欧盟发布新版GMP法令,删除质量受权人定义,2018年04月01日起取代旧版法令

- Jan 29, 2018-

2018-01-25 翻译组 GMP办公室



此前,欧盟官方公报公布了欧盟委员会法令(EU)2017/1572,该法令已于2017年10月05日正式生效(公布后的第20日生效)。法令条款规定,现行版的GMP法令2003/94/EC将于2018年04月01日正式废止,并由新法令(EU)2017/1572所取代。

 

新法令(EU)2017/1572较旧法令2003/94 / EC,主要变化如下:


删除对临床试验用药品的提及。(因欧盟委员会建立了适用于临床试验用药品的指令(EU) 2017/1569,所以临床试验用药品需要从新的GMP指令中移除)

删除了质量受权人;

范围包括了进口操作。

关键生产工序需要定期再验证。这刚好是附件15被持续工艺确认取代的内容。

其他的“新”的技术只是对现有技术的调整,如风险管理、生产企业和上市许可持有人之间的合同要求(除非这些内容与完全与GMP相同);文件管理章节新引入参考数据完整性,对电子数据进行保护防止非法访问;对于上市许可持有人要求需获取可能导致召回的相关信息;自检中增加了可能需要提出预防措施。


摘译如下:


The GMP directive is dead - long live the GMP guideline. It was with this phrase that new kings were announced in France in order to demonstrate the monarchy's continuity. In "New EU GMP Guideline for IMPs" we had reported on the current GMP directive 2003/94/EG being withdrawn and replaced by the new directive 2017/1572. But what about content consistency between the old and the new directive? What are the differences between both GMP directives? What will change, what will stay the same?

GMP法令已经逝去,将永久存在的是GMP指导原则。新国王在法国宣布君主制的延续性是也是用的这句话。在“新的欧盟GMP指导原则(适用于临床试验用药品)”一文中,我们已经提到,现行版的GMP法令2003/94/EG被撤销并由新的法令2017/1572所取代。但是新旧法令内容是否一致?GMP条款有何区别?哪些会被更改,哪些会保持不变?

 

In general, the new directive is a bit more extensive: it has 8 pages, while the one still valid has 5 pages. One page of the new directive is used for a correlation table between the old and the new guideline though.

通常情况下,新的法令会稍微扩展。现行版有5页,新的版本将会有8页,其中1页会列出新旧版本的对比表。

 

If you look into the recitals of the new GMP directive, it will help answer questions about a summary of changes:

如果你仔细阅读新版GMP的序言,就能知道总的改变情况。

 

The fundamental reason for the change was that investigational medicinal products were taken out, as these will be regulated independently of the GMP directive in future.

变化的根本原因是因为临床试验药品被移除了,这些药品的监管将不再属于GMP法令

 

Updates of various definitions - the pharmaceutical quality system is mentioned specifically - are called for.

要求对进行各类定义进行更新——特别是药品质量体系。

 

Technical arrangements concerning the mutual obligations of manufacturer and authorisation holder (if these are separate legal entities) are demanded.

要求生产企业和许可人之间需要有关于共同义务规定的技术协议

 

In addition, quality risk management is now demanded as well so that patients are not threatened by quality defects.

此外,质量风险管理也被要求,以保证患者的安全不会因质量缺陷而受到威胁。

 

Advanced therapy medicinal products are also considered in particular now. These are regulated in individual guidelines. However, GMP principles and guidelines for finished medicinal products shall also be considered on a risk basis according to the specific characteristics of advanced therapy medicinal products.

先进的治疗药物现在也被特别被考虑到了,这些药物依据单独的指导原则监管。GMP的成药原则和指导方针也应根据先进疗法药品的具体特点,在风险的基础上加以考虑。

 

This was with regard to the recitals; let's look at the individual articles now.

这是关于序言部分的,我们现在来看下单个章节。

 

The scope, now called subject matter in Article 1, now includes import as well.

第一条:范围   现在被称为主题,包括了进口。

 

The definitions (Article 2) of medicinal products, clinical trial products, the qualified person and blinding and unblinding were dropped and the definitions of manufacturer and good manufacturing practice were changed slightly. Pharmaceutical quality assurance became pharmaceutical quality system, also with marginal, mainly textual changes (such as the deletion of references to investigational medicinal products).

