Biopharmaceutical Market Research Articles

EYE ON CHINA

Agilent Technologies recognized by Frost & Sullivan as 2013 Laboratory Analytical Instrumentation Company of the Year in China. Verisante Technology, Inc. announces study on nasopharnygeal cancer in China. ICON signs collaboration agreement with the Taiwan National Centre of Excellence for clinical trials and research. MicuRx completes $25 million Series B financing. Connecticut's CURE network welcomes HLK, its first Chinese member company. 2013 BIO Convention in China to connect biotech industry to the world's 2nd largest biopharmaceutical market. Partner State Key Laboratory of Pharmaceutical Biotechnology opened at HKU. Amgen and ShanghaiTech University announce plans for Amgen China R&D center to open on ShanghaiTech campus. CANbridge Life Sciences enters into agreement with Azaya Therapeutics to develop ATI-1123 for lung cancer in China and North Asia.

Biosimilars: company strategies to capture value from the biologics market.

Patents for several biologic blockbusters will expire in the next few years. The arrival of biosimilars, the biologic equivalent of chemical generics, will have an impact on the current biopharmaceuticals market. Five core capabilities have been identified as paramount for those companies aiming to enter the biosimilars market: research and development, manufacturing, supporting activities, marketing, and lobbying. Understanding the importance of each of these capabilities will be key to maximising the value generated from the biologics patent cliff.

Biosimilars; a unique opportunity for Iran national health sector and national pharmaceutical industry.

In 1980s, medicines produced through recombinant DNA technology created a novel opportunity for management of several debilitating and life threatening diseases. However, these medicines are very expensive and therefore not affordable for many patients especially those living in low resourced countries. Biopharmaceuticals mostly have a high unit cost and often prescribed for chronic medical conditions with possibility of long-term use. Therefore, they will impose a burden on either national health care systems or patients’ out of pocket. It is estimated that the average daily treatment of a patient with branded biopharmaceuticals will cost at least 22 times of those for small molecule medicines [1]. Biopharmaceuticals are medicines produced from living organisms via genetic manipulation. Although use of living organisms for production of vaccines has a long history, the first DNA recombinant medicine for human use, human insulin, was approved in the USA in 1982. However, introduction of other biopharmaceuticals including monoclonal antibodies into market later on experienced a much faster pace. Biopharmaceuticals are large and complex molecules which their active substances are mostly polypeptides, glycoproteins, proteins, and nucleic acids. Therefore, it is practically impossible to manufacture an “identical” copy for these molecules. Blood coagulating factors, erythropoietins, gonadotrophins, granulocyte colony stimulating factor (GCSF), human growth hormones (GH), interferons (INF), interleukins and monoclonal antibodies are among the most important marketed biopharmaceuticals in past decades [2]. Despite complexity of their molecules, biopharmaceuticals are very well characterized both for their clinical use and production methods. Biopharmaceuticals are also very sensitive to their production procedures. When the manufacturing process is modified by scaling up or transferring it to alternative facilities, new products might show modified specifications. Even though these manufacturing changes are tightly regulated most of the time they still will cause observable changes in the final product. However, all of these products will be marketed under one single brand name indicating that regulators consider these changes in the range of “highly similar” products. The fact that their administration provides expected clinical outcomes also confirm their comparability. “Biosimilars” are biopharmaceuticals which are manufactured by non originator pharmaceutical companies following expiration of patent period. According to current guidelines and regulations for granting marketing authorization “similarity” should be proven between biosimilar and its corresponding originator biopharmaceutical. Biopharmaceuticals have a very fast growing market. It is reported that 32% of products in development pipeline and 7.5% of marketed medicines are biopharmaceuticals which account for around 10% of pharmaceutical expenditure [3]. It is forecasted that by 2020, biopharmaceuticals will sell around US$23 billion in the EU and US$29 billion in the USA and of course all of this market could be challenged by biosimilars [3]. The biopharmaceutical market has expanded drastically in the past two decades. Although most of these medicines enjoyed exclusivity in the market due to their patent; recent years have witnessed expiration of their patent.

