20140924 ECA新闻：QP声明：EMA公布意见

20140924 ECA新闻：QP声明：EMA公布意见  

2014-09-24 23:10:57|  分类： ECA新|

GMP News
24/09/2014

QP Declaration: EMA publishes Comments

QP声明：EMA公布意见

More than three years ago, the EMA has published two draft documents for a template for the QP's declaration concerning GMP compliance of the API used as starting material and verification of its supply chain called "The QP declaration template":

3年多前，EMA曾经公布过2份草案，一份是用作起始物料的原料药的GMP符合性和供应链确认相关的QP声明模板草案，称为“QP声明模板”：

1. The draft template for the Qualified Person's declaration

授权人声明模板草案

and 和

2. the respective draft Q&A on the template for the Qualified Person's declaration

相应的授权人声明模板的问答草案

The QP Declaration should be provided in support of an application for a new marketing authorisation, variation or renewal of a medicinal product(s) authorised in the Community, using EU or national procedures within the scope of the respective Directives.

QP声明应提交以支持采用欧盟或成员国程序，符合相应的指令适用范围，在欧盟范围内药品新的上市许可申报、变更或更新。

The consultation for the template ended on 30 April 2011. In June 2014, the final version was published together with a template guidance. Now, three months after publication of the final document, the comments from 2011 have been published.

模板征求意见截止日期为2011年4月30日。在2014年6月，EMA公布了最终版本与指南模板。现在，最终版本公布后3个月，EMA公布了2011年以来的意见。

The answers to these comments also give some useful and interesting background information on EMA's expectations when it comes to API supplier auditing and qualification.

对这些意见的回答也显示了EMA在原料工供应商审计和确认方面一些有意思也很有用的期望的背景信息。

The 93 page document shows that some comments provided by the various interest groups - like the European QP Association - have been taken into consideration, and a few suggestions for improvement have been implemented. When it comes to audit information, fewer details are requested now. Confirmation of the supply chain traceability has been deleted; the API "supply chain should be established, qualified and documented and addressed through GMP".

93页的文件显示很有利益相关的人群---例如欧洲QP协会---提交了一些意见，这些意见被EMA考虑了，并采纳了一些好的建议。在审计资料方面，现在只要求很少的详细信息了。删除了对供应链追溯性的确认，原料药“要根据GMP要求，建立、确认、记录和说明原料药供应链”。

The wording of the draft declaration ''I have evaluated each of the named contract acceptors… …. Audit(s) was/were conducted by properly qualified and trained staff….'' has been changed to a more formal phrase, not implying the necessity for a personal check by the QP.

声明草案中用词“我已对每个有名称的合同接受方进行了评估……由有资质和经过培训的员工对其进行了适当的审计……”被修订为更正式的用语，不再暗示必须要由QP亲自进行检查。

But EMA also declined many industry proposals for the QP Declaration:

但EMA也拒绝了行业对QP声明提出的许多建议：

Some stakeholders thought that most of information being requested in the template should be part of GMP audit or supplier qualification programme rather than to inclusion in a regulatory dossier submission. But the template is still part of the regulatory submission. And EMA still considers a maximum three year period for API audits as good practice. Exceptions to this standard might only be possible on a case by case basis, which cannot be generalised.

一些利益相关方认为模板中所要求的约大部分资料应该是GMP审计或供应商确认流程的一部分，而不应包括在申报用的法规文件中。但模板还是被保留作为法规申报的一部分。EMA仍坚持认为将对原料药供应商最长每3年进行一次审计作为良好的规范。该标准的例外情况大概只有根据各案判定，没办法制订通用原则。

The wish that GMP certificates from a relevant Competent Authority can replace audits by the company will remain a wish. EMA refers to its Q&A document*  where it is stated that audits should be performed by or on behalf of the Marketing Authorisation Holder or acceptable third party auditors. However "API manufacturing sites, which have been inspected by an EU Competent Authority and found GMP non-compliant, should not be used as sources of API". Audits by accredited audit bodies who audit on behalf of the contract acceptor are also not accepted. Furthermore the API supplier needs to be assessed and deemed satisfactory before purchase of the material. Only in exceptional cases, e.g. atypical actives, where the QP Declaration is not based on an on-site audit, then other documentation (not the QP template) will need to be submitted according to the guidance document and considered on a case by case basis. It will be possible to share API audits and audit reports, if supported by appropriate contract arrangements.

企业希望使用相关药监当局颁发的GMP证书来替代公司所做的审计，但这还是只能是希望。EMA上用了它的问答文件，其中说明必须由上市许可持有人、或其授权人、或可失道寡助的第三方审计员进行审计。但是“原料药生产场所，如果曾被欧盟相关药监当局检查，且被发现是GMP不符合，则不能作为原料药的来源”。代表合同接受方的有资质审计机构所做的审计也不会被接受。另外，在采购物料前，还要对原料药供应商进行评估，且结果应是令人满意的。只有在例外的情况下，例如，非典型活动，QP声明不是根据现场审计出具，则需要根据指南文件提交其它文件（不采用QP声明模板），这种情况要各案讨论。如果有适当的合同安排，也可以共享原料药审计和审计报告。

The fear of the European QP Association and other stakeholders, that disclosing (internal) audit reports during inspections by the Competent Authorities might trigger a process of parallel audit reports (one for the official part to show during inspection and in parallel a second one used internally) was not acknowledged. So GMP inspectors might request these audit reports during regulatory GMP inspections.

欧洲QP协会和其它利益相关方担心的是，药监当局检查期间会需要公开（内部）审计报告，这可能会促使公司准备两份平行的报告（一份作为正式部分，在检查期间展示给检查官看，另一份则内部使用）。所以在官方GMP检查中，GMP检查官可能会要求看这些审计报告。

The request for a sufficient transition period of 24 months for the implementation of the QP declaration was declined ("not considered necessary").

要求留出24个月的时间使得QP声明模板实施具有充分过渡时间的建议被拒绝了（“被认为没有必要”）。

EMA emphasises that the QP Declaration should cover the designated starting material, as shown in the summary of the route of synthesis given in the DMF. Some stakeholders thought it might be better to refer to an Active Substance Master File (ASMF) and limit the QP Declaration only to the API manufacturing site involved in the last quality relevant manufacturing step.

EMA强调QP声明要涵盖起始物料界定，内容与DMF中提交的合成路线综述相同。一些利益相关方认为如果引用ASMF，且将QP声明仅限于涉及最后质量相关生产步骤的原料药生产场所可能会更好。

* Q&A: Good Manufacturing Practice (GMP), EU GMP guide part II Basic requirements for active substances used as starting materials: GMP compliance for active substances (Q2)

问答：药品优良生产规范（GMP），EU GMP指南第II部分：用作起始物料的活性物质的基本要求：活性物质GMP符合性（Q2）。

http://zhuyujiao1972.blog.163.com/blog/static/986947272014824111057132/