制藥行業(yè)的發(fā)展
 
1994年9月26日出版的《商業(yè)周刊》封面上刊登了一篇關(guān)于生物技術(shù)產(chǎn)業(yè)的訃告。雜志哀嘆,“經(jīng)過了近20年的基因剪接革命,涉及到生物技術(shù)產(chǎn)業(yè)的公司和企業(yè)已經(jīng)擴(kuò)展到超過1000多家，并且籌集了約200億美元的資金。然而,仍然沒有生產(chǎn)出能夠治愈癌癥的方法或生產(chǎn)出能解決第三世界饑餓問題的面包和魚類等生物工程奇跡。”這個(gè)故事反映了生物技術(shù)產(chǎn)業(yè)所面臨的一個(gè)困難時(shí)期。美國(guó)證交所生物指數(shù)1992年達(dá)到頂峰，隨之降低了至少50%，據(jù)估計(jì)，這個(gè)行業(yè)有一半的公司在過去24個(gè)月有足夠的現(xiàn)金，但是多年來(lái)甚至沒有生產(chǎn)出一項(xiàng)產(chǎn)品。“作為美國(guó)高科技產(chǎn)業(yè)最高漲的十年,”這篇文章說,“生物技術(shù)面臨著人們的重新審視，這將是不盡如人意的。”

盡管該dissertation提出生物技術(shù)行業(yè)已經(jīng)生產(chǎn)出了相關(guān)的工具和技術(shù)，證明對(duì)制藥行業(yè)是極具價(jià)值的,但它也指出，利用生物技術(shù)所能完成的產(chǎn)品數(shù)量是非常有限的。
 
The Growth Of The Pharmaceutical Industry Economics Essay
 
The September 26, 1994 issue of Business Week featured an obituary on its front cover. It was for the biotech industry. The magazine bemoaned that “nearly 20 years into the gene-splicing revolution, the industry had ballooned to well over 1,000 public and private companies that have raised about $20 billion. Yet, no one has cured cancer or produced a bioengineered miracle of loaves and fishes for a hungry Third World.” The story reflected a difficult time for the industry. The Amex Biotech Index was off more than 50 percent from its peak in 1992 and an estimated half of the companies that made up the industry had enough cash to last 24 months and were years away from a product. “As a decade as the highest-flying of America’s high-tech industries,” the article said, “biotech faces a reckoning—and it’s going to be ugly.”
 
While the article acknowledged that the industry had produced tools and techniques that had proved valuable to the pharmaceutical industry, it noted there had been few product successes, a string of high-profile clinical failures, and characterized the industry as “choked with copycat, capital hungry companies lacking the critical mass of technology to survive.” Big drug makers were not going to be their salvation either. The story noted the pharmaceutical giants were busy with their own takeover deals and biotech companies bargaining power was eroding with buyers. The attitude at the time was why should they buy today if they wait a few months and get a lower price. “But as resources are stretched thinner in biotech,” the story concluded, “no one can count on salvation. Indeed, investors have finally realized what most gamblers eventually do: After a while, it doesn’t pay to focus too much on any one hand when it’s the long odds that are killing you.
 
A series of highly publicized clinical failures between 1992 and 1994 of experimental drugs aimed at treating sepsis, a potentially fatal infection of the blood, delivered a severe blow to the confidence in the biotechnology industry. In many ways, the Business Week story was simply a reflection of that. [See Sidebar: Investors love affair with biotech waivers].The events that played out during this time seemed worse because they followed boom times for biotech in 1990 and 1991, when, during an 18-month period, 56 companies went public and the industry as a whole raised $5 billion [See Figure 1.1]. The bottom seemed to drop out of the market for the entire biotech sector as investor confidence in the industry's ability to get products through FDA approval was shaken to the core.
 
The industry would never be viewed in the same light again. This series of disappointments for potential blockbuster and life-saving biotechnology drugs contributed to a protracted bear market for biotech stocks. It gave pause when the emergence of monoclonal antibodies was hailed as “magic bullets”. [See Sidebar: Magic bullets or blanks?]. And, it called into question whether the biotechnology industry could create value and generate a return for its investors.
 
