Biopharmaceutical Sector Research Articles

The Evaluation of Research and Development Division through Product Development Process in Biopharmaceutical Company

This study aims to offer the methodology and analyze the performance of Research and Development division of the most significant biopharmaceutical company in Indonesia through improvement of new product development (NPD) process. The methods in this study using the combination of the survey through a questionnaire that already created and modified according to the biopharmaceutical sector in Indonesia and interviews with the principal persons in the company. The respondents are manager level in the various departments such as R&D, product planning, product development and supply chain management. The results stated that R&D has a significant role in providing and determining the new product and must be emphasized as corporate level action. The solutions that offered to the company are conducting organizational development through training & development and collaborative partnership that require world-class skills and knowledge.

High glucose and low specific cell growth but not mild hypothermia improve specific r-protein productivity in chemostat culture of CHO cells.

In the biopharmaceutical sector, Chinese hamster ovary (CHO) cells have become the host of choice to produce recombinant proteins (r-proteins) due to their capacity for correct protein folding, assembly, and posttranslational modification. However, the production of therapeutic r-proteins in CHO cells is expensive and presents insufficient production yields for certain proteins. Effective culture strategies to increase productivity (qp) include a high glucose concentration in the medium and mild hypothermia (28–34 °C), but these changes lead to a reduced specific growth rate. To study the individual and combined impacts of glucose concentration, specific growth rate and mild hypothermia on culture performance and cell metabolism, we analyzed chemostat cultures of recombinant human tissue plasminogen activator (rh-tPA)-producing CHO cell lines fed with three glucose concentrations in feeding media (20, 30 and 40 mM), at two dilution rates (0.01 and 0.018 1/h) and two temperatures (33 and 37 °C). The results indicated significant changes in cell growth, cell cycle distribution, metabolism, and rh-tPA productivity in response to the varying environmental culture conditions. High glucose feed led to constrained cell growth, increased specific rh-tPA productivity and a higher number of cells in the G2/M phase. Low specific growth rate and temperature (33 °C) reduced glucose consumption and lactate production rates. Our findings indicated that a reduced specific growth rate coupled with high feed glucose significantly improves r-protein productivity in CHO cells. We also observed that low temperature significantly reduced qp, but not cell growth when dilution rate was manipulated, regardless of the glucose concentration or dilution rate. In contrast, we determined that feed glucose concentration and consumption rate were the dominant aspects of the growth and productivity in CHO cells by using multivariate analysis.

Innovation Performance and Open Innovation in the UK Bio-Pharmaceutical Sector (WITHDRAWN)

This paper distinguishes between inbound, outbound and coupled open innovation processes along upstream and downstream value chain activities and explores the impact of these open innovation processes on the innovation performance of new entrant and established firms in the UK bio-pharmaceuticals sector between 1991 and 2001. Our findings suggest that there may not always be a statistically significant relationship between open innovation processes and firm innovation performance and that the relationship can be ambiguous. The study supports that the distinction of inbound, outbound and coupled open innovation, offers a meaningful delineation facilitating our understanding of the role of openness in innovation performance of new entrant and established firms.

Dupilumab

ABSTRACT Drugs are broadly defined as any chemical substance that can elicit a physiological effect on the body. Medication is a subgroup of drugs utilized by healthcare providers to diagnose, treat, or prevent diseases from occurring. Therapeutic monoclonal antibodies are immunotherapies that have gained commercial interest over the past 30 years within the biopharmaceutical sector. In addition to cancer and rheumatology diseases, common dermatological pathologies traditionally limited to topical steroid therapies through immunotherapies can now be targeted with specific immunomodulatory drugs. This pharmacological column aims to draw attention to the first targeted monoclonal antibody therapy approved by the Food and Drug Administration for the treatment of moderate-to-severe atopic dermatitis, dupilumab (Dupixent). The purpose of this article is to review dupilumab within the context of atopic dermatitis immunology, standard treatments, indications, mechanisms of action, adverse reactions, and upcoming applications for asthma with relevance to the growing biopharmaceutical sector. As the popularity of immunotherapies has grown, so has the need for nurse practitioners and educators to continue expanding their knowledge base in drug delivery, adverse reaction management, and therapeutic opportunities to advance care.