第二条:药品定义,删除了临床试验用药品、质量受权人、设盲和揭盲。生产企业和药品生产质量管理规范的定义略有改变。药品质量保证成为药品质量体系,也是边际的,主要是文本上的变化(如删除对临床试验药品的引用)。

 

Article 3 on inspections newly includes that the member states shall establish and implement in their inspectorates a properly designed quality system that shall be followed and also updated if necessary.

第三条:关于检查,最近包含了,成员国应该在其检查机构中建立和实施适当设计的可以被遵循的质量体系,必要时需要更新。

 

In Articles 4 (conformity with good manufacturing practice) and 5 (compliance with marketing authorisation), the texts were reworded so that the obligations of the manufacturer and importer are towards the member states now. So now the member states e.g. ensure that GMP are followed.

第四条(符合GMP)和第五条(符合上市许可):文本被重写,以保证生产企业和进口企业的职责都是和成员国之间的,现在成员国的职责举例为,确保遵循GMP。

 

Article 6 (originally called quality assurance system) was renamed to pharmaceutical quality system and slightly updated verbally (e.g. senior management instead of management).

第六条(原来的质量保证体系)更名为药品质量体系,还有一些细微的言辞上的更新(如“高级管理”替代“管理”)。

 

In Article 7 about personnel, import operations with regard to the availability of competent and appropriately qualified personnel were included. References to investigational medicinal products were deleted and the remaining text was modified without significant adjustment of content.

第七条,关于人员,包括了能胜任且经过适当的确认的合格人员的进口操作。删除对临床试验药品的引用,余下的文本没有对内容进行大的修改。

 

Article 8 on premises and equipment was verbally revised and extended to include import operations.

第八条:关于厂房与设备,在语言表达上进行修改和扩展,包含了进口操作。

 

In Article 9 (documentation), references to investigational medicinal products were deleted as well. The demand that the documentation system must also ensure data quality and integrity is newly included. What's also new is the request that electronically stored data must be protected against unlawful access. The other changes are of linguistic nature.

第九条:文件管理,删除对临床试验药品的引用。最新的要求包含了文件系统必须保证数据质量和数据完整性,电子存储数据必须被保护,防止非法访问。其他改变都是语言描述上的。

 

Consequently, references to investigational medicinal products were also deleted in Article 10 (production). Furthermore, the article was verbally revised. It should be noted that the revalidation of critical phases of manufacturing processes is still being demanded.

第十条:生产,删除对临床试验用药品的参考。此外,这一条款也进行了语言描述上的修改。值得注意的是,仍需要对生产工艺的关键工序进行再验证。

 

The complete article on quality control requirements was verbally updated as well and the references to investigational medicinal products were removed. Only the demand that, apart from the retain samples mentioned before, samples shall also be made available to the competent authorities is new.

质量控制整节都进行了语言描述上的更新,删除了对临床试验用药品的引用。最新的要求只有:除之前提到的留样样品外,还需准备样品给主管当局。

 

Apart from verbal adjustments in Article 12 (outsourced operations), import operations were newly included.

第十二条:外包操作,除语言描述的调整外,还新增了进口操作。

 

In Article 13 (complaints and product recall), references to investigational medicinal products (e.g. unblinding) were deleted. The passage that the marketing authorisation holder must be informed about any defect that could result in a recall or an abnormal restriction on supply (a new term as well) is new.

第十四条:投诉和召回,删除了对临床试验用药品的参考(如揭盲)。新增内容为,任何可能导致召回的缺陷或供应有异常限制(包括一个新的条款),都需要通知上市许可持有者。

 

In Article 14 on self-inspections, only the demand for preventive actions that may be required apart from any necessary corrective measures is new. Like the other articles, the complete article was verbally revised.

第十四条:关于自检,最新的要求为,除必要的纠正措施外,可能还需有预防措施。和其他章节条款一样,整篇文章对语言描述进行了修订。

 

The following articles treat process sequences with the guideline itself (repeal of the old guideline and implementation of the new one). The last page shows a correlation table between the old and the new directive (no differences in article allocation) and the Commission Delegated Regulation on GMP for IMPs.

以下文章用指导本身来对待工艺步骤(旧指南的废除和新指南的实施)。最后一页列出了旧指南和新指南的对比表(条款位置没有差异)。还有委员会关于IMP的GMP的授权规定。

 

You will find the new GMP Directive on the EU homepage.

您将在欧盟主页上找到新的GMP法令。