药品进口商新指南概念文件

EMA/238299/2015: 药品进口商新指南概念文件  

13 May 2015

EMA/238299/2015

GMP/GDP Inspectors Working Group

Concept paper on new guidance for importers of medicinal products

药品进口商新指南概念文件

Agreed by GMP/GDP Inspectors Working Group	March 2015
GMP/GDP检查员工作组同意	2015年3月
Start of public consultation	29 May 2015
开始公开征求意见	2015年5月29日
End of consultation (deadline for comments)	29 August 2015
征求意见截止	2015年8月29日

Comments should be sent to adm-gmdpATema.europa.eu

建议请发至上述邮箱

Keywords	Importer, importation of medicinal products, quality control
关键词	进口商、药品进口、质量控制

1.   Introduction 概述

In recent years, the manufacture of medicinal products for the EU market increasingly occurs outside of the EU. While this trend is particularly noted for the manufacture of active substances, it is also evident that a similar trend applies to medicinal product manufacture. Additionally, the supply chains have become more complicated through globalisation and as a result, new falsified medicines legislation has been approved which confers new responsibilities on manufacturers and importers of medicinal products and active substances. By designating importers of medicinal products as manufacturers and subjecting them to the holding of a manufacturing authorisation (MIA), the EU regulatory system already has the basis for a regulatory framework to cope with this situation. As MIA holders, importers are obliged to comply with Good Manufacturing Practice (GMP) requirements such as establishing a pharmaceutical quality system, have adequate personnel and premises for the activities in question, appropriate arrangements for management of complaints and recalls, and procedures in place to control their supply chains.

最近，欧盟境外的但销售到欧盟市场的药品生产商增加。尽管该趋势主要是原料药生产，但药品生产也有相同的趋势。另外，供应链已经变由于全球化而得更加复杂，因此新的假药法规已经被批准，它赋予了药品和原料药生产商和进口商新的职责。通过指定药品进口商作为生产商来管理，并要求他们持有生产许可（MIA），欧盟法规体系已经建立了跟上这种形势的法规框架。作为MIA持有人，进口商有责任符合GMP要求，例如建立一个药品质量体系，具备充足的人员配置，以及进行活动所需的设施，管理投诉和召回的适当安排，以及相关程序来控制其供应链。

However, involved stakeholders may benefit from clarification of expectations and therefore the 2014 work plan of GMP/GDP IWG included a commitment to consider if there is a need for specific guidance for importers.

但是，所牵涉的干系人可以从官方澄清其期望中受益，因此2014年GMP/GDP检查员专家组的工作计划包括了考虑是否需要针对进口商制订一份特定的指南。

2.   Problem statement 问题说明

The increased complexity of supply chains and the observation that most GMP non-compliance statements uploaded into EudraGMDP pertain to third country manufacturers have created new areas where further guidance is desired by both the regulators and the industry. In particular, the requirements applicable to importers of medicinal products and concerning the application of GMP requirements, which are traditionally oriented to activities performed at true manufacturing sites.

供应链的日益复杂，以及上传至EUDRAGMDP的大部分GMP不符合声明包括了第三国生产商，这产生了一个法规人员和制药业需要深入指南的领域。特别是适用于药品进口商的要求，以及GMP要求的适用性，这些要求是之前是由真正的生产场所实施的活动才需要满足的。

3.   Discussion (on the problem statement) 讨论（关于问题说明）

As stated, importation of a pharmaceutical finished product manufactured in a third country requires a MIA, for the site where QP certification occurs and the site that imports and tests the batch.

如上所述，在一个第三国生产的药物制剂进口是需要该场所持有MIA的，在该场所中QP对药品进行认可，实施进口操作，并对药品进行检测。

When a Mutual Recognition Agreement (MRA) is not in place, it is a legal requirement, to test each batch in the EU upon importation before certification by a QP and release in accordance with annex 16 of the GMP Guide. The requirements for the location of testing (‘in a Member State’) and the minimum testing requirements for products manufactured in third countries are set out in Article 51.1(b) of 2001/83/EC for medicinal products for human use and in Article 55.1(b) of Directive 2001/82/EC for medicinal products for veterinary use.

如果没有互认协议（MRA），则法规要求QP在放行产品前对所有进口至欧盟的批次进行检测，然后根据GMP指南附录16放行。在第三国生产进口入欧盟的药品，其检测所在地（成员国内）的要求，以及最低检测要求在2001/83/EC第51.1(b)里针对人用药，在2001/82/EC第55.1(b)中针对兽药进行了规定。

Associated with import testing are some other aspects such as sampling and the segregation between the ‘physical importation site’ versus ‘testing and/or batch release site’ that have become issues subject to discussion by regulators in order to agree a harmonised approach across the EU. Due to this new environment, annex 16, Certification by a Qualified Person and Batch Release, has been revised to, among others, address QP involvement when the testing site is not the releasing site.

与进口检测相结合的是一些其它方面，例如取样，“物理进口场所”与“检测和/或批放行场所”分离，已经成为法规人员要讨论的问题，以使得在整个欧盟能够采用统一的做法。鉴于该新环境，附录16“QP出具批放行证书”已进行了修订，当然其它附录也修订了，用以强调当检测场所不是放行场所时QP的责任。

Since the revision of the ‘Union Format for Manufacturer’s Authorisation’ in 2013, which is also applicable to importers of medicinal products and details importing activities, a more detailed understanding of the importation scenarios has been gained. The Authorisation format includes several elements where the GMP relevance of the importation activities varies and these impact requirements applicable to their quality system, personnel and premises.

