什么是“复杂生产工艺？EMA最近给出回答

20151028 ECA新闻：什么是“复杂生产工艺？EMA最近给出回答  

GMP News
28/10/2015

What are "complex manufacturingprocesses"? A recent reply from the EMA

什么是“复杂生产工艺？EMA最近给出回答

The Variations Regulation (EC) no. 1234/2008 ofthe European Commission defines the procedure for variations of existingmarketing authorisations. The "detailed guidelines for the various categories ofvariations", which were published in the consolidated versionin August 2013 in the European Official Journal, explain the interpretation andapplication of this Variations Regulation.

欧洲委员会的“变更规定（EC）1234/2008”中定义了已有上市许可的变更程序。欧洲官方杂质上于2013年8月公布了“变更分类详细指南”整体更新版本，其中解释了该变更规定的应用和诠释。

Although the "detailedguidelines" describe a number of scenarios of possible variations in somedetail, there are formulations in the Guideline text which requireclarification due to their blur. The EMA adopted such a case in a recent updateof its questions and answers collection"Quality of Medicines Questions and Answers: Part 1" toconcretise the case through a statement.

尽管“详细指南”详细描述了大量的可能变更情景，在指南正文中有一些公式，但有些模糊需要澄清。EMA在最近对其“问答集合“药品质量问答：第1部分””更新中采用了这样一个案例，以在整个声明中具体说明该案例。

It is about the term "complexmanufacturing processes", which is used in two scenarios associated withtype II variations (found in the "detailed guidelines" p 40ff):

这是一个关于术语“复杂生产工艺”的案例，它用在两个关于二类变更的案例（页40ff的“详细指南”）

·        Replacement or addition of a manufacturing site for partor all of the manufacturing process of the finished product (Guideline changecode B.II.b.1) 部分或全部药品生产工艺变更或增加一个生产场所
...
c) Site where any manufacturing operation(s) take place, except batch release,batch control, and secondary packaging, for biological/immunological medicinalproducts, or for pharmaceutical forms manufactured by complex manufacturingprocesses. 微生物/免疫药品，或以下产品，除批放行、批检验和外包装以外的所有生产操作发生的场所，

·        Change in the batch size (including batch size ranges) ofthe finished product (Guideline change code B.II.b.4) 制剂（指南变更代码B.II.b.4）批量变更（包括批量范围）
...
d) The change relates to all other pharmaceutical forms manufactured by complexmanufacturing processes . 与所有用复杂生产工艺生产的其它药品剂型有关的变更

The EMA now clarified this term asfollows: EMA现在澄清此术语如下：

·        Guideline Change Code B.II.b.1: Complex manufacturing processes aregiven when the understanding of the relation between quality characteristics ofthe product and its in vivo efficacy is lacking. This is often the case ininnovative medicines such as products of nanomedicine.

·        指南变更代码B.II.b.1：在缺乏产品质量属性和其体内有效性之间的关系知识时，要定义为复杂生产工艺。通常非创新药，例如纳米医学产品就是这样。

·        Guideline Change Code B.II.b.4: Complex manufacturing processes arethose which contain one or more sub-steps, where a scale-up can lead toproblems.

·        指南变更代码B.II.b.4：复杂生产工艺是指那些包括一个或多个子步骤的工艺，放大生产可能会产生问题。

In both scenarios, the approvingauthority will decide on a case by case basis. If the applicant submits thevariation as a Type IB, he must provide a valid justification that theproduction process is not "complex". However, in doubt the authority mayupgrade the variation to a Type II. Therefore, the EMA recommends that theapplicant clarifies the situation with the authority before submitting thevariation.

在两种情形下，负责批准的药监部门要根据实际案例来做出决定。如果申报者作为IB类变更提交，则必须提交有效的论述，证明生产工艺并不“复杂”。但是，如果药监当局有疑问的话，可能会将其升级为II类变更，因此EMA建议申报者在提交变更之前，提前与药监当局就实际情况进行澄清。

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