EMA在共用设施中生产不同药品使用风险辨识建立健康暴露限度指南.pdf

1、 page 1 of 16 北京齐力佳咨询 提供 2015 20 November 2014 EMA/CHMP/CVMP/SWP/169430/2012 Committee for Medicinal Products for Human Use(CHMP)Committee for Medicinal Products for Veterinary Use(CVMP)2014年11月20日 EMA/CHMP/CVMP/SWP/169430/2012 欧洲药品管理局人用医药产品委员会 欧洲药品管理局兽用医药产品委员会 Guideline on setting health based expo

2、sure limits for use in risk identification in the manufacture of different medicinal products in shared facilities 在共用设施在共用设施中中生产不同药品使用风险辨识建立健康暴露限度指南生产不同药品使用风险辨识建立健康暴露限度指南 Draft Agreed by Safety Working Party 安全工作组同意草案 December 2012 2012年12月 Adoption by CVMP for release for consultation 兽用药委员会采用发放征求

3、意见 November 2012 2012年11月 Adoption by CHMP for release for consultation 人用药委员会采用发放征求意见 13 December 2012 2012年12月13日 End of consultation(deadline for comments)结束征求意见（意见截止期）30 June 2013 2013年6月30日 Adoption by CVMP 兽用药委会采纳 11 September 2014 2014年9月11日 Adopted by Safety Working Party 安全工作组织采纳 October 20

4、14 2014年10月 Adoption by CHMP 人用药委员会采纳 20 November 2014 2014年11月20日 Date for coming into effect 生效日期 01 June 2015 2015年6月 Keywords 关键词关键词 Shared facilities,risk identification,exposure limits,toxicological data,residual active substances,PDE.共享设施，风险辨识共享设施，风险辨识，暴露限度，暴露限度，毒理学数据，残留活性物质，每日毒理学数据，残留活性物质，每日

5、允许暴露量允许暴露量 page 2 of 16 北京齐力佳咨询 提供 2015 Guideline on setting health based exposure limits for use in risk identification in the manufacture of different medicinal products in shared facilities 在共用设施在共用设施中中生产不同药品使用风险辨识建立健康暴露限度指南生产不同药品使用风险辨识建立健康暴露限度指南 Table of contents 目录目录 Executive summary 概要概要.3 1.

6、Introduction(background)介绍（背景）介绍（背景）.3 2.Scope 范围范围.3 3.Legal basis 法律基础法律基础.4 4.Determination of health based exposure limits 确定基于健康暴露限度确定基于健康暴露限度.4 4.1 Calculation of a Permitted Daily Exposure(PDE)PDE（每日允许暴露量）计算.4 4.2 Use of clinical data临床数据使用.6 4.3 Extrapolation to other routes of administratio

7、n 其他给药途径推断.6 5.Specific considerations 具体注意事项具体注意事项.7 6.Reporting of the PDE determination strategy.PDE确定策略报告确定策略报告.9 7.Implementation 实施实施.9 8.Definitions 定义定义.9 References:参考文献参考文献.10 Annex 附件附件.11 page 3 of 16 北京齐力佳咨询 提供 2015 Executive summary 概要概要 When different medicinal products are produced i

8、n shared facilities,the potential for cross-contamination is a concern.Medicinal products provide a benefit to the intended patient or target animal;however as a cross contaminant,they provide no benefit to the patient or target animal and may even pose a risk.Hence,the presence of such contaminants

9、 should be managed according to the risk posed which in turn are related to levels that can be considered safe for all populations.To this end,health based limits through the derivation of a safe threshold value should be employed to identify the risks posed.The derivation of such a threshold value(

10、e.g.permitted daily exposure(PDE)or threshold of toxicological concern(TTC)should be the result of a structured scientific evaluation of all available pharmacological and toxicological data including both non-clinical and clinical data.Deviation from the main approach highlighted in this guideline t

11、o derive such safe threshold levels could be accepted if adequately justified.当在共用设施生产不同的药用产品时，潜在交叉污染是受到关注的。药用产品提供为患者或者目标动物提供预期医疗溢处，然而，交叉污染，没有向病人或者目标动物提供任何溢处，甚至可能带来风险。因此，应限制药用产品污染物在一个对所有人群认为是安全的水平。为此，基于健康限度，通过推导安全阀值应该被用于识别风险。偏离阀值（如，每日允许暴露（PDE）或毒理学相关阀值（TTC）应来自结构化的对包括非临床和临床数据的所有药理学与毒理学数据科学评价。如果有充分合理的理

12、由，来自这条指导原则中强调的主要方法获得的安全阀值水平偏离可以接受。1.Introduction(background)第一章：第一章：介绍（背景）介绍（背景）During the manufacture of medicinal products accidental cross-contamination can result from the uncontrolled release of dust,gases,vapours,aerosols,genetic material or organisms from active substances,other starting mate

13、rials,and other products being processed concurrently,as well as from residues on equipment,and from operators clothing.Due to the perceived risk,certain classes of medicinal product have previously been required to be manufactured in dedicated or segregated self-contained facilities including,“cert

14、ain antibiotics,certain hormones,certain cytotoxics and certain highly active drugs”.Until now no official guidance is available in order to assist manufacturers to differentiate between individual products within these specified classes.Chapters 3 and 5 of the GMP guideline have been revised to pro

15、mote a science and risk-based approach and refer to a“toxicological evaluation”for establishing threshold values for risk identification.医药产品生产过程中无法控制的意外可能导致交叉污染,如粉尘、气体、蒸汽、气溶胶，遗传物质或生物活性物质，其他原料、或者其他产品同时生产时，以及设备和操作人员衣服残留。由于预知风险，某些类型的医药产品以前需要专用的或隔离的独立的生产设施，包括“某些抗生素、某些激素、某些细胞毒性和某些高活性药物”。直到现在没有官方的指南能够帮助生

16、产商去区分这些单个产品和这些特定类别之间的不同。GMP指南修订了章节3和5，用于促进科学和风险基础的方法，参见“毒理学评价”用于建立风险辨识阀值。Cleaning is a risk reducing measure and carry-over limits for cleaning validation studies are widely used in the pharmaceutical industry.A variety of approaches are taken in order to establish these limits and often do not take account of the available pharmacological and toxicological data.Hence,a more scientific case by case approach is warranted for risk identification and to support risk reduction measures for all class