Society-nature-technology (SNT) nexus: Institutional causes and cures of national morbidities

This article explores a nexus between society, nature and technology (SNT) in the context of a biomedical problem-solution through innovation project for a new product development in the biopharmaceutical sector. The nexus implies that social intervention is an antecedent to and consequence of nature as a type of morbidity. The central proposition is that national morbidities are partially resulting of national institutions such as policy and culture, and the national institutions partially constitute the response to through industrialisation processes and cultural habits. Based on the data from China and India as two comparable socio-culture contexts, we draw on six types of national morbidities: diabetes, infections, cancer, hepatitis, respiratory dysfunction and hypertension. An analysis shows that diabetes and infectious diseases projects exist more in India; cancer, hepatitis and hypertension projects exist more in China; and contrary to prediction, respiratory dysfunction project appears more in India than China. There are some statistical differences between the North and South regions. The discussion explains the SNT nexus in a broader context suggests two types of interventions: preventive and curing. The preventive intervention comes before nature (morbidity), and the curing intervention occurs after the formation of morbidity. We suggest that preventive institutional intervention for education can be more effective than curing intervention. The prevention mechanism induces awareness; the curing mechanism induces treatment solutions. Our argument supports the social development as much as industrialisation, and not pure industrialisation alone.

Global Competition and Biotechnology Industry: A Review

The biotechnology industry is a relatively new a distinct field that involve using living organism to produce desired product. This industry includes firms that develop, manufacture, and market pharmaceutical products, agricultural products, environmental control product, e.t.c. based on advanced biotechnology research. Although the growth in the global biotechnology industry neared double digits the past two years, the threat of entry into the market is weak due to high barriers to entry. However, because of the ease and low-cost production using biotechnology, it has increased competition in some product. Leading European nations with strong biotech sectors such as the UK and Germany are investing heavily in regenerative medicine (RM), seeking competitive advantage in this emerging sector. However, in the broader biopharmaceutical sector the European Union (EU) is outperformed by the US on all metrics, reflecting longstanding problems: limited venture capital finance, a fragmented patent system, and relatively weak relations between academia and industry. The current global downturn has exacerbated these difficulties. The crisis comes at a time when the European Union is reframing its approach to the governance of innovation and renewing its commitment to the goal of making Europe the leading player in the global knowledge economy.

Using extensional flow to reveal diverse aggregation landscapes for three IgG1 molecules.

Monoclonal antibodies (mAbs) currently dominate the biopharmaceutical sector due to their potency and efficacy against a range of disease targets. These proteinaceous therapeutics are, however, susceptible to unfolding, mis‐folding, and aggregation by environmental perturbations. Aggregation thus poses an enormous challenge to biopharmaceutical development, production, formulation, and storage. Hydrodynamic forces have also been linked to aggregation, but the ability of different flow fields (e.g., shear and extensional flow) to trigger aggregation has remained unclear. To address this question, we previously developed a device that allows the degree of extensional flow to be controlled. Using this device we demonstrated that mAbs are particularly sensitive to the force exerted as a result of this flow‐field. Here, to investigate the utility of this device to bio‐process/biopharmaceutical development, we quantify the effects of the flow field and protein concentration on the aggregation of three mAbs. We show that the response surface of mAbs is distinct from that of bovine serum albumin (BSA) and also that mAbs of similar sequence display diverse sensitivity to hydrodynamic flow. Finally, we show that flow‐induced aggregation of each mAb is ameliorated by different buffers, opening up the possibility of using the device as a formulation tool. Perturbation of the native state by extensional flow may thus allow identification of aggregation‐resistant mAb candidates, their bio‐process parameters and formulation to be optimized earlier in the drug‐discovery pipeline using sub‐milligram quantities of material.

What management strategies can a pharmaceutical company implement to sustain innovation?

The discovery and development of life-saving drugs have been central to improving health worldwide. However, the state of pharmaceutical innovation has been recently challenged due to falling industry outputs, with breakthrough therapies remaining elusive for many companies. Sustaining drug innovations is a top priority for pharmaceutical executives. This researcher examines existing literature to explore patterns and trends in managing the sustainability of drug innovations. An initial survey of articles on general, non-pharmaceutical industry specific strategies for sustaining innovation provides a definition for sustained product innovation. Strategic themes such as organizational structure and culture, a firm's ability to adapt to changes, the role of customers as well as knowledge and technology management across industries are discussed. A brief history of strategic innovation in the biopharmaceutical sector provides context in building a conceptual framework for levers of management strategies that practitioners and academics can use to understand and sustain drug innovations at the firm level. Findings reveal that pharmaceutical companies who adapt their organizational culture, knowledge and technology levers to the cycles of scientific advances within the constraints of their regulatory and market environments are most likely to succeed. These levers of management strategies seem to be mediated by the firm’s absorptive capacity and their ability to form strategic alliances with other organizations.

