Quality risk management in pharmaceutical development

The objective of ICH Q8, Q9 and Q10 documents is application of systemic and science based approach to formulation development for building quality into product. There is always some uncertainty in new product development. Good risk management practice is essential for success of new product development in decreasing this uncertainty. In quality by design paradigm, the product performance properties relevant to the patient are predefined in target product profile (TPP). Together with prior knowledge and experience, TPP helps in identification of critical quality attributes (CQA’s). Initial risk assessment which identifies risks to these CQA’s provides impetus for product development. Product and process are designed to gain knowledge about these risks, devise strategies to eliminate or mitigate these risks and meet objectives set in TPP. By laying more emphasis on high risk events the protection level of patient is increased. The process being scientifically driven improves the transparency and reliability of the manufacturer. The focus on risk to the patient together with flexible development approach saves invaluable resources, increases confidence on quality and reduces compliance risk. The knowledge acquired in analysing risks to CQA’s permits construction of meaningful design space. Within the boundaries of the design space, variation in critical material characteristics and process parameters must be managed in order to yield a product having the desired characteristics. Specifications based on product and process understanding are established such that product will meet the specifications if tested. In this way, the product is amenable to real time release, since specifications only confirm quality but they do not serve as a means of effective process control.     

Søren Bisgaard’s contributions to Quality Engineering: Design of experiments

Abstract

This article examines Søren’s impact on the design and analysis of experiment through three of his published articles in ASQ journals. These articles demonstrate Søren’s unique blend of engineer and statistician with the ability to see the big picture both of the solution to the specific problem and of the solution strategy for good practice. Søren was a giant in our field who was struck down too early in life by mesothelioma at the age of 58 years. His work, and more importantly his impact on his colleagues, has continued to influence the profession.     

Using Experimental Design to Optimize the Process Parameters in Fluidized Bed Granulation

In this study many parameters were screened for a small-scale granulation process for their effect on the yield of granules between 75 and 500 μm and the geometrical granule mean size (d50). First a Plackett-Burman design was applied to screen the inlet air temperature, the inlet flow rate, the spray rate, the nozzle air pressure, the nozzle spray diameter, and the nozzle position. The Plackett-Burman design showed that the key process parameters were the inlet flow rate and the spray rate and probably also the inlet air temperature. Afterward a fractional factorial design (2^5?2) was applied to screen the remaining parameters plus the nozzle aircap position and the spraying time interval. The fractional factorial design showed that the nozzle air pressure was also important. As the target values for the granule yield (between 75 and 500 μm) and the geometric mean granule size (between 300 and 500 μm) were reached during the screening experiments, further optimization was not considered necessary.     

A statistical engineering strategy for mixture problems with process variables

Experimenting with both mixture components and process variables, especially when there is likely to be interaction between these two sets of variables, is discussed. We consider both design and analysis questions within the context of addressing an actual mixture/process problem. We focus on a strategy for attacking such problems, as opposed to finding the best possible design or best possible model for a given set of data. In this sense, a statistical engineering framework is used. In particular, when we consider the potential of fitting parsimonious linear additive or nonlinear models as opposed to larger linearized models, we find potential to reduce the size of experimental designs. It is difficult in practice to know what type of model will best fit the resulting data. Therefore, an integrated, sequential design and analysis strategy is recommended. Using two published data sets and one new data set, we find that in some cases nonlinear models, or linear additive models —with no process/mixture interaction terms, enable reduction of experimentation on the order of 50%. In other cases, additive or nonlinear models will not suffice. We therefore provide guidelines as to when such an approach is likely to succeed, and propose an overall strategy for these types of problems.     

体验设计与数字媒体

在美国、欧洲和中国,数字媒体设计已经迅速发展起来,数字媒体设计已经扩展到其它许多领域——商品工业、计算机高技术业、商业、娱乐业等等。因此,今天的数字媒体设计在新世纪正在扮演重要的角色,并为中国设计提供了新的增长机会和挑战,因为许多人认为数字媒体时代是跟随计算机的数字媒体时代,是支持下一个体验经济的时代。     

基于设计科学的产品设计研究方法综述

目的 智能设计需要符合设计规律的推理机制。目前工业设计师主要是以个人主观意图进行设计,面对国家经济发展的需求,有必要在设计实践的同时,采用科学的方法探究设计规律。方法 采用文献研究方法对比分析设计科学、管理科学、情报学、工程科学领域中有关产品设计方法的研究成果,从设计科学的内涵、研究对象、研究范式和研究方法进行综述,重点对设计思维、设计知识研究方法进行了分析。结论 设计科学是采用科学的研究方法研究人的思维、设计对象、设计过程和设计结果。设计科学研究方法不仅需要规范性研究范式,也需要描述性研究范式,采用基于科学范式的科学方法探究设计规律,才能真正助推智能设计、设计科学和设计学科的发展。     

