Perspectives on the flexibility analysis for continuous pharmaceutical manufacturing processes

Pharmaceutical continuous manufacturing,especially under the context of COVID-19 pandemic,is regarded as an emerging technology that can guarantee the adequate quality assurance and mitigate process risk while guaranteeing the desirable economic performance.Flexibility analysis is one approach to quantitively assess the capability of chemical process to guarantee feasible operation in face of variations on uncertain parameters.The aim of this paper is to provide the perspectives on the flexibility analysis for continuous pharmaceutical manufacturing processes.State-of-the-art and progress in the flexibility analysis for chemical processes including concept evolution,mathematical model formulations,solution strategies,and applications are systematically overviewed.Recent achievements on the flexibility/feasibility analysis of the downstream dosage form manufacturing process are also touched upon.Further challenges and developments in the field of flexibility analysis for novel continuous manufacturing processes of active pharmaceutical ingredients along with the integrated continuous manufacturing processes are identified.

Next 10 years in pharmaceutical manufacturing information technology

Today the ASEAN Pharmaceutical manufacturing companies are still focusing on their local countries,with the exception of a fewlarge regionals who are already and increasingly looking and capable to export to the outside markets such as Europe.This means that the majority of companies producing medicinal products to higher regulatory standards have less international experience/exposure in handling the GMP requirements demanded by PIC/s[1].In addition most of their processes are manual with legacy practices,and mostly the data and controls are in paper with a very high amount of data made with pen and paper on numerous human reviews of documentation mainly to assess the data is complete but not for accuracy of the data at the time that action could be taken—data integrity on paper has been shownto be highly questionable.

Impact of H1N1, H7N9, ASFV, dengue virus and COVID-19 on pharmaceutical manufacturing firms' R&D investments and economic consequences: Evidence from China

Objective:To determine the impact of major disease epidemics on pharmaceutical manufacturing firms'Research&Development(R&D)investments and economic consequences.Methods:The sample consists of 1582 firm-year observations from 2009 to 2022 in China,of which,26.6%of pharmaceutical companies are involved in the diagnosis and treatment of prevalent diseases.Linear models using R&D investments,patent applications,operating performances and stock returns as dependent variables are constructed separately to examine the response of pharmaceutical companies to disease epidemics and the resulting economic consequences.Results:The prevalence of five major diseases led to a 17.5%increase in the amount of R&D investment and an 87.8%rise in the ratio of R&D investment to total assets by disease-related pharmaceutical companies,compared to unrelated pharmaceutical companies.Further evidence indicated that the patent applications for disease-related firms increased by 44.3%relative to unrelated firms after the epidemics.Though the impacts of the epidemics on firms’operating performances were insignificant in the short term,a major disease epidemic was associated with an increase in stock returns of 67.4%and 44.6%,respectively,as measured by the capital asset pricing model and Fama-French five-factor model.Additional analysis revealed that the impacts of the epidemics on R&D investments and patent applications were more pronounced for non-state-owned enterprises than state-owned enterprises.Conclusions:This study demonstrates that disease-related pharmaceutical firms respond to the disease epidemics through increasing R&D investment.More patent applications and higher market value are the main gains from the firms’increased investments in R&D following the epidemic,rather than the improvements of short-term operating performances.

Study on Carbon Emission Efficiency Evaluation and Influencing Factors of Chinese Pharmaceutical Manufacturing Industry

To measure the carbon emission efficiency of China’s pharmaceutical manufacturing industry, explore the factors affecting the carbon emission efficiency of China’s pharmaceutical manufacturing industry, and provide reference for improving the carbon emission efficiency of China’s pharmaceutical manufacturing industry and promoting the government to formulate macro policies. Based on the data of the pharmaceutical manufacturing industry in 30 provinces of China from 2010 to 2019, and based on the SBM model and ML (Malmquist-Luenberger) index model, the carbon emission efficiency of the pharmaceutical manufacturing industry was calculated and its dynamic change was investigated, and the Tobit model was further used to explore the influencing factors of the carbon emission efficiency of the pharmaceutical manufacturing industry. The carbon emission efficiency of China’s inter-provincial pharmaceutical manufacturing industry has steadily improved. The carbon emission efficiency of the eastern region is higher than that of the western region, and that of the western region is higher than that of the central region. The eastern region is dominated by technological progress, and there is room for improvement in technological efficiency. The central and western regions are dominated by technological efficiency. Compared with technological efficiency, technological progress needs to be further improved. Environmental regulation, industrial agglomeration and technological innovation level positively affect carbon emission efficiency, while foreign investment level has no significant impact on carbon emission efficiency.

