论中药质量源于设计(1)
[摘要]药品质量源于设计(quality by design，QbD)，形成于生产过程，优化提高于生命周期。该文在回顾制药QbD发展历程的基础上，围绕质量设计、质量控制和质量改进详细解读了制药QbD实施方略。在分析中药研发和生产应用QbD难点和特点的基础上，提出中药QbD的“四全”模式，即全局设计、全息分析、全面控制和全程优化，体现了中药质量设计的系统观和整体观。在全局设计中，构建以临床疗效为导向和以多学科理论知识为基础的中药质量问题空间和解决方案空间。全息分析中重视“析”的方法和技术，具备更高层次的中药质量理解和设计整合功能。提出综合应用检验质量控制、统计质量控制、预测质量控制和智能质量控制实现中药产品质量一致性和工艺系统可靠性。全程优化致力于生命周期内的中药质量和过程能力改进。实施QbD有利于化解中药研发和制造生态系统内在矛盾，为中药质量和产业效益的提升提供保障。
[关键词]质量源于设计； 中药； 设计思维； 质量一致性； 工艺系统可靠性
[Abstract]The pharmaceutical quality was built by design， formed in the manufacturing process and improved during the product′s lifecycle Based on the comprehensive literature review of pharmaceutical quality by design (QbD)， the essential ideas and implementation strategies of pharmaceutical QbD were interpreted Considering the complex nature of Chinese medicine， the "4H" model was innovated and proposed for implementing QbD in pharmaceutical development and industrial manufacture of Chinese medicine product "4H" corresponds to the acronym of holistic design， holistic information analysis， holistic quality control， and holistic process optimization， which is consistent with the holistic concept of Chinese medicine theory The holistic design aims at constructing both the quality problem space from the patient requirement and the quality solution space from multidisciplinary knowledge Holistic information analysis emphasizes understanding the quality pattern of Chinese medicine by integrating and mining multisource data and information at a relatively high level The batchtobatch quality consistence and manufacturing system reliability can be realized by comprehensive application of inspective quality control， statistical quality control， predictive quality control and intelligent quality control strategies Holistic process optimization is to improve the product quality and process capability during the product lifecycle management The implementation of QbD is useful to eliminate the ecosystem contradictions lying in the pharmaceutical development and manufacturing process of Chinese medicine product， and helps guarantee the cost effectiveness
[Key words]quality by design (QbD)； Chinese medicine； design thinking； quality consistence； process system reliability
1985年，著名質量管理学家Julan J M博士在总结其质量管控经验和方法的基础上，提出质量源于设计(quality by design，QbD)[1]，与Deming的质量十四点原则和PDCA循环[2]、Feigenbaum的全面质量管理(TQC)[3]、今井正明的持续改善(Kaizen)[4]等方法和理念共同奠定了现代质量管理的基础。进入21世纪，人用药品注册技术国际协调会(ICH)认识到科学知识可提高产品开发和控制的自由度，并于2003年成立质量专家工作组(EWG)，针对创建新的适用于产品生命周期的制药质量体系达成一致认识[5]。2005年，在ICH Q8指南中定义了制药QbD[6]，旨在将先进的管理学原则和以科学为本的药品研发制造规律融合集成，以提高药品质量，更好地保护患者利益。 (徐冰 史新元 吴志生 张燕玲 王耘 乔延江)
[关键词]质量源于设计； 中药； 设计思维； 质量一致性； 工艺系统可靠性
[Abstract]The pharmaceutical quality was built by design， formed in the manufacturing process and improved during the product′s lifecycle Based on the comprehensive literature review of pharmaceutical quality by design (QbD)， the essential ideas and implementation strategies of pharmaceutical QbD were interpreted Considering the complex nature of Chinese medicine， the "4H" model was innovated and proposed for implementing QbD in pharmaceutical development and industrial manufacture of Chinese medicine product "4H" corresponds to the acronym of holistic design， holistic information analysis， holistic quality control， and holistic process optimization， which is consistent with the holistic concept of Chinese medicine theory The holistic design aims at constructing both the quality problem space from the patient requirement and the quality solution space from multidisciplinary knowledge Holistic information analysis emphasizes understanding the quality pattern of Chinese medicine by integrating and mining multisource data and information at a relatively high level The batchtobatch quality consistence and manufacturing system reliability can be realized by comprehensive application of inspective quality control， statistical quality control， predictive quality control and intelligent quality control strategies Holistic process optimization is to improve the product quality and process capability during the product lifecycle management The implementation of QbD is useful to eliminate the ecosystem contradictions lying in the pharmaceutical development and manufacturing process of Chinese medicine product， and helps guarantee the cost effectiveness
[Key words]quality by design (QbD)； Chinese medicine； design thinking； quality consistence； process system reliability
1985年，著名質量管理学家Julan J M博士在总结其质量管控经验和方法的基础上，提出质量源于设计(quality by design，QbD)[1]，与Deming的质量十四点原则和PDCA循环[2]、Feigenbaum的全面质量管理(TQC)[3]、今井正明的持续改善(Kaizen)[4]等方法和理念共同奠定了现代质量管理的基础。进入21世纪，人用药品注册技术国际协调会(ICH)认识到科学知识可提高产品开发和控制的自由度，并于2003年成立质量专家工作组(EWG)，针对创建新的适用于产品生命周期的制药质量体系达成一致认识[5]。2005年，在ICH Q8指南中定义了制药QbD[6]，旨在将先进的管理学原则和以科学为本的药品研发制造规律融合集成，以提高药品质量，更好地保护患者利益。 (徐冰 史新元 吴志生 张燕玲 王耘 乔延江)