Developing the Subcutaneous Drug Delivery Route

Biopharmaceuticals and biosimilars now represent the majority of the top 10 selling drugs. High development costs and requirement for most to be administered intravenously are noted drawbacks. Recent advances in subcutaneous drug delivery methods offer a viable alternative route for parenteral drug administration. Comparison studies have highlighted equivalent drug efficacies coupled with substantial cost savings. Allied to these developments are new closed-loop drug delivery systems which have the potential to revolutionize the biopharmaceutical sector through active patient engagement. First demonstrated in the insulin marketplace, these efforts represent formal embodiments of the precision medicine approach to disease management. This review will highlight key considerations for subcutaneous drug delivery, including patient preferences, drug formulation and needle and device design. We also provide an overview of the market evolution of subcutaneously administered drugs, highlighting those currently in clinical development, and predict areas for future innovation.

Just how good an investment is the biopharmaceutical sector?

Uncertainty surrounding the risk and reward of investments in biopharmaceutical companies poses a challenge to those interested in funding such enterprises. Using data on publicly traded stocks, we track the performance of 1,066 biopharmaceutical companies from 1930 to 2015-the most comprehensive financial analysis of this sector to date. Our systematic exploration of methods for distinguishing biotech and pharmaceutical companies yields a dynamic, more accurate classification method. We find that the performance of the biotech sector is highly sensitive to the presence of a few outlier companies, and confirm that nearly all biotech companies are loss-making enterprises, exhibiting high stock volatility. In contrast, since 2000, pharmaceutical companies have become increasingly profitable, with risk-adjusted returns consistently outperforming the market. The performance of all biopharmaceutical companies is subject not only to factors arising from their drug pipelines (idiosyncratic risk), but also from general economic conditions (systematic risk). The risk associated with returns has profound implications both for patterns of investment and for funding innovation in biomedical R&D.

Analysis of the effects of chemical ageing of ethylene-propylene diene monomer by chemical, spectroscopic, and thermal means

Ethylene-propylene diene monomer (EPDM) failures due to material degradation poses a major risk in the biopharmaceutical industry, which can result in long periods of production downtime. It is suspected that a key cause of this EPDM degradation is due to the chemical solutions used in equipment cleaning processes, resulting in crosslinking of the EPDM polymer bulk. However, the mechanisms responsible for crosslink formation, and whether other degradation sources are also present, has never been investigated in the public domain. Twenty four virgin samples were utilised for testing, twelve of which were subject to common chemical cleaning solutions used in the biopharmaceutical sector. The chemical solutions under investigation were aqueous solutions of NaOH, NaClO, H3PO4, and the interaction between 100 °C H2O and NaClO. The characterisation of the degradation process was conducted via chemical, spectroscopic and thermal means. The results show that degradation of the polymer bulk proceeds predominantly via crosslinking for all exposure types, due to oxidative damage and the formation and recombination of free radicals. Loss of plasticiser in the polymer matrix and thermo-oxidative damage are contributory degradation mechanisms. NaOH and H3PO4 exposure results in an accelerated rate of crosslinking compared to NaClO in the early stages of exposure.

Structure-Based Design of Potent and Selective Ligands at the Four Adenosine Receptors

The four receptors that signal for adenosine, A1, A2A, A2B and A3 ARs, belong to the superfamily of G protein-coupled receptors (GPCRs). They mediate a number of (patho)physiological functions and have attracted the interest of the biopharmaceutical sector for decades as potential drug targets. The many crystal structures of the A2A, and lately the A1 ARs, allow for the use of advanced computational, structure-based ligand design methodologies. Over the last decade, we have assessed the efficient synthesis of novel ligands specifically addressed to each of the four ARs. We herein review and update the results of this program with particular focus on molecular dynamics (MD) and free energy perturbation (FEP) protocols. The first in silico mutagenesis on the A1AR here reported allows understanding the specificity and high affinity of the xanthine-antagonist 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX). On the A2AAR, we demonstrate how FEP simulations can distinguish the conformational selectivity of a recent series of partial agonists. These novel results are complemented with the revision of the first series of enantiospecific antagonists on the A2BAR, and the use of FEP as a tool for bioisosteric design on the A3AR.

