欧盟GMP附录一对隔离器的最新要求

秘制红烧肉

[color=rgba(0, 0, 0, 0.9)]4.10 The transfer of equipment and materials into and out of the cleanrooms and critical zones is one of the greatest potential sources of contamination. Any activities with the potential to compromise the cleanliness of cleanrooms or the critical zone should be assessed and if they cannot be eliminated, appropriate controls should be implemented.

[color=rgba(0, 0, 0, 0.9)]设备和物料转移进出洁净室和关键区域是最大的可能污染源之一。所有可能导致洁净室或关键区域的洁净度受影响的活动均应进行评估；如果无法消除，则应实施适当的控制。

[color=rgba(0, 0, 0, 0.9)]4.11 The transfer of materials, equipment, and components into the grade A or B areas should be carried out via a unidirectional process. Where possible, items should be sterilised and passed into these areas through double-ended sterilisers (e.g. through a double-door autoclave or depyrogenation oven/tunnel) sealed into the wall. Where sterilisation upon transfer of the items is not possible, a procedure which achieves the same objective of not introducing contamination should be validated and implemented, (e.g. using an effective transfer disinfection process, rapid transfer systems for isolators or, for gaseous or liquid materials, a bacteria-retentive filter). The removal of items from the grade A and B areas (e.g. materials, waste, environmental samples) should be carried out via a separate unidirectional process. If this is not possible, time-based separation of movement (incoming/exiting material) by procedure should be considered and controls applied to avoid potential contamination of incoming items.

[color=rgba(0, 0, 0, 0.9)]物料、设备和组分应单向传送进入A级或B级区。如可能，物品应通过密封在墙内的双向灭菌器（例如，通过双门灭菌器或除热原箱/隧道）灭菌后传入该区域。如果不能进行物品转移灭菌，应验证并采用一种实现相同目的（不引入污染）的规 程（例如，使用有效的转移消毒程序，隔离器的快速转移系统或者，气态或液态物料的细菌截留过滤器）。应通过单独的单向流从A级和B级区移出物品（例如，物料、废物、环境样品）。 如果无法实现，应考虑按规程分时移动（物料进/出），并进行控制以避免对进入的物品的潜 在污染。

[color=rgba(0, 0, 0, 0.9)]4.18 Isolators or RABS, which are different technologies, and the associated processes, should be designed to provide protection through separation of the grade A environment from the environment of the surrounding room. The hazards introduced from entry or removal of items during processing should be minimized and supported by high capability transfer technologies or validated systems that robustly prevent contamination and are appropriate for the respective technology.

[color=rgba(0, 0, 0, 0.9)]隔离器或RABS是不同的技术，及其相关工艺应经过设计，通过将A级环境与周围房间环境分隔来提供保护。应尽量减少工艺过程中物品进出所带来的危害，并通过高性能转移技术或经过验证的系统提供支持，其能有效防止污染且适合于各自的技术。

[color=rgba(0, 0, 0, 0.9)]4.13 For pass-through hatches and airlocks (for material and personnel), the entry and exit doors should not be opened simultaneously. For airlocks leading to the grade A and grade B areas, an interlocking system should be used. For airlocks leading to grade C and D areas, a visual and/or audible warning system should be operated as a minimum. Where required to maintain area segregation, a time delay between the closing and opening of interlocked doors should be established.

[color=rgba(0, 0, 0, 0.9)]（物料和人员用）传递窗和气锁的进出的门不应同时打开。进入A级区和B级区的气锁应使用互锁系统。进入C级和D级区的气锁至少应采用可视和/或声音警报系统。如果需要保持区域分隔，则应规定互锁门打开和关闭之间的时间间隔。

[color=rgba(0, 0, 0, 0.9)]4.14 Cleanrooms should be supplied with a filtered air supply that maintains a positive pressure and/or an airflow relative to the background environment of a lower grade under all operational conditions and should flush the area effectively. Adjacent rooms of different grades should have an air pressure difference of a minimum of 10 Pascals (guidance value). Particular attention should be paid to the protection of the critical zone. The recommendations regarding air supplies and pressures may need to be modified where it is necessary to contain certain materials (e.g. pathogenic, highly toxic or radioactive products or live viral or bacterial materials). The modification may include positively or negatively pressurized airlocks that prevent the hazardous material from contaminating surrounding areas. Decontamination of facilities (e.g. the cleanrooms and the heating, ventilation, and air-conditioning (HVAC) systems) and the treatment of air leaving a clean area, may be necessary for some operations. Where containment requires air to flow into a critical zone, the source of the air should be from an area of the same or higher grade.

[color=rgba(0, 0, 0, 0.9)]洁净室应采用过滤送风，在所有操作条件下保持相对低级别背景环境的正压和/或气流，并应对该区域进行有效吹扫。不同级别的相邻房间应保持至少10Pa压差（指导值）。要特别注意对关键区域的保护。如需要包括特定物料（例如，致病性、高毒性或放射性药品，或活病毒或细菌物料），则可能需要修订建议的送风和压力值。修订可包括正压或负压气锁，保护周围区域不受危害性物料污染。有些操作可能需要进行设施除污染（例如，洁净室和HVAC系统）和洁净区排气处理。如果密闭控制需要有空气流入关键区域，则空气应来自相同或更高级别的区域。

[color=rgba(0, 0, 0, 0.9)]4.16 Indicators of air pressure differences should be fitted between cleanrooms and/or between isolators and their background. Set points and the criticality of air pressure differences should be considered within the CCS. Air pressure differences identified as critical should be continuously monitored and recorded. A warning system should be in place to instantly indicate and warn operators of any failure in the air supply or reduction of air pressure differences (below set limits for those identified as critical). The warning signal should not be overridden without assessment and a procedure should be available to outline the steps to be taken when a warning signal is given. Where alarm delays are set, these should be assessed and justified within the CCS. Other air pressure differences should be monitored and recorded at regular intervals.