自从2013年“生产商许可统一格式”修订后，我们对进口情况获得了更详细的了解。这份格式也适用于药品进口商和零售进口活动。许可格式包括几个要素，其中有进口活动的GMP相关性，以及适用于其质量体系、人员和设施的影响性要求。

Another issue that has prompted discussions is establishing a common understanding of the term ‘import’. This can be particularly complex in the context of global commercial activities and there may be little-known implications in this regard even when the physical location of medicinal products remains within the EU.

另一个需要讨论的问题是对术语“进口”建立一个统一的理解。在全球商业活动的环境，这可能会很复杂，即使药品的物理地址是在欧盟境内，关于此点可能我们所知甚少。

In view of this, it seems valuable to provide additional guidance on the GMP requirements that are of particular relevance to importers and on the extent those requirements apply to the different entities involved in importation activities. Suitability of these requirements to investigational medicinal products will also be considered.

考虑到此，似乎提供一个关于进口商，以及进口活动牵涉的不同实体的不同GMP要求的附加指南更有价值。还要考虑临床药品是否适用这些要求。

4. Recommendation 建议

GMP/GDP IWG agreed to draft a specific guidance for import authorisation holders. This document most likely would take the form of a new annex (annex 21). The scope of the project will be focused on importation activities not addressed in detail in the GMP guide and annexes, taking into consideration recent changes in GMP chapters and annexes as well as changes in other regulatory documents.

GMP/GDP专家组同意针对进口许可持有人起草一份特别指南。该文件很可能会采用新的附录方式（附录21）。项目范围将聚焦于GMP指南和附录中未详细说明的进口活动，同时考虑最近GMP章节和附录的变化，以及其它法规文件的变化。

5. Proposed timetable 提议的时间表

Concept paper for discussion and adoption in IWG: March 2015

概念文件在IWG讨论和采纳：2015年3月

Release of concept paper for public consultation: May 2015

公布概念文件征求公众意见：2015年5月

Deadline for comments on concept paper: August 2015

征求意见截止：2015年8月

First draft of new annex draft guidance for discussion in IWG: September 2015

新附录草案指南第一稿在IWG讨论：2015年9月

Release of new annex draft guidance for public consultation: January 2016

新附录草案指南公布征求公众意见：2016年1月

Deadline for comments on new annex draft guidance: End April 2016

新附录草案指南征求意见截止：2016年4月底

Final draft of new annex draft guidance for discussion in GMP/GDP IWG: November 2016

新附录草案指南第一稿在GMP/GDP IWG讨论：2016年11月

Expected date for adoption by European Commission - March 2016

预计由EC采纳日期：2016年3月

6. Resource requirements for preparation文件制订所需资源要求

A rapporteur team from Spain (AEMPS) has been nominated which will form a drafting group together with experts from the competent authorities of Sweden, Ireland, UK, Finland and Portugal. This concept paper will be circulated to PIC/S Secretariat to establish whether the new annex should be included in the list of documents subject to harmonisation in accordance with the co-operation agreement between PIC/S and EMA, in which case there is a possibility of participation of experts from non-EU PIC/S participating authorities in the drafting group. Participation of experts from the IWG and
public consultations would be as per the usual drafting procedure.

已提名一个西班牙报告团队与瑞典、爱尔兰、英国、芬兰和葡萄牙的药监机构专家一起组成一个草案制订组。该概念文件将送至PIC/S秘书处传阅，以评估是否要将新的附录加入文件清单，以根据PIC/S和EMA之间的合作协议进行协调一致。这时，可能会需要非欧盟的PIC/S专家加入草案制订组。来自IWG的专家的参与和公众的意见将与常规起草程序相同。

It is expected that most work will be completed by email and by teleconference.

期望大部分工作通过电子邮件和电话来完成。

7. Impact assessment (anticipated) 影响性评估（参与的）

The industry and GMP inspectors will benefit from more specific guidance on importers requirements regarding quality system, personnel and premises in a current increasingly complex environment.

在目前日益复杂的环境中，制药业和GMP检查员将受益于更专业的进口商关于质量体系、人员和设施要求的特定指南。

This new annex would have a positive impact for both industry and regulators by incorporating importation activities to the new regulatory concepts, clarifying requirements and contributing to a harmonised approach across the EU. It is not intended to create new requirements.

通过将进口活动与新的法规概念相结合，该新附录将对制药业和法规人员产生良好的影响，澄清相关要求，益于整个欧盟的协调性方法。该附录无意创建新的要求。

8. Interested parties  利益相关方

EMA (GMP/GDP IWG, QWP, BWP) and PIC/S

EMA（GMP/GDP IWG, QWP, BWP）和PIC/S

Industry – manufacturers/importers and wholesale distributors of medicinal products

行业---生产商/进口商和批发分销商

National competent authorities

国家药监机构

9. References to literature, guidelines, etc.参考文献、指南等

GMP Directives 2003/94/EC and 91/412/EEC

Directives 2001/83/EC and 2001/82/EC

Directive 2011/62/EU amending Directive 2001/83/EC

GMP Guide including its annexes

GDP Guide

The Compilation of Union procedures

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