In the pharmaceutical industry, HEPA filters are used as terminal filters for the processing or filtration of air in production spaces. They are mandatory in sterile production, although they are sometimes also used in the manufacture of solid or semisolid dosage forms. Amongst the HEPA or high-efficiency particulate air filters are Filter Classes H13 to H14 (DIN 1822), the latter with a retention rate of 99.995%. But how often do they need to be changed?

在制藥行業(yè)，高效過濾器（HEPA）用于生產(chǎn)空間空氣的處理和過濾的終端過濾器。無(wú)菌生產(chǎn)要求強(qiáng)制使用高效過濾器，而固體和半固體劑型的生產(chǎn)有時(shí)也會(huì)使用。H13至H14（DIN1822）是高效過濾器的兩種，后者截留率為99.995%。但多久必須更換一次呢？

One can frequently find internal company guidelines according to which the filters should be changed annually, regardless of monitoring results. Is that sensible? An exact number, meaning the maximum duration of use for HEPA filters in months, cannot be found in the relevant GMP guidelines. According to GMP, the filter has to be free of leaks. This is verified by qualification and regularly performed leak tests as per ISO 14644-3, which are mandatory for sterile facilities. According to the technical interpretation of the Annex 1 (PIC/S PI 032-2), leak tests are to be performed every six months in A/B zones and every twelve months in C/D zones. The FDA Aseptic Guide demanDS?a regular inspection. The requirements of Annex 1 can be applied here as well. Leaks may be repaired; those repaired areas may only take up 0.5% of the filter surface per filter.

我們經(jīng)?？吹皆诠緝?nèi)部文件中，要求每年更換過濾器，而不管檢測(cè)結(jié)果如何。這是否合理？在相關(guān)的GMP指南中并沒有高效過濾器可以使用期限的具體數(shù)值。根據(jù)GMP的要求，過濾器不得有泄漏，這需要通過確認(rèn)和定期執(zhí)行ISO14644-3中的泄漏測(cè)試，無(wú)菌車間來(lái)說(shuō)這是必須的。根據(jù)附錄1（PIC/S PI032-2）的技術(shù)詮釋，A/B級(jí)每6個(gè)月進(jìn)行泄漏測(cè)試，C/D級(jí)則為12個(gè)月。FDA無(wú)菌指南要求進(jìn)行定期檢查。附錄1的要求在這里也適用。泄漏是可以修補(bǔ)的，但修補(bǔ)的面積不能超過單個(gè)過濾器面積的0.5%。

However, not only the integrity of the HEPA filter is relevant. The load of the filter (layer) and thus the pressure drop at the filter is also important. If the pressure drop at the filter rises, the energy demand of the ventilation system increases to maintain the necessary air change rates. This pressure drop at the filter can increase to the performance limits of the ventilation system. To protect the HEPA filters, preliminary filters are used - usually fine particulate air filters like F7 und F9 filters (EN779). Those have to be replaced regularly and protect the HEPA filters from clogging.

From a practical viewpoint, one could say that the maximum duration of use depends directly on the pressure drop. Changing the filters only makes sense if the pressure drop gets too high for the performance of the ventilation system or if the cost of energy demand lies above the cost of a filter change. The filters do have to pass the leak tests (see above), of course. In practice, several companies do not use a filter for more than eight years. As mentioned before, though, this is not a legally binding value, but merely based on experience.

從實(shí)踐角度來(lái)看，我們可以說(shuō)最長(zhǎng)使用期限直接取決于上下游壓差。只有在上下游壓差達(dá)到一定數(shù)值影響到通風(fēng)系統(tǒng)的性能，或者是能量需求超過過濾器更換成本時(shí)，過濾器更換才有意義。但是，過濾器必須能通過泄漏測(cè)試（如上所述）。事實(shí)上，很多公司并不會(huì)使用一個(gè)過濾器超過8年。正如前述，并沒有法規(guī)規(guī)定這樣的值，這都只是根據(jù)經(jīng)驗(yàn)得來(lái)的。

高效過濾器更換問題

咨詢內(nèi)容：老師您好，小容量注射劑車間空調(diào)系統(tǒng)的高效過濾器必須定期更換嗎？如不定期更換，只在空調(diào)驗(yàn)證時(shí)更換風(fēng)量不合格房間高效和撿漏不合格高效可以嗎？

CFDA審核查驗(yàn)中心回復(fù)：你好，更換高效過濾器根據(jù)空調(diào)驗(yàn)證時(shí)風(fēng)量和撿漏是必須的，但同時(shí)也應(yīng)制定出具體高效過濾器最長(zhǎng)使用周期，故還是應(yīng)該有定期的概念。同時(shí)必須定期進(jìn)行過濾器完整性測(cè)試。

潔凈區(qū)A級(jí)高效過濾器檢漏

咨詢內(nèi)容：潔凈區(qū)A級(jí)高效過濾器檢漏是否可以使用 塵埃粒子計(jì)數(shù)器 掃描檢漏，如果可以，那么判斷無(wú)泄漏的標(biāo)準(zhǔn)是多少。

CFDA審核查驗(yàn)中心回復(fù)：高效過濾器檢漏一般在非關(guān)鍵區(qū)域可以使用塵埃粒子計(jì)數(shù)器，但A級(jí)潔凈區(qū)高效過濾器不推薦使用塵埃粒子計(jì)數(shù)器掃描檢漏。

來(lái)源：無(wú)塵無(wú)菌潔凈室專家