The Role of Pre-IPO Financial Indicators and Intermediaries in Aftermarket Performance and Survival in the US Biopharmaceutical Market

This paper examines factors affecting the stock price, net proceeds, and subsequent survival of biopharmaceutical firms that have gone public between 1996 and 2007 in the USA. We find that the financial condition of biopharmaceutical firms going public has deteriorated. The results also indicate that the financial condition of the firm prior to its going public and the intermediaries associated with the firm and initial public offering have little effect on first-day price increases. The findings, however, indicate that several of these financial indicators, and having prestigious underwriters, do have a significant effect on the amount of net proceeds received by the firm.

Fluorescence-based tools to improve biopharmaceutical process development

Background Process optimization and control are essential to match biopharmaceutical market demands. Early-steps in the development of new processes require screening hundreds of transfected clones in order to select those with the best expression characteristics, and identifying optimal environmental conditions for these clones to grow and express the protein of interest. While some culture systems include in situ analysis of cell density, most often by optical density or capacitance measurements, the majority of them still rely on off-line, laborious and time-consuming protocols for recombinant protein analysis. Spectroscopic methods have been proposed in literature to support bioprocesses development, because they are non-invasive and provide data on multiple components present in the culture bulks, thereby increasing information on process performance [1]. Here, we developed a fluorescence-based method for real-time monitoring of viable cells and antibody titers in bioreactor cultures, and extended this strategy for high throughput analysis of cellular productivity in 96well plates.

Methods, Processes and Comparative Yield Economics for the Production of Antibodies and Recombinant Proteins

Antibodies for therapy and diagnostics make up one of the fastest growing segments of the biopharmaceutical market. This review provides an overview of methods and processes for the selection and production of therapeutic and diagnostic recombinant proteins, including monoclonal and polyclonal antibodies. This overview also includes a comparative economic summary of current and some potential expression systems for manufacture of these highly functional recombinant proteins and antibodies, and explores the future direction of the antibody industry.

Recombinant protein production and streptomycetes

The biopharmaceutical market has come a long way since 1982, when the first biopharmaceutical product, recombinant human insulin, was launched. Just over 200 biopharma products have already gained approval. The global market for biopharmaceuticals which is currently valued at over US$99 billion has been growing at an impressive compound annual growth rate over the previous years. To produce these biopharmaceuticals and other industrially important heterologous proteins, different prokaryotic and eukaryotic expression systems are used. All expression systems have some advantages as well as some disadvantages that should be considered in selecting which one to use. Choosing the best one requires evaluating the options--from yield to glycosylation, to proper folding, to economics of scale-up. No host cell from which all the proteins can be universally expressed in large quantities has been found so far. Therefore, it is important to provide a variety of host-vector expression systems in order to increase the opportunities to screen for the most suitable expression conditions or host cell. In this overview, we focus on Streptomyces lividans, a Gram-positive bacterium with a proven excellence in secretion capacity, as host for heterologous protein production. We will discuss its advantages and disadvantages, and how with systems biology approaches strains can be developed to better producing cell factories.

Biopharmaceuticals: Scalable, disposable filtration systems address market challenges

Disposable filtration technologies now offer a robust, flexible and economic solution for the manufacture of therapeutic proteins in the current biopharmaceutical market. Lynne Deakin, Field Applications Specialist with 3M Purification explains.

Immunotoxicity and Immunogenicity of Biopharmaceuticals: Design Concepts and Safety Assessment

The biopharmaceutical market has grown steadily since the early 1980s and today over 150 protein biopharmaceuticals have been approved for clinical use. These products often exhibit forms of immunotoxicity that often only come to light during clinical studies. The predictive value of animal studies and traditional in vitro screens is questionable, with few existing methods able to predict immunotoxicity in a way that is useful for estimating risk for entire patient populations for a specific, and often unique, product. Here, the relative merits of rational design and alternative strategies for immunotoxicity testing are considered with reference to the outcomes of preclinical and clinical studies on biopharmaceuticals. Specific reference is made to the prediction of immunogenicity using organotypic models, transgenic models of autoimmunity and immunogenicity as well as rodent models of hypersensitivity, immunosuppression and immunostimulation. The role played by human cell-based assays and in silico prediction models that have been developed and validated for the assessment of chemical classes is also appraised.

