20150624 ECA新闻：ICH公布新问答指南 （分享）

20150624 ECA新闻：ICH公布新问答指南  

GMP News
24/06/2015

ICH Publishes New Question and Answer Guideline

ICH公布新问答指南

Already in October 2012 the International Conference on Harmonisation (ICH) has started to develop the ICH Q7 Q&As. At this time a Final Concept Paper was published.

在2012年10月，ICH就开始制订ICH Q7A的问答。这次ICH公布了最终概念文件。

Now the ICH has published the ICH Q7 Questions and Answers on GMP for Active Pharmaceutical Ingredients. It is the intension of the guideline to clarify uncertainties due to different interpretations of requirements laid down in the ICH Q7 Guideline. The Q&A provides a table which aims to show the link between each Q&A and the relevant Sections of ICH Q7 and other ICH Quality guidance. Very much of the content of the new Guideline has been provided by the Pharmaceutical Inspection Co-operation Scheme (PIC/S). The PIC/s has been involved by selecting and reviewing relevant Q&As. In addition questions were developed based on responses from an ICH survey. The preface of the Q&A document states that ICH Q7 should be applied in combination with the principles laid down for development and manufacturing in ICH Q11 (see definition of API starting material; see also ICH Q8(R2) Part II), Quality Risk Management (ICH Q9), and Pharmaceutical Quality Systems (ICH Q10).

现在ICH已经公布了ICH Q7A关于原料药GMP的问答，其意在于澄清一些对ICH Q7A指南中给定的要求有不同解释的不确定性问题。该问答给出了一个表格，其意在显示每个问答和相关ICH Q7章节及其它ICH质量指南之间的联系。新指南的许多内容已经由PICS提供。PICS已经选择和审核了相关的问答。另外一些是根据ICH调查回复制订的问题。问答文件的前方说明了ICH Q7应与ICH Q11（参见原料药起始物料，也请参见ICH Q8(R2)第二部分）、质量风险管理（ICH Q9）和药品质量体系（ICH Q10）中给出的研发和生产原则相结合来使用。

The document is structured according to the chapter of ICH Q7. Already for the scope of the ICH Q7 the Question and Answer Guide provides a very frequently asked question:

文件是根据ICH Q7的章节顺序来组织的。关于ICH Q7的范围，问答指南里有一个很常见的问题：

Should GMP according to ICH Q7 be applied for manufacturing Steps before the defined ‘API starting material' i.e., Steps not identified in grey in Table 1?

根据ICH Q7的GMP是否适用于所定义的“原料药起始物料”之前的生产步骤，即表1中未标示为灰色的步骤？

ICH Q7 does not apply to Steps prior to the introduction of the API starting material. However, there is an expectation that an appropriate level of controls suitable for the production of the API starting material should be applied [ICH Q7, Section 1.3]. Normally, the ‘API-starting material’ is defined in the regulatory filing by the applicant and approved in the regulatory reviewing process. Additional guidance is provided to define and justify ‘API starting material’ derived from various sources [ICH Q11, Section 5]; for master cell banks, see [ICH Q5B; ICH Q5D].

ICH Q7不适用于原料药起始物料之前的步骤。但是，应该具备与原料药起始物料生产相适应的适当水平的控制【ICH Q7,第1.3部分】。一般来说，“原料药起始物料”是在法规申报文件中进行定义并在法规审核过程中获得批准的。另有指南提供了如何界定和论述了不同来源的“原料药起始物料”【ICH Q11第5部分】，关于母细胞库，参见【ICH Q5B,ICH Q5D】。

Clarification is provided to nearly all additional chapters such as Quality Management, Personnel, Buildings and Facilities (Containment), Process Equipment (Cleaning), Documentation and Records, Material Management, Production and In-Process Controls, Storage and Distributions, Laboratory Controls, Validation, Change Control, Rejection and Reuse of Materials, Complaints and Recall, Contract Manufacturing (including Laboratories), Agents, Brokers, Traders, Distributors, Repackers and Relabellers. Also questions on specific manufacturing steps such as APIs manufactured by Cell Culture and Fermentation and APIs used in Clinical Trials are covered.

该文件几乎提供了针对所有章节的澄清，如质量管理、人员、厂房与设施（隔离）、工艺设备（清洁）、文件记录、物料管理、生产和中控、存贮和销售、化验室控制、验证、变更控制、拒收和物料回收使用、客户投诉和召回、合同生产（包括合同化验室）、代理、经销商、贸易商、分销商、再包装商和再贴标商。还有关于特定的生产步骤的问答，例如细胞培养和发酵生产的原料药，以及临床试验用原料药。

Among the many interesting Q&As here is one regarding Building and Facilities:

有许多有意思的问答，这里是其中一个关于建筑和设施的

When are dedicated production areas expected?

什么时候需要使用专用生产区域？

ICH Q7 expects dedicated production areas for highly sensitising materials such as penicillins and cephalosporins because of the patient risk (e.g., anaphylactic shock to penicillin-allergic patients) from trace amounts of these compounds in other medicines [ICH Q7, Section 4.40]. For materials of an infectious nature or high pharmacological activity or toxicity, a risk-based approach should be used to determine appropriate containment measures, which may include validated inactivation, cleaning and/or dedicated production areas [ICH Q7, Section 4.41]. While ICH Q7 does not define high pharmacological activity or toxicity, these are generally determined by evaluating relevant animal and human data collected during research and development. Important considerations in this evaluation of pharmacological activity or toxicity may include Occupational Exposure Limit (OEL), Permitted Daily Exposure (PDE), Acceptable Daily Exposure (ADE), Threshold for Toxicological Concerns (TTC), No Observed Adverse Effect Level (NOAEL) [ICH S Guidelines, ICH E2E, Section 2.1.1], and the consequences of cross-contamination [ICH Q9, Section 4.3].

ICH Q7期望对于高致敏物料如青霉素和头孢类物料使用专用车间，因为这些化合物在其它药品中的痕量残留会引起患者风险（即青霉素过敏患者的致命休克）【ICH Q7,第4.40部分】。对于具有感染性的物料，或高活性或高毒性物料，应采用基于风险的方法来确定适当的隔离措施，这些措施可以包括经过验证的灭活、清洁和/或专用生产区域【ICH Q7，第4.41部分】。但ICH Q7并没有对高药物活性或高毒性进行定义，这一般是通过研发期间收集的动物或人类相关数据进行评估来决定的。在该评估中要重点考虑的问题包括职业暴露限（OEL）、允许日暴露量（PDE）、可接受日暴露量（ADE）、毒性关注阈（TTC）、未观察到不良影响水平（NOAEL）【ICH S 指南，ICH E2E，第2.1.1部分】，以及交叉污染的后果【ICH Q9，第4.3部分】。

The Question and Answer Guideline on ICH Q7 will be covered by a session at the 18th European API Conference organised by APIC/CEFIC on 4-6 November in Amsterdam. APICs President Anthony Storey (Pfizer) and Francois Vandeweyer, Janssen Pharmaceutica, Belgium, will lead the session.  

在由APIC/CEFIC11月4-6日在阿姆斯特丹举办的第18次欧洲原料药会议上，将会包括ICH Q7问答指南。APIC主席ANTHONY STOREY（辉瑞）和FRANCOIS VANDEWEYER，比利时杨森将主导本次研讨会。

感谢分享！！！