A Case Study in Design of Expermints: Improving the Manufacture of Viscose Fiber

This case study illustrates how statistical techniques help improve the quality of a manufacturing process. The study shows how well designed experiments advance one's understanding of the underlying process, and it emphasizes the importance of experimentation for attaining knowledge. The investigation involves the production of a certain viscose fiber. The results of a simple fractional factorial experiment with ten factors in 32 runs point to useful strategies for improving fiber strength and fiber elongation. The study also investigates the relationship between the strength and the thickness of the fiber.     

民间美术在平面设计中的应用研究

目的探究民间美术在平面设计中的应用及发展策略。方法以民间美术对平面设计的思维拓展和内涵作为理论支持,分别从招贴设计、包装设计和标志设计3方面辅以实例进行论证,最后探讨民间美术在平面设计中的发展方式。结论将民间美术独特的形式、丰富的内涵融入平面设计中,是平面设计突破传统局限,创造全新的、富含民族特色的设计作品的绝佳之选。     

Design resilience in the fuzzy front end (FFE) context: an empirical examination

This study provides a detailed understanding of the flexibilities that affect performance of innovation projects in the fuzzy front end (FFE) stage. We use the ambidextrous theory approach along with theories on flexibility to propose key drivers of design resilience in innovation projects. A set of six in-depth case studies across a variety of contextual settings is used to investigate important sources of flexibilities that contribute to design resilience. The effects of different design flexibility on the firms’ design resilience are examined. Specifically, an in-depth examination of ‘within case’ trends suggested key design flexibilities to be further examined in the ‘across case’ analyses. Our findings provide valuable insights about the enabling design flexibilities and contextual effects of design resilience in the FFE stage of innovation projects. Based on the findings from the case studies, four sources of design flexibility emerged that vary in terms of their influence on design resilience: (1) iterative learning, (2) modularity, (3) engineering change management and (4) design reuse. Patterns from the ‘across case’ analyses were then used to isolate specific types of design flexibilities that are important for design resilience and organisational resilience. We also provide categorisation of these drivers of design resilience in the context of passive flexibility and active flexibility practices. One of the major contributions of the study is that it provides a detailed categorisation of design resilience in relation to organisational resilience.     

包装设计流程的活性分析模型研究

在资讯化社会快速发展的背景下,通过使用活性系统分析法及工具分析复杂的商业包装设计流程,尝试构建了通用包装设计流程的概念模型,并提出了如何改良的建议和想法。根据改良后的概念模型,开发出了一套集知识管理信息为一体,具有简易操作界面设计的软件工具。利兹大学设计学院的硕士生们,通过对奶酪乳制品进行包装设计的实践创作对软件进行了测试,测试反馈的结果为完善软件的设计提供了一定的支持和帮助。     

Using experimental design to optimize the process parameters in fluidized bed granulation

In this study many parameters were screened for a small-scale granulation process for their effect on the yield of granules between 75 and 500 μm and the geometrical granule mean size (d50). First a Plackett-Burman design was applied to screen the inlet air temperature, the inlet flow rate, the spray rate, the nozzle air pressure, the nozzle spray diameter, and the nozzle position. The Plackett-Burman design showed that the key process parameters were the inlet flow rate and the spray rate and probably also the inlet air temperature. Afterward a fractional factorial design (2^5-2) was applied to screen the remaining parameters plus the nozzle aircap position and the spraying time interval. The fractional factorial design showed that the nozzle air pressure was also important. As the target values for the granule yield (between 75 and 500 μm) and the geometric mean granule size (between 300 and 500 μm) were reached during the screening experiments, further optimization was not considered necessary.     

Design procedures in architectural design: applications in CAAD

Normally, CAAD systems are used at the production end of the design process. Yet there is great potential, particularly with the graphics facility offered by these systems, to use them at the beginning or formative part of the design process.

One problem with this direction lies in the procedures for using these systems. This paper compares traditional procedures for using graphic information with computer-aided procedures and discusses the relative merits of the approaches for the designer.     

