USP30_1208-无菌实验----隔离系统的验证(摘译).doc

USP30 NF25 1208 STERILITY TESTING VALIDATION OF ISOLATOR SYSTEMS 无菌实验无菌实验 隔离系统的验证隔离系统的验证 摘译可供全自动无菌检查系统参考的部分 Performance Qualifications PQ 性能确认 The PQ phase verifies that the system is functioning in compliance with its operator requirement specifications At the completion of the PQ phase the efficacy of the decontamination cycle and if appropriate the adequacy of decontaminating chemical venting are verified All PQ data are adequately summarized reviewed and archived PQ 阶段要确认的是系统的运行功能符合操作人员所要求的标准 PQ 完成时 净化循环的效验以及在适当的情况下化学物品通风净化的适用性被确认 所有 的 PQ 数据应该进行充分地总结 回顾及归档 Cleaning Verification In general cleaning is not critical for sterility testing applications However residual products are a concern in multiproduct testing particularly for aggressive antimicrobial agents because these materials could interfere with the ability of subsequent tests to detect low levels of contamination in the product 清洁确认 一般而言 清洁对于无菌检测的实施并不关键 然而 在多批产品 检测中残留产品是一个值得注意的问题 特别是具有强烈抑菌性的试剂 这些 物质可能影响到后续检测实验对产品中低水平污染的检测能力 Concerns about contamination with the product are heightened when it is an inherently antimicrobial powder because powders are more readily disseminated Cleaning to a level at which no visible contamination is present is adequate for sterility test isolator systems and is a suitable operator requirement specification The cleaning method frequency equipment and materials used to clean the isolator are documented 如果产品本身是一种抑菌性的粉末 由于粉末容易散布 那么应该提高对产品 带来的污染的关注 清洁程度达到无肉眼可见污染物的水平 对于无菌检测隔 离系统是足够的 也适合于操作规范要求 应用于隔离系统的清洁方法 清洁 频次 所使用的设备和材料都应有文件记录 Decontamination Validation The interior surfaces of the isolator the equipment within the isolator and the materials brought into the isolator are treated to eliminate all bioburden 净化验证 对隔离器内表面 隔离器内部设备以及被携带入隔离器的物质都 应进行处理以清除所有的生物负载 The decontamination methods used to treat isolators test articles and sterility testing supplies are capable of reproducibly yielding greater than a three log reduction against highly resistant biological indicators see Biological Indicators for Sterilization 1035 as verified by the fraction negative or total kill analysis methods 用于处理隔离器 检测物品以及无菌性检测供应品的净化方法对于高抗性的生 物指示剂能够产生超过 3 个对数值的削减作用 见 Biological Indicators for Sterilization 1035 as verified by the fraction negative or total kill analysis methods 这已通过部分阴性或全杀灭分析方法确认 Total kill analysis studies are suitable for BIs with a population of 103 spores per unit while fraction negative studies are suitable for BIs with a population of 105 or greater 全杀灭分析研究适用于数量为 103个孢子每单位的 BIs 而 fraction negative studies 适用于 105或更高 A sufficient number of BIs are used to prove statistical reproducibility and adequate distribution of the decontaminating agent Particular attention is given to areas that pose problems relative to the concentration of the agent A larger number of BIs may be required in isolators that are heavily loaded with equipment and materials The ability of the process to reproducibly deliver a greater than three log kill is confirmed in three consecutive validation studies 足够的 BIs 数量用于证明数据的重复性以及净化剂足够的分布 应特别关 注由于试剂浓度引起问题的区域 装备了大量设备和物料的隔离器可能需要更 大量的 BIs 三次连续验证研究确定了重复产生一个大于 three log 杀灭过程的 能力 The operator establishes a frequency for re decontamination 1S USP30 of the isolator The frequency may be as short as a few days or as long as several weeks depending on the sterility maintenance effort see Maintenance of Asepsis within the Isolator Environment 操作员应设立隔离器重复净化的频次 根据灭菌的持续效果其频次可以短 至几天也可以长至几周 Change to read PACKAGE INTEGRITY VERIFICATION 包装完整性验证 Some materials are adversely affected by decontaminating agents which can result in inhibition of microbial growth Of concern are the penetration of decontaminating agents into product containers accessory supplies such as filter sets and tubing or any material that could come in contact with product media or dilution fluids used in the sterility test It is the responsibility of the operator to verify that containers media and supplies are unaffected by the decontamination process 净化剂对某些材料的作用是有害的 这会抑制微生物的生长 值得关注的是净 化剂对产品包装的穿透 诸如过滤装置和管道等附件物品 以及任何可能与无 菌检测用产品 培养基和稀释掖接触的材料 操作人员有责任确定容器 培养 基和配备物品不受净化程序的影响 Screw capped tubes bottles or vials sealed with rubber stoppers and crimp overseals have proven very resistant to the penetration of commonly used decontaminating agents Wrapping materials in metal foil or placing them in a sealed container will prevent contact with the decontaminating agent however these procedures may also result in some surfaces not being decontaminated In some cases the use of shorter duration decontamination cycles and reduced concentrations may be necessary to minimize penetration of decontaminating agents into the package or container Cycles that provide a less than three log kill of resistant BIs may be acceptable provided microbiological analysis of the environment proves that the isolator s are free of recoverable bioburden 在一般情况下 使用带螺纹帽试管 瓶子 采用橡胶塞的小瓶以及多重折叠封 口的方法都被证明对穿透有很好的阻抗 采用金属薄膜包装材料或将物品放入 密封容器中可以避免其与净化剂接触 然而这样也可能造成某些表面无法净化 到 某些情况下 采用短时间的净化循环以及降低净化剂浓度可以减少净化剂 穿透包装或容器中 In many cases the operator will choose to treat the surfaces of product containers under test with the decontaminating agent in order to minimize the likelihood of bioburden entering the isolator It is the responsibility of the operator to demonstrate via validation studies that exposure of product containers to the decontaminating agent does not adversely affect the ability of the sterility test to detect low levels of contamination within these test articles It is suggested that the ability of the package to resist contamination be examined using both chemical and microbiological test procedures 在多数情况下 操作员会采用净化剂处理通过测验的产品容器的表面来降低微 生物进入隔离器的可能性 操作员有责任通过验证研究来论证产品包装物接触 净化剂不会影响到无菌检测中对这些物品内低水平