[技术帖] EMA公布生物技术药品工艺验证指南最终版本

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EMA publishes finalised Process Validation Guideline for Biotech Products

EMA公布生物技术药品工艺验证指南最终版本

Approximately two years ago the EMA published a draft guideline on process validation for the manufacture of biotech products. Now the final guideline has been published under the title 'Guideline on process validation for the manufacture of biotechnology-derived active substances and data to be provided in the regulatory submission'. 

约2年前，EMA公布了生物技术药品生产工艺验证指南草案，现在正式版本公布，标题为“生物技术制备的活性物质生产工艺验证和法规申报中需要提交的数据指南”。

The scope of the guideline is to provide guidance on the data to be included in a regulatory submission to demonstrate that the active substance manufacturing process is in a validated state. The guideline focuses on recombinant proteins and polypeptides, their derivates, and products of which they are components (e.g. conjugates). But it is explicitly mentioned that the principles could also be applied to vaccines or plasma-derived products and other biological products, as appropriate.

指南的范围是提供关于法规申报中需要包括的数据指南，用以证明活性物质生产工艺处于验证状态。指南关注的是复合蛋白和多肽、其衍生物以及以其（例如，配位体）作为组分的药品。但它清楚提到这些原则也可以应用于疫苗和血浆制品以及其它生物药品（适用时）。

Process validation is mentioned as life cycle, comparable to Annex 15 and to the EMA guideline on process validation for finished products . Also comparable to both, the guideline offers a traditional or an enhanced  (with reference to ICH Q 11) approach to process validation. A combination of both approaches is possible as well. This 'hybrid approach' is in line with the other new European process validation guidelines, too. 

工艺验证以生命周期形式提出，与附录15和EMA制剂工艺验证指南具有可比性。指南还提供了传统的和加强的工艺验证方法（参照ICH Q11），也与上述两指南具有可比性。两种方法的联合也是可能的。这种“混合方法”也与其它新的欧洲工艺验证指南保持一致。

Process validation is divided into two parts:

工艺验证分为2部分：

• process characterisation, where the commercial manufacturing process is defined

  工艺属性确定，如果是界定商业生产工艺的话

• process verification, where the final manufacturing process as established based on process evaluation studies performs effectively in routine manufacturing.
  

• 工艺核查，如果是最终生产工艺基于日常生产中有效实施的工艺评估研究的话

Process characterisation itsself is also divided into two parts:

工艺属性确定本身也分为两部分：

• process development, which includes studies to reach a potential design of a future manufacturing process

  工艺研发，其中包括达到对未来生产工艺的潜在设计的研究

• process evaluation which includes studies on small and/or commercial scales, providing evidence that the complete manufacturing process has been appropriately designed to design the full operating ranges of the manufacturing process.
  

  工艺验证，其中包括对小规模和/或商业规模的研究，它提供证据证明已适当设计出了完整的生产工艺，可以用于设计完整的生产工艺操作范围。

It is explicitly mentioned that subsequent to succesfull process validation product quality and process performance must be maintained in a state of control during routine production. This ongoing process verification is normally not part of submission data, with the exception of e.g. niche products, which could not be fully validated at the time of the regulatory submission.

指南中清楚提到成功的工艺验证之后，必须在常规生产中将药品质量和工艺表现维持在受控状态。这种持续工艺验证一般并不是申报数据的一部分，当然也有例外，如利基产品，它在提交法规申报的时候可以不需要进行全面验证。

There is no number of validation runs mentioned in this guideline and concurrent validation could  be considered only in exceptional circumstances (e.g. medical need is mentioned) and after consultation with the regulatory authorities.

在该指南中并没有提到验证轮次的数量，只有在例外情形下，征求过药监当局意见之后，才可以考虑使用同步验证（例如，提到了药品需求）。

 

来源：Julia Blog，感谢朱玉姣老师。