An Evaluation of the Coupling Coordination of Technological Innovation System in China’s Marine Biopharmaceutical Industry

The marine biopharmaceutical industry(MBI)has been considered as an important part of the blue economy.The high-quality development of this industry depends on the high-level coordinated development of technological innovation system(TIS).In the present study,the coupling mechanism of industrial innovation input subsystem and innovation output subsystem was analyzed for the first time.On this basis,the development level and coupling coordination level of TIS in China’s MBI during 2008-2018 were empirically evaluated with the capacity coupling coordination model.Then,the obstacle factors were diagnosed and recognized with the obstacle model.The results showed that the innovation input index fluctuated at a low level in China’s MBI.The innovation output index has basically maintained a growth trend,whereas the quality of development was not high.Although the coupling coordination level of TIS showed a positive change as mild disordered→primary coordinated→well-coordinated,the development type of innovation system has changed from the lagging output of innovation into the lagging input of innovation.Insufficient input of innovation factors remained the main obstacle to the improvement of coordination level.Based on the above analysis,suggestions were put forward from the perspectives of policy and fund guarantees to improve the coupling coordination level in China’s MBI.

Research on the Construction of Evaluation Model for the Development of Biopharmaceutical Park in China

Objective To study the influencing factors on the development of biopharmaceutical park,and to construct an evaluation model of the influencing factors for biopharmaceutical park in China.Methods By analyzing various factors affecting biopharmaceutical parks,an evaluation index system of biopharmaceutical parks and an evaluation model of influencing factors of biopharmaceutical park development based on fuzzy group decision making were established.Results and Conclusion Factors such as research and development(R&D)funding investment,incentive for transformation of scientific and technological achievements,and industrial clusters have a greater impact on the development of biopharmaceutical industrial parks in China.Local governments should increase the investment in R&D funding.Besides,they should pay attention to the incentive of transformation of scientific and technological achievements to improve the innovation ability of enterprises.Meanwhile,they should promote the clustering of high-tech enterprises to comprehensively enhance the healthy development of biopharmaceutical parks in China.

Research on the Countermeasures for the Development of Biopharmaceutical Industrial Parks in China

Objective To systematically analyze the current development status of biopharmaceutical industrial park in China,sort out the problems and put forward some countermeasures and suggestions.Methods Relevant literature was searched and reviewed to find out the problems faced by the development of biopharmaceutical industrial parks in China.Results and Conclusion Biopharmaceutical industrial parks are developing rapidly due to their unique industrial clustering advantages,but there are problems such as lack of overall planning at the top level,insufficient government support,imperfect talent support services and weak innovation capacity of the parks.It is recommended to promote the rapid development of biopharmaceutical industrial parks and biopharmaceutical enterprises by strengthening top-level design,increasing government support,focusing on talent introduction,and enhancing the innovative strength of the parks.

The potential of ionic liquids in biopharmaceutical engineering

Biopharmaceuticals,such as proteins,peptides,nucleic acids and vaccines,bring about great hopes for the prevention and treatment of various diseases,but the industrialization of these products still faces challenges such as structural instability,inefficient bioactivity and low bioavailability.Ionic liquids(ILs),the marvelous solvent media with inimitable and tunable properties,may provide alternative solutions to overcome the above problems of biopharmaceutical industry.Progress has gradually been made through studies by combination of ILs with biomacromolecules.The applications involved the stabilization,protection,and delivery of biopharmaceuticals.Recent trends are being forwarded to using ILs in vaccines and nucleic acid drugs.However,challenges remain on the toxicity and safety issues.Besides,the cost of adding ILs to the benefits of biopharmaceuticals need to be considered.

