Quality by Test was the only way to guarantee quality of drug products before FDA launched current Good Manufacturing Practice. To clearly understand the manufacture processes, FDA generalized Quality by Design(QbD) i...Quality by Test was the only way to guarantee quality of drug products before FDA launched current Good Manufacturing Practice. To clearly understand the manufacture processes, FDA generalized Quality by Design(QbD) in the field of pharmacy, which is based on the thorough understanding of how materials and process parameters affect the quality profile of final products. The application of QbD in drug formulation and process design is based on a good understanding of the sources of variability and the manufacture process. In this paper,the basic knowledge of QbD, the elements of QbD, steps and tools for QbD implementation in pharmaceutics field, including risk assessment, design of experiment, and process analytical technology(PAT), are introduced briefly. Moreover, the concrete applications of QbD in various pharmaceutical related unit operations are summarized and presented.展开更多
Automotive torque converters have recently been designed with an increasingly narrower profile for the purpose of achieving a smaller axial size and reducing weight. Design of experiment(DOE) and computational fluid d...Automotive torque converters have recently been designed with an increasingly narrower profile for the purpose of achieving a smaller axial size and reducing weight. Design of experiment(DOE) and computational fluid dynamics(CFD) techniques are applied to improve the performance of a flat torque converter. Four torque converters with different flatness ratios(0.204, 0.186, 0.172, and 0.158) are designed and simulated first to investigate the effects of flatness ratio on their overall performance, including efficiency, torque ratio, and impeller torque factor. The simulation results show that the overall performance tends to deteriorate as the flatness ratio decreases. Then a parametric study covering six geometric parameters, namely, inlet and outlet angles of impeller, turbine, and stator is carried out. The results demonstrate that the inlet and outlet angles play an important role in determining the performance characteristics of a torque converter. Furthermore, the relative importance of the six design parameters is investigated using DOE method for each response(stall torque ratio and peak efficiency). The turbine outlet angle is found to exert the greatest influence on both responses. After DOE analysis, an optimized design for the flat torque converter geometry is obtained. Compared to the conventional product, the width of the optimized flat torque converter torus is reduced by about 20% while the values of stall torque ratio and peak efficiency are only decreased by 0.4% and 1.7%, respectively.The proposed new optimization strategy based on DOE method together with desirability function approach can be used for performance enhancement in the design process of flat torque converters.展开更多
The sample preparation of samples conlaining bovine serum albumin(BSA),e.g..as used in transdermal Franz diffusion cell(FDC) solutions,was evaluated using an analytical qualily-by-design(QbD)approach.Traditional...The sample preparation of samples conlaining bovine serum albumin(BSA),e.g..as used in transdermal Franz diffusion cell(FDC) solutions,was evaluated using an analytical qualily-by-design(QbD)approach.Traditional precipitation of BSA by adding an equal volume of organic solvent,often successfully used with conventional HPLC-PDA,was found insufficiently robust when novel fused-core HPLC and/or UPLC-MS methods were used.In this study,three factors(acetonitrile(%).formic acid(%) and boiling time(min)) were included in the experimental design to determine an optimal and more suitable sample treatment of BSAcontaining FDC solutions.Using a QbD and Derringer desirability(D) approach,combining BSA loss,dilution factor and variability,we constructed an optimal working space with the edge of failure defined as D〈0.9.The design space is modelled and is confirmed to have an ACN range of 83 ± 3% and FA content of 1 ±0.25%.展开更多
To explore the forming process and mechanism of the surface texture of laser micropits,this paper presents the thermal model of laser machining based on the Neumann boundary conditions and an investigation on the effe...To explore the forming process and mechanism of the surface texture of laser micropits,this paper presents the thermal model of laser machining based on the Neumann boundary conditions and an investigation on the effects of various parameters on the processing.The surface profile and quality of the formed micropits were analyzed using NanoFocus 3D equipment through a design of experiment(DOE).The results showed that more intense melting and splashing occurred with higher power density and narrower pulse widths.Moreover,the compressive stress is an important indicator of the damage effects,and the circumferential thermal stress is the primary factor influencing the diameter expansion.During the process of laser machining,not only did oxides such as CuO and ZnO generate,the energy distribution also tended to decrease gradually from region#1 to region#3 based on an energy dispersive spectrometer(EDS)analysis.The factors significantly affecting the surface quality of the micropit surface texture are the energy and pulse width.The relationship between taper angle and energy is appropriately linear.Research on the formation process and mechanism of the surface texture of laser micropits provides important guidance for precision machining.展开更多