Unintended Consequences: How Introducing a Manufacturing and Export Exemption to Supplementary Protection Certificates Would Weaken Global Standards of IP Protection and Result in Direct Losses to Europe's Research-Based Biopharmaceutical Industry

Background: In October 2015 the European Commission (EC) released its report Upgrading the Single Market: More Opportunities for People and Business, which includes a stated intention to explore an option for implementing a Supplementary Protection Certificate (SPC) manufacturing and export exemption, expected to boost economic growth and job creation within the generics and biosimilars industry. However, such an exemption’s impact on the innovative research-based biopharmaceutical industry and on the international level of intellectual property (IP) protection remains in question. Methodology: Using evidence from the existing literature, a sample of 30 top-selling drugs, and France and Sweden as the primary source for SPC status within the EU we construct an econometric model and estimate potential annual losses to the global and the European innovative research-based biopharmaceutical industries. Results: This study finds that implementation of an EU-wide SPC manufacturing and export exemption would potentially result in annual losses ranging between USD2.675 billion and up to USD5.35 billion to the global innovative biopharmaceutical industry, with approximately USD1.34 billion to USD2.27 billion of these attributed to the European innovative biopharmaceutical industry. Translating these losses to current levels of biopharmaceutical sector employment and R&D investment the effect of the introduction of an EU-wide SPC manufacturing and export exemption could be between 4,500-7,700 direct job losses (with an additional 19,000-32,000 indirect job losses) and a decrease of between EUR215 million to EUR364 million in R&D investment. Conclusion: In light of these findings, we conclude that a manufacturing and export exemption is likely to have a detrimental effect on the European research-based biopharmaceutical industry and is unlikely to provide a significant and sustained positive economic impact on the European generics industry.

Chemical ageing effects on the mechanical behaviour of ethylene-propylene diene monomer

Ethylene-propylene diene monomer (EPDM) elastomer diaphragm failures due to material degradation pose a major risk in the biopharmaceutical industry, as they can result in long periods of production downtime. It is suspected that a key cause of this EPDM degradation is due to the chemical solutions used in equipment cleaning processes. However this has never been empirically investigated in the public domain. Twenty four virgin samples were utilised for testing, twelve of which were subject to common chemical cleaning solutions used in the biopharmaceutical sector. The chemical solutions under investigation were aqueous solutions of NaOH, NaClO, H3PO4, and the interaction between 100 °C H2O and NaClO. The characterisation of the degradation process was conducted by mechanical testing. The results show that degradation of the polymer bulk proceeds predominantly via crosslinking for all exposure types. NaOH and H3PO4 exposure results in an accelerated rate of crosslinking compared to NaClO in the early stages of exposure.

Subcutaneous drug delivery: An evolving enterprise.

Recent advances in subcutaneous drug delivery and device design are transforming the biopharmaceutical sector and improving patient care.

Science-industry R&D cooperation effects on firm’s appropriation strategy

PurposeThe purpose of this paper is to show how science-industry R&D cooperation (SIRC) generates effects on the strategy developed by firms to appropriate the benefits of innovations. Given the plurality of cooperation patterns between firms and public R&D institutions and the variety of appropriation mechanisms used by firms to protect generated knowledge or to strengthen their market position, this paper investigates to what extent different forms of cooperation are associated with different effects on appropriation strategy.Design/methodology/approachAs evidence of this, the authors carry out a multiple case study, covering nine biopharmaceutical Argentine firms whose innovation projects are developed in cooperation with public R&D institutions. Using critical dimensions identified by public-private R&D cooperation literature, the paper analyzes the characteristics of cooperation in the cases studied, looking for different patterns. Given the existence of various appropriation mechanisms identified by appropriability literature, the paper analyzes how firms use (or not) those mechanisms within the specific context of jointly generated innovation.FindingsThe paper shows that SIRC generates opposing effects on the various appropriation mechanisms used by firms, both challenging and strengthening them. Likewise, the identification of three cooperation patterns in Argentine biopharmaceutical sector, namely, contract R&D, internalization and coordination, allows appreciating how each pattern affects differently the appropriation mechanisms used by firms, being the coordination one, the most functional to the appropriation strategy of firms analyzed.Research limitations/implicationsThe arguments presented here are necessarily limited to the biopharmaceutical Argentine sector, which is strategic to the country, for accumulated capabilities in scientific and business aspects. The analysis could be enriched by extending it to other industries with similar innovation characteristics and to other countries, where patents have a similar weight (emerging countries) or a different one (developed countries).Practical implicationsInnovation and public-private collaboration policies may benefit from the analysis presented here, which helps to assess advantages and challenges of different SIRC logics on firms’ appropriation issues and to considerate which aspects allow cooperation and appropriation combining in a more virtuous form.Originality/valueThere is no paper that explicitly examines the effects generated by different SIRC patterns on the appropriation strategy of firms, conceived as a combination of different mechanisms which may include patents but is not limited to them.

