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.

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.

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 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 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.

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.

Estimating the Three-Stage Cost Malmquist Productivity Index in the Taiwan Biotech and Biopharmaceutical Industry

This paper estimates and decomposes the output-oriented three-stage cost Malmquist productivity index of the Taiwan Residents biotech and biopharmaceutical （B＆BP） industry in 2004-2007 periods. The empirical estimations proceed in three stages. Following the methodology of Yang and Huang （2009） with the assumption of variable return to scale （VRS） in the first stage, the original cost Malmquist productivity index （CM） is decomposed into five sources of productivity change： pure technical efficiency change, technical change, allocative efficiency change （AEC）, input-price effect, and cost scale efficiency change. The method of Yang and Huang （2009） is an excellent contribution, but it did not deal with the exogenous environmental variables and noises. In the second stage, the original input variables are adjusted by the exogenous environmental variables. Finally, adjusted input variables produced by the second stage are reused for obtaining the reality of CM in the third stage.

Basic regulatory science behind drug substance and drug product specifications of monoclonal antibodies and other protein therapeutics

In this review,we focus on providing basics and examples for each component of the protein therapeutic specifications to interested pharmacists and biopharmaceutical scientists with a goal to strengthen understanding in regulatory science and compliance.Pharmaceutical specifications comprise a list of important quality attributes for testing,references to use for test procedures,and appropriate acceptance criteria for the tests,and they are set up to ensure that when a drug product is administered to a patient,its intended therapeutic benefits and safety can be rendered appropriately.Conformance of drug substance or drug product to the specifications is achieved by testing an article according to the listed tests and analytical methods and obtaining test results that meet the acceptance criteria.Quality attributes are chosen to be tested based on their quality risk,and consideration should be given to the merit of the analytical methods which are associated with the acceptance criteria of the specifications.Acceptance criteria are set forth primarily based on efficacy and safety profiles,with an increasing attention noted for patient-centric specifications.Discussed in this work are related guidelines that support the biopharmaceutical specification setting,how to set the acceptance criteria,and examples of the quality attributes and the analytical methods from 60 articles and 23 pharmacopeial monographs.Outlooks are also explored on process analytical technologies and other orthogonal tools which are on-trend in biopharmaceutical characterization and quality control.

A factor score clustering approach to analyze the biopharmaceutical sector in the Chinese market during COVID-19

The biopharmaceutical sector is of considerable interest during the COVID-19 pandemic.This study aims to investigate the biopharmaceutical sector using the Shenwan Industry Classification and provides insights into investment strategies.We combine factor and cluster analyses to reduce data dimensions and detect their latent similarities.Specifically,the biopharmaceutical sector is divided into six categories based on second-level industry classification.It is observed that medical devices,medical services,biological products,and chemical pharmaceuticals maintained their upward tendency,while Chinese medicine and pharmaceutical commerce declined slightly.We also develop optimal investment strategies using various metrics for different investor types.

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.

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.

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.

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.

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.

Biopharmaceutics classification system(BCS)-based biowaiver for immediate release solid oral dosage forms of moxifloxacin hydrochloride(Moxiflox GPO) manufactured by the Government Pharmaceutical Organization(GPO)

Literature and experimental data relevant to the decision to allow a waiver of in vivo bioequivalence(BE)testing for approval of immediate release(IR)solid dosage forms containing moxifloxacin hydrochloride as the API manufactured by the Government Pharmaceutical Organization(GPO)are evaluated.The solubility of moxifloxacin hydrochloride determined by the shake flask method in six different pH mediums(1.2,4.5,5.4,6.4,6.8 and 7.5)was 4.988±0.1962,27.012±0.4138,21.668±0.5165,47.200±0.8095,73.438±1.7310 and 196.475±4.4624 mg/mL,respectively.The Dose/Solubility(D/S)Ratio of the highest strength(400 mg)available in the market of moxifloxacin tablets was 80.192,14.808,18.460,8.475,5.447 and 2.036 mL,respectively.