1116 MICROBIOLOGICAL EVALUATION OF CLEAN ROOMS AND OTHER CONTROLLED ENVIRONMENTS
                          洁净室微生物评价与其它控制环境
The purpose of this informational chapter is to review the various issues that relate to aseptic processing of bulk drug substances, dosage forms, and in certain cases, medical devices; and to the establishment, maintenance, and control of the microbiological quality of controlled environments.
    此章节报告的目的是综述了涉及到大量药剂的物料、剂型的无菌处理的各种问题，以及在某些情况下的医疗器械；和微生物的质量控制的环境建立、维护和控制。
This chapter includes discussions on (1) the classification of a clean room based on particulate count limits; (2) microbiological evaluation programs for controlled environments; (3) training of personnel; (4) critical factors in design and implementation of a microbiological evaluation program; (5) development of a sampling plan; (6) establishment of microbiological Alert and Action levels; (7) methodologies and instrumentation used for microbiological sampling; (8) media and diluents used; (9) identification of microbial isolates; (10) operational evaluation via media fills; and (11) a glossary of terms. Excluded from this chapter is a discussion of controlled environments for use by licensed pharmacies in the preparation of sterile products for home use, which is covered under Pharmaceutical Compounding—Sterile Preparations 797 There are alternative methods to assess and control the microbiological status of controlled environments for aseptic processing. Numerical values included in this chapter are not intended to represent absolute values or specifications, but are informational. Given the variety of microbiological sampling equipment and methods, one cannot reasonably suggest that the attainment of these values guarantees the needed level of microbial contr
ol or that excursions beyond values in this chapter indicate a loss of control. The improper application of microbiological sampling and analysis may cause significant variability and the potential for inadvertent contamination. Sampling media and devices, and methods indicated in this chapter, are not specifications but only informational.
此章节内讨论的内容包括有：（1）基于微粒子数界限的洁净室级别；（2）受环境控制的微生物评价程序；（3）人员培训；（4）设定的临界因素和执行的微生物评价程序；（5）抽样检验方法的开展；（6）微生物警报和动态级别的建立；（7）用于微生物样品的方法和检测装备；（8）培养基和稀释液的使用；（9）微生物的分离鉴定；（10）使用的培养基的可用性评价；（11）名词解释。尽管一些已获许可的制药公司按着“制药组合—无菌准备<797>，准备了用于无菌产品的环境控制，但此章节的讨论不包括这些。对于无菌处理，可用替代的方法来评估和控制受控环境的微生物的情况 。本章节内包括的数字值并不代表是绝对值或规定值，但可作为参考。这里所提供的不同的微生物取样设备和方法，任何一个都不能合理地表明，获得的这些数值的可得到保证，可获得需要的微生物控制水平，或者远远超过此章节内提出的数值的也表明已失去控制。一些不合适的微生物抽样方法和分析会导致严重的可变性并且会造成因疏忽而造成污染的可能。此章节内提及的取样用的培养基和设备、
方法，并不是规定的方法，但仅供参考。
values翻译A large proportion of sterile products are manufactured by aseptic processing. Because aseptic processing relies on the exclusion of microorganisms from the process stream and the prevention of microorganisms from entering open containers during filling, product bioburden as well as microbial bioburden of the manufacturing environment are important factors relating to the level of sterility assurance of these products.
    经灭菌处理生产出来的大部分无菌产品，由于无菌加工依赖于从生产流程中排除微生物和防止在灌装期间微生物进入开放容器，因此产品的生物负载以及生产环境的微生物负载量是保证这些产品达到无菌水平的重要因素。
Establishment of Clean Room Classifications
洁净室级别的建立
The design and construction of clean rooms and controlled environments are covered in Federal Standard 209E. This standard of air cleanliness is defined by the absolute concentr
ation of airborne particles. Methods used for the assignment of air classification of controlled environments and for monitoring of airborne particulates are included. This federal document only applies to airborne particulates within a controlled environment and is not intended to characterize the viable or nonviable nature of the particles.
联邦标准209E包含覆盖了洁净室的设计与建设以及其环境的监控。此空气洁净度标准是由空气中活动的微粒子的绝对浓度所规定的，包括了对受控环境的空气级别的赋值或对空气微粒的监控所采用的方法。此联邦文件仅用于环境控制的空气微粒的检测，但并不对微粒的活性与非活性作出描述。
The application of Federal Standard 209E to clean rooms and other controlled environments in the pharmaceutical industry has been used by manufacturers of clean rooms to provide a specification for building, commissioning, and maintaining these facilities. However, data available in the pharmaceutical industry provide no scientific agreement on a relationship between the number of nonviable particulates and the concentration of viable microorganisms. The criticality of the number of nonviable particulates in the electronic industry makes the application of Federal Standard 209E a necessity, while the pharmaceutical industry has a greater concern for viable particulates (i.e., microorganisms) rather than total particulates as specified in Federal Standard 209E. A definite concern for counts of total particulates in injectable products exists in the pharmaceutical industry (see Particulate Matter in Injections 788).
洁净室联邦标准209E的使用，以及制药业一直使用的由洁净室的制造商规定的标准建筑物、投运状况和设施维护的其他受控制的环境。然而，在制药业中获得的数据表明非活性微粒数与活性微生物浓度之间的关系，还没有得到科学的统一看法。电子业中的非活性微粒临界值促进了联邦标准209E的应用的必要性，而制药业则更关注对活的微粒子（即微生物）的监控，
而不是对联邦标准209E中所指定的总微粒子数。关于制药业中的注射产品的总微粒子的确切计数见“注射物品的微粒子<788>。”
The rationale that the fewer particulates present in a clean room, the less likely it is that airborne microorganisms will be present is accepted and can provide pharmaceutical manufacturers and builders of clean rooms and other controlled environments with engineering standards in establishing a properly functioning facility.
洁净室中出现的微粒子越少，则可接受的空气中微生物的可能性就越小，并且还能为药品生产企业和洁净室的建造者，以及建立一个达到工程标准可正常运作的设施的受控环境提供依据。
Federal Standard 209E, as applied in the pharmaceutical industry is based on limits of all particles with sizes equal to or larger than 0.5 µm. Table 1 describes Airborne Particulate Cleanliness Classes in Federal Standard 209E as adapted to the pharmaceutical industry. The pharmaceutical industry deals with Class M3.5 and above. Class M1 and M3 relate to the electronic industry and are shown in Table 1 for comparison purposes. It is generally ac
cepted that if fewer particulates are present in an operational clean room or other controlled environment, the microbial count under operational conditions will be less, provided that there are no changes in airflow, temperature, and humidity. Clean rooms are maintained under a state of operational control on the basis of dynamic (operational) data.

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