Most companies in operation up until that time owed their origins to the confidence that investors had in the hopes, dreams, and aspirations of the management of these biotechnology companies and their ability to bring novel products and services to the marketplace. By and large, the industry became victim of its own enthusiasm. It exhibited too much optimism over the speed at which scientific discoveries could be translated into products to improve health, agriculture, and industrial products.
 
It was a tipping point for the industry. Biotech investors from that period on became discriminating. They learned to judge companies on their individual merits of success or failure, rather than applying the same set of rules to the whole industry.
 
The difficulties the industry faced in 1994 would not be an isolated moment in its development. It would find itself standing at the precipice several times more with naysayers predicting its demise when capital markets turned hostile [See Figure 1.2] and clinical trials failed.
 
Remarkably, 25 years after I published my first annual report on the life sciences, the biotechnology industry has matured and thrived. It is a continuing story of success.
 
Product sales, R&D expenditures, employment, and market capitalization have climbed virtually every year. [See Figure 1.3].
 
It would have been hard for most people then to imagine the enormous value that biotechnology companies would eventually create. Few would have thought that by 2009, the pioneering biotech Genentech would grow to surpass the market cap of the world’s leading pharmaceutical company Pfizer. Genentech, Amgen, and a handful of other biotechnology companies were very successful in executing on their plans to become fully integrated pharmaceutical companies (FIPCOs). [See Sidebar: The Development of a Fully Integrated Pharmaceutical Company]
 
In those early years, many companies aspired to become fully integrated companies with their own internal research, development, regulatory, manufacturing, sales and marketing operations However, such a business model carried higher risk and demanded major capital investment. As the industry matured, and the financing environment changed along with investor expectations, so did business strategies. [See Figure 1.4]
 
Though times today are still challenging, the industry has made impressive progress. Five of the top 10 selling drugs in the world are biologics and sales of biotech drugs account for 31 percent of the sales of the top 100 selling drugs, according to EvaluatePharma. They also forecast that biotech products will account for 48 percent of the sales from the top 100 products in 2016 and eight of the top ten drugs will be biologics. [See Figure 1.5]. That compares to just 15 percent in 2000.
 
The bioscience industry in the United States alone employed 1.4 million people in 2008, according to the Battelle/BIO State Biosciences Initiatives 2010 report. With a total of 649 public companies identified across the biosciences including agriculture, drugs, medical devices, and research, Battelle found these companies generated $577.3 billion in revenue in 2009. During the last decade, state governments have increasingly begun to target the biopharmaceutical industry and the larger biosciences because they are economic engines providing high-wage, high-skilled jobs across a range of occupations. National employment in the biopharmaceutical sector grew by 29 percent between 2001 and 2008, exceeding not only total private sector job growth by eight times, but also job growth of other high technology sectors, such as software and computer services, computer and related equipment, finance and insurance, and aerospace. Even during the initial recession year of 2007 to 2008, the number of biopharmaceutical industry jobs grew by 1.4 percent, while overall private sector employment declined by 0.7 percent.
 
The U. S. biopharmaceutical industry sector is projected to continue to grow. The Bureau of Labor Statistics projects that the pharmaceutical sector, defined as including pharmaceutical and medicine manufacturing, will add 17.6 million jobs between 2008 and 2018, growing at an annual rate of 0.6 percent compared to a 0.9 percent decrease in overall manufacturing employment. Output of the pharmaceutical sector is projected to grow at an annual rate of 3.3 percent reaching $194.5 billion in 2018.
 
Biotechnology today is not only being used to develop new therapeutics, but also being harnessed to address some of the most challenging problems we face today including feeding the planet, cleaning our environment, and providing new sources of renewable energy. [See Figure 1.6 & 1.7]
 
None of these achievements would have been possible without the tremendous technological developments that have occurred since the dawn of the industry. From the early 1970s when recombinant DNA technology was first developed, there has been an explosion of knowledge in biotechnology. We have seen the introduction of PCR, chemical DNA synthesis, DNA sequencing, monoclonal antibodies, antisense techniques, labs-on-a-chip, gene therapy, stem cells, and genomics through to systems biology.
 
