以风险为基础的上市后药品抽验模式研究
摘要
随着科技进步,药品市场国际化,药品质量问题越来越引起全球关注,据WHO初步估计掺假药占全世界药品销售额的10%,在某些发展中国家可高达50%。在全球越来越复杂的药品市场环境中,传统的按计划抽验模式已经无法满足监管机构的监管需要。单纯以抽验合格率来表征药品质量水平的方式缺乏科学性,越来越多的高科技掺假手段,药品研发时遗留的质量安全隐患,无法在应用标准检验方法后得到客观评价。在我国药品风险高发的现实阶段,探索如何提高抽验效率,通过药品检验手段如何控制药品安全风险是值得研究的课题。
本研究试图以风险管理和质量源于设计的理念为理论支撑和出发点,试图探讨如何建立符合我国国情的以风险管理为基础的药品检验模式,以便提高药品监管效率,从而最终保障公众用药安全。在探讨此问题的过程中,借鉴美欧的先进药品检验理念是至关重要的环节,但是,美欧与我国的药品市场发展阶段处于不同历史时期,借鉴国外先进经验的同时,如何建立适合我国国情的药品检验模式是本研究意欲解决的关键问题。
本研究采用文献和比较研究方法,以风险理论为核心,比较我国与美欧上市后药品抽验理念、程序、评价方法和对监管支撑作用的差异,选择4个评价抽验品种(其中2个中药品种,2个化药品种)进行质量风险指数和聚类分析评价,并结合我国国情,设计我国上市后药品抽验模式。
由于我国药品生产企业众多,流通环节众多,社会信用体系尚未完全建立,影响药品安全的风险因素较发达国家复杂而且众多,与我国相比,美欧等发达国家已经建立了完善的市场竞争和药品监管体系,药品安全影响因素相对固定而且容易把握,而我国与美欧的监管环境差异直接影响抽验理念。
本研究结果显示,药品市场监督抽验和评价抽验的目的、抽验方案设计是药品上市后抽验模式设计的关键,不同抽验模式的抽验结果公布方式和对监管的支撑作用也应有所不同。药品市场监督抽验应以高风险的品种作为监管对象,关注过程控制,与GMP检查、GSP检查相结合,最终检验结果直接为监管机构采取行政监管和行政处罚措施提供依据。而评价抽验则不同,评价抽验的目标将以质量源于设计的理念为出发点,依据评价抽验结果发现药品标准、药品注册中存在的问题,同时评价不同厂家产品的风险情况,为药品标准修订与提高、注册变更以及药品监管措施提供关键技术支撑,甚至可以扩展至为药品价格制定等提供参考依据。
本研究指出,国家制定的相关抽验技术规定为指导性内容,在抽验的具体实施和结果分析过程中,还有很多值得探索的方法,如统计分析方法中聚类分析方法的应用,更能体现不同厂家同品种药品质量的差异,可以给药品监管、药品定价提供有价值的科学参考依据。
With the development of science and technology and the internationalization of the drug market, drug quality problems have attracted more and more global attentions. According to the preliminary estimate of WHO, sales volume of counterfeit drugs accounts for10%of the whole drug sales around the world. And in some developing countries, the amount reaches up to50%. The conventional sampling and testing model can no longer meet the marketing surveillance demads of the authorities under the increasingly complex market circumstances. To simply characterize the quliaty level of drugs by percent of pass is unscientific. An increasing number of high-technology adulterate means and potential safety hazard bequeathed at the phase of research and development makes it difficult to assese the drug objectively using criterial surveil approaches. At the high incidence stage of drug risks, it is necessary and worthy for us to probe into what we should do to improve the efficiency of sampling and testing and how to control safety risks of drugs using testing methds.
This research aims at exploring how to establish a risk-based drug sampling and testing model corresponding with our national conditions so as to improve the efficiency of surveillance and ensure the safty use of drug for the public.The theory support and starting point of this research is quality risk management and the concept of Quality By Design. To borrow ideas from US and Europe is of great importance in the process of this question. However, the US and Europe drug markets are on different development phases and historical period compared with ours, so it is critical to establish a model corresponding with our national conditions when learning from others'experiences.
This research uses literature research, comparative research methods, index analysis and cluster analysis and other statistical analysis methods to compare the concept, procedure, evaluation methodology, supporting functions for drug supervision between our nation, US and Europe.Our core idea is the theory of risk management. We have chosen four assessment sampling and testing breeds (including two traditional Chinese medicine breeds and two chemical medicine breeds) and conducted quality risk evaluation to design our own maketing sampling and testing model.
Becaulse there are a large number of manufacturers and intermediate links in our nation and the social credit system has not been fully set up, more factors would affect the drug safety compared with developed contries. The developed contries like US and Europe have already set up a full equipped market competition and marketing surveillance system and the safety influencing factors of drug would be grasped more easily. The research holds the point that the differences of surveillance environment directly influence the sampling and testing idea.
This research holds the opinion that there should have some differences between marketing surveillance and assessment sampling and testing in their objectives, project designs, result announcements, supporting functions for drug supervision. The marketing surveillance sampling and testing should choose high risk products, focus on process control, be accompanied with GMP and GSP inspection, and the final results should give supports directly for surveillance and punishment. The assessment sampling and testing's objective should be on the point of Quality By Design to find the problems on drug standard and drug registry on the basis of the testing results. At the same time, to evaluate the risk situations of different manufactures, revise the standard and registration and give support for surveillance, it even may be helpful for drug pricing.
