20160127 ECA新闻：是否允许在水系统里最终灭菌过滤？

20160127 ECA新闻：是否允许在水系统里最终灭菌过滤？  

GMP News
27/01/2016

Are Terminal Sterile Filters in Water Systems permissible?

是否允许在水系统里最终灭菌过滤？

One of the most frequently asked questions in the pharmaceutical environment is why so much effort is made for purification and storage/ distribution of water for pharmaceutical use. Especially microbial contamination - the highest risk - could be avoided by using terminal sterile filters at the points-of-use.

在制药环境中最常被问到的一个问题是为什么要做这么多努力来对制药用水进行精制和存贮/分配。尤其是微生物污染----最高风险---可以在最终使用点处使用无菌过滤来避免。

Answering the question whether terminal sterile filters are allowed first requires reviewing the legal requirements and standards as well as the guidelines on the topic water. On some points, the EU GMP Guides lays the specifications for premises and equipment. Closely related to the terminal sterile filters, you can find the following instructions:

在回答是否允许使用最终无菌过滤的问题时，首先要审核法规要求和标准以及关于水的指南。在一些问题点上，EU GMP指南对设施和设备设置了标准。与最终无菌过滤有着紧密关系的指示有以下：

• EC GMP 3.38: "Equipment should be installed in such a way as to prevent any risk of error or of contamination."
• EU GMP 3.38：“设备安装应防止任何错误带来的风险，及污染带来的风险”
• EC GMP 3.39: "Production equipment should not present any hazards to the products".
• EU GMP 3.39：“生产设备不应对产品具有任何危害”
• EC GMP 3.36: "Manufacturing equipment should be designed so that it can be easily and thoroughly cleaned."
• EU GMP 3.36：“生产设备设计应易于彻底清洁”
• EC GMP Annex 1: "Water treatment plants and distribution systems should be designed, constructed and maintained so as to ensure a reliable source of water of an appropriate quality."
• EU GMP附录1：“水处理工厂和分配系统的设计、构造和维护应确保水具备适当的品质”
  

Many guidelines also provide references to terminal filters. Please read here an extract from a Japanese Guideline:

许多指南也提供了最终过滤的参考。以下是一份日本指南中的摘要：

"Sterile drug products produced by aseptic processing (Japan 2006)

“无菌工艺生产的无菌药品（日本2006）

As a rule, sterilizing filters should not be placed at water use points since the filters could mask microbiological contamination in the water system. Endotoxins could also be released from dead microorganisms retained in the filters. If the use of filters is unavoidable, the interval of replacement should be based on validation results."

作为规则，灭菌过滤不应安装在用水点，因为过滤器在水系统中可能掩盖微生物污染。内毒素也可能从微生物尸体中释放，滞留在过滤器中。如果不能避免使用过滤器，其更换频率应基于验证结果来确定。”

The instructions with regard to terminal filters in this Japanese document are clear: basically, terminal filters shouldn't be used. Indeed, they would provide a false security and can't be - in this application - compared to the sterile filtration in sterile production. Here, the integrity of filters is checked before and after their utilisation for each batch.

在此日本文件中关于最终过滤器的要求是很清楚的，一般来说，不应使用最终过滤器。实际上，它们会带来安全假象，不能---在此应用中---与无菌生产中的无菌过滤相比。生产中，过滤器的完整性要在用于每批生产的前后分别检查。

There may be exceptions, though. Filters can't be used to mask too high CFU-values. Moreover, one should be able to justify the use of such filters instead of ensuring the quality required trough system design, validation and monitoring. Normally, this shouldn't be easy.

当然可能有例外。过滤器不能用于掩盖很高的CFU值。另外，公司应该可以论述为什么使用此类过滤器，而不是通过系统设计、验证和监测来确保所需的质量。一般来说，后者会更容易一些。

http://zhuyujiao1972.blog.163.com/blog/static/986947272016027112326913/