Constituting the reasonable control models of the wrinkle limit blank holder forces is the sticking point of the processes of the deep drawing with variable blank-holder forces, especially in the square-box forming. T...Constituting the reasonable control models of the wrinkle limit blank holder forces is the sticking point of the processes of the deep drawing with variable blank-holder forces, especially in the square-box forming. To begin with, a mode of segmenting flange of the square-box into eight zones is put forward according to the fact that the uniformity of flange deforming can be improved by control-ling segment blank-holders. Considering the integral influence of shear stress, a new concept, strain relaxation factor is defined. Hereby, the law of distribution of stress and stain in the deforming flange of square-box is achieved. Then based on these mechanical analysis models and the energy principle, the wrinkling flexivity functions of the straight flange and the circle flange are given, and the corresponding formulae of wrinkling limit blank-holder force in these two situations are also educed. In these processes, ply-anisotropy, strain hardening, thickness and friction are considered. In the end, a calculating example is designed to validate the rationality of the formulae of wrinkling limit blank-holder force, at the same time, the influences of the ply-anisotropy exponent and the strain hardening exponent on the wrinkle limit blank holder forces are also analyzed.展开更多
Objective To provide suggestions for helping marketing authorization holders(MAHs)to develop an effective and compliant pharmacovigilance system.Methods The construction strategies of pharmacovigilance system of the m...Objective To provide suggestions for helping marketing authorization holders(MAHs)to develop an effective and compliant pharmacovigilance system.Methods The construction strategies of pharmacovigilance system of the multinational pharmaceutical companies were analyzed based on the requirements of regulations and laws.Results and Conclusion There are some gaps between local and multinational pharmaceutical companies in the construction of pharmacovigilance system.We can learn from the experience of multinational pharmaceutical companies to improve the pharmacovigilance system,which includes building a sound pharmacovigilance organizational structure,establishing a series of operational system files and cultivating professional talents.MAHs of China should improve the structure of enterprise pharmacovigilance system.Besides,members of Drug Safety Committee should be department managers with higher position so that they can fulfil the responsibilities of risk assessment.If MAHs possess a large variety and quantity of products,a Drug Safety Committee should be established to ensure the timely discovery of risks.In addition,MAHs should pay attention to the implementation of related regulations and laws on pharmacovigilance and establish compliant,effective and operatable files combing with the actual operation of pharmacovigilance system.Finally,MAHs should introduce and train pharmacovigilance talents,and hire pharmacovigilance experts as consultants to solve the problem of talent shortage.展开更多
The aim of this study was to provide insights into the current status and primary methodologies employed by marketing authorization holders(MAHs)for signal detection.These insights are intended to offer valuable refer...The aim of this study was to provide insights into the current status and primary methodologies employed by marketing authorization holders(MAHs)for signal detection.These insights are intended to offer valuable references for regulatory authorities in shaping pertinent regulatory policies.We conducted purposive sampling interviews with personnel responsible for pharmacovigilance(PV)within MAHs,in accordance with“Good Pharmacovigilance Practice(GVP)”.The interviews covered six predefined topics with open-ended discussions,including signal collection,signal detection,signal evaluation,clustered signal detection,and current challenges and issues.A total of 26 MAHs were interviewed,comprising 14 foreign-owned and 12 domestic enterprises.Foreign-owned enterprises,along with some local innovative pharmaceutical companies,utilized Oracle’s Argus and Empirica for adverse drug reaction information storage and computer-aided quantitative signal detection,respectively.The majority of domestic enterprises used the Taimei system for data storage and qualitative analysis,although a few employed other systems.Foreign-owned MAHs had comprehensive drug vigilance systems,aligning with established standards such as those of the European Union and the United States.Domestic innovative MAHs had more comprehensive drug vigilance systems compared to traditional domestic MAHs.Their signal detection approaches drew inspiration from the practices of foreign MAHs.This work synthesized findings related to the state of PV practices within these MAHs,shedding light on the challenges,achievements,and potential pathways for improvement.展开更多
