USP30_1208-无菌实验----隔离系统的验证(摘译)

USP30-NF25
（1208）STERILITY TESTING— VALIDATION OF ISOLATOR SYSTEMS
无菌实验----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-decontamination1S (U SP30)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 w ithin 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污染的检测。

建议对包装抗污染的能力应该采用化学和微生物的检测程序。

Bacteriostasis and fungistasis validation tests must be performed using actual test articles that have been exposed to all phases of the decontamination
process (see Sterility Tests 71). This applies to medicinal device packages as well as pharmaceutical container and closure systems.
Validation studies determine whether both sterility test media and environmental control media meet the requirements for Gro wth Promotion Test
of Aerobes, Anaerobes, and Fungi under Sterility Tests 71 .
抗细菌和抗真菌验证检测的执行必须采用确实暴露于净化程序全过程的检测物品。

（见<71>无菌性检测）这应用于医学设备包装以及药物容器和包装系统。

验证研究是确定无菌检测培养基和环境控制培养基是否都符合<71>无菌检测中需氧菌、厌氧菌和真菌的促生长实验的要求。