坐等ICH Q3D（第4阶段）：国家法规修订和实施已延迟！

红花鼠尾草

Waiting for ICH Q3D (Step 4): Revision and Implementation of national Regulations delayed!
坐等ICH Q3D（第4阶段）：国家法规修订和实施已延迟！
For over the past 3 years, the testing of metallic impurities has been the subject of ICH's efforts on harmonisation. The committee is responsible for the creation of guidelines for the pharmaceutical and APIs industry to be used - when finalised - in the three economic zones Europe, USA and Japan. The publication of a final guideline goes through a 4-step process; in the fifth and last step, the document is incorporated (i.e. "adopted") into the respective guidelines fund by the three partners.
在过去3年多时间中，金属杂质的检测已成为ICH努力协调的主题。委员会负责建立指南，提供给三个经济地区：欧盟、美国和日本的制剂和原料药企业使用。最终的指南要经过4个阶段方可公布，在最后的第5阶段，指南将与三方相应的指南相结合（即被采纳）。
At the end of 2011, the draft of a ICH Q3D guideline was published as a pre-step 2 document which first contained the requirements on the testing of metallic impurities in medicinal products and APIs. At the end of July 2013, the Draft Consensus Guideline "Guideline for Elemental Impurities" (step 2b document) was released and open for comments 6 months long. After considering all the comments received, the corresponding adaptation of the content and its publication should take place in June 2014. That was at least the working plan presented by the ICH Expert Working Group in the agenda of the ICH meeting which took place from 31 May till 5 June in Minneapolis. It stated: "Step 4 of the ICH Q3D Guideline is expected in June 2014". If this deadline can't be respected, the adoption of the finalised guideline would be expected only in autumn this year.
在2011年年底，ICH Q3D指南的草案已作为第2阶段文件发布，它包括了对制剂和原料药中金属杂质的检测要求。在2013年7月底，达成共识的指南草案“元素杂质指南”（第2b阶段文件）公开6个月征求意见。在考虑了各方所提交的建议后，应该在2014年6月对内容进行相应的修改并公布。至少这是ICH专家工作组在5月31日至6月5日在明尼阿波尼斯召开的ICH会议议程的工作计划。其中宣称“ICH Q3D指南的第4阶段将在2014年6月完成”。如果未能遵守该期限，则对该指南终稿的采用将只能是在今年秋天。
The delay in the acceptation and publication of the ICH Q3D guideline (step 4) also has consequences on the revision of some important national regulations in the three ICH regions.
ICH Q3D指南（第4阶段）的接受和公布延迟也会影响到ICH三方地区内一些重要的国家法规修订：
EMA's "Guideline on the Specification Limits for Residues of Metal Catalysts or Metal Reagents" from 2008 contains provisions about the testing of impurities through 14 metals in different dosage forms as well as a classification for those metals. The scope of this guideline includes newly developed as well as already authorised medicinal products. For the latter, a 5-year transition period had been set which ended on 1st September 2013. As at this time, the publication date of the ICH Q3D Draft Consensus Guideline couldn't be determined, the validity period of EMA's guideline for "legacy" medicinal products was suspended. It thus still applies - until the publication of the ICH Q3D (step 4) - only to medicinal products prior authorisation.
EMA在2008年的“金属催化剂和试剂残留限度指南”中包括了对不同剂型中14种金属杂质的测试，以及对这些金属的分类。该指南的范围包括一些新研发的药品和已经批准的药品。对于已经批准的药品，设定了一个5年的过渡期，该过渡期于2013年9月1日结束。这次，ICH Q3D共识草案的公布无法确定，因此EMA指南对“遗留”药品的生效日期将不能决定。所以，在ICH Q3D（第4阶段）公布前，该指南将仅适用于预批准的产品。
Chapter 5.20 "Metal Catalysts or Metal Reagents Residues" of the European Pharmacopeia includes the complete requirements of EMA's guideline and is referenced in the monograph 2034. Because of this cross-reference in a general monograph, Chapter 5.20 becomes binding. Moreover, as the implementation date of the monograph 2034 was the 1st of April 2014, Chapter 5.20 (as thus the provisions of EMA's guideline) would have been applying since that date. The European Pharmacopeia Commission found the solution out of this dilemma and suspended the publication of Ph. Eur. Supplement 8.1 which contains the monograph 2034 with the cross-reference to Chapter 5.20. This approach has been justified in a press release of the EDQM published on 29 August 2013 (see also our News dated 26 September 2013).
欧洲药典5.20“金属催化剂和试剂残留”包括了EMA指南的全部要求，并被通论2034所引用。由于该通论的交叉引用，5.20章成为强制规定。更有甚者，由于通论2034实施日期为2014年4月1晶，5.20章（即EMA指南的所有条款）将自该日期起生效。欧洲药典委员会对此两难境地的解决方式是将含有交叉引用5.20章通论2034的EP增补版本8.1推迟出版。该方法在2013年8月29日出版的一份EDQM出版物上已进行了说明（参见我们2013年9月26日新闻）。
USP's General Chapters <232> Elemental Impurities - Limits and <233> Elemental Impurities - Procedures were published in their revised form on 1st March 2014 in the Pharmacopoeial Forum 40(2) with 90-day comment period. The USP released a detailed schedule for each revision step of the Chapters <232> and <233>. According to the "USP Revision and Implementation Plan", both chapters should apply to the pharmacopoeial monographs as of 1 December 2015. That date also corresponds to the validity date of the "General Notices section 5.60.30" which will implement the chapters. A Q&A document provides more details about the revision procedure.
USP的通论<232>“元素杂质---限度”和<233>“元素杂质---检测方法”修订版已在2014年3月1日的药典论坛40（2）上公布，征求意见期为90天。USP发布了一份<232>和<233>每次修订步骤详细的时间表。根据“USP修订和实施计划”，两章均会从2015年9月1日起适用于药典各论。该日期也对应着“通则部分5.60.30”的生效日期。一份“问答文件”提供了关于该修订程序的详细信息。
The current situation is unsatisfactory for the pharmaceutical industry as it is not clear how different the expected final ICH Q3D guideline is from last year's published draft (step 2). Furthermore, long-term preparation (investments in technology and resources) is difficult. In particular, uncertainties remain with regard to large volume parenterals and the inclusion of already marketed medicinal products. Another issue concerns the different standards used in ICH and non-ICH regions which will emerge when the final ICH Q3D will be binding. How should global pharmaceutical industry as well as supervisory and licensing authorities manage that? The answer to that question is currently still open.
目前的情形使制药企业很不满意，因为不清楚ICH Q3D指南的终搞会与去年出版的草案（第2阶段）有多少区别。另外，进行长时间的准备（技术和资源方面的投资）也很困难。特别是该指南是否适用大输液和已上市药品尚不确定。另一个问题是在ICH地区和非ICH地区间所采用的不同标准在ICH Q3D形成终稿时会合并。全球制药企业及监管和证书管理机构该如何处理此事？该问题目前仍无答案。

yuansoul

你也是 某云的同学？

幻影

谢谢分享。

一沙一叶

第四季度应该会推出吧

liuqygood2005

了解下，多谢