Is the United States Still Dominant in the Global Pharmaceutical Innovation Network?

The dramatic growth of research and development activities in the pharmaceutical sector in emerging economies raises the question of whether the United States still keeps its dominant role in the global pharmaceutical innovation landscape. This paper focuses on investigating the role of the United States in global pharmaceutical innovation, and differs from previous studies by shifting attention to a network analytic perspective to track the global distribution of pharmaceutical inventions. Our sample is composed of key patents covering all new drugs approved by the Food and Drug Administration between 1996 and 2010. The results show that the United States still dominates in the global pharmaceutical innovation network, especially when it comes to essential core inventions. However, the United States shows a slightly decreasing prominence in the networks of either total new drugs or New Molecular Entity (NME) drugs in the time period 2006–2010 as compared to previous time periods, revealed by subtle traces of network centralities.     

全球生物制药产业发展态势

传统化学制药的黄金时代结束,新化学药品数量下降,而生物技术药物已成为当今最活跃和发展最迅速的领域。随着基因组和蛋白质组研究的深入,越来越多与人类疾病发展相关的靶标被确定,生物制药将有更多的机会获得突破性进展。综述了全球生物制药产业发展的几个态势,主要有：（1）全球生物制药产业的研究成果数量增长迅速;（2）生物制药依然是生物技术产业的重点领域,生物技术药物市场发展规模逐渐扩大,市场集中度高,主要集中于美国和大的跨国公司;（3）生物技术新药在新药研发中的比重越来越大,逐渐成为新药研发主流;（4）生物制药企业间通过加强联盟,来增强新药研发能力和降低新药研发成本;（5）各国政府均重视生物制药产业的发展,出台一系列相关政策。（6）生物疫苗、基因工程药物和基因药物具有良好的市场前景。     

Government Regulations and the Use of Drugs

I have tried to trace the new drug development pattern from 1766, when Withering obtained his medical degree, to the present.The role of governmental authority as defined by the 1962 Kefauver-Harris amendments to the 1906 law and the subsequently issued regulations has been summarized. Four phases of testing in man have been detailed.Something of the scientific or research capability of the pharmaceutical industry has been presented.It is concluded that in the period of over two hundred years of medical education in the United States, the university hospital has become more and more the focus of medical research, teaching and practice in the community. The safety and effectiveness in the use of drugs in the future will depend upon the liaison and rapport of the industry physicians, government officials and the university hospital teacher-clinical investigators (phase 1 and 2) in designing the most critical studies of the safety and effectiveness of new drugs.Whether the medical profession as we know it will participate more in the future than has been possible since 1962 in mass clinical trial (phase 3) before new drug approval by governmental authority remains to be seen.The final approbation or disapproval of a drug after NDA approval (phase 4) will continue to be in the hands of the participating physician as long as he can establish scientifically that the drug is the best possible agent for him to use in healing the sick and comforting the dying.     

The economics of personalized medicine: commercialization as a driver of return on investment

Optimizing commercialization of drugs is the sine qua non of the pharmaceutical industry and intensive work has been done to characterize fully the drivers of drug adoption and understand the resources required to optimize those drivers for full adoption of drugs. Conversely, while the pharmaceutical industry is actively embracing the new personalized medicine (PM) paradigm, much work remains to be done to understand fully what drives adoption of targeted therapies and how to resource those drivers appropriately. While the industry is slowly learning from its early missteps, progress is still inhibited by a lack of understanding of the specific hurdles that individual development teams face in developing and commercializing targeted therapies and the requirement for budgets specifically aimed at driving test adoption. This article considers the benefits of optimizing commercial planning in the PM space and the potential negative impact in potentially failing to optimize that planning. Real world insights are used to illustrate that a far broader commercial lens is required in the PM space and will touch on functional areas not usually included in the context of 'commercial' decisions.     

Medicine and industry: a necessary but conflicted relationship

Medicine and industry are bound together by mutual needs. The development and utilization of new drugs and medical devices requires both the scientific and clinical expertise of physicians, and the resources and entrepreneurial ethos of business. The medicine-industry partnership has contributed to dramatic improvements in medical care. The increasing influence of the pharmaceutical and medical equipment industry in medicine has, however, raised concerns about costs and regulation, as well as about medicine's traditional independence and objectivity. Some critics feel that the fundamental obligation of business to provide profit for shareholders conflicts with physicians' traditional role as disinterested advocates of patients' interests. Nonetheless, with about 15% of the U.S. economy now devoted to health care, an ongoing and ro-bust relation between business and medicine seems inevitable. A mutually productive relationship between medicine and industry is essential for continued innovation and improvement in health care. Continuous and open dialogue, such as that in the following articles, is necessary to resolve conflicts and achieve this goal.     