Biopharmaceuticals for prevention of COVID-19:A scoping review

The COVID-19 epidemic caused by SARS-CoV-2 virus has turned into a worldwide pandemic.Therefore,health officials all around the world have strived for developing efficient preventive and treatment methods to deal with this global crisis.Amongst them,monoclonal antibodies,anti-TNFs,and convalescent plasma appear to be effective against this disease.In addition,clinical trials are currently being conducted for viral targeting vaccines.This review summarizes major advances using biopharmaceuticals in the treatment and prevention strategies against COVID-19 that have occurred in the global medicinal system from its introduction until March 2022.

Personnel Cultivation Program for Innovative and Entrepreneurial Biopharmaceutical Discipline under the Credit System

Biopharmaceutical discipline is an interdisciplinary subject with strong comprehensiveness and wide coverage. Under the background of credit system,it is an important task for application-oriented undergraduate colleges and universities to optimize the cultivation program for innovative and entrepreneurial bio-pharmaceutical professionals. According to the characteristics of biopharmaceutical discipline,Binzhou University biopharmaceutical teaching and research office,based on the social demand for biopharmaceutical discipline talents,defined the principle of optimizing the cultivation of innovative and entrepreneurial biopharmaceutical discipline talents,and constructed the cultivation program of innovative and entrepreneurial biopharmaceutical discipline talents under the credit system. The development of this cultivation program is expected to build a new mode for cultivating high-level biopharmaceutical professionals with strong innovative spirit and entrepreneurial potential.

Exploration and Practice on the Construction Mode of Biopharmaceutical Training Base in Application-based Colleges and Universities

By using the methods of literature analysis,field investigation,exploration and research,experience summary,comparative inductive analysis,etc.,through the search of the latest literature and policy materials,production enterprises and domestic application-based undergraduate universities with related majors have been investigated on the spot.By analyzing the failed cases and drawing lessons from the successful experience,this paper explores the transformation and practical construction of the biopharmaceutical training base in application-based colleges and universities.This paper innovates and designs a new construction mode of biopharmaceutical training base in application-based universities,which provides reliable experience and valuable research results for the construction or transformation of biopharmaceutical training base in application-based colleges and universities.It has a very important potential value for promoting the social and economic benefits.

Analysis of Technological Opportunities in Liaoning Biopharmaceutical Industry from the Perspective of Innovation Subject

Objective To provide suggestions for supporting the key innovation subjects in Liaoning biopharmaceutical industry and selecting high quality cooperation partners from other provinces and cities.Methods Through statistical analysis of the invention patent data of biological pharmaceutical industry in Liaoning Province and other provinces,Excel was used to draw charts and to identify technical opportunities and other provinces.Then the innovation subjects in Liaoning Province and other provinces were studied separately to realize these opportunities.That is,the high quality partners from other provinces were selected for key innovative subjects in Liaoning Province.Results and Conclusion The key innovation subjects in the core technology field of Liaoning biopharmaceutical industry are Shenyang Agricultural University and Dalian University of Technology,which can be supported by emphasis.Their high quality partners in Beijing,Jiangsu Province and Guangdong Province are China Agricultural University,Jiangnan University and South China Agricultural University respectively.

Research on the Status Quo and Countermeasures of Patent Application in Liaoning Biopharmaceutical Industry Based on Patent Map

Objective To study the patent map and the relevant theories of the patent development of biopharmaceutical industry for conducting a comprehensive and in-depth analysis of the problems in patent application in Liaoning biopharmaceutical industry.Methods Literature review,information visualization method,empirical analysis method and comparative analysis method were used to research the problems in the patent application.Results and Conclusion While developing biopharmaceutical industry,Liaoning provincial government should strengthen the protection of pharmaceutical patents,creating a new R&D mode of“university+research institutes+enterprises+individuals”to broaden the scope of technical fields.Then,its biopharmaceutical industry will be developed in an all-round way.Besides,it should closely follow the national development direction so that the biopharmaceutical industry in Liaoning Province will have a bright future.

