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.
在制藥環(huán)境中最常被問到一個問題：既然微生物污染----最高風險---可以在終端使用點處使用除菌過濾，為什么要做這么多努力來對制藥用水進行精制和儲存/分配？
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:
在回答是否允許使用終端除菌過濾的問題時，首先回顧法規(guī)要求和標準以及關于水的指南。在一些問題點上，EU GMP指南對設施和設備設置了標準。與終端除菌過濾有著緊密關系的要求有以下：
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：“設備安裝應防止任何錯誤或污染帶來的風險”
EC GMP 3.39: "Production equipment should not present any hazards to the products".
EU GMP 3.39：“生產(chǎn)設備不應對產(chǎn)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：“生產(chǎn)設備設計應易于徹底清潔”
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附錄1：“水處理和分配系統(tǒng)的設計、構造和維護應確保水具備適當?shù)馁|(zhì)量”
Many guidelines also provide references to terminal filters. Please read here an extract from a Japanese Guideline:
許多指南也提供了終端過濾的參考。以下是一份日本指南中的摘要：
"Sterile drug products produced by aseptic processing (Japan 2006)
“無菌工藝生產(chǎn)的無菌藥品（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."
原則上，除菌過濾不應安裝在用水點，因為過濾器在水系統(tǒng)中可能掩蓋微生物污染。內(nèi)毒素也可能從微生物尸體中釋放，滯留在過濾器中。如果不能避免地使用過濾器，應基于驗證的結果來確定其更換頻率。”
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.
在此日本文件中關于終端過濾器的要求是很清楚的，一般來說，不應使用終端過濾器。實際上，它們會帶來安全假象，不能與無菌生產(chǎn)中的無菌過濾相比。生產(chǎn)中，過濾器的完整性需要在用于每批生產(chǎn)的前后分別檢查。
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.
當然可能有例外。過濾器不能用于掩蓋很高的CFU值。另外，公司應論述為什么使用此類過濾器而不通過系統(tǒng)設計、驗證和監(jiān)測來確保所需水的質(zhì)量。一般來說，這很困難。
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