Research and Practice on Curriculum Reform of Chinese Pharmaceutical Manufacturing Major against the Backdrop of"Comprehensive Health"

Against the backdrop of Comprehensive Health,the Chinese Pharmaceutical Manufacturing major faces both opportunities and challenges.This paper describes some problems encountered in the development of the Chinese Pharmaceutical Manufacturing major,puts forward some suggestions and measures to adapt to the training of talents of Chinese pharmaceutical manufacturing against the backdrop of Comprehensive Health,and discusses the practical research on curriculum reform.

The Relationship between the Performance of Listed Companies in Pharmaceutical Manufacturing and Inventory Turnover, Operating Rate

As an important part of the pharmaceutical industry, the pharmaceutical manufacturing industry is always at the battlefield of the international public health and health industry. At the same time, as a basic and strategic sub-industry in China's manufacturing industry, the medical manufacturing industry closely related to people’s livelihood which is not only related to social Responsibility but also plays a key role in China's economy today. For the Chinese people, the new medical reforms and the irreversible aging of the population have increased the nation’s total expenditure on health care. From January to October 2017, the pharmaceutical industry’s main business income was RMB 2,410.29 billion, a year-on-year increase of 13.10%. This is a 4.50 percentage point higher than the 10.30% growth rate in 2016. However, even if the circumstance of this industry is getting better, high growth also has a drag on the national health insurance system and the standard of living of the people. This article chooses to analyze the financial and operating-level factors of China's pharmaceutical manufacturing listed companies such as Inventory turnover rate and operating rate. Study the impact on the performance of China's pharmaceutical manufacturing listed companies. The results of the study will fill gaps in the research of this industry and help pharmaceutical manufacturing listed companies choose the right capital size, liabilities, and expansion strategies, and more effectively absorb the current development dividends of China’s “four new economy”, and use them rationally and effectively. Markets and complex and limited capital and resources of enterprises, as China's industry benchmarks continue to guide the rapid growth of the market. on the other hand, to help investor the empirical point of view better choice of investment targets. This paper uses data from 2007-2016 for randomly selecting 19 companies from 118 medical manufacturing listed companies classified by China Securities Regulatory Commission. After dealing with panel data, multiple inspections are performed on panel data. To avoid the deviation from the actual level of the regression results, the panel-corrected standard deviation model was used to derive the relationship between the operating-level factors of pharmaceutical manufacturing listed companies and their performance. The results of the study indicate that there is a positive correlation between Inventory turnover rate, operating rate and performance, which fills the domestic empirical research on this issue. This area of industry company performance is blank.

Empirical Study of the Relations between Executive Compensation Gap and R&D Investment in Pharmaceutical Manufacturing Enterprises

Objective To study the correlation between executive compensation gap and R&D investment of pharmaceutical manufacturing enterprises in China by taking 53 pharmaceutical manufacturing companies in Shanghai and Shenzhen stock exchanges from 2015 to 2017 as research samples. Methods Multiple linear regression methods was used to study the relationship and influence between executive compensation gap and R&D investment in pharmaceutical manufacturing industry based on championship theory and principal-agent theory. Results and Conclusion There is a significant positive correlation between executive compensation gap in pharmaceutical manufacturing industry and enterprise R&D investment. Listed pharmaceutical manufacturing enterprises should design reasonable salary gap between senior executives and carry out reasonable research and development activities to promote the sustainable development of pharmaceutical manufacturing enterprises. This study provides theoretical basis for optimizing executive compensation gap and increasing R&D investment in pharmaceutical manufacturing industry.