基于社会网络分析和共词分析的制药技术领域研究

目的:深入研究制药技术领域的发展态势。方法:本研究以Pub Med数据库中收录的制药技术领域研究论文为研究对象,采用社会网络分析、共词分析等定量方法,结合药学专业知识的定性分析,从论文数量年度分布、国家/地区分布及合作网络、研究主题等多个角度开展研究。结果:研究发现:第一,全球制药技术领域共有研究论文95381篇,近几年正处于快速发展阶段;第二,论文发表集中在美国、中国和日本等国家;第三,在定量分析的基础上,结合药学专业知识,共得到15个研究主题,包括点击化学、晶型药物、纳米微球药物等。结论:美国在制药技术领域处于主导地位,中国发文量已经具备一定优势,但发文量和国际影响力与美国相比还是存在较大差距;通过对制药技术领域研究主题的深入分析可以全面把握制药技术领域的研究现状和发展态势。     

Polypharmacology and supercomputer-based docking: opportunities and challenges

Polypharmacology, the ability of drugs to interact with multiple targets, is a fundamental concept of interest to the pharmaceutical industry in its efforts to solve the current issues of the rise in the cost of drug development and decline in productivity. Polypharmacology has the potential to greatly benefit drug repurposing, bringing existing pharmaceuticals on the market to treat different ailments quicker and more affordably than developing new drugs, and may also facilitate the development of new, potent pharmaceuticals with reduced negative off-target effects and adverse side effects. Present day computational power, when combined with applications such as supercomputer-based virtual high-throughput screening (docking) will enable these advances on a massive chemogenomic level, potentially transforming the pharmaceutical industry. However, while the potential of supercomputing-based drug discovery is unequivocal, the technical and fundamental challenges are considerable.     

美国生物医药产业竞争力分析与启示

进入生物经济时代以来,以生物医药产业为代表的生物技术产业正在引领人类新一波技术产业革命。我国针对生物医药产业作出的战略部署已经取得了明显成效,但与美国等生物医药强国相比仍有较大的竞争差距。采用波特钻石模型构建了生物医药产业国际竞争力理论分析框架,以美国为例分析其生物医药产业在要素状况、企业结构和竞争、需求条件、相关及支持性产业、政府和发展机会六个方面的竞争优势,并基于此提出了我国发展生物医药产业的政策建议,从而为我国生物医药产业发展提供政策参考。     

Overcoming obstacles to developing new analgesics

Despite substantial investment by the pharmaceutical industry over several decades, there has been little progress in developing new, efficacious and safe analgesics. As a result, many large pharmaceutical companies are leaving the area of pain medication. Nevertheless, the chances of success could increase if analgesic drug development strategy changed. To achieve such a paradigm shift we must understand why development of drugs for pain relief is so challenging.     