Identification of process parameters,their effects and contributions to the outcomes of the system using experimental approach could be a daunting,time consuming,and costly course.Using proper statistical methods,i.e....Identification of process parameters,their effects and contributions to the outcomes of the system using experimental approach could be a daunting,time consuming,and costly course.Using proper statistical methods,i.e.,Taguchi method,could significantly reduce the number of required experiments and statistical significance of the parameter can be identified.Friction stir welding is one of those welding techniques with many parameters which have different effects on the quality of the welds.In friction stir welding the tool rotational speed(RPM)and transverse speed(mm/min)influence the strength(i.e.,hardness distribution)of the stirred zone.In this study,these two factors are investigated to determine the effect they will have on the hardness in the stirred zone of the friction stir welds and how the two factors are related to one another for as-cast magnesium alloy AM60 with nominal chemical composition of Mg-(5.5-6.5)Al-(0.24-0.6)Mn-0.22Zn-0.1Si.Experimental data was taken at three different tool rotational speeds and three different transverse speeds.The data obtained was then analyzed using a 32 factorial design to find the contribution of these parameters.It was determined that both tool rotational speed and transverse speed possess significant effects on the stir zone hardness.Also,the interactions between the two factors were statistically assessed.展开更多
Quality by Test (Qb T) was the only way to guarantee the quality of drug products before FDA launches current Good Manufacturing Practice (c GMP)[1], which is an approach without clear understanding of the processes. ...Quality by Test (Qb T) was the only way to guarantee the quality of drug products before FDA launches current Good Manufacturing Practice (c GMP)[1], which is an approach without clear understanding of the processes. In order to solve this problem,FDA generalized Quality by Design (QbD) in the field of pharmacy (2)In pharmaceutical industry, Qb D brings cost-efficiency and simplicity of manufacturing process into reality.展开更多
Selecting the remanufacturing system as object of the study, the buffer capacity is served as control variable, and design of experiment(DOE) and simulation are used to analyze the effect that uncertain quality of ret...Selecting the remanufacturing system as object of the study, the buffer capacity is served as control variable, and design of experiment(DOE) and simulation are used to analyze the effect that uncertain quality of returns acts on system performance. The remanufacturing time and the recovery rate in each station are used to represent the quality level of the returns, and the variance of remanufacturing time is used to denote the variability of returns’ quality. Three factors(the variability, the proportion and the recovery rate) of different quality levels in returns are considered. By analyzing the variance and the range of the simulation results, some important conclusions are obtained: recovery rate affects the remanufacturing cost by far, and the variability has the minimum influence;furthermore, for the returns, the more obvious of the dispersion degree, the higher proportion of the high-level quality, and the higher of the recovery rate, the lower the cost of remanufacturing will be.展开更多
To promote the pose accuracy performance of a spatial parallel kinematic Mechanism( PKM) in service,a workshop oriented tolerance synthesis method based on design of experiment( DOE) is proposed,which involves two con...To promote the pose accuracy performance of a spatial parallel kinematic Mechanism( PKM) in service,a workshop oriented tolerance synthesis method based on design of experiment( DOE) is proposed,which involves two consecutive stages. In the first stage of DOE,the tolerance factor sensitivities are obtained according to initial tolerance settings with the consideration of the current manufacturing capacity,and the second stage of DOE makes use of them to produce multiple tolerance allocations which can adapt to current manufacturing capacity. A tolerance synthesis procedure is developed and integrated in tolerance design system for PKM. Comparing the results with peer method,the validity and practicability of this method is verified.展开更多