Process analytical technologies and self-optimization algorithms in automated pharmaceutical continuous manufacturing

The pharmaceutical industry is now paying increased attention to continuous manufacturing.While the revolution to continuous and automated manufacturing is deepening in most of the top pharma companies in the world,the advancement of automated pharmaceutical continuous manufacturing in China is relatively slow due to some key challenges including the lack of knowledge on the related technologies and shortage of qualified personnels.In this review,emphasis is given to two of the crucial technologies in automated pharmaceutical continuous manufacturing,i.e.,process analytical technology(PAT)and self-optimizing algorithm.Research work published in recent 5 years employing advanced PAT tools and self-optimization algorithms is introduced,which represents the great progress that has been made in automated pharmaceutical continuous manufacturing.

Advances in Medical Applications of Additive Manufacturing

In the past few decades,additive manufacturing(AM)has been developed and applied as a cost-effective and versatile technique for the fabrication of geometrically complex objects in the medical industry.In this review,we discuss current advances of AM in medical applications for the generation of pharmaceuticals,medical implants,and medical devices.Oral and transdermal drugs can be fabricated by a variety of AM technologies.Different types of hard and soft clinical implants have also been realized by AM,with the goal of producing tissue-engineered constructs.In addition,medical devices used for diagnostics and treatment of various pathological conditions have been developed.The growing body of research on AM reveals its great potential in medical applications.The goal of this review is to highlight the usefulness and elucidate the current limitations of AM applications in the medical field.

Flexibility analysis for continuous ibuprofen manufacturing processes

Continuous ibuprofen(a widespread used analgesic drug)manufacturing is full of superiorities and is a fertile field both in industry and academia since it can not only effectively treat rheumatic and other chronic and painful diseases,but also shows great potential in dental diseases.As one of central elements of operability analysis,flexibility analysis is in charge of the quantitative assessment of the capability to guarantee the feasible operation in face of variations on uncertain parameters.In this paper,we focus on the flexibility index calculation for the continuous ibuprofen manufacturing process.We update existing state-of-the-art formulations,which traditionally lead to the max-max-max optimization problem,to approach the calculation of the flexibility index with a favorable manner.Advantages regarding the size of the mathematical model and the computational CPU time of the modified method are examined by four cases.In addition to identifying the flexibility index without any consideration of control variables,we also investigate the effects of different combinations of control variables on the flexibility property to reveal the benefits from taking recourse actions into account.Results from systematic investigations are expected to provide a solid basis for the further control system design and optimal operation of continuous ibuprofen manufacturing.

Smart Process Manufacturing for Formulated Products

We outline the smart manufacturing challenges for formulated products, which are typically multicom- ponent, structured, and multiphase. These challenges predominate in the food, pharmaceuticals, agricul- tural and specialty chemicals, energy storage and energetic materials, and consumer goods industries, and are driven by fast-changing customer demand and, in some cases, a tight regulatory framework. This paper discusses progress in smart manufacturing namely, digitalization and the use of large data- sets with predictive models and solution- nding algorithms in these industries. While some progress has been achieved, there is a strong need for more demonstration of model-based tools on realistic prob- lems in order to demonstrate their bene ts and highlight any systemic weaknesses.

中药工业智能制造转型模式及监管问题探讨

中药制药工业质量控制水平的提升需要以科技创新为引领,以先进制药工程技术为支撑。智能制造融合了先进制造技术与信息技术,已经成为提高制造业质量与效益的先进生产方式。本研究聚焦中药工业实施智能制造重大战略工程,根据中药产品质量及其制造流程的特点,结合中药制药工业面临的管控问题以及智能制造技术特征,提出中药产业发展智能制造的转型方向,核心包括由基于经验的控制向以数据为驱动力的控制转型、产品检验向过程管控转型、分散向集成转型,以及药品制造向药品全生命周期服务转型等领域的突破。总结近年来中药标杆性企业在智能制造技术研究方面取得的成果以及产业转化进展,讨论中药产业在智能制造转型过程中面临的监管问题,以期为中药工业实施智能制造项目的系统架构规划与技术路线设计提供参考。