Follow-on Biologics: A New Play for Big Pharma: Healthcare 2010

The U.S. pharmaceutical industry plays a vital role in shaping the face of American healthcare. As an industry rooted in innovation, its continued evolution is inherent. With major patent expirations looming and thin product pipelines, the industry now must consider new directions to maintain growth and stability. Follow-on biologics, derived from living organisms and marketed after the patent expiration of similar therapies, represent a growing opportunity for big pharmaceutical firms, as discussed during Yale’s Healthcare 2010 conference in April. Key characteristics of follow-on biologics make them a worthwhile investment for big pharma companies: They command high prices, will likely have fewer entrants than generics due to high barriers to entry, and play to the existing strengths of big pharma firms. With the recent healthcare legislation providing the way for consistent Food and Drug Administration (FDA) regulation, the timing seems right to continue the push into this new and growing market.At a time when healthcare issues are on the mind of every American, it would serve us well to consider the future of one of the most influential players in the sector: pharmaceutical companies. National health expenditures for pharmaceutical products are hovering around 10 percent, meaning that one out of every 10 dollars that we, as a nation, spend on healthcare goes toward drugs. These drugs regulate our cholesterol levels, promote the growth of white blood cells in cancer patients, manage our restless leg syndrome, help us sleep better at night, and provide myriad other benefits to our health and well-being. Yet, for all the benefits that the pharmaceutical industry provides, it is also criticized by many for the expense of its products and the high profit margins that these products command. The growing popularity of biologics — treatments derived from living organisms, such as antibodies and interleukins — has particularly increased the price of drugs in the United States. The current price of the average biologic is more than 20 times that of a traditional, chemically synthesized small-molecule drug. There is a trade-off between high prices and innovative new therapies. Moreover, pharmaceutical companies themselves argue justifiably that prices account not only for the price of production, but also for the research and development (R&D) for that therapy as well as numerous others that did not make it all the way through the regulatory process and to the clinic.In recent years, we have witnessed the breakdown of the well-oiled innovation machinery of the traditional big pharma company. While R&D departments spent more and more (well over $1B per drug), they did not see promising results in the form of late-stage drug candidates [1]. Over time, this led to a strategic shift in portfolio management within big pharma companies toward an acquisition-heavy plan to build up their pipeline of drugs. In-house R&D projects were cut, and layoffs of scientific staff were rampant. This phenomenon continues, with 2009 bearing witness to the most mergers and acquisitions in the pharmaceutical industry to date. Industry-wide consolidation aimed to find complementary development projects and synergies in manufacturing and emerging markets. What has been the effect of all of this? The answer is not as hopeful as the pharmaceutical industry would have liked. A giant “patent cliff” still persists, referring to a number of blockbuster drugs that will go off patent over the next two years and cause a dramatic decrease in sales for big pharma firms. Without a strong pipeline to fill in the valley with new product sales, big pharma companies have begun scrambling to find new ways to generate revenue.Meanwhile, the biotech industry’s foray into therapeutics has been a wild success story. From the 1980s to the present, biologics have reshaped the face of medicine in many disease areas. The spawn of highly innovative, nimble biotech firms, biologic drugs are large, complex molecules grown in living cells rather than synthesized chemically like small molecules. For example, Enbrel is a fusion protein that acts as a tumor necrosis factor (TNF) inhibitor to stop inflammation. This drug is being widely prescribed for rheumatoid arthritis as well as psoriasis, among other indications, with sales last year reaching $5.9 billion, up 9.3 percent from 2008 [2]. Enbrel was first developed by Immunex and released in 1998. Immunex was acquired by a rival biotech firm, Amgen, in 2001 [3], and subsequent marketing of the drug in the United States was jointly undertaken by Amgen and Wyeth (now taken over by Pfizer in the mega-merger of 2009). Enbrel’s is the classic story of the modern biologic: a novel therapy developed at a small biotech firm and acquired or licensed up the food chain to feed bigger firms’ appetites for late-stage assets.Enbrel is by no means unique; there are many blockbuster biologics on the market. Like Enbrel, many of them will reach the end of their patent life soon. Enbrel’s patent expiration is set for 2012, at which time it will be exposed to potential competition from generic versions. Therefore, though there are many novel biologics therapies that can provide new ways of treating patients, there is also a huge opportunity for generic versions of biologics that did not exist even one decade ago. This opportunity is hard to quantify, but one recent estimate shows that biologics responsible for $20B in annual sales will go off patent by 2015 [4]. Unsurprisingly, small-molecule generics firms are flocking to this space. Teva, the world’s largest generics manufacturer, has partnered with the Lonza Group to make and sell so-called follow-on biologics. These treatments are similar, but not identical, to preceding biologics whose patents expired. Meanwhile, Novartis’s generics arm, Sandoz, has increased capacity in biomanufacturing to ramp up its efforts. Big pharma itself has made motions of interest in the business of follow-on biologics, as witnessed by the dedicated division of Merck, BioVentures, established in late 2008 for the development of follow-on biologics. Interestingly, even Pfizer is testing a follow-on version of Enbrel, now in phase 2 clinical trials [5]. With a big market opportunity and a number of firms interested, follow-on biologics will surely play an important role in shaping the future of the pharma industry.For large pharmaceutical firms, what is needed is a way to diversify and mitigate risk, a way to supplement their rollercoaster sales figures year after year. Follow-on biologics may be a smart play for big pharma companies. Like their generic cousins, biologics manufacturing has strong economies of scale that big pharma firms can leverage. But unlike generics, there are higher barriers to entry because of the technical challenges of manufacturing biologics and the necessary clinical proofs of equivalency. Pharmaceutical companies already are practiced at navigating the global clinical-trials arena and should be able to exercise a significant competitive advantage in this area, especially over the existing generics manufacturers attempting a play in the follow-on biologics market. It has been estimated that the investment necessary to bring a follow-on biologic to market is eight to 10 years and will cost $100-$200M [6]. This investment of time and capital is substantial and tends to favor larger firms with significant R&D budgets. However, to put the investment into perspective, this is only one-tenth of the cost of developing a full-scale innovative pharmaceutical product and has less associated risk of failure — a proposition that the big pharma industry should find appealing. Additionally, the trend for current follow-on biologics on the market in the European Union (EU) and United States has been to use traditional detailing and marketing practices to compete with branded products. This, too, puts big pharma at a competitive advantage over other players lacking an army of detailing pharmaceutical reps, who can use their established relationships with doctors and medical personnel to promote new follow-on biologics.One counter-argument to the case for a move into follow-on biologics is that the new healthcare reform, the Patient Protection and Affordable Care Act (PPACA), passed in March of this year will harm any would-be generic biologics makers with its 12-year exclusivity for branded biologics. However, while this length of time is significantly longer than the proposed five years that generics proponents pushed for, the surety of a secure path forward through the FDA for follow-on biologics outweighs the downside of lengthy biologics exclusivity. It is reasonable to hope that within two to three years, the FDA will have functional guidelines for the regulation of this nascent market. Now more than at any other time in the past, the ambiguity associated with government regulation is manageable. And if big pharma becomes more intentional about entering the follow-on biologics market, its powerful lobby, PhRMA, could influence the way that the details of the FDA regulations are written.If the pharma industry does find the follow-on biologics market appealing and makes a bet on it for supplementary revenue, what can we expect from the patient perspective? It could mean greater access at cheaper prices, but the dynamics are much more nuanced. The economics of the small-molecule generics market likely will not be transferrable to the follow-on biologics market. High barriers to entry, high fixed costs of manufacturing, and marketing expenses will more likely manifest themselves in a market that has a small number of firms with relatively small price drops upon introduction of follow-on therapies. In small-molecule generics, the price typically decreases by about 80 percent from the original branded drug price after one year of generic competition. However, in current follow-on markets in the EU, this has not been the case. Since its introduction of biosimilars regulation in 2004, the EU has successfully introduced numerous follow-on biologics for three classes of branded drugs. The results hint at what might be expected for U.S. firms: By 2008 in Germany, biosimilars had captured an estimated 14 percent to 30 percent market share and discounted prices by 25 percent [7]. The U.S. story of follow-on biologics will likely mirror that of EU biosimilars rather than that of small-molecule generics.With healthcare legislation passed and the inevitable refocusing on bending the cost curve in healthcare expenditures, big pharma firms may be able to boost their reputation with the public as well as their bottom line with a continued push into follow-on biologics. The decreased risk of approval and steady returns will help diversify pharmaceutical companies’ volatile revenue streams, while concurrently winning favorable public opinion by promoting price reductions for some of the most expensive drugs available. The cost savings to consumers will increase access for patients as FDA regulation is finalized and more and more follow-on biologics enter the market. This could be a win-win scenario for big pharma and for patients.     

