EU GMP附录1（2022版）公用系统要求要点汇总

The nature and extent of controls applied to utility systems should be commensurate with the risk to product quality associated with the utility. The impact should be determined via a risk assessment and documented as part of the CCS. 作为CCS的一部分，应通过风险评估确定公用系统对产品质量的影响程度。

In general, higher risk utilities are those that:
i. Directly contact product e.g., water for washing and rinsing, gases and steam for sterilisation. 和产品直接接触的设备部件/容器密封件/除菌过滤器等清洗用水，灭菌用蒸汽和压缩空气，都属于高风险的介质。
ii. Contact materials that will ultimately become part of the product.比如顶空充氮的制剂产品，氮气制备系统就属于高风险。
iii. Contact surfaces that come into contact with the product.
iv. Otherwise directly impact the product.

Results for critical parameters and critical quality attributes of high risk utilities should be subject to regular trend analysis to ensure that system capabilities remain appropriate. 对于被定义为高风险的公用设施，其运行的关键参数、提供介质的关键质量属性应作趋势分析。

水系统：

Water flow should remain turbulent through the pipes in water distribution systems to minimize the risk of microbial adhesion, and subsequent biofilm formation. The flow rate should be established during qualification and be routinely monitored. 通过PQ确定流速合格范围，并日常监测流速。（通常设计流速不低于1m/s）

Water for injections (WFI) should be produced from water meeting specifications that have
been defined during the qualification process, stored and distributed in a manner which minimizes the risk of microbial growth (e.g., by constant circulation at a temperature above 70°C). WFI应不低于70℃保温循环。

Where 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 condensationformation on the filter (e.g., by heating). 如果WFI储罐安装了呼吸器，则其不应引入污染源，使用前/后应进行完整性测试，应通过保温措施避免其产生冷凝水。

To minimize the risk of biofilm formation, sterilisation, disinfection or regeneration of water systems should be carried out according to a predetermined schedule and as a remedial action following out-of-limit or specification results. 水系统应定期或者当水质出现异常时进行灭菌、消毒、再生处理，以控制微生物膜的风险。Disinfection of a water system with chemicals should be followed by a validated rinsing/flushing procedure. Water should be tested after disinfection/regeneration.使用化学试剂对水系统进行消毒后应使用验证过的程序进行冲洗，并且应取样检测。Chemical testing results should be approved before the water system is returned to use and microbiological/endotoxin results verified to be within specification and approved before batches manufactured using water from the system are considered for certification/release. 水系统投入使用前应确认化学检测项目均合格，产品批次放行前应确认微生物和内毒素检测结果均合格。

Alert levelsshould be based on the initial qualification data and thereafter periodically reassessed on data obtained during subsequent re-qualifications, routine monitoring, and investigations. 首次PQ后应建立警戒限，并且随着数据积累定期评估警戒限的合理性。Sampling programmes should reflect the requirements of the CCS and should include all outlets and points of use, at a specified interval, to ensure that representative water samples are obtained for analysis on a regular basis. CCS应输出水系统的取样监控策略，取样点应包括所有出水口和使用点。Sample plans should be based on the qualification data, should consider the potential worst case sampling locations and should ensure that at least one representative sample is included every day of the water that is used for manufacturing processes. 取样计划应基于PQ结果，包括最差点，日常生产时，每天至少应对其中一个代表性点位进行取样。
Alert level excursions should be documented and reviewed, and include an investigation to determine whether the excursion is a single (isolated) event or if results are indicative of an adverse trend or system deterioration. Each action limit excursion should be investigated to determine then probable root causes and any potential impact on the quality of products and manufacturing processes as a result of the use of the water. 对于超警戒限事件，应调查确认是偶发事件还是系统性恶化。对于超行动限事件，应调查确认根本原因，进行影响评估。

WFI systems should include continuous monitoring systems such as Total Organic Carbon
(TOC) and conductivity, as these may give a better indication of overall system performance than discrete sampling. Sensor locations should be based on risk. WFI系统应在线监测TOC和电导率，监测点位应基于评估。

灭菌用蒸汽：

Steam condensateshould meet the current monograph for WFI of the relevant Pharmacopeia (microbial testing is not mandatory for steam condensate). A suitable sampling schedule should be in place to ensure that representative pure steam is obtained for analysis on a regular basis. Other aspects of the quality of pure steam used for sterilisation should be assessed periodically against validated parameters. These parameters should include the following (unless otherwise justified): non-condensable gases, dryness value(dryness fraction) and superheat. 纯蒸汽应定期进行取样检测，冷凝后的纯蒸汽应达到WFI的质量标准（微生物限度非强制），还包括非凝结性气体、干燥度、过热度这几个指标。

气体和真空系统：

Gases that come in direct contact with the product/primary container surfaces should be of appropriate chemical, particulate and microbial quality. All relevant parameters, including oil and water content, should be specified, taking into account the use and type of the gas, the design of the gas generation system and, where applicable, comply with the current monograph of the relevant Pharmacopeia or the product quality requirement. 与产品或内包材直接接触的气体，化学性质、颗粒、微生物应符合适当的质量标准。应基于其用途、气体类型、制备系统的设计，制定含油量、含水量的质量标准，以满足药典或产品质量的要求。

Gases used in aseptic processes should be filtered through a sterilising grade filter (with a
nominal pore size of a maximum of 0.22 µm) at the point of use. Where the filter is used on a batch basis (e.g., for filtration of gas used for overlay of aseptically filled products) or as product vessel vent filter, then the filter should be integrity tested and the results reviewed as part of the batch certification/release process. 无菌工艺中使用的气体，在使用点应安装除菌过滤器。比如无菌灌装后的产品需要顶空充氮气，或装有产品的容器安装有呼吸器，则产品批次放行时应确认该过滤器在本批生产结束后的完整性测试合格。Any transfer pipework or tubing that is located after the final sterilizing grade filter should be sterilised. When gases are used in the process, microbial monitoring of the gas should be performed periodically at the point of use. 在终端除菌过滤器的后端安装的输送管路，在生产前应经过灭菌。应定期从使用点取样检测工艺气体的微生物负载。

Where backflow from vacuum or pressure systems poses a potential risk to the product, there should be mechanism(s) to prevent backflow when the vacuum or pressure system is shut off. 真空或者压力系统应当设置防止系统关闭时发生气体倒流的装置（比如止回阀），避免对产品造成污染。

供暖、制冷、液压系统：