利用纳滤传质模型定量计算迷迭香酸分子状态的实验教学设计

该文设计了利用纳滤传质模型定量计算迷迭香酸分子状态的教学实验。实验以丹参中代表性的酚酸为研究对象,计算了迷迭香酸的纳滤膜通量、传质系数和截留率,构建了迷迭香酸分子态比例定量计算数学模型,对制药过程中的醇沉、树脂吸附、澄清过滤、浓缩、干燥等工艺的转移率和成分存在状态进行了相关性分析,研究了制药工艺成分量值传递的内在机制。实验结果表明,迷迭香酸存在状态对制药工艺中的成分转移率有重要影响。这一结论对提升生产过程的规范化和标准化很有意义。本实验与制药生产热点问题相结合,通过科研反哺教学,有助于增强学生的科研素养和实践能力,并实现科研应用与教学拓展的协同提升。

管理层薪酬差距对医药制造企业技术创新影响

企业为了保持在市场上长期稳定和市场竞争力,创新成为必不可少的一环,优化企业薪酬结构有利于激发企业活力并进一步促进企业技术创新。本文选取中国2010—2021年A股上市公司中医药制造企业的数据,采用多种回归模型对管理层内外部薪酬差距对企业技术创新的影响进行实证。研究发现,对于医药制造企业,管理层内外部薪酬差距对企业技术创新具有正向作用。对于模型的选取,管理层内部薪酬差距数据的右偏特性使其对技术创新绩效的影响使用Tobit模型更为妥当;对于管理层外部薪酬差距,双重差分模型和Logit模型结合使用更为适合,Logit模型可以从整体上分析,而双重差分模型可以将政策影响纳入其中。医药制造企业可以适当提高关键管理层的薪酬水平,拉大管理层内外薪酬差距,激发管理者工作积极性,提高企业技术创新动力与效率。

我国医药制造业研发投入状况及其影响的实证研究

目的 分析我国医药制造业研发投入现况,探索其对科技创新产出的影响,进而为卫生健康科技创新投入提出相关建议。方法 收集2009年1月至2020年12月我国内地31个省、自治区、直辖市(不含港、澳、台)医药制造业研究与试验发展(R&D)支出、R&D活动企业数、R&D人员数、R&D人员全时当量、年人均卫生费用、每千人卫生人员数、人均受教育年限和有效发明专利数等数据,运用描述性统计分析医药制造业研发投入的变化趋势、区域差距,建立面板数据计量经济学模型,分析医药制造业研发投入对有效发明专利数的影响作用。结果 2009—2020年,我国医药制造业R&D经费投入总量从154.5亿元上升到906.5亿元,总体增长486.7%,年均增长17.5%。面板计量经济学模型结果显示,创新企业个数、医药制造业研发投入和年人均卫生费用对有效发明专利数的影响有统计学意义,具体为:每增加1个R&D活动企业,有效发明专利增加3.884个;R&D投入每增加1万元,有效发明专利增加0.004个;年人均卫生费用每增加1元,有效发明专利增加0.081个。结论 2009—2020年,我国医药制造业研发投入对科技创新作用的推动作用具有积极意义,建议未来进一步加强对医药创新企业的支持,继续增加医药制造业研发投入,并促进健康服务业发展,以加快我国卫生健康科技创新。

医药制造企业“漂绿”行为的组态路径研究——基于MOA理论的定性比较分析

为分析企业“漂绿”行为的影响因素,以2022年48家医药制造企业为研究对象,以MOA理论为理论基础,采用fsQCA方法探讨动机、机会和能力三方面要素组合对企业“漂绿”行为的影响。研究发现:单个因素都不是构成医药制造企业高“漂绿”行为的必要条件;驱动医药制造企业“漂绿”行为的路径有3条,分别命名为“外部压力下一股独大型”“同构压力与环境规制共驱型”“外部压力与内部制衡共驱型”;盈利能力和同构压力存在替代效应,两者都可在股权制衡力度弱以及媒体监督强的组合中,致使企业产生“漂绿”行为。研究结论有助于从组态视角丰富企业“漂绿”行为驱动因素的相关研究,为治理企业“漂绿”行为提供战略性参考。