SCooP: an accurate and fast predictor of protein stability curves as a function of temperature.

The molecular bases of protein stability remain far from elucidated even though substantial progress has been made through both computational and experimental investigations. One of the most challenging goals is the development of accurate prediction tools of the temperature dependence of the standard folding free energy ΔG(T). Such predictors have an enormous series of potential applications, which range from drug design in the biopharmaceutical sector to the optimization of enzyme activity for biofuel production. There is thus an important demand for novel, reliable and fast predictors. We present the SCooP algorithm, which is a significant step towards accurate temperature-dependent stability prediction. This automated tool uses the protein structure and the host organism as sole entries and predicts the full T-dependent stability curve of monomeric proteins assumed to follow a two-state folding transition. Equivalently, it predicts all the thermodynamic quantities associated to the folding transition, namely the melting temperature Tm, the standard folding enthalpy ΔHm measured at Tm, and the standard folding heat capacity ΔCp. The cross-validated performances are good, with correlation coefficients between predicted and experimental values equal to [0.80, 0.83, 0.72] for ΔHm, ΔCp and Tm, respectively, which increase up to [0.88, 0.90, 0.78] upon the removal of 10% outliers. Moreover, the stability curve prediction of a target protein is very fast: it takes less than a minute. SCooP can thus potentially be applied on a structurome scale. This opens new perspectives of large-scale analyses of protein stability, which is of considerable interest for protein engineering. The SCooP webserver is freely available at http://babylone.ulb.ac.be/SCooP. fapucci@ulb.ac.be, jkwasigr@ulb.ac.be or mrooman@ulb.ac.be. Supplementary data are available at Bioinformatics online.

India promotes industry-academia R&D collaborations

India has approved the first-ever industry-academia partnership program to accelerate discovery research and enable development of products such as vaccines, biotherapeutics, and diagnostics. Called the Biopharma Mission, it is aimed at improving the health of India’s population through affordable product development, a goal in line with Prime Minister Narendra Modi’s government’s recently released National Health Policy. The new effort, which includes training a skilled workforce, is expected to enhance India’s technological and product development capabilities in the biopharmaceutical sector so it becomes globally competitive in the next 10–15 years, the government says in a statement. The program will aim to enhance technology transfer capabilities in the public and private sectors and enable start-ups and small and medium-size enterprises to build the capacity for sharing innovative research. The $250 million initiative, which includes $125 million in a loan from the World Bank, is expected to roll ou...

Формирование стратегических альянсов в инновационном секторе экономики: подход опционных игр в биофармацевтической отрасли

Формирование стратегических альянсов в инновационном секторе экономики: подход опционных игр в биофармацевтической отрасли

Operational complexity of foreign innovation projects and the inter-organisational alliance in the biopharmaceutical industry in China

ABSTRACTContrary to the perceived assumption that operational complexity of innovation projects predicts operations inside the organisation, we propose the opposite argument that operational complexity of foreign innovation projects increases the inter-organisational alliance formation. The evidence from the clinical trials innovation projects in the biopharmaceutical sector supports the operational complexity-alliance (OCA) proposition in China at three levels: institutional (legal and cultural), technological (purpose and methodology) and dispositional (organisation type and its experience). Institutional complexity shows that the legal difference between the home and host country positively predicts the inter-organisational alliance. Similarly, in national cultural differences, power distance, uncertainty and long-term orientation support the OCA proposition. Technological complexity reveals that explorative purpose and complex methodologies support the OCA proposition. The organisation’s disposition reveals that the industrial firm predicts the inter-organisational alliance more than the non-industrial organisation does. Concerning the organisation’s experience, it negatively predicts the inter-organisational alliance. Therefore, it appears that organisational discretion from the operational complexities leads to the structural change to reduce the cost of operations through externalisation rather than internalisation.