A five-step method framework is proposed by combing improved value stream mapping with simulation and design of experiment(DOE) to design the lean system for engineer-to-order(ETO) manufacturing,and lean practice impl...A five-step method framework is proposed by combing improved value stream mapping with simulation and design of experiment(DOE) to design the lean system for engineer-to-order(ETO) manufacturing,and lean practice implementation path is decided.Meanwhile,a real company case like HAVC is taken to display the application of the framework.The results indicate that compared to supermarket Kanban,constant work in process(Conwip) has the broader applicability in ETO manufacturing and the critical business process,like purchasing of key parts,and has more significant effects on value stream performance.Therefore,it should have priority in lean practice implementation.展开更多
中医药发展已上升到国家战略层面,在医药行业贯彻实施"中国制造2025"战略的新形势下,中药生产过程质量控制是中药工业需要加快突破的关键领域之一。对中药生产过程质量控制领域在工艺设计、分析检测、过程建模、制造装备等方...中医药发展已上升到国家战略层面,在医药行业贯彻实施"中国制造2025"战略的新形势下,中药生产过程质量控制是中药工业需要加快突破的关键领域之一。对中药生产过程质量控制领域在工艺设计、分析检测、过程建模、制造装备等方面的关键共性问题进行解析,综述了中药生产过程质量控制体系中工艺过程理解、生产过程实时分析方法开发、过程控制策略建立3个方面的研究进展;并结合企业研究实践,介绍了质量源于设计(quality by design,Qb D)、过程分析技术(process analytical technology,PAT)、实验设计(design of experiment,DOE)、多变量统计分析等关键技术在上述3个研究方向中的应用进展,分析了实际工业应用的难点问题并对其应用前景进行展望,旨在为中药企业应用和提升生产过程质量控制技术提供参考。展开更多
基于欧-Ⅵ排放法规,将柴油机整个工况区按照稳态试验循环(world harmonized stationary cycle,WHSC)和瞬态测试循环(world harmonized transient cycle,WHTC)试验循环的散点分布及世界非超限排放(world not to exceed,WNTE)法规要求等...基于欧-Ⅵ排放法规,将柴油机整个工况区按照稳态试验循环(world harmonized stationary cycle,WHSC)和瞬态测试循环(world harmonized transient cycle,WHTC)试验循环的散点分布及世界非超限排放(world not to exceed,WNTE)法规要求等划分为不同的区域,分区域选择合理且适量的工况点,寻找各工况其电控参数合适的边界,并基于V优选法进行试验设计;给定各区域拟达到的排放物控制范围,基于Matlab中基于模型标定(modelbased on calibration toolbox,MBC)工具箱对某高压共轨柴油机进行满足欧-Ⅵ排放法规要求且油耗最低的优化标定,获取各电控参数的全脉谱。并将其导入集成校准和应用工具(integrated calibration and application tools,INCA),且在试验台架上进行WHSC、WHTC及WNTE试验验证。试验结果表明:WHSC试验循环的氮氧化物(NO_x)排放和油耗率(有效燃油消耗率)与MBC模型预测值非常接近,偏差皆在1%以内,并满足欧-ⅥWHSC、WHTC及WNTE试验循环排放限值要求且油耗最低。展开更多
基金financially supported by Talents Project of Liaoning Province, China (LR2013047)
文摘Quality by Test was the only way to guarantee quality of drug products before FDA launched current Good Manufacturing Practice. To clearly understand the manufacture processes, FDA generalized Quality by Design(QbD) in the field of pharmacy, which is based on the thorough understanding of how materials and process parameters affect the quality profile of final products. The application of QbD in drug formulation and process design is based on a good understanding of the sources of variability and the manufacture process. In this paper,the basic knowledge of QbD, the elements of QbD, steps and tools for QbD implementation in pharmaceutics field, including risk assessment, design of experiment, and process analytical technology(PAT), are introduced briefly. Moreover, the concrete applications of QbD in various pharmaceutical related unit operations are summarized and presented.
基金Supported by National Natural Science Foundation of China(Grant No.51575393)
文摘Automotive torque converters have recently been designed with an increasingly narrower profile for the purpose of achieving a smaller axial size and reducing weight. Design of experiment(DOE) and computational fluid dynamics(CFD) techniques are applied to improve the performance of a flat torque converter. Four torque converters with different flatness ratios(0.204, 0.186, 0.172, and 0.158) are designed and simulated first to investigate the effects of flatness ratio on their overall performance, including efficiency, torque ratio, and impeller torque factor. The simulation results show that the overall performance tends to deteriorate as the flatness ratio decreases. Then a parametric study covering six geometric parameters, namely, inlet and outlet angles of impeller, turbine, and stator is carried out. The results demonstrate that the inlet and outlet angles play an important role in determining the performance characteristics of a torque converter. Furthermore, the relative importance of the six design parameters is investigated using DOE method for each response(stall torque ratio and peak efficiency). The turbine outlet angle is found to exert the greatest influence on both responses. After DOE analysis, an optimized design for the flat torque converter geometry is obtained. Compared to the conventional product, the width of the optimized flat torque converter torus is reduced by about 20% while the values of stall torque ratio and peak efficiency are only decreased by 0.4% and 1.7%, respectively.The proposed new optimization strategy based on DOE method together with desirability function approach can be used for performance enhancement in the design process of flat torque converters.
