基于风险防止药品生产中交叉污染以及 “共用设施中不同药品生产风险识别所用基于健康的暴露限设定指南” 实施问题 (EMA/CHMP/CVMP/SWP/169430/2012) | Draft agreed by SWP, vSWP and GMP/GDP Inspectors WG | September 2016 | | SWP，vSWP和GMP/GDP检查员WG通过草案 | 2016年9月 | | Adopted by CVMP for release for consultation | 8 November 2016 | | CVMP通过并发布征求公众意见 | 2016年11月8日 | | Adopted by CHMP for release for consultation | 15 December 2016 | | CHMP通过并发布征求公众意见 | 2016年12月15日 | | Start of public consultation | January 2017 | | 开始征求公众意见 | 2017年1月 | | End of consultation (deadline for comments) | 30 April 2017 | | 征求意见截止 | 2017年3月30日 |
Comments should be provided using this template.The completed comments form should be sent to adm-gmdp@ema.europa.eu 意见应使用上述链接的模板填写并提交至上述邮箱。
Q1. Do companies haveto establish Health Based Exposure Limits (HBELs) for all products? 公司是否必须为所有产品建立基于健康的暴露限（HBEL）？ A: Yes, HBELs should be established forall products. HBELs for highly hazardous products are expected to be completedin full as per the EMA guide (EMA/CHMP/CVMP/SWP/169430/2012) or equivalent. SeeQ2 for products/active substances considered to be highly hazardous. Productsthat do not fall into the highly hazardous category may be addressed as per Q4. 是的，所有产品都应建立HBEL。高有害产品的HBEL应按EMA指南（EMA/CHMP/CVMP/SWP/169430/2012）或等同的要求制订。参见问答2中应作为高有害产品考虑的产品/活性物，不在高有害类别的产品可以按问答4的内容处理。 Q2. Whatproducts/active substances are considered to be highly hazardous? 什么样的药品/活性物质应作为高有害物质考虑？ A: Highly hazardous products are thosethat can cause serious adverse effects at low doses and that therefore wouldbenefit from a full toxicological assessment in order to derive a safe HBEL. 高有害物质是指低剂量即可能导致严重不良反应，因而需要进行全面毒性评估以制订安全的HBEL的物质。 Highly hazardous products areidentified based on their inherent toxicological and pharmacologicalcharacteristics and include the groups below (this list is not an exhaustivelist and if evidence is available indicating that the product may cause adverseeffects at low doses by other mechanisms it should be considered as highlyhazardous). 高有害物质应根据其内在毒性和药学特性进行识别，并分为以下几类（此清单并不是穷尽清单，如果有证据显示该产品可能因其它机制由低剂量即导致不良反应，则也应作为高有害物质考虑）。 Manufacturers should consider, via asafety assessment against the guidance below, if products/active substancesshould be considered highly hazardous. Evidence indicating a product or activesubstance falls within any of the categories below should result in a productbeing considered highly hazardous. If in doubt, manufacturers should considerthe product potentially highly hazardous and apply the EMA guide(EMA/CHMP/CVMP/SWP/169430/2012) in full to derive a safe HBEL. 如果药品/活性物质应作为高有害物质，则生产商应根据以下指南进行安全评估。显示一种药品或活性物质属于以下某个类别的证据应能证明一种药品作为高有害物质来考虑。如果有疑问，则生产商应将该物质作为潜在高有害物质考虑，并全面应用EMA指南（EMA/CHMP/CVMP/SWP/169430/2012）来建立安全HBEL。 1. Genotoxic (specifically mutagenic) compoundsthat are known to be, or highly likely to be, carcinogenic to humans. Compoundsof this group are easily identifiable, since genotoxicity would be related tothe pharmacology, e.g. as DNA alkylating cytostatics, and their use is usuallyrestricted to oncology indications with respective warning statements in theSummary of Product Characteristics. 基因毒性（尤其是基因诱变）化合物一般是，或者非常可能是，对人类致癌的。此类化合物一般易于识别，因为基因毒性一般与药学相关，例如，是DNA烷基化细胞抑制剂，它们的使用一般局限于肿瘤症状，在产品特性摘要上有相关的警示声明。 2. Compounds that can produce reproductiveand/or developmental effects at low dosages, for example where evidence existsof such effects being caused by a clinical dose of <10 mg/day="" (veterinarydose="" equivalent="" 0.2="" mg/kg/day)="" or="" dosages="" in="" animal="" studies="" of="" ≤1=""> 低剂量即可以产生生殖反应和/或发育反应的化合物，例如，有证据证明此类反应是由临床剂量<10mg （兽药剂量等于0.2mg/kg/天）或兽用研究≤1=""> 3. Compounds that can produce serious targetorgan toxicity or other significant adverse effects at low doses, for examplewhere evidence exists of such effects being caused by a clinical dose of <10mg ay="" (veterinary="" dose="" equivalent="" 0.2="" mg/kg/day)="" or="" dosages="" in="" animal="" studiesof="" ≤1=""> 低剂量即可能会导致目标器官严重毒性，或其它重大不良反应的化合物，例如，有证据证明此类反应是由临床剂量<10mg （兽药剂量等于0.2mg/kg/天）或兽用研究≤1=""> 4. Compounds with a high pharmacological potencyi.e. recommended daily dose of <1 mg="" (veterinary="" dose="" equivalent="" 0.02=""> 具有高药效的化合物，即，建议日剂量<1mg> 5. Compounds with a high sensitising potential. 具有高致敏可能性的化合物。
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