This research shows that according to the regulations of our nation, many methods are worthy of exploring for marketing surveillance sampling and testing and drug evaluation sampling and testing, such as Cluster Analysis of Statistical Analysis. On the basis of drug risk evaluation, sampling and testing can be valuable references for drug surveillance, drug pricing, and reflecting the differences in manufactures.
本研究试图以风险管理和质量源于设计的理念为理论支撑和出发点,试图探讨如何建立符合我国国情的以风险管理为基础的药品检验模式,以便提高药品监管效率,从而最终保障公众用药安全。在探讨此问题的过程中,借鉴美欧的先进药品检验理念是至关重要的环节,但是,美欧与我国的药品市场发展阶段处于不同历史时期,借鉴国外先进经验的同时,如何建立适合我国国情的药品检验模式是本研究意欲解决的关键问题。
本研究采用文献和比较研究方法,以风险理论为核心,比较我国与美欧上市后药品抽验理念、程序、评价方法和对监管支撑作用的差异,选择4个评价抽验品种(其中2个中药品种,2个化药品种)进行质量风险指数和聚类分析评价,并结合我国国情,设计我国上市后药品抽验模式。
由于我国药品生产企业众多,流通环节众多,社会信用体系尚未完全建立,影响药品安全的风险因素较发达国家复杂而且众多,与我国相比,美欧等发达国家已经建立了完善的市场竞争和药品监管体系,药品安全影响因素相对固定而且容易把握,而我国与美欧的监管环境差异直接影响抽验理念。
本研究结果显示,药品市场监督抽验和评价抽验的目的、抽验方案设计是药品上市后抽验模式设计的关键,不同抽验模式的抽验结果公布方式和对监管的支撑作用也应有所不同。药品市场监督抽验应以高风险的品种作为监管对象,关注过程控制,与GMP检查、GSP检查相结合,最终检验结果直接为监管机构采取行政监管和行政处罚措施提供依据。而评价抽验则不同,评价抽验的目标将以质量源于设计的理念为出发点,依据评价抽验结果发现药品标准、药品注册中存在的问题,同时评价不同厂家产品的风险情况,为药品标准修订与提高、注册变更以及药品监管措施提供关键技术支撑,甚至可以扩展至为药品价格制定等提供参考依据。
本研究指出,国家制定的相关抽验技术规定为指导性内容,在抽验的具体实施和结果分析过程中,还有很多值得探索的方法,如统计分析方法中聚类分析方法的应用,更能体现不同厂家同品种药品质量的差异,可以给药品监管、药品定价提供有价值的科学参考依据。
With the development of science and technology and the internationalization of the drug market, drug quality problems have attracted more and more global attentions. According to the preliminary estimate of WHO, sales volume of counterfeit drugs accounts for10%of the whole drug sales around the world. And in some developing countries, the amount reaches up to50%. The conventional sampling and testing model can no longer meet the marketing surveillance demads of the authorities under the increasingly complex market circumstances. To simply characterize the quliaty level of drugs by percent of pass is unscientific. An increasing number of high-technology adulterate means and potential safety hazard bequeathed at the phase of research and development makes it difficult to assese the drug objectively using criterial surveil approaches. At the high incidence stage of drug risks, it is necessary and worthy for us to probe into what we should do to improve the efficiency of sampling and testing and how to control safety risks of drugs using testing methds.
This research aims at exploring how to establish a risk-based drug sampling and testing model corresponding with our national conditions so as to improve the efficiency of surveillance and ensure the safty use of drug for the public.The theory support and starting point of this research is quality risk management and the concept of Quality By Design. To borrow ideas from US and Europe is of great importance in the process of this question. However, the US and Europe drug markets are on different development phases and historical period compared with ours, so it is critical to establish a model corresponding with our national conditions when learning from others'experiences.
This research uses literature research, comparative research methods, index analysis and cluster analysis and other statistical analysis methods to compare the concept, procedure, evaluation methodology, supporting functions for drug supervision between our nation, US and Europe.Our core idea is the theory of risk management. We have chosen four assessment sampling and testing breeds (including two traditional Chinese medicine breeds and two chemical medicine breeds) and conducted quality risk evaluation to design our own maketing sampling and testing model.
Becaulse there are a large number of manufacturers and intermediate links in our nation and the social credit system has not been fully set up, more factors would affect the drug safety compared with developed contries. The developed contries like US and Europe have already set up a full equipped market competition and marketing surveillance system and the safety influencing factors of drug would be grasped more easily. The research holds the point that the differences of surveillance environment directly influence the sampling and testing idea.
This research holds the opinion that there should have some differences between marketing surveillance and assessment sampling and testing in their objectives, project designs, result announcements, supporting functions for drug supervision. The marketing surveillance sampling and testing should choose high risk products, focus on process control, be accompanied with GMP and GSP inspection, and the final results should give supports directly for surveillance and punishment. The assessment sampling and testing's objective should be on the point of Quality By Design to find the problems on drug standard and drug registry on the basis of the testing results. At the same time, to evaluate the risk situations of different manufactures, revise the standard and registration and give support for surveillance, it even may be helpful for drug pricing.
This research shows that according to the regulations of our nation, many methods are worthy of exploring for marketing surveillance sampling and testing and drug evaluation sampling and testing, such as Cluster Analysis of Statistical Analysis. On the basis of drug risk evaluation, sampling and testing can be valuable references for drug surveillance, drug pricing, and reflecting the differences in manufactures.
引文
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[2]肖磊,刘玲.国内外质量管理研究现状比较[J]中国管理信息化,2010,13(23)：44
[3]何国伟.质量体系的发展[J]质量论坛,2005,1：11-15
[4]李野.药品质量管理的特点[J]中国药事,2005,19(8)：474-475
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