GMP潔凈室HVAC系統(tǒng)，是否可以在夜間關(guān)閉？

Can the ventilation of GMP clean rooms be switched off overnight?
GMP潔凈室的通風(fēng)系統(tǒng)是否可以在夜間關(guān)閉？

The ventilation systems of clean rooms consume a lot of energy, especially power for the ventilating fan, refrigerating capacity for cooling and dehumidification in summer as well as heating for warming and steam for humidification in winter. Therefore, the question comes up again and again whether one might switch off the ventilation of the rooms overnight or when they are not used in order to save energy.

潔凈室的通風(fēng)系統(tǒng)耗費(fèi)巨大能源，特別是通風(fēng)系統(tǒng)的風(fēng)扇、夏天致冷和除濕以及冬天加熱和加濕用蒸汽。因此，一直就有這個(gè)問題：公司是否可以在晚上或不用的時(shí)候關(guān)閉房間的通風(fēng)，以節(jié)約能源？

It is not advised to switch off the ventilation system completely, it is rather advised not to do it. Premises, pressure conditions, microbiology, everything would be out of control during that time. This would make the subsequent measures for the restoration of the GMP-compliant state very complex because each time a requalification would be necessary to reach the normal GMP-compliant state.

一般不建議完全關(guān)閉通風(fēng)系統(tǒng)，事實(shí)上最好不要這樣做。設(shè)施、壓差條件、微生物，在此期間所有東西都有可能失控。這會(huì)讓之后的恢復(fù)GMP符合狀態(tài)所需的措施非常復(fù)雜，因?yàn)槊看味家鲈俅_認(rèn)，來達(dá)到正常的GMP符合狀態(tài)。

But a reduction in the performance of the ventilation systems (reduction of the air volume by reducing the performance of the ventilation system) is possible, and is already carried out in some companies. Here too, however, the GMP-compliant state must be achieved prior to using the clean room again and this procedure must be validated.

但是，可以降低通風(fēng)系統(tǒng)的頻率（通過減少通風(fēng)系統(tǒng)的頻率來減少換氣量），已經(jīng)有一些公司在這么做了。但是，在重新使用潔凈室之前還是必須達(dá)到GMP符合狀態(tài)，并且該程序必須經(jīng)過驗(yàn)證。

For this purpose the following points must be observed:

為此必須要觀察以下幾點(diǎn)：

The reduction can only be carried out so far that the clean room specific limits prescribed for the relevant case are not violated in general. These limits have to be defined in each case for the operating status and the reduction mode including permissible minimum and maximum values, such as clean room class (particle count with equivalent particle size), product specific values (temperature, relative humidity), pressure conditions (pressure difference between the rooms). Note that the values in reduction mode have to be chosen in such a way that the facility has reached the GMP-compliant state in due time before production begins (integration of a time program). This state depends on different parameters such as building material and performance of the system etc. The pressure conditions should be maintained all the time, this means that a reversion of the flow direction is not allowed.

降低通風(fēng)系統(tǒng)的頻率只能達(dá)到一個(gè)指定的程度，以確保維持特定個(gè)例中的潔凈室的特定限度。在每個(gè)個(gè)例中，這些運(yùn)行狀態(tài)下的和降低頻率狀態(tài)下的限度必須定義，其中包括允許的最小和最大值，例如潔凈室級(jí)別（粒子數(shù)和相關(guān)的粒徑）、產(chǎn)品特定的值（溫度、相對(duì)濕度）、壓差條件（房間之間的壓差）。注意，在降低頻率的模式下的值的選擇必須使得設(shè)施在生產(chǎn)開始之前的規(guī)定時(shí)間內(nèi)（時(shí)間計(jì)劃結(jié)合在其中）達(dá)到GMP符合狀態(tài)。此狀態(tài)取決于不同的參數(shù)，例如建筑材料和系統(tǒng)性能等。應(yīng)在所有的時(shí)間內(nèi)都維持壓差條件，這表示不允許氣流逆向。

Furthermore, the installation of an independent clean room monitoring system is recommended in any case in order to constantly monitor and document the above mentioned clean room specific parameters. Thus, the conditions of the area concerned can be monitored and documented at any time. In the case of deviations (reaching of a limit) and in the individual case it is possible to access the measurement and control technology of the ventilation system and to carry out the relevant adjustments.

