1、 World Health OrganizationWHO Technical Report Series, No. 961, 2011WHO技术报告丛书961，2011Annex 6WHO good manufacturing practices for sterile pharmaceutical products附件6无菌药品良好生产规范IntroductionFollowing implementation of these WHO good manufacturing practices (GMP) guidelines (1) within the context of the W
2、HO Prequalication of Medicines Programme, clarifying, editorial modications have been proposed. These changes were adopted for maintenance purposes. In order to ease reading the full guideline has been reproduced again as an Annex to the current report of the WHO Expert Committee on Specications for
3、 Pharmaceutical Preparations.引言以下WHO药品质量管理规范（GMP）（1）指南在WHO预审药物设计、阐明、编辑修改中已经被提出。这些变更的应用以维护的目的。为了便于阅读，整篇指南已被重新编制并作为WHO药品标准专家委员会报告的一个附件。WHO good manufacturing practices for sterile pharmaceutical productsWHO无菌药品良好生产规范1. GENERAL CONSIDERATIONS31 总则32. QUALITY CONTROL32 质量控制33. SANITATION43卫生44. MANUFACT
4、URE OF STERILE PREPARATIONS54 无菌产品的生产55. STERILIZATION195.灭菌196. TERMINAL STERILIZATION206. 最终灭菌207. ASEPTIC PROCESSING AND STERILIZATION BY LTRATION247. 无菌操作和过滤灭菌248. ISOLATOR TECHNOLOGY268. 隔离技术269. BLOW/LL/SEAL TECHNOLOGY279. 吹/灌/封技术2710. PERSONNEL2810. 人员2811. PREMISES3011.厂房3012. EQUIPMENT3312.
5、 设备3313. FINISHING OF STERILE PRODUCTS3413. 无菌产品完成341. General considerations1 总则1.1 The production of sterile preparations should be carried out in clean areas, entry to which should be through airlocks for personnel and/or for equipment and materials. Clean areas should be maintained to an appropr
6、iate standard of cleanliness and supplied with air that has passed through lters of the required efciency. 1.1 无菌产品的生产应在洁净区进行，人员和/或设备和物料进入洁净区应通过气闸室进入。洁净区应保持适当的洁净度标准并提供经过有效的过滤的空气。1.2 The various operations of component preparation (such as those involving containers and closures), product preparation
7、, lling and sterilization should be carried out in separate areas within the clean area. These areas are classied into four grades (see section 4).1.2 组件的准备（如相关的容器和密闭包装），产品的制备、灌装和灭菌操作应在洁净区内分区域进行。这些洁净区分为四个等级（见第4节）。1.3 Manufacturing operations are divided here into two categories:rst, those where the
8、product is terminally sterilized; and second, those which are conducted aseptically at some or all stages.1.3 生产操作在此可以划分为两类：第一，仅在最后阶段灭菌的产品；第二，部分或全部工序采用无菌生产工艺的产品。2. Quality control2 质量控制2.1 The sterility test applied to the nished product should only be regarded as the last in a series of control mea
9、sures by which sterility is assured. The test should be validated for the product(s) concerned.2.1成品的无菌检测仅作为一系列确保无菌度的控制措施的最后一步。相关产品的无菌度检测应进行验证。2.2 Samples taken for sterility testing should be representative of the whole of the batch but should, in particular, include samples taken from parts of the
10、 batch considered to be most at risk of contamination, for example: for products that have been lled aseptically, samples should include containers lled at the beginning and end of the batch and after any signicant interruption of work; for products that have been heat sterilized in their nal contai
11、ners, consideration should be given to taking samples from that part of the load that is potentially the coolest.2.2 无菌度检测取样的样品应能代表整个批次，并且应包括最容易受到污染风险的部位的样品。l 无菌灌装的产品，取样应包括灌装前、灌装后和有明显中断的时候。l 仅在在最后步骤进行高温灭菌的产品，应考虑从最凉处取样。2.3 The sterility of the nished product is assured by validation of the sterilizat
12、ion cycle in the case of terminally sterilized products, and by “media simulation” or “media ll” runs for aseptically processed products. Batch-processing records and, in the case of aseptic processing, environmental quality records, should be examined in conjunction with the results of the sterilit
13、y tests. The sterility test procedure should be validated for a given product. Pharmacopoeial methods should be used for the validation and performance of the sterility test. In those cases where parametric release has been authorized in place of sterility testing special attention should be paid to
14、 the validation and the monitoring of the entire manufacturing process.2.3 最终产品的无菌度检测，如果是仅在最后步骤灭菌的产品，应确保整个灭菌周期的验证，如果是无菌工艺生产的产品，应确保进行了 “培养基模拟”和“培养基灌装”。批生产记录和环境质量记录（无菌生产过程中的）应结合无菌度检测结果进行检查。对给出的产品应进行无菌度检测验证。验证和无菌度检测应使用药典的方法。如果授权使用参数放行取代无菌度检测，应注意特别关注验证和整个生产过程的监测。2.4 For injectable products the water for
15、 injection and the intermediate, if appropriate, and nished products should be monitored for endotoxins, using an established pharmacopoeial method that has been validated for each type of product. For large-volume infusion solutions, such monitoring of water or intermediates should always be done, in addition to any tests required by an approved monograph for the nished product. When a sample fails a test, the cause of the failure should be investigated and necessary action should be taken. Alternative methods to those in the pharmacopoeias may be used if the