Coping with the Regulatory Realities of Follow-on Biologics and the Nuances of US and European Regulations

It is well recognized that biopharmaceuticals provide great value in treating a number of chronic diseases but that the costs of these therapies have often been prohibitive. As patents and market exclusivity expire on a number of innovator products, there is an opportunity to develop follow-on versions of these products that have the potential to reduce health care costs worldwide. Presented here is a history of regulation, examples of approved molecules, terminology, and the current state of regulatory approaches open to follow-on biologics seeking market approval in the United States. Additionally, the regulations established by the European Union and the pending US legislation are reviewed. It is thought that new legislation will be available in the near future for the development of follow-on biologics that will facilitate improved competition in the US biopharmaceutical market.

Technological progresses in monoclonal antibody production systems

Monoclonal antibodies (mAbs) have become vitally important to modern medicine and are currently one of the major biopharmaceutical products in development. However, the high clinical dose requirements of mAbs demand a greater biomanufacturing capacity, leading to the development of new technologies for their large-scale production, with mammalian cell culture dominating the scenario. Although some companies have tried to meet these demands by creating bioreactors of increased capacity, the optimization of cell culture productivity in normal bioreactors appears as a better strategy. This review describes the main technological progresses made with this intent, presenting the advantages and limitations of each production system, as well as suggestions for improvements. New and upgraded bioreactors have emerged both for adherent and suspension cell culture, with disposable reactors attracting increased interest in the last years. Furthermore, the strategies and technologies used to control culture parameters are in constant evolution, aiming at the on-line multiparameter monitoring and considering now parameters not seen as relevant for process optimization in the past. All progresses being made have as primary goal the development of highly productive and economic mAb manufacturing processes that will allow the rapid introduction of the product in the biopharmaceutical market at more accessible prices.

Emerging PEGylated drugs

PEGylation is a pharmaceutical technology that involves the covalent attachment of polyethylene glycol (PEG) to a drug to improve its pharmacokinetic, pharmacodynamic, and immunological profiles, and thus, enhance its therapeutic effect. Currently, PEGylation is used to modify proteins, peptides, oligonucleotides, antibody fragments, and small organic molecules. Research groups are striving to improve the consistencies of PEGylated drugs and to PEGylate commercialized proteins and small organic molecules. Furthermore, the PEGylations of novel medications, like oligonucleotides and antibody fragments, are being pursued to improve their bioavailabilities. This active research in the PEGylation field and the continued growth of the biopharmaceutical market predicts that PEGylated drugs have a bright future.

Accelerated Examination & Grant of Japanese Biotechnology Patents

Abstract The healthcare transformational capacity of biotechnology intellectual property makes it fundamental that such biotech patents are issued promptly in order to have clarity and certainty in the research community and the marketplace. In these economically challenging times, accelerated patent grants will make biotech patent owners more attractive to investors and licensors ensuring their survival. Japanese universities have aggressively patented and licensed their biotech research and utilized the accelerated patent system to procure the world's first ever induced pluripotent stem cells (iPS) patent. This article examines the various accelerated examination procedures available at the Japan Patent Office and how biotechnology patent applicants can secure early patent protection in Japan, the world's second largest biopharmaceutical market.

Overexpression of human erythropoietin in tobacco does not affect plant fertility or morphology

Human erythropoietin (EPO) is a leading product in the biopharmaceutical market, but functional EPO has only been produced in mammalian cells, which limits its application and drives up the production costs. Using plants to produce human proteins may be an alternative way to reduce the cost. However, a recent report demonstrated that overexpression of the human EPO gene (EPO) in tobacco or Arabidopsis rendered males sterile and retarded vegetative growth, which raises concern whether EPO might interfere with hormone levels in transgenic plants. In the present study, we demonstrated that overexpressing EPO with additional 5′-His tag and 3′ ER-retention peptides in tobacco did not cause any developmental defect compared to GUS plants. With our method, all 20 transgenic plants grew on selective medium and, further confirmed by PCR, were fertile. Most of them grew similarly compared to GUS plants. Only one transgenic plant (EPO2) was shorter in plant height but had twice the life span compared to other transgenic plants. When 11 randomly selected EPO plants, along with the abnormal plant EPO2, were subjected to RT-PCR analysis, all of them had detectable EPO transcripts. However, their protein levels varied considerably; seven of them had detectable EPO proteins analyzed by western blot. Our results indicate that overexpressing human EPO protein in plants does not have detrimental effects on growth and development. Our transformation systems allow us to further explore the possibility of glycoengineering tobacco plants for producing functional EPO and its derivatives.