VOC emitted by biopharmaceutical industries:Source profiles,health risks,and secondary pollution

The biopharmaceutical industry contributes substantially to volatile organic compounds(VOCs)emissions,causing growing concerns and social developmental conflicts.This study conducted an on-site investigation of the process-based emission of VOCs from three biopharmaceutical enterprises.In the workshops of the three enterprises,26 VOCs were detected,which could be sorted into 4 classes:hydrocarbons,aromatic hydrocarbons,oxygen-containing compounds,and nitrogen-containing compounds.Ketones were the main components of waste gases,accounting for 44.13%-77.85%of the overall VOCs.Process-based source profiles were compiled for each process unit,with the fermentation and extraction units of tiamulin fumarate being the main source of VOC emissions.Dimethyl heptanone,vinyl acetate,diethylamine,propylene glycol methyl ether(PGME),and benzene were screened as priority pollutants through a fuzzy comprehensive evaluation system.Ground level concentration simulation results of the Gauss plume diffusion model demonstrated that the diffusivity of VOCs in the atmosphere was relatively high,indicating potential non-carcinogenic and carcinogenic risks 1.5-2 km downwind.Furthermore,the process-based formation potentials of ozone and secondary organic aerosols(SOAs)were determined and indicated that N-methyl-2-pyrrolidone,dimethyl heptanone,and PGME should be preferentially controlled to reduce the ozone formation potential,whereas the control of benzene and chlorobenzene should be prioritized to reduce the generation of SOAs.Our results provide a basis for understanding the characteristics of VOC emission by biopharmaceutical industries and their diffusion,potentially allowing the development of measures to reduce health risks and secondary pollution.

Cyclodextrin Based Host-Guest Inclusion Complex, an Approach to Enhancing the Physicochemical and Biopharmaceutical Application of Poorly Water-soluble Drugs

Host-guest inclusion complexes have been extensively studied for drug delivery applications.The host molecule,typically cyclodextrin,creates a cavity,in which the guest molecule,such as a drug,can be encapsulated.This encapsulation can protect the drug from degradation,improve its solubility and stability,and enhance its bioavailability.Moreover,host-guest inclusion complexes can facilitate targeted drug delivery by selectively releasing drugs at the site of action.Various techniques,such as covalent bonding,non-covalent interactions,and self-assembly have been used to form these complexes.Host-guest inclusion complexes have shown great potential for improving the efficacy and safety of drug delivery systems.This mini review summarizes the application and recent progress of the cyclodextrin-based host-guest inclusion complex,highlighting the enhanced physicochemical and biopharmaceutical application of pharmaceutical drugs via formulation of its inclusion complex.

Bioreactor control systems in the biopharmaceutical industry:a critical perspective

Industrial-scale bioprocessing underpins much of the production of pharmaceuticals,nutraceuticals,food,and beverage processing industries of the modern world.The proftability of these processes increasingly leverages the economies of scale and scope that are critically dependent on the product yields,titers,and productivity.Most of the processes are controlled using classical control approaches and represent over 90%of the industrial controls used in bioprocessing industries.However,with the advances in the production processes,especially in the biopharmaceutical and nutraceutical industries,monitoring and control of bioprocesses such as fermentations with GMO organisms,and downstream processing has become increasingly complex and the inadequacies of the classical and some of the modern control systems techniques is becoming apparent.Therefore,with increasing research complexity,nonlinearity,and digitization in process,there has been a critical need for advanced process control that is more efective,and easier process intensifcation and product yield(both by quality and quantity)can be achieved.In this review,industrial aspects of a process and automation along with various commercial control strategies have been extensively discussed to give an insight into the future prospects of industrial development and possible new strategies for process control and automation with a special focus on the biopharmaceutical industry.