Medical Product Development, Innovation, and Life-Cycle Regulation: The Challenges for Biostatistics

The article provides a perspective on the challenges for biostatistics as well as on contributions that biostatisticians are making and can make to medical product development and regulation and what the future might be in these areas. The current environment in the United States for pharmaceutical development and regulation is discussed along with the expectations that the public has for how medical products should contribute to public heath. The globalization of research and the use of study designs that incorporate multi-regional populations present new challenges for design and inference. The emerging interest in and development of the science of safety assessment and quantitative approaches to risk evaluation is considered. Guidance development, especially in the area of clinical trials design, continues to be one of the needs that FDA is asked to meet. Guidance development is proceeding for non-inferiority study designs, adaptive designs, multiple endpoints in clinical trials, and missing outcome data in clinical trials. Biostatisticians will be asked and challenged to take on leadership roles in new areas such as personalized medicine, biomarker and genomics, development of new tools for visual display of clinical data, quality assurance and monitoring in clinical trials.     

Tailor-made pharmacotherapy: future developments and ethical challenges in the field of pharmacogenomics

Pharmacogenomics is the study of the myriad interactions between genes and pharmacotherapy. Developments in pharmacogenomics have changed and will affect pharmaceutical research, drug development and the practice of medicine in a significant way. In this article, we make an inventory of the ethical implications that might arise as a result of possible developments in pharmacogenomics and investigate whether the present ethical framework will be able to adequately answer arising questions. We think that many of the questions related to the consequences of pharmacogenomics are answerable along the lines of present ethical thinking. We also believe, however, that many 'changes of degree' may result in a 'change of kind.' We therefore think that pharmacogenomics may potentially have such a profound influence on scientific research and the pharmaceutical industry, the practice of medicine and society at large, that this will generate its own unique dynamic, which will require new ethical research. We suggest that the notion of 'responsibility' will be a major focus of such research.     