還有，建議安裝一個(gè)獨(dú)立的潔凈室監(jiān)測(cè)系統(tǒng)，這樣可以連續(xù)監(jiān)測(cè)并記錄上述潔凈室指定參數(shù)。這樣，所關(guān)注的區(qū)域的條件應(yīng)可以在任何時(shí)間進(jìn)行監(jiān)測(cè)和記錄。如果有偏差發(fā)生（達(dá)到限度），在個(gè)案中有可能具備測(cè)量和通風(fēng)系統(tǒng)控制技術(shù)，進(jìn)行相關(guān)調(diào)整。

During the reduction attention should be paid to ensuring that no unpredicted external interfering influences such as the entry of persons are allowed. For this the installation of a corresponding entry control is advised. In the case of an electronic locking system the entry authorisation can be linked with the above mentioned time program as well as with the independent clean room monitoring system so that entry is authorised only subject to compliance with the predefined requirements.

在降低風(fēng)機(jī)頻率時(shí)，要注意確保沒有非預(yù)期的外來干擾影響，例如，人員進(jìn)入。這種情況建議使用相應(yīng)的人員進(jìn)出控制。如果使用的是電子鎖系統(tǒng)，進(jìn)出權(quán)限可以與上述時(shí)間計(jì)劃相關(guān)聯(lián)，以及與獨(dú)立的潔凈室監(jiān)測(cè)系統(tǒng)相關(guān)聯(lián)，這樣，進(jìn)出授權(quán)必須要符合預(yù)定的要求。

In principal, both states must be qualified first and then requalified in regular intervals and the customary measurements for the regular operating status such as the recovery time measurement in case of a complete failure of the facility must be carried out. In the case a clean room monitoring system exists it is in principal not required - as mentioned above - to carry out further measurements at the start of operations after reduction mode if the procedure is validated. Special focus should be put on the procedure of restarting since temporary reversions of the flow direction are possible, for instance.

原則上來說，兩種狀態(tài)都必須先確認(rèn)，然后進(jìn)行定期再確認(rèn)。通常，常規(guī)運(yùn)行狀態(tài)下的測(cè)量，例如設(shè)備完全失效情形下恢復(fù)時(shí)間測(cè)量是必須要進(jìn)行的。如果存在有潔凈室監(jiān)測(cè)系統(tǒng)，程序經(jīng)過驗(yàn)證的話，原則上不需要---如上所述---在降低通風(fēng)頻率后重新開始運(yùn)行時(shí)進(jìn)行進(jìn)一步測(cè)量。特別要注意的是重新開始運(yùn)行時(shí)的程序，因?yàn)?，比如氣流方向短時(shí)逆向是有可能發(fā)生的。

All in all about 30 % of the energy costs can be saved depending on the mode of operation and the shift model but additional investment costs might have to be offset.

總體來說，根據(jù)運(yùn)行模式和當(dāng)班模式的不同，大概能節(jié)約30%左右的能源，但可能會(huì)被額外的投資成本所抵消。

WHO非無菌空調(diào)GMP指南

GOOD MANUFACTURING PRACTICES FOR HEATING, VENTILATION AND AIR-CONDITIONING SYSTEMS FOR NON-STERILE PHARMACEUTICAL DOSAGE FORMS: PART 2 INTERPRETATION OF PART 1 – GMP FOR HVAC SYSTEMS

非無菌制劑暖通空調(diào)GMP指南：第二部分——HVAC系統(tǒng)的GMP要求

It is recommended that the HVAC system be operational on an ongoing basis. Where a manufacturer decides to use energy saving modes or switch some selected AHUs off at specified intervals such as overnight, weekends or extended periods of time, care should be taken to ensure that materials and products are not affected. In such cases, the decision, procedures and records should be sufficiently documented and should include risk assessment, standard operating procedures (SOPs), records and validation. This includes procedures and records for the start-up and shut-down sequence of air handling units.

建議HVAC系統(tǒng)持續(xù)運(yùn)行。當(dāng)決定在特定時(shí)間使用節(jié)能模式或選擇關(guān)閉部分AHU，如夜間、周末或很長時(shí)間，應(yīng)關(guān)注確保物料和產(chǎn)品不受影響。這種情況下，應(yīng)充分記錄該決定、規(guī)程和記錄，并包括風(fēng)險(xiǎn)評(píng)估、標(biāo)準(zhǔn)操作規(guī)程（SOP）、記錄和驗(yàn)證。這包括風(fēng)機(jī)處理單元（AHU）的開啟和關(guān)閉順序的規(guī)程和記錄。

GB 50457-2019
醫(yī)藥工業(yè)潔凈廠房設(shè)計(jì)標(biāo)準(zhǔn)

9.2.15 無菌藥品生產(chǎn)的潔凈區(qū)凈化空氣調(diào)節(jié)系統(tǒng)應(yīng)保持連續(xù)運(yùn)行，維持相應(yīng)的潔凈級(jí)別。在非生產(chǎn)期間，凈化空氣調(diào)節(jié)系統(tǒng)可以采用低頻運(yùn)行等模式，但仍應(yīng)保持醫(yī)藥潔凈室相應(yīng)級(jí)別和對(duì)周圍低級(jí)別潔凈區(qū)的正壓。因故停機(jī)再次開啟空氣凈化系統(tǒng)，應(yīng)當(dāng)進(jìn)行必要的測(cè)試以確認(rèn)滿足其規(guī)定的潔凈度級(jí)別要求。

