GMP洁净室HVAC系统，是否可以在夜间关闭？

Can the ventilation of GMP clean rooms be switched off overnight?

GMP洁净室的通风系统是否可以在夜间关闭？

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.

洁净室的通风系统耗费巨大能源，特别是通风系统的风扇、夏天致冷和除湿以及冬天加热和加湿用蒸汽。因此，一直就有这个问题：公司是否可以在晚上或不用的时候关闭房间的通风，以节约能源？

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.

一般不建议完全关闭通风系统，事实上最好不要这样做。设施、压差条件、微生物，在此期间所有东西都有可能失控。这会让之后的恢复GMP符合状态所需的措施非常复杂，因为每次都要做再确认，来达到正常的GMP符合状态。

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，可以降低通风系统的频率（通过减少通风系统的频率来减少换气量），已经有一些公司在这么做了。但是，在重新使用洁净室之前还是必须达到GMP符合状态，并且该程序必须经过验证。

For this purpose the following points must be observed:

为此必须要观察以下几点：

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.

降低通风系统的频率只能达到一个指定的程度，以确保维持特定个例中的洁净室的特定限度。在每个个例中，这些运行状态下的和降低频率状态下的限度必须定义，其中包括允许的最小和最大值，例如洁净室级别（粒子数和相关的粒径）、产品特定的值（温度、相对湿度）、压差条件（房间之间的压差）。注意，在降低频率的模式下的值的选择必须使得设施在生产开始之前的规定时间内（时间计划结合在其中）达到GMP符合状态。此状态取决于不同的参数，例如建筑材料和系统性能等。应在所有的时间内都维持压差条件，这表示不允许气流逆向。

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.

还有，建议安装一个独立的洁净室监测系统，这样可以连续监测并记录上述洁净室指定参数。这样，所关注的区域的条件应可以在任何时间进行监测和记录。如果有偏差发生（达到限度），在个案中有可能具备测量和通风系统控制技术，进行相关调整。

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.

在降低风机频率时，要注意确保没有非预期的外来干扰影响，例如，人员进入。这种情况建议使用相应的人员进出控制。如果使用的是电子锁系统，进出权限可以与上述时间计划相关联，以及与独立的洁净室监测系统相关联，这样，进出授权必须要符合预定的要求。

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.

原则上来说，两种状态都必须先确认，然后进行定期再确认。通常，常规运行状态下的测量，例如设备完全失效情形下恢复时间测量是必须要进行的。如果存在有洁净室监测系统，程序经过验证的话，原则上不需要---如上所述---在降低通风频率后重新开始运行时进行进一步测量。特别要注意的是重新开始运行时的程序，因为，比如气流方向短时逆向是有可能发生的。

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.

总体来说，根据运行模式和当班模式的不同，大概能节约30%左右的能源，但可能会被额外的投资成本所抵消。

WHO 非无菌空调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

非无菌制剂暖通空调GMP指南：第二部分——HVAC系统的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.

建议HVAC系统持续运行。当决定在特定时间使用节能模式或选择关闭部分AHU，如夜间、周末或很长时间，应关注确保物料和产品不受影响。这种情况下，应充分记录该决定、规程和记录，并包括风险评估、标准操作规程（SOP）、记录和验证。这包括风机处理单元（AHU）的开启和关闭顺序的规程和记录。

GB 50457-2019

医药工业洁净厂房设计标准

9.2.15 无菌药品生产的洁净区净化空气调节系统应保持连续运行，维持相应的洁净级别。在非生产期间，净化空气调节系统可以采用低频运行等模式，但仍应保持医药洁净室相应级别和对周围低级别洁净区的正压。因故停机再次开启空气净化系统，应当进行必要的测试以确认满足其规定的洁净度级别要求。

GB 50457-2019

医药工业洁净厂房设计标准

条文说明

“在非生产时间，由于洁净室内主要污染源(操作人员)的撤离，室内的发尘量大大降低，为了节省运行费用，在满足洁净级别和正压的前提条件下，可以采用降低空气净化系统风量方法。”

“对于无菌生产核心区建议维持正常生产运行时的关键参数，对于其他医药洁净室需维持的正压值应根据产品特性、生产运行时的情况，QA部门质量验证的结果及企业自身生产管理水平而定。”

新版GMP指南（2023版）

厂房设施和设备分册 

3.6.2.4 节能模式下的风量平衡

非生产模式作为净化空调系统的一个运行模式，应保持连续运行，维持相应的净化级别和对周围区域的正压，维持良好的气流方向。净化空调系统的送风量变化、不同洁净区域的风量变化、洁净室风量的变化，都需要净化空调系统来实现机组风量、区域风量及洁净室风量的再平衡。

• 无菌区风量可维持规范范围内的下限运行。

• 其他洁净区可以较大幅度降低运行风量。

  
  

说明：由于净化空调系统送风管道内压力的差异，不同区域风量变化存在差异，当系统总风量降低时，不同区域风量的降低存在区别，净化空调系统的风量平衡就会被破坏，从而造成洁净室的压力梯度紊乱。同时，为维持区域正压，净化空调系统的新风量应依据正压需要进行调整。

净化空调系统生产模式动态工艺运行、非生产模式运行都需要再平衡系统风量区域的风量。

实施方式：

• 首先完成非生产模式下净化空调系统的系统送风量、洁净区域送风量的测算设置好非生产模式下的需求风量；

• 净化空调系统采用设置好的非生产模式风量运行，进行相关的环境参数测试并通过测试的参数对风量进行调整；

• 通过测试确认在满足环境净化级别及正压需求下的各风量，确认非生产模式下净化空调系统的运行设定参数；

• 采用非生产模式运行，再次确认洁净环境的净化级别和参数，并确认生产模式与非生产模式的自动切换过程。

经过确认后的非生产模式可以作为净化空调系统的一个运行模式，在生产结束后，自动切入非生产模式运行。