Potentialities of induced pluripotent stem (iPS) cells for treatment of diseases

Induced pluripotent stem (iPS) cell research has been growing a new height throughout the world due to its potentialities in medical applications. We can explore several therapeutic applications through the iPS cell research. In this review, we have first discussed the development of iPS cells, reprogramming factors, and effectiveness of iPS cells. Then we have emphasized the potential applications of iPS cells in pharmaceutical and medical sectors, such as, study of cellular mechanisms for spectrum of disease entities, disease-specific iPS cell lines for drugs discovery and development, toxicological studies of drugs development, personalized medicine, and regenerative medicine.     

Antidepressants and advertising: psychopharmaceuticals in crisis

As the efficacy and science of psychopharmaceuticals has become increasingly uncertain, marketing of these drugs to both physicians and consumers continues to a central part of a multi-billion dollar per year industry in the United States. We explore how such drug marketing portrays idealized scientific relationships between psychopharmaceuticals and depression; how multiple stakeholders, including scientists, regulatory agencies, and patient advocacy groups, negotiate neurobiological explanations of mental illness; and how the placebo effect has become a critical issue in these debates, including the possible role of drug advertising to influence the placebo effect directly. We argue that if and how antidepressants "work" is not a straightforward objective question, but rather a larger social contest involving scientific debate, the political history of the pharmaceutical industry, cultural discourses surrounding the role of drugs in society, and the interpretive flexibility of personal experience.     

RNAi therapeutic and its innovative biotechnological evolution

Recently, United States Food and Drug Administration (FDA) and European Commission (EC) approved Alnylam Pharmaceuticals' RNA interference (RNAi) therapeutic, ONPATTRO? (Patisiran), for the treatment of the polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis in adults. This is the first RNAi therapeutic all over the world, as well as the first FDA-approved treatment for this indication. As a milestone event in RNAi pharmaceutical industry, it means, for the first time, people have broken through all development processes for RNAi drugs from research to clinic. With this achievement, RNAi approval may soar in the coming years. In this paper, we introduce the basic information of ONPATTRO and the properties of RNAi and nucleic acid therapeutics, update the clinical and preclinical development activities, review its complicated development history, summarize the key technologies of RNAi at early stage, and discuss the latest advances in delivery and modification technologies. It provides a comprehensive view and biotechnological insights of RNAi therapy for the broader audiences.     

China's growing biomedical industry

The biomedical industry in China is developing rapidly, and new biological drugs are increasing their share of the pharmaceutical market based on people's needs. China is the largest producer and user of vaccines in the world, but the existing production of vaccines is far from enough to meet the needs of the market. The entire market of biological drugs in China is still smaller than that for traditional medicines and chemicals. Therefore, the biopharmaceutical industry has the potential to be the rising star in the pharmaceutical market in the future.     

Biotechnological studies in the Far-Eastern Region of Russia

Achievements and problems in both the studies on natural bioactive compounds from the Far-Eastern higher plants and marine invertebrates and development of the corresponding biotechnologies concerning new drugs and food supplements, as well as pharmaceutical leads are discussed. Special emphasis is made on recent results from the Far-eastern Institutions belonging to the Russian Academy of Sciences, and their application in both medicine and the food industry, as well as on peculiarities of biological and chemical diversity in the North-Western part of Asia and adjoining seas.     

The greening of biotechnology: the growth of the US biotechnology industry

The growth and advancement of biotechnology worldwide has been the focus of many studies, and at the heart of this advancement has been a new industry of small biotechnology firms in the United States. Since the early 1970s more than 300 small companies have been founded in the United States to work with the new technologies of genetic engineering, monoclonal antibody production, and in related areas. In addition, many major corporations in the United States have sought entry into biotechnology. Hundreds of new companies have been founded to interact with the biotechnology firms and large corporations, supplying reagents, equipment, fermentation expertise and serving a variety of other ancillary functions. Nowhere else in the world has a biotechnology industry been initiated to such a large degree. Today, the average US biotechnology firm is six to seven years old. The current state of the US biotechnology industry, historical perspectives, major trends and some future outlooks will be described below.     

转化医学：现代医学发展的动力

Translational medicine is a class of medicalresearch that proposes a two-way interaction betweenlaboratory and clinical research[1].Elias A.Zerhouni,the director of the National Institutes of Health(NIH),     

2014年江苏省医药产业发展报告

江苏省作为传统医药大省,是全国医药产业发展的重要组成部分,但仍存在诸多不足,极大地影响了其可持续发展。通过资料查询, 将江苏省与山东、河南、广东、吉林、浙江、湖北等医药产业重点省份进行比较,多方位分析江苏省医药产业发展现状,揭示眼下全省 医药产业发展中的主要问题所在,为全省医药产业健康发展建言献策