基金the Special Research Fund of Ghent University(BOF 01D23812 to Lien Taevernier and BOF O1J22510 to Evelien Wynendaele and Professor Bart De Spiegeleer)the Institute for the Promotion of Innovation through Science and Technology in Flanders(IWT 101529 to Matthias D'Hondt)for their financial funding
文摘The sample preparation of samples conlaining bovine serum albumin(BSA),e.g..as used in transdermal Franz diffusion cell(FDC) solutions,was evaluated using an analytical qualily-by-design(QbD)approach.Traditional precipitation of BSA by adding an equal volume of organic solvent,often successfully used with conventional HPLC-PDA,was found insufficiently robust when novel fused-core HPLC and/or UPLC-MS methods were used.In this study,three factors(acetonitrile(%).formic acid(%) and boiling time(min)) were included in the experimental design to determine an optimal and more suitable sample treatment of BSAcontaining FDC solutions.Using a QbD and Derringer desirability(D) approach,combining BSA loss,dilution factor and variability,we constructed an optimal working space with the edge of failure defined as D〈0.9.The design space is modelled and is confirmed to have an ACN range of 83 ± 3% and FA content of 1 ±0.25%.
基金the National Science and Technology Major Project(Grant No.21010098)the National Key Technologies R&D Program of Henan(Grant No.162102210048)+1 种基金Henan Provincial Key Laboratory of High Performance Bearing Technology(Grant No.2016ZCKF02)the platform of Henan Collaborative Innovation Center for Advanced Manufacturing of Mechanical Equipment.
文摘To explore the forming process and mechanism of the surface texture of laser micropits,this paper presents the thermal model of laser machining based on the Neumann boundary conditions and an investigation on the effects of various parameters on the processing.The surface profile and quality of the formed micropits were analyzed using NanoFocus 3D equipment through a design of experiment(DOE).The results showed that more intense melting and splashing occurred with higher power density and narrower pulse widths.Moreover,the compressive stress is an important indicator of the damage effects,and the circumferential thermal stress is the primary factor influencing the diameter expansion.During the process of laser machining,not only did oxides such as CuO and ZnO generate,the energy distribution also tended to decrease gradually from region#1 to region#3 based on an energy dispersive spectrometer(EDS)analysis.The factors significantly affecting the surface quality of the micropit surface texture are the energy and pulse width.The relationship between taper angle and energy is appropriately linear.Research on the formation process and mechanism of the surface texture of laser micropits provides important guidance for precision machining.
文摘Identification of process parameters,their effects and contributions to the outcomes of the system using experimental approach could be a daunting,time consuming,and costly course.Using proper statistical methods,i.e.,Taguchi method,could significantly reduce the number of required experiments and statistical significance of the parameter can be identified.Friction stir welding is one of those welding techniques with many parameters which have different effects on the quality of the welds.In friction stir welding the tool rotational speed(RPM)and transverse speed(mm/min)influence the strength(i.e.,hardness distribution)of the stirred zone.In this study,these two factors are investigated to determine the effect they will have on the hardness in the stirred zone of the friction stir welds and how the two factors are related to one another for as-cast magnesium alloy AM60 with nominal chemical composition of Mg-(5.5-6.5)Al-(0.24-0.6)Mn-0.22Zn-0.1Si.Experimental data was taken at three different tool rotational speeds and three different transverse speeds.The data obtained was then analyzed using a 32 factorial design to find the contribution of these parameters.It was determined that both tool rotational speed and transverse speed possess significant effects on the stir zone hardness.Also,the interactions between the two factors were statistically assessed.
文摘Quality by Test (Qb T) was the only way to guarantee the quality of drug products before FDA launches current Good Manufacturing Practice (c GMP)[1], which is an approach without clear understanding of the processes. In order to solve this problem,FDA generalized Quality by Design (QbD) in the field of pharmacy (2)In pharmaceutical industry, Qb D brings cost-efficiency and simplicity of manufacturing process into reality.
