20150422 ECA新闻：“辅料正式风险评估指南”的新要求

20150422 ECA新闻：“辅料正式风险评估指南”的新要求  2015-04-22 22:07:57|  分类： ECA新闻

GMP News
22/04/2015

The new requirements of the "Guidelines on the formalised risk assessment for excipients"

“辅料正式风险评估指南”的新要求

The most important document so far as concerns "GMP for excipients" was published in the Official Journal of the European Union this year on 21 March. It has the somewhat ponderous title "Guidelines of 19 March 2015 on the formalised risk assessment for ascertaining the appropriate good manufacturing practice for excipients of medicinal products for human use" (document classification: 2015/C 95/02). We reported on this in our news "EU Commission issues two final Guidelines: GMP for Excipients and GDP for APIs".

到目前关于“辅料GMP”的最重要的文件于2015年3月21日在官方杂志上公布了。它有一个很冗长的题目“2015年3月19日人用药品辅料适当GMP确认时正式风险评估指南”（文件分类号2015/C 95/02）。我们在我们新闻“EU委员会签发2份正式指南：辅料GMP和原料药GDP”中报告过此事。

During the longer than two years period after the publication of the draft of these guidelines the fundamental principles for ascertaining the appropriate good manufacturing practice formulated in the draft were the main guides and the pharmaceutical industry had time to adapt to these requirements. But the now valid final guidelines differ considerably from the draft document. This means the companies concerned are now faced with additional requirements and they face the challenge to implement these requirements for medicinal products being in the process of development immediately and for medicinal products already authorised until 21 March 2016.

在这些指南的草案公布后长达2年多期间，在草案中给出的适当GMP确定方式基本原则是主要的指南，制药行业有时间来采纳这些要求。但现在，生效的最终指南与草案文件有很大差异。这表示受影响的公司现在要面临另外的要求，他们面临实施这些要求的挑战，那些正在研发中的药品需要立即符合这些要求，而已上市的药品则要在2016年3月21日 之前符合这些要求。

The following summary lists the newly formulated additional requirements from the final document that were not already included in the guideline draft.

以下总结列出了最终文件版本中最新的制剂附加要求，它们在指南草案中并没有包括。

Determination of appropriate GMP based on type and use of excipient

基于辅料类型和用途决定适当的GMP要求

The manufacturing authorisation holder should take into consideration the following:

生产许可持有人应考虑以下内容：

• potential for any impurities carried over from other processes, in absence of dedicated equipment and/or facilities;
• 当没有专用设备和/或设施时，从其它工艺带入杂质的可能性
• cold chain management, if appropriate;
• 冷链管理，适用时
• supply chain complexity;
• 供应链复杂性
• stability of excipient;
• 辅料稳定性
• packaging integrity evidence;
• 包装完整性证据
• known fraudulent adulterations related to the use and function of each single excipient;
• 与每个辅料的用途和功能有关的已知欺诈掺假
• other factors identified or known to be relevant to assuring patient safety for each excipient;
• 保证各辅料患者安全性有关的已识别或已知的因素
• qualification program of suppliers;
• 供应商确认程序
• change management and deviation management system;
• 变更管理和偏差管理体系
• environmental controls and storage conditions.
• 环境控制和存贮条件
  

Confirmation of application of appropriate GMP

确认适当的GMP申报

Once the appropriate GMP for the excipient and the risk profile of the excipient manufacturer have been determined, ongoing risk review should be performed through mechanisms such as:

一旦决定了辅料的GMP要求水平，以及辅料生产商的风险情况，应通过例如以下的机制来实施持续风险审核：

• monitoring and trend analysis of excipient quality;
• 对辅料质量进行监测和趋势分析
• observed organisational, procedural or technical/process changes at the excipient manufacturer;
• 在辅料生产商处所看到的该组织机构的、程序上的或技术方面/工艺变更
• questionnaires;
• 问卷
• based on the outcome of the risk review, the established control strategy should be reviewed and revised if needed.
• 根据风险审核的结果，所建立的控制策略应在需要时进行审核和修订
  

The requirements for ascertaining and ensuring the appropriate GMP laid down in the new guidelines are rather challenging as a whole. The initial expense is enormous since the "GMP made-to-measure" has to be defined not only for each single excipient but also for each pharmaceutical form (if the same excipient is used in different pharmaceutical forms). The pharmaceutical companies concerned must now extent their risk profiles for excipients already drawn up according to the new requirements. Additionally, the appropriate GMP and the required two risk profiles (for the excipient and the manufacturer of the excipient) must be drawn up for all authorised products in less than one year (!).

新指南中给定的GMP水平的确定和保证要求整体来说很具有挑战性。启动费用会很大，因为“相当水平的GMP”必须进行定义，不仅仅是针对每一个辅料，还要针对每个制剂剂型（如果相同的辅料用于不同的制剂剂型）。受影响的制药公司必须现在延伸其已作出的辅料风险概况评估，以符合新的要求。另外，必须对所有已上市的药品在不到1年的时间内确定出适当的GMP水平和要求2个风险概况（对于辅料和辅料生产商）。

The new guidelines are also part of the EU GMP-Guideline Part III (Eudralex - Volume 4). They can be found there in the respective national language of the EU member states.

新的指南也是EU GMP指南第3部分（欧盟药事法----卷4）的一部分。在那里可以找到各欧盟成员国官方语言版本。