Polysaccharide-based chromatographic adsorbents for virus purification and viral clearance

Viruses still pose a significant threat to human and animal health worldwide.In the fight against viral infections,high-purity viral stocks are needed for manufacture of safer vaccines.It is also a priority to ensure the viral safety of biopharmaceuticals such as blood products.Chromatography techniques are widely implemented at both academic and industrial levels in the purification of viral particles,whole viruses and virus-like particles to remove viral contaminants from biopharmaceutical products.This paper focuses on polysaccharide adsorbents,particulate resins and membrane adsorbers,used in virus purification/removal chromatography processes.Different chromatographic modes are surveyed,with particular attention to ion exchange and affinity/pseudo-affinity adsorbents among which commercially available agarose-based resins(Sepharose®)and cellulose-based membrane adsorbers(Sartobind®)occupy a dominant position.Mainly built on the development of new ligands coupled to conventional agarose/cellulose matrices,the development perspectives of polysaccharide-based chromatography media in this antiviral area are stressed in the conclusive part.

Combination of a biopharmaceutic classification system and physiologically based pharmacokinetic models to predict absorption properties of baicalein in vitro and in vivo

Objective: To determine the in vitro and in vivo absorption properties of active ingredients of the Chinese medicine, baicalein, to enrich mechanistic understanding of oral drug absorption.Methods: The Biopharmaceutic Classification System(BCS) category was determined using equilibrium solubility, intrinsic dissolution rate, and intestinal permeability to evaluate intestinal absorption mechanisms of baicalein in rats in vitro. Physiologically based pharmacokinetic(PBPK) model commercial software GastroPlus~(TM) was used to predict oral absorption of baicalein in vivo.Results: Based on equilibrium solubility, intrinsic dissolution rate, and permeability values of main absorptive segments in the duodenum, jejunum, and ileum, baicalein was classified as a drug with low solubility and high permeability. Intestinal perfusion with venous sampling(IPVS) revealed that baicalein was extensively metabolized in the body, which corresponded to the low bioavailability predicted by the PBPK model. Further, the PBPK model predicted the key indicators of BCS, leading to reclassification as BCS-II. Predicted values of peak plasma concentration of the drug(C_(max)) and area under the curve(AUC)fell within two times of the error of the measured results, highlighting the superior prediction of absorption of baicalein in rats, beagles, and humans. The PBPK model supported in vitro and in vivo evidence and provided excellent prediction for this BCS class II drug.Conclusion: BCS and PBPK are complementary methods that enable comprehensive research of BCS parameters, intestinal absorption rate, metabolism, prediction of human absorption fraction and bioavailability, simulation of PK, and drug absorption in various intestinal segments across species. This combined approach may facilitate a more comprehensive and accurate analysis of the absorption characteristics of active ingredients of Chinese medicine from in vitro and in vivo perspectives.

Comparing different domains of analysis for the characterisation of N-glycans on monoclonal antibodies

With the size of the biopharmaceutical market exponentially increasing,there is an aligned growth in the importance of data-rich analyses,not only to assess drug product safety but also to assist drug development driven by the deeper understanding of structure/function relationships.In monoclonal antibodies,many functions are regulated by N-glycans present in the constant region of the heavy chains and their mechanisms of action are not completely known.The importance of their function focuses analytical research efforts on the development of robust,accurate and fast methods to support drug development and quality control.Released N-glycan analysis is considered as the gold standard for glycosylation characterisation;however,it is not the only method for quantitative analysis of glycoform heterogeneity.In this study,ten different analytical workflows for N-glycan analysis were compared using four monoclonal antibodies.While observing good comparability between the quantitative results generated,it was possible to appreciate the advantages and disadvantages of each technique and to summarise all the observations to guide the choice of the most appropriate analytical workflow according to application and the desired depth of data generated.