Objective To ensure the quality and safety of drugs in the whole cycle of pharmaceutical commissioned production under the drug marketing authorization holder(MAH)system,and to establish a perfect quality management s...Objective To ensure the quality and safety of drugs in the whole cycle of pharmaceutical commissioned production under the drug marketing authorization holder(MAH)system,and to establish a perfect quality management system for it.Methods Literature review was used to study the factors that influenced the quality management system of pharmaceutical commissioned production because the implementation of MAH system in China was late,and the experience accumulated by pharmaceutical industry was not enough.Results and Conclusion Based on the MAH system,it is of great significance to establish the quality management system for pharmaceutical commissioned production.展开更多
In the article,we provide a sharp lower bound for the weighted Lehmer mean of the complete p-elliptic integrals of the first and second kinds,which is the extension of the previous results for complete p-elliptic inte...In the article,we provide a sharp lower bound for the weighted Lehmer mean of the complete p-elliptic integrals of the first and second kinds,which is the extension of the previous results for complete p-elliptic integrals.展开更多
The forming defects, including thinning, rupture, wrinkling and springback, usually arising in producing a side-door impact beam, were investigated by trial and numerical simulation. A temperature-related constitutive...The forming defects, including thinning, rupture, wrinkling and springback, usually arising in producing a side-door impact beam, were investigated by trial and numerical simulation. A temperature-related constitutive model specific to the temperature range from 350 °C to 500 °C was established and used for the numerical simulation. The trial and numerical simulation were conducted to clarify the quantitative characteristics of forming defects and to analyze the effects of process parameters on the forming defects. Results show that the rupture situation is ameliorated and the springback is eliminated in the aluminum alloy hot stamping. The wrinkling severity decreases with increasing blank holder force (BHF), but the BHF greater than 15 kN causes the rupture at the deepest drawing position of workpiece. The forming defects are avoided with lubricant in the feasible ranges of process parameters: the BHF of 3 to 5 kN and the stamping speed of 50 to 200 mm/s.展开更多
文摘Constituting the reasonable control models of the wrinkle limit blank holder forces is the sticking point of the processes of the deep drawing with variable blank-holder forces, especially in the square-box forming. To begin with, a mode of segmenting flange of the square-box into eight zones is put forward according to the fact that the uniformity of flange deforming can be improved by control-ling segment blank-holders. Considering the integral influence of shear stress, a new concept, strain relaxation factor is defined. Hereby, the law of distribution of stress and stain in the deforming flange of square-box is achieved. Then based on these mechanical analysis models and the energy principle, the wrinkling flexivity functions of the straight flange and the circle flange are given, and the corresponding formulae of wrinkling limit blank-holder force in these two situations are also educed. In these processes, ply-anisotropy, strain hardening, thickness and friction are considered. In the end, a calculating example is designed to validate the rationality of the formulae of wrinkling limit blank-holder force, at the same time, the influences of the ply-anisotropy exponent and the strain hardening exponent on the wrinkle limit blank holder forces are also analyzed.
基金Integration Application Status and Problems Investigation of ICH Q8,Q9,Q10 across the Product Life Cycle(No.20210605).
文摘Objective To provide suggestions for helping marketing authorization holders(MAHs)to develop an effective and compliant pharmacovigilance system.Methods The construction strategies of pharmacovigilance system of the multinational pharmaceutical companies were analyzed based on the requirements of regulations and laws.Results and Conclusion There are some gaps between local and multinational pharmaceutical companies in the construction of pharmacovigilance system.We can learn from the experience of multinational pharmaceutical companies to improve the pharmacovigilance system,which includes building a sound pharmacovigilance organizational structure,establishing a series of operational system files and cultivating professional talents.MAHs of China should improve the structure of enterprise pharmacovigilance system.Besides,members of Drug Safety Committee should be department managers with higher position so that they can fulfil the responsibilities of risk assessment.If MAHs possess a large variety and quantity of products,a Drug Safety Committee should be established to ensure the timely discovery of risks.In addition,MAHs should pay attention to the implementation of related regulations and laws on pharmacovigilance and establish compliant,effective and operatable files combing with the actual operation of pharmacovigilance system.Finally,MAHs should introduce and train pharmacovigilance talents,and hire pharmacovigilance experts as consultants to solve the problem of talent shortage.
