国内外防止交叉污染的药品共线生产质量管理法规和监管模式的比较

Comparison of National and International Quality Management Regulations and Regulatory Modes for Collinear Production of Drugs to Prevent Cross Contamination

交叉污染是指不同原料、辅料及产品之间发生的相互污染。当使用共用设施设备生产不同药品时,潜在的交叉污染就成为了一项极其关键的风险管控问题。近年来,全球许多药品监管机构或组织针对共用设施、共线生产质量管理以及产生的交叉污染,更新发布了相关法规和指南。但目前,共用设施下的交叉污染及相关缺陷项目(如多产品共线评估、清洁验证有效性等)依然高频出现在其发布的GMP检查不符合项中。本文从药品共线生产质量管理基本原则,即法律法规要求、药品上市许可持有人主责、产品的生命周期和清洁验证的生命周期,以及质量风险管理等方面,论述了全球不同药品监管机构或组织对药品共线生产质量管理和交叉污染的监管要求,并汇总形成了相应的管理流程和方法,以供相关监管人员和药品生产企业人员参考。

Cross contamination is the mutual contamination of different raw materials,excipients and finished products.Potential cross contamination is a very critical risk control issue when different drug products are manufactured in shared facilities.In recent years,different regulatory authorities or organizations have issued and updated the regulations and guidelines against shared facilities,collinear production management and cross contamination.Cross contamination in shared facilities and related defect items(such as collinear production assessment and cleaning validation)still frequently appear in the Good Manufacturing Practice(GMP)non-conformance items issued by many drug regulatory agencies or organizations around the world.This paper discussed the regulatory requirements of different regulatory authorities or organizations on cross contamination and collinear production management mainly from the following aspects:requirements of laws and regulations,drug marketing authorization holder’s principle responsibility,product lifecycle,cleaning validation lifecycle and quality risk management.Besides,it also summarized relevant management procedures and methods,expecting to provide reference for relevant regulators and personnel of drug-manufacturing enterprises.