Do pharmaceutical Water Systems need a sterile Ventilating Filter?

制藥用水系統是否需要無菌呼吸過濾器？

Pharmaceutical water systems (PW and WFI) require a ventilating filter on the storage tank. It prevents dirty ambient air from being sucked into the system when water is withdrawn from the tank. This is often referred to as a sterile filter. However, there are numerous requirements for "real" sterile filtration according to the current EU GMP Annex 1. But is sterile filtration necessary at all for this application?

制藥用水系統（PW 和 WFI）需要在儲罐上安裝呼吸過濾器。當水從水箱中抽出時，它可以防止骯臟的環境空氣被吸入儲罐中。這通常被稱為無菌過濾器。但是，根據當前的歐盟GMP附錄1，對“真正的”無菌過濾有許多要求。但是，對于這種應用，無菌過濾是必須的嗎？

First of all, it is important to understand that pharmaceutical water systems, neither PW nor WFI systems, are or have to be sterile. The maximum permissible bacterial counts are specified in the pharmacopoeias (max. 100 cfu / ml for PW and max. 10 cfu /100 ml for WFI). PW and WFI bulk is therefore not "sterile" water. Therefore, no "sterile filter" is required as a vent filter. Even though tank vent filters are usually 0.2 µm filters, which are also used similarly for sterile filtration, they should not be called sterile filters for this application.

首先，有必要要了解制藥用水系統，無論是純化水系統還是注射用水系統，都不是無菌或不是必須無菌。藥典中規定了最大允許細菌計數（PW最大100 cfu / ml，WFI最大10 cfu / 100 ml）。因此，PW和WFI不是“無菌”水。因此，不需要“無菌過濾器”作為呼吸過濾器。盡管儲罐的呼吸過濾器通常是0.2μm過濾器，也類似地用于無菌過濾，但對于此應用，它們不應稱為無菌過濾器。

However, testing of the integrity of the WFI tank filter is necessary.

但是，有必要對WFI儲罐的過濾器進行完整性測試 

The current EU GMP Annex 1 requires it for WFI systems:

當前的歐盟GMP附錄1要求：

6.11Where WFI storage tanks are equipped with hydrophobic bacteria retentive vent filters, the filters should not be a source of contamination and the integrity of the filter tested before installation and after use. Controls should be in place to prevent condensation formation on the filter (e.g. by heating).

6.11如果WFI儲罐裝有疏水性細菌滯留呼吸過濾器，則過濾器不應成為污染源，并應在安裝前和使用后測試過濾器的完整性。應采取適當的控制措施，以防止過濾器上形成冷凝（例如通過加熱）。

我國GMP《無菌藥品》附錄-2025征求意見稿：

第四十九條  注射用水儲罐的通氣口應當安裝不脫落纖維的疏水性除菌濾器；在安裝前和使用后測試過濾器完整性，并采取措施（如加熱）防止過濾器形成冷凝水。

The requirement to test such WFI tank filters "in place" for integrity and to sterilise them has - after long discussion - been deliberately deleted from the now valid Annex 1. The majority of the authors could be convinced that such a strict requirement would have meant unnecessary additional costs and additional GMP risks for 99% of the WFI systems - and would thus ultimately harm rather than benefit the patient.

經過長時間的討論，對這種WFI儲罐過濾器進行“在線”完整性測試并對其進行消毒的要求已從現行版附錄1中刪除。大多數撰寫人員相信，太過嚴格的要求將意味著99%的WFI系統將產生不必要的額外費用和額外的GMP風險 - 因此最終會損害而不是使患者受益。