基于风险的高活性原料药车间设计创新策略
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摘要
医药原料药的种类繁多,高活性原料药(HAPI)因其具有高选择性在原料药中占有极其重要的地位。但其可能导致癌症、基因突变,在低剂量时的生殖毒性及可能具有高度潜在致敏性等,在其工业化设计中,必须对人体的摄入量及环境中的暴露量做严格的量化控制,才能保证药品生产过程安全。而目前的GMP规范及其实施指南只对这类药品做了原则性规定,本文提出在具体产品设计中,还需要做更深入的设计细化,设计针对性的控制策略,确保达到安全生产的目的。
There exist many active pharmaceutical ingredient(API). Highly API(HAPI) play an extremely important role due to its high selectivity or potential to cause cancer, gene mutation, reproductive toxicity at low doses and high potential sensitization. In the industrial design, the intake of human body and amount of exposure in the environment must be strictly quantified to ensure the safety in drug production process. However, current GMP specification and the implementation guidelines only provide simple principles for such drugs. This paper advocated more in-depth design refinement and design targeted control strategy in specific product design ensure the safety of production.
There exist many active pharmaceutical ingredient(API). Highly API(HAPI) play an extremely important role due to its high selectivity or potential to cause cancer, gene mutation, reproductive toxicity at low doses and high potential sensitization. In the industrial design, the intake of human body and amount of exposure in the environment must be strictly quantified to ensure the safety in drug production process. However, current GMP specification and the implementation guidelines only provide simple principles for such drugs. This paper advocated more in-depth design refinement and design targeted control strategy in specific product design ensure the safety of production.
引文
[1]国家食品药品监督管理局药品认证管理中心. ICHQ7A:活性药物成分的GMP指南[G].《ICH质量管理文件汇编》,2010:204.
[2]ACGIH. 2015TLVs?and BEIs?[M]. 2015:3.
[3]HSE(Health and safty executive). EH40/2005 Workplace exposure limits[M]. 2015:8.
[4]ISPE. Baseline Guide Vol 7:Risk-Based Manufacture of Pharma Products[M]. 2017.
[5]中华人民共和国国家卫生和计划生育委员会.药品生产质量管理规范(2010年修订)[S]. 2011:10.
[6]U. S. Code of Federal Regulations,Title 21,Food and Drugs,Current Good Manufacture Practices[S]. 2018:part211.46.
[7]EEC. Good Manufacturing Practice(GMP)guidelines,EUDRALEX-VOLUME4[S]. 2015:4.
[8]Sven Oliver Gottlieb.《高活性药品生产设施设计》[R].2013:12.
[9]常新量.《高活性药品的风险管控措施》[R]. 2018:40.
[10]傅慰祖.美国政府工业卫生学家会议(ACGIH)2000年生产环境化学物质阈限值(变动部分)[J].劳动医学,2000,17(3):192-193.
[11]万东毅.原料药车间设计中的职业安全卫生要求[J].中国药业,2006,15(15):22-23.
[12]金文俊.基于EHS激素API中间体车间设计[D].上海:华东理工大学,2017.
[13]柏常洪,姬胜利.试论原料药多功能车间的设计[J].医药工程设计,2010,31(3):22-23.
[14]EMA.不同药品公用设施的生产商中用于风险识别而设定以健康为基础的接触极限的指南[M]. 2014:11,20.
[15]ISO. 14644-3.《洁净室和相关受控环境-第三部分:测试方法》[S]. 2005:12.
[16]ISO. 14644-7.《洁净室和相关受控环境-第七部分:隔离装置》[S]. 2004:10.
[2]ACGIH. 2015TLVs?and BEIs?[M]. 2015:3.
[3]HSE(Health and safty executive). EH40/2005 Workplace exposure limits[M]. 2015:8.
[4]ISPE. Baseline Guide Vol 7:Risk-Based Manufacture of Pharma Products[M]. 2017.
[5]中华人民共和国国家卫生和计划生育委员会.药品生产质量管理规范(2010年修订)[S]. 2011:10.
[6]U. S. Code of Federal Regulations,Title 21,Food and Drugs,Current Good Manufacture Practices[S]. 2018:part211.46.
[7]EEC. Good Manufacturing Practice(GMP)guidelines,EUDRALEX-VOLUME4[S]. 2015:4.
[8]Sven Oliver Gottlieb.《高活性药品生产设施设计》[R].2013:12.
[9]常新量.《高活性药品的风险管控措施》[R]. 2018:40.
[10]傅慰祖.美国政府工业卫生学家会议(ACGIH)2000年生产环境化学物质阈限值(变动部分)[J].劳动医学,2000,17(3):192-193.
[11]万东毅.原料药车间设计中的职业安全卫生要求[J].中国药业,2006,15(15):22-23.
[12]金文俊.基于EHS激素API中间体车间设计[D].上海:华东理工大学,2017.
[13]柏常洪,姬胜利.试论原料药多功能车间的设计[J].医药工程设计,2010,31(3):22-23.
[14]EMA.不同药品公用设施的生产商中用于风险识别而设定以健康为基础的接触极限的指南[M]. 2014:11,20.
[15]ISO. 14644-3.《洁净室和相关受控环境-第三部分:测试方法》[S]. 2005:12.
[16]ISO. 14644-7.《洁净室和相关受控环境-第七部分:隔离装置》[S]. 2004:10.