Study and ICH validation of a reverse-phase liquid chromatographic method for the quantification of the intact monoclonal antibody cetuximab

Cetuximab （CTX） is a potent chimeric mouse/human monoclonal antibody （mAb） approved worldwide for treatment of metastatic colorectal cancer. Among the various biological and physical analyses per- formed for full study on this biopharmaceutic, the determination of the concentration preparations throughout manufacturing and subsequent handling in hospital is particularly relevant. In the present work, the study and validation of a method for quantifying intact CTX by reverse-phase high-perfor- mance liquid chromatography with diode array detection （（RP）HPLC/DAD） is presented. With that end, we checked the performance of a chromatographic method for quantifying CTX and conducted a study to validate the method as stability-indicating in accordance with the International Conference on Harmo- nization guidelines （ICH） for biotechnological drugs; therefore, we evaluated linearity, accuracy, preci- sion, detection and quantification limits, robustness and system suitability. The specificity of the method and the robustness of the mAb formulation against external stress factors were estimated by compre- hensive chromatographic analysis by subjecting CTX to several informative stress conditions. As de- monstrated, the method is rapid, accurate, and reproducible for CTX quantification. It was also suc- cessfully used to quantify CTX in a long-term stability study performed under hospital conditions.

Theory of Global Sustainable Development Based on Microalgae in Bio and Industrial Cycles, Management-Changing Decisions in Areas of Climate Change and Waste Management

The paper provides requested management-changing decisions through implementation of conclusions of Global Sustainable Development theory based on including of microalgae in Bio and Industrial Cycles in the area of waste-related management challenges within creating market opportunities for industry through expansion of resource efficiency use across global supply chains and new design and building sustainable development with contemporary manufacturing of value added products. A truly coherent waste management and other production policy (biofuel, biopharmaceuticals, food, feed and perfumery additives) and mitigation of Climate Change are ways to bring these traces closer to cost effective manufacturing, improving of resource efficiency use, well being economy and human health. Offered technological change dramatically increase biomass feedstock resources, reduce waste origin of greenhouse emission (since 13%-17%), organics sent to landfill, pyrolyses, etc. and create a model that all elements along the waste value chain create economic, societal and/or environmental value.

Literature Review on the Development of New Drugs Based on TRIZ

Objective To promote the application of TRIZ theory in the new drug R&D and the innovative development of medical devices.Methods TRIZ can be literally translated as“theory of inventive problem resolving”,focusing on clarifying and solving contradictions in the system.This article introduces the TRIZ theory and the general process of new drug development.It collects literature in the field of new drug development and medical devices and refers to ideas for solving problems in some successful cases of applying TRIZ theory in other fields.Results and Conclusion After summarizing the general ideas of TRIZ to solve the problems,it is concluded that attention should be paid to applying TRIZ theory in the development of new drug and medical devices.

Application of naturalβ-glucans as biocompatible functional nanomaterials

Naturally-occurringβ-glucans are mostly investigated for their antitumor activity and immunomodulatory property.They have been widely regarded as a natural source for functional foods and pharmaceuticals.However,the physico-chemically stable and biocompatible properties ofβ-glucans are rarely explored as a coating material for nanomaterials to overcome the problems of aggregation and cytotoxicity.This article reviews on the exploration ofβ-glucans,in particular those derived from mushrooms,as a natural coating material to modify the surface properties of bioactive substances as a relatively simple and cost-effective strategy to produce stable and biocompatible nanohybrids used for biopharmaceutical use.It is envisaged that suchβ-glucan-based coating method will provide new opportunities to design biocompatible functional nanomaterials for wider clinical applications.

Engineering Plants as Platforms for Production of Vaccines

Microbial pathogens have always posed serious threats and challenges to human existence. Pathogenic microbes causing epidemic and pandemic outbreaks have the potential of effacing life on earth. Vaccines are used as prophylactic as well as treatment measures against diseases and are effective in eradicating deadly pathogens. Conventional vaccines though effective, have high production costs, involve tedious purification processes and have biosafety issues, requiring time-consuming biosafety tests for commercial production. Plant-based vaccines offer several advantages over the conventional systems such as ease of production, storage, higher yields, stability and safety. The review discusses significance, advantages, comparisons, prospects and challenges or constraints in the production of plant-based vaccines and antibodies.