Bioproduction de protéines thérapeutiques

The increase in importance of the biopharmaceutical market generates enormous needs in production of therapeutic molecules. The world capacities of production, mainly therapeutic proteins, impossible to obtain by chemical synthesis, are at present insufficient. Besides the economic aspects in set, play, the question of the technologies used to produce these molecules is important: the tried(felt) technologies (bacteria, yeasts, cells of mammals), used for a long time rather widely remain expensive, or see their limited field of application; the innovative technologies (avian cells, animal and plant transgenic, among others), as for them, again have to show their ability.

Engineering eukaryotic protein factories

The biopharmaceuticals market is currently outperforming the pharmaceuticals market and is now valued at US$ 48 billion with an average annual growth of 19%. Behind this success is a 100-fold increase in productivities of eukaryotic expression systems. However, the productivity per cell has remained unchanged for more than 10 years. The engineering of the ER-resident protein folding machinery is discussed together with an overview of signal transduction pathways activated by heterologous protein overexpression to increase cell specific productivities.

Russia through the prism of the world biopharmaceutical market

Trends in the Russian pharmaceutical biotechnology and related fields representing the major sector of domestic biotech are reviewed through the prism of the world biopharmaceuticals market. A special emphasis is placed on biogenerics and follow-on biologics. The revival of national pharmbiotech is seen in close cooperation between private companies and the state, academia and industry. One of the first positive steps toward promoting development of domestic biopharmaceuticals is the Federal Program of subsidized supply of expensive pharmaceuticals (Dopolnitel'- noe Lekarstvennoe Obespechenie). The program allows the Russian government to purchases expensive drugs to be provided free of cost to certain preferential categories of individuals. As an example, production of recombinant human insulin by the largest Russian fundamental biotechnological institute, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry under the trademark Insuran (Insulin produced by the Russian Academy of Science) is reviewed. Some prospects and problems of Russian biotech research related to medical area are briefly discussed.

Next issue (July 2007): Biotech in Russia

AbstractEdited by Professor Michael Rabinovich, Moscow, RussiaHighlight articles:Russia through the prism of the world biopharmaceutical market– Main trends of biosensor development in Russia– Novel Russian monoclonal antibody‐based therapeutic agents– Genetic and molecular backgrounds for the novel sustainable agro‐technologies– Russian safety assessment of plant GMOs– Biotechnological studies in the Far‐Eastern Region of Russia– Preclinical immunological trials of candidate DNA vaccines for HIV– Russian DNA chips... and much more: Read the next issue of BTJ!

GE and Parker Domnick Hunter link up to serve the biopharmaceutical market

In the UK, GE Healthcare and Parker Domnick Hunter, a division of Parker Hannifin, have entered into an exclusive agreement to supply and distribute products for biopharmaceutical purification.

Biopharmaceuticals in China

The biopharmaceutical industry, whose products are produced mainly by recombinant DNA technology, antibody technologies and cytotechnology, is the most important sector in industrial biotechnology, and is one of the most rapidly growing high-tech industries. The global market for biopharmaceuticals had been growing at annual growth rates of 15-33% over the last 8 years, and sales exceeded 55 billion dollars in 2005. This review presents an overview of the Chinese biopharmaceutical industry, listing the global top-selling biopharmaceuticals in 2005, and briefly describes the major biotech drugs approved by the Chinese State Food and Drug Administration, such as recombinant cytokines, therapeutic antibodies, recombinant vaccines, and gene therapy products.