基金the National Natural Science Foundation of China(No.51565028)the Innovation and Entrepreneurship Talents Training Project of Lanzhou City(No.2018-RC-25)
文摘Selecting the remanufacturing system as object of the study, the buffer capacity is served as control variable, and design of experiment(DOE) and simulation are used to analyze the effect that uncertain quality of returns acts on system performance. The remanufacturing time and the recovery rate in each station are used to represent the quality level of the returns, and the variance of remanufacturing time is used to denote the variability of returns’ quality. Three factors(the variability, the proportion and the recovery rate) of different quality levels in returns are considered. By analyzing the variance and the range of the simulation results, some important conclusions are obtained: recovery rate affects the remanufacturing cost by far, and the variability has the minimum influence;furthermore, for the returns, the more obvious of the dispersion degree, the higher proportion of the high-level quality, and the higher of the recovery rate, the lower the cost of remanufacturing will be.
基金Sponsored by the National Defense Basic Scientific Research Program(Grant No.A0320110019)the Shanghai Science and Technology Innovation Action Plan(Grant No.11DZ1120800)
文摘To promote the pose accuracy performance of a spatial parallel kinematic Mechanism( PKM) in service,a workshop oriented tolerance synthesis method based on design of experiment( DOE) is proposed,which involves two consecutive stages. In the first stage of DOE,the tolerance factor sensitivities are obtained according to initial tolerance settings with the consideration of the current manufacturing capacity,and the second stage of DOE makes use of them to produce multiple tolerance allocations which can adapt to current manufacturing capacity. A tolerance synthesis procedure is developed and integrated in tolerance design system for PKM. Comparing the results with peer method,the validity and practicability of this method is verified.
文摘A five-step method framework is proposed by combing improved value stream mapping with simulation and design of experiment(DOE) to design the lean system for engineer-to-order(ETO) manufacturing,and lean practice implementation path is decided.Meanwhile,a real company case like HAVC is taken to display the application of the framework.The results indicate that compared to supermarket Kanban,constant work in process(Conwip) has the broader applicability in ETO manufacturing and the critical business process,like purchasing of key parts,and has more significant effects on value stream performance.Therefore,it should have priority in lean practice implementation.
文摘中医药发展已上升到国家战略层面,在医药行业贯彻实施"中国制造2025"战略的新形势下,中药生产过程质量控制是中药工业需要加快突破的关键领域之一。对中药生产过程质量控制领域在工艺设计、分析检测、过程建模、制造装备等方面的关键共性问题进行解析,综述了中药生产过程质量控制体系中工艺过程理解、生产过程实时分析方法开发、过程控制策略建立3个方面的研究进展;并结合企业研究实践,介绍了质量源于设计(quality by design,Qb D)、过程分析技术(process analytical technology,PAT)、实验设计(design of experiment,DOE)、多变量统计分析等关键技术在上述3个研究方向中的应用进展,分析了实际工业应用的难点问题并对其应用前景进行展望,旨在为中药企业应用和提升生产过程质量控制技术提供参考。
文摘基于欧-Ⅵ排放法规,将柴油机整个工况区按照稳态试验循环(world harmonized stationary cycle,WHSC)和瞬态测试循环(world harmonized transient cycle,WHTC)试验循环的散点分布及世界非超限排放(world not to exceed,WNTE)法规要求等划分为不同的区域,分区域选择合理且适量的工况点,寻找各工况其电控参数合适的边界,并基于V优选法进行试验设计;给定各区域拟达到的排放物控制范围,基于Matlab中基于模型标定(modelbased on calibration toolbox,MBC)工具箱对某高压共轨柴油机进行满足欧-Ⅵ排放法规要求且油耗最低的优化标定,获取各电控参数的全脉谱。并将其导入集成校准和应用工具(integrated calibration and application tools,INCA),且在试验台架上进行WHSC、WHTC及WNTE试验验证。试验结果表明:WHSC试验循环的氮氧化物(NO_x)排放和油耗率(有效燃油消耗率)与MBC模型预测值非常接近,偏差皆在1%以内,并满足欧-ⅥWHSC、WHTC及WNTE试验循环排放限值要求且油耗最低。