评估。这里需要有一个机制，当供应商做出任何可能对GMP状态或生产或检测参数产生影响的变更时，必须在此变更实施前得到发包方的同意。供应商还必须在发现任何可能对所提供的服务产生影响的偏差/不符合性/投诉时立即通知发包方。这需要进行评估，要制订相应的措施。

The use of Brokers:
Some raw materials are only available at reasonable costs if purchased throughan intermediary, i.e. a Broker. If the material is critical to the process,e.g. an API or a key excipient this can give an added complexity to the processand this must be fully investigated with the Quality and Regulatory units beinginvolved, before any orders are placed.

经销商的使用

有一些原料只能通过支付一定合理的成本来通过一个中间商采购，即经销商。如果物料对工艺来说是关键的，例如，一种原料药或一种关键辅料，可能会对工艺产生额外的复杂性，在订货之前，必须会同质量和法规部门进行全面调查。

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