GB 50457-2019
醫(yī)藥工業(yè)潔凈廠房設(shè)計(jì)標(biāo)準(zhǔn)
條文說明

“在非生產(chǎn)時(shí)間，由于潔凈室內(nèi)主要污染源(操作人員)的撤離，室內(nèi)的發(fā)塵量大大降低，為了節(jié)省運(yùn)行費(fèi)用，在滿足潔凈級(jí)別和正壓的前提條件下，可以采用降低空氣凈化系統(tǒng)風(fēng)量方法?！?/span>

“對(duì)于無菌生產(chǎn)核心區(qū)建議維持正常生產(chǎn)運(yùn)行時(shí)的關(guān)鍵參數(shù)，對(duì)于其他醫(yī)藥潔凈室需維持的正壓值應(yīng)根據(jù)產(chǎn)品特性、生產(chǎn)運(yùn)行時(shí)的情況，QA部門質(zhì)量驗(yàn)證的結(jié)果及企業(yè)自身生產(chǎn)管理水平而定?！?/p>

新版GMP指南（2023版）

廠房設(shè)施和設(shè)備分冊(cè)

3.6.2.4 節(jié)能模式下的風(fēng)量平衡

非生產(chǎn)模式作為凈化空調(diào)系統(tǒng)的一個(gè)運(yùn)行模式，應(yīng)保持連續(xù)運(yùn)行，維持相應(yīng)的凈化級(jí)別和對(duì)周圍區(qū)域的正壓，維持良好的氣流方向。凈化空調(diào)系統(tǒng)的送風(fēng)量變化、不同潔凈區(qū)域的風(fēng)量變化、潔凈室風(fēng)量的變化，都需要凈化空調(diào)系統(tǒng)來實(shí)現(xiàn)機(jī)組風(fēng)量、區(qū)域風(fēng)量及潔凈室風(fēng)量的再平衡。

1、無菌區(qū)風(fēng)量可維持規(guī)范范圍內(nèi)的下限運(yùn)行。

2、其他潔凈區(qū)可以較大幅度降低運(yùn)行風(fēng)量。

說明：由于凈化空調(diào)系統(tǒng)送風(fēng)管道內(nèi)壓力的差異，不同區(qū)域風(fēng)量變化存在差異，當(dāng)系統(tǒng)總風(fēng)量降低時(shí)，不同區(qū)域風(fēng)量的降低存在區(qū)別，凈化空調(diào)系統(tǒng)的風(fēng)量平衡就會(huì)被破壞，從而造成潔凈室的壓力梯度紊亂。同時(shí)，為維持區(qū)域正壓，凈化空調(diào)系統(tǒng)的新風(fēng)量應(yīng)依據(jù)正壓需要進(jìn)行調(diào)整。

凈化空調(diào)系統(tǒng)生產(chǎn)模式動(dòng)態(tài)工藝運(yùn)行、非生產(chǎn)模式運(yùn)行都需要再平衡系統(tǒng)風(fēng)量區(qū)域的風(fēng)量。

實(shí)施方式：

1、首先完成非生產(chǎn)模式下凈化空調(diào)系統(tǒng)的系統(tǒng)送風(fēng)量、潔凈區(qū)域送風(fēng)量的測(cè)算設(shè)置好非生產(chǎn)模式下的需求風(fēng)量；

2、凈化空調(diào)系統(tǒng)采用設(shè)置好的非生產(chǎn)模式風(fēng)量運(yùn)行，進(jìn)行相關(guān)的環(huán)境參數(shù)測(cè)試并通過測(cè)試的參數(shù)對(duì)風(fēng)量進(jìn)行調(diào)整；

3、通過測(cè)試確認(rèn)在滿足環(huán)境凈化級(jí)別及正壓需求下的各風(fēng)量，確認(rèn)非生產(chǎn)模式下凈化空調(diào)系統(tǒng)的運(yùn)行設(shè)定參數(shù)；

采用非生產(chǎn)模式運(yùn)行，再次確認(rèn)潔凈環(huán)境的凈化級(jí)別和參數(shù)，并確認(rèn)生產(chǎn)模式與非生產(chǎn)模式的自動(dòng)切換過程。

經(jīng)過確認(rèn)后的非生產(chǎn)模式可以作為凈化空調(diào)系統(tǒng)的一個(gè)運(yùn)行模式，在生產(chǎn)結(jié)束后，自動(dòng)切入非生產(chǎn)模式運(yùn)行。