什么是“复杂生产工艺：？EMA最近给出回答

julia朱玉姣

GMP News
28/10/2015

What are "complex manufacturing processes"? 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 of the European Commission defines the procedure for variations of existing marketing authorisations. The "detailed guidelines for the various categories of variations", which were published in the consolidated version in August 2013 in the European Official Journal, explain the interpretation and application 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 "detailed guidelines" describe a number of scenarios of possible variations in some detail, there are formulations in the Guideline text which require clarification due to their blur. The EMA adopted such a case in a recent update of its questions and answers collection "Quality of Medicines Questions and Answers: Part 1" to concretise 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 "complex manufacturing processes", which is used in two scenarios associated with type 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 part or all of the manufacturing process of the finished product (Guideline change code 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 medicinal products, or for pharmaceutical forms manufactured by complex manufacturing processes. 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) of the 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 complex manufacturing 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 as follows: EMA现在澄清此术语如下：

• Guideline Change Code B.II.b.1: Complex manufacturing processes are given when the understanding of the relation between quality characteristics of the product and its in vivo efficacy is lacking. This is often the case in innovative 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 are those which contain one or more sub-steps, where a scale-up can lead to problems.
• 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 approving authority will decide on a case by case basis. If the applicant submits the variation as a Type IB, he must provide a valid justification that the production process is not "complex". However, in doubt the authority may upgrade the variation to a Type II. Therefore, the EMA recommends that the applicant clarifies the situation with the authority before submitting the variation.

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。

大呆子

嗯，是不是可以简单地说，变更生产场地、变更批量、其它影响质量的变更

这句话不好理解：
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，

    似乎应该还包括其它的检验操作场地的变更？

friendly521

路过看看学习学习

红茶.

大呆子 发表于 2015-10-29 07:55
嗯，是不是可以简单地说，变更生产场地、变更批量、其它影响质量的变更

这句话不好理解：

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，

这个“以下产品”应该是“以下附表所列产品。”

尼采

感谢分享   

wct0526

謝謝分享...

是是而非

基本明白了

xhf123456

学习一下

empty1983

大呆子 发表于 2015-10-29 07:55
嗯，是不是可以简单地说，变更生产场地、变更批量、其它影响质量的变更

这句话不好理解：

“Site where any manufacturing operation(s) take place, except batch release, batch control, and secondary packaging, for biological/immunological medicinal products, or for pharmaceutical forms manufactured by complex manufacturing processes.”
此处的batch control不应该理解为批检验。