欧洲药监局--工艺验证指南更新意向书

Concept Paper on the Revision of the Guideline on Process Validation工艺验证指南更新意向书欧洲药品管理局，2010年2月25日发布1. IntroductionThis concept paper addresses the need to update the guideline on Process Validation1. This guideline was originally adopted in February 2001. With the development of new ICH guidelines Q8, Q9 and Q10, this guideline is being reviewed in order to implement the concepts highlighted in the ICH guidelines.该指南旨在适应ICH不断提高的要求，改动后将Q8，Q9和Q10的一些理念也融合了进去。

2. Problem statementThe current guideline does not reflect the recent regulatory developments on Process Analytical Technology (PAT), Quality by Design (QbD) and Real-Time Release Testing (RTRT).当前的指南没有考虑目前生产过程控制技术、质量源于设计和实时放行测试方面的发展。

3. Discussion (on the problem statement) 讨论(基于上述问题)即将出台的这份指南是基于ICHQ8、Q9和Q10这些先进指南的综合考虑而出台的。

根据这些新指南的出台，对于工艺控制以及传统验证批的概念提出了全新的理解(根据这些指南的定义，可能颠覆对传统的工艺验证批次以及工艺过程控制的理解)。

工艺验证的目的还是基于产品的工艺设计范围能够满足其预设的质量规格要求。

ICH Q8、Q9和Q10提供了一个结构化的方法去定义产品的关键质量属性、设计空间、工艺和控制策略(结构化的方法，是不是指明确了判别程序？？？)。

ICHQ8将覆盖面延伸至药物研发阶段，因此涵盖了非传统定义的工艺验证。

持续性的工艺确认[见ICH Q8(R2)术语表]可用作初始商业批的验证方案或者贯穿于产品生命周期内的产品工艺变更的持续改进工作。

相比之下，现行的工艺验证指南关注的是传统方法定义的数个验证批次去评估工艺是处于可控状态的。

更新后的工艺验证指南，将与ICH Q8、Q9和Q10接轨，并扩大当前传统验证的涵盖范围。

当前指南的附件将纳入到新版验证指南的正文中(也就是说新版验证指南就没有附件了)。

新版验证指南将明确ICH Q8、Q9和Q10的摄入深度，申请者提交申请时将要求采用非传统的持续性确认方法来评估经验证工艺的稳定可控性。

FDA已经修订了工艺验证指南，并已经将ICH Q8、Q9和Q10的理念融入了进去。

修订后的工艺验证指南将体现出在这方面的协调统一性(也就是与国际趋势保持一致，向FDA的指南方向去靠)。

The current guideline was developed before the elaboration of the new ICH guidelines Q8 Pharmaceutical Development, Q9 Risk Management and Q10 Quality Systems. With these new guidelines, additional opportunities are available to verify the control of the process by alternative means to the manufacture of traditional process validation batches. The main objective of process validation remains that a process design yields a product meeting its pre-defined quality criteria. ICH Q8, Q9 and Q10 provide a structured way to define product critical quality attributes, design space, the manufacturing process and the control strategy. ICH Q8 refers to an ‘enhanced’ approach to pharmaceutical development which includes an alternative to the traditional process validation. Continuous process verification [see definition in ICH Q8(R2) glossary] can be utilised in process validation protocols for the initial commercial production and for manufacturing process changes for the continual improvement throughout the remainder of the product lifecycle. In contrast, the current note for guidance on process validation refers only to the more traditional approach of the manufacture of a number of validation batches to confirm that the process is under control. A revision to the note for guidance on process validation will bring it in line with ICH Q8, Q9 and Q10 documents and add the ‘enhanced’ approach to the current ‘traditional’ approach. The annexes of the current guideline will be included in the revised guideline. The revised guideline will also clarify to what extent ICH Q8, Q9 and Q10 should be followed when an applicant wishes to use alternative methods of process validation including continuous verification. The FDA guidance on process validation5 has been recently revised to take into account ICH Q8, Q9 and Q10. The revision to the note for guidance on process validation will provide a more harmonised approach.4. Recommendation 推荐质量工作委员会推荐更新后的工艺验证指南，其内容涵盖了ICH Q8、Q9和Q10的理念，包括持续性验证和监控理念(也就是说验证不是做完3批就完事，还要进行持续性验证和监控)。

The Quality Working Party recommends the revision of the Note for Guidance on Process Validation in order to include the concepts defined in ICH Q8, Q9 and Q10 including continuous validation and monitoring.修订后的指南将不会要求已经批准上市的药品重新照此要求去操作后递交申请；但是在此之后递交的新申请材料，将会考量企业如何利用ICH Q8、Q9和Q10中描述风险管理工具在高效的质量管理体系下，对扩大化的工艺概念所要求的内容予以评估(看企业如何利用ICH Q9描述的风险管理工具，在Q10所描述的高校质量管理体系中对Q8所描述的扩大化的工艺涵盖范围进行有效评估)The revised guideline will not introduce new requirements on medicinal products already authorised and on the market, but it will clarify how companies can take advantage of the new possibilities given when applying enhanced process understanding coupled with risk management tools under an efficient quality management system as described by ICH Q8, Q9 and Q10 guidelines.5. Proposed timetable 倡议时间表验证指南草案预计将在这份概念篇内容经CHMP和CVMP采纳后后公示6至9个月(预计公示时间为2010年第三季度)，预期于公示期(公开征集意见的时间段)后六个月内成稿(2011年第四季度)。

It is anticipated that the draft guideline could be published for 6 months external consultation 9 months after the adoption on the concept paper by CHMP and CVMP (3Q 2010) and that it could be finalised within 6 months after the expiration of the external consultation period (4Q 2011).6. Resource requirements for preparation 参与人员及单位指南将由质量工作委员会、与EU/EEA合作的经授权的GMDP检查团(负责GMP/GDP检查)、EMEA PAT Team(EMEA关于精神学药品的评估团队)、生物制剂工作委员会(BWP)、免疫学工作委员会(IWP)和中草药评估委员会(HMPC).The development of the guideline will be carried out by Quality Working Party, in co-operation with EU/EEA competent authorities the GMDP Inspectors Working Group, the EMEA PAT Team, the Biologics Working Party (BWP), the Immunologicals Working Party (IWP) and the Herbal Medicinal Products Committee (HMPC).质量工作委员会将从上述成员中委派报告起草人负责：The QWP will appoint a rapporteur among its members who will:●在指南形成过程中，在质量工作委员会充当讨论的组织者●Lead the discussion at QWP during the development of the guideline●起草指南草案●Prepare the draft guideline●在指南公示征集意见前，负责审核内部讨论意见●Review internal comments before the guideline is published for external consultation ●起草用于公示征集意见的指南草案●Prepare a new draft for publication●在公示期结束后，审核外部征集的修改意见●Review the external comments received after the expiration of the externalconsultation period is expired●起草审评意见综述资料●Prepare the overview of comments●起草最终定稿的草案●Prepare a new draft for finalisation指南将在质量工作委员会及其他必要的会议(将花费3/4的预期时间)和在质量工作委员会/利益团体会议进行讨论。