国内外设计思维研究热点、趋势及展望

目的 为了更好地把握设计思维相关研究的全局特征,掌握当前设计思维研究进展,对相关文献研究热点和趋势进行可视化图谱分析,探究我国未来设计思维的发展趋势。方法 运用CiteSpace及VOSviewer软件,结合定性的文献研究法,对CNKI与Web of Science数据库中的参考文献进行科学图谱绘制,从研究广度和深度两个方面进行可视化分析,梳理国内外设计思维的研究脉络。结论 国内外设计思维相关文献数量呈上升趋势,国内研究以空间设计、服务与产品设计、艺术教育、其他设计以及思维方式为热点,近年来开辟了乡村振兴、创客教育、STEM教育等研究领域。国外研究热点聚焦于设计管理、创造力、计算机思维、教育以及可持续发展,数字化技术的应用是国外设计思维研究的新方向。     

Design through making: crafts knowledge as facilitator to collaborative new product development

Collaboration between manufacturers and craft makers is believed by many crafts theorists to offer new originality, insight and specialist expertise to design for production. In practice, however, there exists a discrepancy between this ideal and a reality of unreconcilable cultural and methodological differences. This paper documents and discusses such a collaboration as an example of best practice with implications for managers, educators, designers and craft makers. It identifies a new role for craft makers with the appropriate knowledge and experience to act as bridges within companies, facilitating the adoption of design methodologies appropriate to changing priorities in the manufacturing industries.     

采用VBA在AutoCAD中实现设计知识管理

提出了采用VBA技术在AutoCAD中实现设计知识管理的开发方法.从需求出发,设计了功能模块并构建了系统结构.根据设计知识的特点,提出了采用"类"抽象非结构化的知识表达方法及其界面定制的原理;介绍了结构化和非结构化知识管理的具体实现,用户可以在产品设计过程中查询和存储设计知识和经验.     

计算机辅助统计过程控制的设计与实现

文章通过分析实现计算机辅助统计过程控制所需要解决的几个主要问题,提出了计算机辅助统计过程控制系统的整体功能设计方案,并对系统具体功能模块和系统关键技术实现方法进行了详细介绍,最后运用实例对系统的开发做了进一步的说明.     

Power of experimental design studies for the validation of pharmaceutical processes: case study of a multilayer tablet manufacturing process

Experimental design studies (EDS) are already widely used in the pharmaceutical industry for drug formulation or process optimization. Rare are the situations in which this methodology is applied for validation purposes. The power of this statistical tool, key element of a global validation strategy, is demonstrated for a multilayer tablet manufacturing process. Applied to the Geomatrix® system generally composed of one compression and three granulation processes, time and strictness gains are non-negligible. Experimental design studies are not used in this work for modeling. Introduced at each important step of the process development, they allow for the evaluation of process ruggedness at pilot scale and specifications for full production. A demonstration of the complete control of key process parameters is given, identified throughout preliminary studies.     

浅谈陶瓷膜装置在制药生产中设计和选型时应注意的问题

在制药生产中,发酵液的特点是菌丝浓度高、黏度大.陶瓷膜在制药生产中主要应用在预处理方面,由于设计和选型上的失误,导致使用效果并不理想.指出在设计和选型时特别要引起重视的方面有管路设计、膜芯孔径大小、串联级数、以及循环泵的选型.     

基于全生命周期理念的制造业设计转型路径研究

目的 探究中国制造业高质量发展策略和工业设计转型升级路径。方法 以全生命周期理念为思想指引,根据制造业的发展现状以及工业设计与制造业的三个发展时期,对制造业高质量发展的设计策略及设计转型路径模式进行探讨。结果 在全生命周期理念的指导下,总结出企业全生命周期设计思维模型、工业设计赋能制造业高质量发展的设计策略模型以及覆盖全生命周期的制造业设计转型路径思路。结论 以全生命周期设计思维为指导,总结出数字化转型、全生命周期管理、全生命周期评价、设计服务与体验、全产业链融合、设计教育新范式等六大制造业设计转型和高质量发展路径。     

Media milling process optimization for manufacture of drug nanoparticles using design of experiments (DOE)

Design of experiments (DOE), a component of Quality by Design (QbD), is systematic and simultaneous evaluation of process variables to develop a product with predetermined quality attributes. This article presents a case study to understand the effects of process variables in a bead milling process used for manufacture of drug nanoparticles. Experiments were designed and results were computed according to a 3-factor, 3-level face-centered central composite design (CCD). The factors investigated were motor speed, pump speed and bead volume. Responses analyzed for evaluating these effects and interactions were milling time, particle size and process yield. Process validation batches were executed using the optimum process conditions obtained from software Design-Expert® to evaluate both the repeatability and reproducibility of bead milling technique. Milling time was optimized to <5?h to obtain the desired particle size (d90?相似文献