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.

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.

Analysis of Compliance Management Practice of American Drug Registration Applicants and Its Enlightenment to China

In order to achieve the goal of drug safety, effectiveness and quality control, corporate compliance management construction is significant. Therefore, this paper systematically analyzes the seven elements of compliance management for U.S. pharmaceutical manufacturers as described in the Compliance Program Guidance for Pharmaceutical Manufacturers issued by the HHS-Office of Inspector General, as well as further analyzes the implementation of the guidance by representative multinational companies in different drug registration stages. Finally, some suggestions and implications are proposed to strengthen the construction of compliance management for Chinese drug registration applicants based on the former practical experience.

Three-Year Consecutive Field Application of Erythromycin Fermentation Residue Following Hydrothermal Treatment:Cumulative Effect on Soil Antibiotic Resistance Genes

Fermentation-based antibiotic production results in abundant nutrient-rich fermentation residue with high potential for recycling,but the high antibiotic residual concentration restricts its usefulness(e.g.,in land application as organic fertilizer).In this study,an industrial-scale hydrothermal facility for the treatment of erythromycin fermentation residue(EFR)was investigated,and the potential risk of the long-term soil application of treated EFR promoting environmental antibiotic resistance development was evaluated.The treatment effectively removed bacteria and their DNA,and an erythromycin removal ratio of up to approximately 98%was achieved.The treated EFR was utilized as organic fertilizer for consecutive field applications from 2018 to 2020,with dosages ranging from 3750 to 15000 kg·hm^(-2),resulting in subinhibitory levels of erythromycin(ranging from 0.83-76.00μg·kg^(-1))in soils.Metagenomic shotgun sequencing was then used to characterize the antibiotic resistance genes(ARGs),mobile genetic elements(MGEs),and bacterial community composition of the soils.The soil ARG abundance and diversity did not respond to the treated EFR application in the first year,but gradually changed in the second and third year of application.The highest fold change in relative abundance of macrolide-lincosamide-streptogramin(MLS)and total ARGs were 12.59 and 2.75 times,compared with the control(CK;without application),respectively.The soil MGEs and taxonomic composition showed similar temporal trends to those of the ARGs,and appeared to assist in driving increasing ARG proliferation,as revealed by correlation analysis and structural equation models(SEMs).The relative abundance of particular erm resistance genes(RNA methyltransferase genes)increased significantly in the third year of treated EFR application.The close association of erm with MGEs suggested that horizontal gene transfer played a critical role in the observed erm gene enrichment.Metagenomic binning results demonstrated that the proliferation of mac genecarrying hosts was responsible for the increased abundance of mac genes(efflux pump genes).This study shows that sub-inhibitory levels of erythromycin in soils had a cumulative effect on soil ARGs over time and emphasizes the importance of long-term monitoring for assessing the risk of soil amendment with treated industrial waste.

Metagenomic insights into microorganisms and antibiotic resistance genes of waste antibiotic fermentation residues along production,storage and treatment processes

Antibiotic fermentation residue(AFR)is nutrient-rich solid waste generated from fermentative antibiotic production process.It is demonstrated that AFR contains high-concentration of remaining antibiotics,and thus may promote antibiotic resistance development in receiving environment or feeding farmed animals.However,the dominate microorganisms and antibiotic resistance genes(ARGs)in AFRs have not been adequately explored,hampering understanding on the potential antibiotic resistance risk development caused by AFRs.Herein,seven kinds of representative AFRs along their production,storage,and treatment processes were collected,and multiple methods including amplicon sequencing,metagenomic sequencing,and bioinformatic approaches were adopted to explore the biological characteristics of AFRs.As expected,antibiotic fermentation producer was found as the predominant species in raw AFRs,which were collected at the outlet of fermentation tanks.However,except for producer species,more environment-derived species persisted in stored AFRs,which were temporarily stored at a semi-open space.Lactobacillus genus,classified as Firmicutes phylum and Bacilli class,became predominant bacterial taxa in stored AFRs,which might attribute to its tolerance to high concentration of antibiotics.Results from metagenomic sequencing together with assembly and binning approaches showed that these newly-colonizing species(e.g.,Lactobacillus genus)tended to carry ARGs conferring resistance to the remaining antibiotic.However,after thermal treatment,remaining antibiotic could be efficiently removed from AFRs,and microorganisms together with DNA could be strongly destroyed.In sum,the main risk from the AFRs was the remaining antibiotic,while environment-derived bacteria which tolerate extreme environment,survived in ARFs with high content antibiotics,and may carry ARGs.Thus,hydrothermal or other harmless treatment technologies are recommended to remove antibiotic content and inactivate bacteria before recycling of AFRs in pharmaceutical industry.

Micro/nano flow chemistry by Beyond Limits Manufacturing

In September 2018,we proposed the cutting-edge concept of“Beyond Limits Manufacturing”(BLM).BLM technology is based on the three-dimensional inner engraving or precise outer engraving of ultra-fast laser,to invent micro/nano scale flow chips or devices,which makes it possible for the microform,integration,economy,safety,high efficiency,green and intelligence of research,development and manufacturing process,so as to realize transformational manufacturing in the era of Industry 4.0.In this paper,we reviewed the representative results we made in the field of micro/nano flow chemistry during the implementation of the BLM major project(December 2019 to August 2023),and discussed its application prospects in micro/nano flow chemistry.