基金China National Key Research and Development Program(Grant No.2020YFC2009000 and 2020YFC2009001)National High Level Hospital Clinical Research Funding(Grant No.BJ-2023-200)the project funding from the Drug Evaluation Center of the National Medical Products Administration(Grant No.CDRW20214001).
文摘The aim of this study was to provide insights into the current status and primary methodologies employed by marketing authorization holders(MAHs)for signal detection.These insights are intended to offer valuable references for regulatory authorities in shaping pertinent regulatory policies.We conducted purposive sampling interviews with personnel responsible for pharmacovigilance(PV)within MAHs,in accordance with“Good Pharmacovigilance Practice(GVP)”.The interviews covered six predefined topics with open-ended discussions,including signal collection,signal detection,signal evaluation,clustered signal detection,and current challenges and issues.A total of 26 MAHs were interviewed,comprising 14 foreign-owned and 12 domestic enterprises.Foreign-owned enterprises,along with some local innovative pharmaceutical companies,utilized Oracle’s Argus and Empirica for adverse drug reaction information storage and computer-aided quantitative signal detection,respectively.The majority of domestic enterprises used the Taimei system for data storage and qualitative analysis,although a few employed other systems.Foreign-owned MAHs had comprehensive drug vigilance systems,aligning with established standards such as those of the European Union and the United States.Domestic innovative MAHs had more comprehensive drug vigilance systems compared to traditional domestic MAHs.Their signal detection approaches drew inspiration from the practices of foreign MAHs.This work synthesized findings related to the state of PV practices within these MAHs,shedding light on the challenges,achievements,and potential pathways for improvement.
文摘Objective To ensure the quality and safety of drugs in the whole cycle of pharmaceutical commissioned production under the drug marketing authorization holder(MAH)system,and to establish a perfect quality management system for it.Methods Literature review was used to study the factors that influenced the quality management system of pharmaceutical commissioned production because the implementation of MAH system in China was late,and the experience accumulated by pharmaceutical industry was not enough.Results and Conclusion Based on the MAH system,it is of great significance to establish the quality management system for pharmaceutical commissioned production.
基金Supported by the National Natural Science Foundation of China(11971142)the Natural Science Foundation of Zhejiang Province(LY19A010012)the key Scientific Research Projects of Hunan Provincial Department of Education in 2021(21A0526)。
文摘In the article,we provide a sharp lower bound for the weighted Lehmer mean of the complete p-elliptic integrals of the first and second kinds,which is the extension of the previous results for complete p-elliptic integrals.
基金Project(P2014-15)supported by the State Key Laboratory of Materials Processing and Die&Mould Technology,Huazhong University of Science and Technology,ChinaProject supported by the Beijing Laboratory of Metallic Materials and Processing for Modern Transportation,China
文摘The forming defects, including thinning, rupture, wrinkling and springback, usually arising in producing a side-door impact beam, were investigated by trial and numerical simulation. A temperature-related constitutive model specific to the temperature range from 350 °C to 500 °C was established and used for the numerical simulation. The trial and numerical simulation were conducted to clarify the quantitative characteristics of forming defects and to analyze the effects of process parameters on the forming defects. Results show that the rupture situation is ameliorated and the springback is eliminated in the aluminum alloy hot stamping. The wrinkling severity decreases with increasing blank holder force (BHF), but the BHF greater than 15 kN causes the rupture at the deepest drawing position of workpiece. The forming defects are avoided with lubricant in the feasible ranges of process parameters: the BHF of 3 to 5 kN and the stamping speed of 50 to 200 mm/s.
