WHO草案建立清洁验证残留限度的考量要点

1、WHO草案：建立清洁验证残留限度的考量要点使用共用设施生产时清洁验证中为识别污染风险而建立残留限度的不同方法一包括HBEL考量要点1. Introduction and background 概述与背景42. Scope 范围 53. Glossary 术语 54. Traditional approach 传统方法65. New approaches 新方法 65.1 Documentation 文件记录 75.2 Equipment 设备 75.3 Detergents and solvents 清洁剂和溶剂75.4 Sampling 取样 85.5 Cleanability studie

2、s 清洁能力研究 85.6 Risk assessment and risk control 风险评估和风险控制95.7 Technical and organizational controls 技术和组织控制措施95.8 Health Based Exposure Limits (HBELs) setting 基于健康的暴露限 度(HBEL)设置 95.9 Acceptance criteria 可接受标准 11根据治疗用途分组 5.10Grouping by therapeutic use125.11Analytical procedures 分析方法125.12Data integri

3、ty数据完幣性135.13Cleaning validation end cleaningverification清洁验证和清洁核查135.14Visually clean 目视清洁 145.15Cleaning verification and processcapability清洁核查和工艺能力145.16Personnel 人员145.17Quality metrics and performance indicators 质量量度和性能指标145.18Life cycle生命周期 15References参考文献161.Introduction and background 概述与背景

4、The World Health Organization (WHO) has published theguideline entitled Good Manufacturing Practices forpharmaceutical products: main principles in the WHO TechnicalReport Series, No. 986, Annex 乙 2014 (1).WHO在2014年TRS 986附录2发布了题为“药品GMP：主则”的 指 南。.The WHO Supplementary guidelines on good manufacturin

5、g practice: validation were published in 2006 end were supported by seven appe ndices .In 2019, the WHO Good menu facturing practices: guidelines on validation (2) were updated and republished Some of the seven appendices were also individually updated between 2013 and 2019:WHO的“GMP补充指南：验证”于2006年发布，

6、有7个附录作为 支持文件。2019年，WHO的“GMP：验证指南”进行了更新并重新 发布。7个附录中有几个分别于2013年和2019年进行了更新。 Appendix 1. Validation of heating, ventilation end air conditioning systems (3).附录HVAC系统的验证Appendix 2. Validation of water systems for pharmaceutical use (4).附录2：制药用水系统的验证Appendix 3. Cleaning validation (5).:清洁验证3附录.Appendix 4

7、. Analytical procedure validation (6).附录4：分析方法验证Appendix 5. Validation of computerized systems (7).附录5：计算机化系统的验证Appendix 6. Guidelines on qualification (8).附录6：确认指南Appe ndix 7. Non -sterile process validation (9).附录7：非无菌工艺验证Appendix 3, relating to cleaning validation (5), was not updated at that tim

8、e .Its revisi or however; was discussed during an informal consultation held in Geneva, Switzerland, in July 2019 The outcome of the discussion was presentedtoPharmaceuticalSpecifications for Expert Committee on the WHOProducts (ECSPP) meeting in October 2019. The ECSPP ack no wledged the importance

9、 of harm on ization in regulatory expectations with regards to cleaning validation approaches The Expert Committee recommended a “ Points to consider document be prepared in order to describe the current approaches used in cleaning validation and highlighting the complexities invoIved in order to es

10、tablish a common understand! ng. A revision of the re leva nt appe ndix would the n be considered by the Expert Committee thereafter.与清洁验证有关的附录3当时未更新。但在2019年7月瑞士 H内瓦 的非正式沟通期间对其修订进行了讨论，讨论结果于2019年10月提 交给了 ECSPP会议。ECSPP T解清洁验证方法的监管要求保持一致的 重要性，因此专家委员会建立起草一份“考量要点”文件，以阐述当 前清洁验证中所用方法，强调其所涉及的复杂性，以求对此达成共识。 鉴

11、于此，专家委员会随后考虑要对相关附录进行修订。Many menufacturers produce products in multi-product facilities where there is arisk of contamination end cross-contamination. Some of the mein principles of good man ufacturing prac tices (GMP) in elude the preventi on of mix-ups and the prevent!on of contamination and cross-

12、contamination. It is therefore important that and contamination for risks all identify menufacturerscross-contamination and identify and implement the appropriatecontrols to mitigate these risks These controls include, forexample, technicel and organizational measures, dedicated facilities, closed s

13、ystems, cleaning and cleaning validation.许多生产商会在多产品设施中生产多个产品，这时就会存在污染和交 叉污染的风险。优良生产规范（GMP）的一些重要原则包括有防止混 淆和防止污染与交叉污染，因此生产商识别所有污染与交叉污染，识 别实施适当控制措施以降低这些风险就非常重要。这些控制措施包括 例如技术和组织措施、使用专用设施、封闭系统、清洁和清洁验证。2. Scope 范围The scope of this document is to discuss the differentpossible approaches - including methods

14、 that account for pharmacological and toxicological data （Health-Based ExposureLimits HBEL） - that could be used when establishing safeCarryover limits when manufacturing in shared facilities.木文件的范围是讨论在为使用共用设施生产建立安全残留限度时可 采用的不同方法一包括应用药理学和毒理学数据（基于健康的暴露限（HBEL）的方法。This document further provides clarifi

15、cation on cleaning validation end presents points to consider when reviewing the invalidation cleaning to approaches and status current multiproduct facilities. It reflects the current regulatory guida nee and expectations .It further focuses on approaches where HBELs setting need to be considered in cleaning and cleaning validation approaches木文还对清洁验证进行了澄清，提出回顾多产品设施中当前清洁验证 状态和方法的考量要点。它反映了当前的监管指南和要求。其中还关 注了清洁和清洁验证方法中需要考虑HBEL时的方法。The principles should be applied inmanufacturingfacilities