《中国医药产业高质量发展状况调研(2021-2023)》研究报告综述

目的:了解“十四五”以来我国医药产业高质量发展转轨和运行状况,梳理监管政策在产业高质量发展转轨中的影响和作用,探讨医药产业迈向高质量发展进程中面临的挑战,对进一步深化医药产业高质量发展提出思考和策略建议。方法:通过文献研究、问卷调查、访谈、专家咨询等方式,获取相关政策信息、数据、业界观点等,同时组织专家研讨作为项目研究支撑。结果:我国医药产业积极应对经济下行压力,表现出了良好的产业发展韧性,新药审评上市数量、审评速度与新药临床价值都跃升到新高度,与此同时,中药行业发展表现相对突出,药品制造升级稳步推进,监管科学项目成果丰富。结论:我国医药产业正在以高质量发展转型为方向积极进行深度调整,目前已在研发创新、制造升级、中药守正创新等方面取得了积极进展,同时在研发策略与资金支持、中药传承创新、国际化发展、保障供应链稳定可控等方面仍然存在挑战,建议在进一步转变研发策略、建立多元化筹资体系、完善国际化配套政策、坚持中药特色监管、深化监管科学行动计划、强化监管能力建设、促进“三医”协同等方面发力,有效助推医药产业高质量发展。

数字化转型背景下企业绿色创新绩效组态分析--基于TOE框架的fsQCA研究

绿色创新作为企业高质量发展的关键选择,在不同的数字化转型模式下呈现出不同的绿色创新绩效。文章以中国A股医药制造企业为研究对象,基于TOE框架选取技术、组织和环境三个维度以及6个具有代表性的前因条件,采用模糊集定性比较分析方法,从组态视角探讨了不同数字化转型条件下企业获得高绿色创新绩效的条件组合。研究发现,高绿色创新绩效可归纳为雄狮型(数字技术应用驱动型)和群狼型(数字转型战略-数字合作环境共同驱动型)两种模式;数字技术应用与数字技术人才两个条件变量之间存在替代效应。企业应充分认识到不同条件组态的殊途同归效应,主动适应所在地的数字环境条件,注重数字组织与数字环境的适配,从而有效开展绿色创新活动。

膜分离技术在中药现代化中的应用:进展、难点及发展方向

综述了膜技术在中药现代化进程中包括有效成分的提取和浓缩、中药制剂的制备等方面的应用,探讨了膜技术在中药制药中面临的挑战,基于膜污染与使用寿命、规模化应用等提出了解决思路。针对目前膜技术在中药现代化中的应用多数仍处于实验探索研究阶段这一现状,从膜材料创新等角度结合可持续发展、绿色制药等理念对未来的发展方向作了展望。

医药制造企业技术竞合平衡能提高产品创新绩效吗?

医药制造企业产品(药品)创新会带来巨大的经济效益和社会效益,药企如何在技术领域平衡竞争与合作的双元关系以提升产品创新绩效,成为学界和业界普遍关注的议题。在改进传统机械平衡法的基础上,采用有机平衡法探究企业技术竞合平衡对产品创新绩效的作用,以2007~2022年沪深两市215家医药制造企业为样本,运用面板负二项模型进行实证检验。研究结果发现:医药制造企业平衡技术竞争与技术合作两种矛盾关系不仅会产生机会主义风险,还会消耗组织资源、挤占产品创新所需资源,导致技术竞合平衡与产品创新绩效存在显著的负向关系;严格的地区知识产权保护将提高药品侵权成本,抑制竞合伙伴的机会主义行为,地区知识产权保护显著削弱了医药制造企业技术竞合平衡与产品创新绩效之间的负向关系。