[color=rgba(0, 0, 0, 0.9)]洁净室和/或隔离器与其背景之间应安装压差计。应在CCS上考虑压差设置点和关键程度。认为关键的压差点应进行连续监测和记录。应安装报警系统，在送风不合格或压差降低（低于这些认为关键的压差点的设置限度）时立即显示并警示操作人员。未经评估不得消警，应制订程序列出报警时需采取的措施步骤。如果设置了报警延时，则应在CCS内进行评估和论证。其它压差应按指定时间间隔监测和记录。

[color=rgba(0, 0, 0, 0.9)]4.17 Facilities should be designed to permit observation of production activities from outside the grade A and B areas (e.g. through the provision of windows or remote cameras with a full view of the area and processes to allow observation and supervision without entry). This requirement should be considered when designing new facilities or during refurbishment of existing facilities.

[color=rgba(0, 0, 0, 0.9)]设施的设计应可从A级和B级区的外面观察里面的生产活动（例如，通过可全面查看该区域和工艺的窗户或远程摄像，不需要进入即可观察和监督）。在设计新设施或改造现有设施时应考虑此要求。

[color=rgba(0, 0, 0, 0.9)]4.21 The materials used for glove systems (for both isolators and RABS), should be demonstrated to have appropriate mechanical and chemical resistance. The frequency of glove replacement should be defined within the CCS.

4.21 应证明手套系统（用于隔离器和RABS）的材料具有适当的机械和化学抗性。更换手套的频率应在CCS中定义。

[color=rgba(0, 0, 0, 0.9)]i. Isolators:

[color=rgba(0, 0, 0, 0.9)]a. For isolators, leak testing of the glove system should be performed using a methodology demonstrated to be suitable for the task and criticality. The testing should be performed at defined intervals. Generally glove integrity testing should be performed at a minimum frequency of the beginning and end of each batch or campaign. Additional glove integrity testing may be necessary depending on the validated campaign length.

[color=rgba(0, 0, 0, 0.9)]Glove integrity monitoring should include a visual inspection associated with each use and following any manipulation that may affect the integrity of the system.

[color=rgba(0, 0, 0, 0.9)]For manual aseptic processing activities where single unit or small batch sizes are produced, the frequency of integrity verification may be based on other criteria, such as the beginning and end of each manufacturing session.

[color=rgba(0, 0, 0, 0.9)]b. Integrity / leak testing of isolator systems should be performed at defined intervals.

[color=rgba(0, 0, 0, 0.9)]i. 隔离器：

[color=rgba(0, 0, 0, 0.9)]a. 对于隔离器，手套系统的检漏测试所用的方法应经过证明适用其任务和关键程度。 应定期进行测试。通常，手套完整性测试至少应在每个批次或阶段性生产的开始和 结束时进行。根据经过验证的阶段性生产长短，可能需要进行额外的手套完整性测 试。

[color=rgba(0, 0, 0, 0.9)]手套完整性监测应包括与每次使用相关的目视检查，以及可能影响系统完整性的任 何操作后的目视检查。

[color=rgba(0, 0, 0, 0.9)]对于生产单剂量或小批量的手动无菌工艺活动，完整性确认的频率可基于其它标准 （例如每个生产周期的开始和结束）。

[color=rgba(0, 0, 0, 0.9)]b. 应定期进行隔离器系统的完整性/检漏测试。

[color=rgba(0, 0, 0, 0.9)]4.22 Decontamination methods (cleaning and bio-decontamination, and where applicable inactivation for biological materials) should be appropriately defined and controlled. The cleaning process prior to the bio-decontamination step is essential; any residues that remain may inhibit the effectiveness of the decontamination process. Evidence should also be available to demonstrate that the cleaning and bio-decontamination agents used do not have adverse impact on the product produced within the RABS or isolator.

[color=rgba(0, 0, 0, 0.9)]应适当地规定和控制净化方法（清洁和生物净化，以及适用时生物材料的灭活）。生物净化步骤之前的清洁是至关重要的；任何残留物可能会抑制净化工艺的有效性。还应提供证据证明使用的清洁和生物净化剂不会对RABS或隔离器内生产的产品产生不良影响。

[color=rgba(0, 0, 0, 0.9)]i. For isolators

[color=rgba(0, 0, 0, 0.9)]The bio-decontamination process of the interior should be automated, validated and controlled within defined cycle parameters and should include a sporicidal agent in a suitable form (e.g. gaseous or vaporized form). Gloves should be appropriately extended with fingers separated to ensure contact with the agent. Methods used (cleaning and sporicidal bio-decontamination) should render the interior surfaces and critical zone of the isolator free from viable microorganisms.

[color=rgba(0, 0, 0, 0.9)]i. 对于隔离器

[color=rgba(0, 0, 0, 0.9)]内部的生物净化过程应是自动化的、经过验证的并控制在规定的周期参数范围内，并应包括适当形式的杀孢子剂（例如气态或汽化形式）。手套应适当伸展，手指分开以 确保与杀孢子剂接触。所用方法（清洁和杀孢子生物净化）应使隔离器的内部表面和关键区域没有活微生物。

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