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.

A MICROCOMPUTER PROGRAM PACKAGE FOR PHARMACOKINETICS AND BIOPHARMACEUTICS

In this paper, a microcomputer program package for pharmacokinetics and biopharmaceutics (PKBP) was presented. This package is applicable to various calculations for pharmacokinetics and biopharmaceutics. Some mathematical models and computing methods were developed. It has been used over 200 users.

Market Knowledge and Stakeholder Considerations for the Biopharmaceutics Sector—Incorporating User Value and Societal Needs in Therapeutic Interventions

Purpose: Many health systems are considered ill-equipped to adequately meet future demand. Although academic entrepreneurs and small and medium-sized enterprises (SMEs) drive health technology innovation, they often suboptimally consider important market and stakeholder requirements. This can result in missed opportunities to improve health system performance, address demand-supply gaps, and achieve financial rewards. Market intelligence can provide crucial information in this regard, but scientifically sourced guidance on how to perform market research for biopharmaceutics is scarce. Our objective was, therefore, to create and provide an easily accessible biopharmaceutics market research toolbox that can be perused by academic entrepreneurs and SMEs to improve the alignment of their developments with stakeholder needs. Design: Guided by market orientation theory, we interviewed senior managers and commercialisation experts from the biopharmaceutics sector. We asked them which information they consider most relevant, and how they collect, analyse and respond to new information to align product features, positioning and stakeholder-relationship management with market needs. Findings: Our innovator toolbox consists of a high-level overview of market intelligence considerations mapped against a novel innovation framework, a stakeholder reasoning and value model, and detailed considerations (checklists) per stakeholder of biopharmaceutics interventions. Originality: We provide here the first market orientation-based overview of market intelligence considerations for the biopharmaceutics sector. Although primarily collated for academic entrepreneurs and SMEs, our innovator toolbox for the biopharmaceutics sector can help all stakeholders better understand their orientation towards markets.

Classification of natural products as sources of drugs according to the biopharmaceutics drug disposition classification system(BDDCS)

Natural products(NPs) are compounds that are derived from natural sources such as plants, animals, and microisms. Therapeutics has benefited from numerous drug classes derived from natural product sources. The Biopharmaceutics Drug position Classification System(BDDCS) was proposed to serve as a basis for predicting the importance of transporters and enzymes in determining drug bioavailability and disposition. It categorizes drugs into one of four biopharmaceutical classes according to their water solubility and extent of metabolism. The present paper reviews 109 drugs from natural product sources: 29% belong to class 1(high solubility, extensive metabolism), 22% to class 2(low solubility, extensive metabolism), 40% to class 3(high solubility, poor metabolism), and 9% to class 4(low solubility, poor metabolism). Herein we evaluated the characteristics of NPs in terms of BDDCS class for all 109 drugs as wells as for subsets of NPs drugs derived from plant sources as antibiotics. In the 109 NPs drugs, we piled 32 drugs from plants, 50%(16) of total in class 1, 22%(7) in class 2 and 28%(9) in class 3, none found in class 4; Meantime, the antibiotics were found 5(16%) in class 2, 22(71%) in class 3, and 4(13%) in class 4; no drug was found in class 1. Based on this classification, we anticipate BDDCS to serve as a useful adjunct in evaluating the potential characteristics of new natural products.

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.

Biopharmaceutics classification evaluation for paris saponin Ⅶ

To study the biopharmaceutics characteristics of paris saponin Ⅶ(PSⅦ). The solubility of PSⅦ was evaluated by measurement of the equilibrium solubility in different solvents and media. The permeability of PSⅦ was evaluated by measuring the oil/water partition coefficient(lgP_(app)) and determining the apparent permeability coefficient(PC_(app)) on a mono-layer Caco-2 cell model. The effects of p-glycoprotein and multidrug resistance related protein 2 on PSⅦ transport in mono-layer Caco-2 cell model were further investigated. Finally, the small intestinal absorption of PSⅦ was investigated in rat. In solvents of different pH, the equilibrium solubility of PSⅦ was quite low, and the dose number of PSⅦ was larger than 1. The lgP_(app) of PSⅦ was less than 0. The apparent permeability coefficient [PC_(app)(AP-BL)] of PSⅦ in mono-layer Caco-2 cell model was less than 14.96 × 10^(-6) cm·s^(-1), and the efflux ratio of PSⅦ in mono-layer Caco-2 cell model was less than 1. The transport rate of PSⅦ in mono-layer Caco-2 cell model was not affected by the inhibitors of p-glycoprotein and multidrug resistance related protein 2. After oral administration, PSⅦ could be detected in rat intestinal contents, but could not be detected in the small intestinal mucosa. PSⅦ showed low solubility and permeability,which would result in low oral bioavailability in clinic. PSⅦ belonged to Class IV compound in biopharmaceutics classification system.

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 History of Pharmacokinetics in Cuba： Role of Universities

A university is a higher academic institution with a mission to educate individuals in order to help nations reach their developmental goals. It implies teaching innovative disciplines through the most advanced scientific and pedagogical methods, in harmony with recent international standards and national needs. Some of these innovative disciplines turn out to be a valuable driving-force of the transformation in a country. An example of such transforming disciplines is the PK （pharmacokinetics） in Cuba, considered by many as exclusive of developed countries, it shows significant contributions to the current success of the local biopharmaceutical industry, and particularly to the scientific achievements of several biotechnological centers. Noteworthily, the academic activities and scientific work performed at the UH （University of Havana） and other colleges across the Island are closely related to this success. While passing through the different stages of transformation at academic institutions in the country, we discuss herein the most significant milestones in the history of the Pharmacokinetics in Cuba.

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.

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.

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.

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.

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.