We are now one decade into what has become known as The Biotechnology Century. Driven by a powerful array of enabling technologies (such as genomics, high-throughout sequencing, screening, and combinatorial chemistry) there has been a rapid succession of advances in the traditional life sciences (biochemistry, pharmacology, molecular and cellular biology, immunology, and genetics). These advances not only aid in accelerating drug discovery and development, but, at the other end of the spectrum, provide the tools to speed up clinical research (by identifying potential respondents for treatment) and move us toward the development of individual, customized medicine.
 
Biotechnology is allowing us to find answers to nature’s most perplexing questions surrounding how genes function both normally and in a perturbed state. Molecular imaging, barcoding molecules, and biomarkers are cracking open windows that are providing an initial glimpse into what soon may be possible. Eventually we will be able to predict cellular events, and even control them as they occur.
 
The convergence of information technology and biotechnology are leading us down a path towards personalized medicine where new diagnostic technologies and wireless monitors provide early warnings of impending health problems. We are moving to the kind of predictive and preventive care that will remake the medical world and address the problems of access, delivery, and affordability that are plaguing healthcare systems today.
 
Personalized medicine is bringing about a change in the way we approach healthcare. We are moving from a paradigm that just treats sickness, to one that embraces wellness. This means refocusing a reactive, sporadic, disease-oriented healthcare system to one that is personalized, predictive, preventative, and strategic.
 
The tipping point for personalized medicine came in 2004 with the publication of a seminal report from the FDA entitled, “Innovation or Stagnation? Challenge and Opportunity on the Critical Path to New Medical Products.” It stated that despite the billions of dollars the biotech and pharma industries were spending on R&D and the new technologies at their disposal, fewer new products were actually reaching the agency. For this reason, it gave the industry a failing grade on its innovative ability to discover and commercialize next generation therapies.
 
The report noted that even with the boom in genomics, proteomics, and nanotechnology, there had been a downward trend in the number of innovative medical product applications to the FDA and its counterpart agencies throughout the world. New scientific advances had not had a fundamental impact on patient care.
 
The revolution in biomedical science had raised new hope for the prevention, treatment, and cure of serious illnesses. However, there were growing concerns that many of new scientific discoveries were not yielding more effective, more affordable, and safer medical products for patients. The reason put forth was that the medical product development path was becoming increasingly challenging, inefficient, and costly. As a result, the number of new drug and biologic applications submitted to FDA had declined significantly. In contrast, the costs of product development had soared.
 
What was the problem? In FDA’s view, the applied sciences needed for medical product development had not kept pace with the tremendous advances in the basic sciences. The new science was not being used to guide the development of technology in the same way that it was accelerating discovery. Researchers were not performing enough applied scientific work to create new tools to get better answers about the safety and efficacy of new products faster, cheaper, and more accurately. In many cases, developers had no choice but to use the tools and approaches of the twentieth century to assess twenty-first century candidates. As a result, the vast majority of investigational products that enter clinical trials fail. Often, product development programs must be abandoned after extensive investment of time and resources. This high failure rate drives up costs, and developers are forced to use the profits from a decreasing number of successful products to subsidize a growing number of expensive failures.
 
A new product development toolkit - containing powerful new scientific and technical methods such as computer-based predictive models, biomarkers for safety and effectiveness, and new clinical evaluation techniques--was urgently needed to improve the critical path from laboratory concept to commercial product. These tools would support the earlier termination of drugs, which will be toxic in humans and cause rare events that are unlikely to be identified in clinical trials.
 
The report served as a wake-up call for the pharmaceutical industry, which was at that point still rooted in a business model of developing mass market drugs. It also catalyzed creation of the Critical Path Initiative—FDA's national strategy for transforming the way FDA-regulated products—human drugs, biological products, medical devices, and veterinary drugs—are developed, evaluated, and manufactured [See Personalized Medicine chapter].
 
We have now entered the era of genomic medicine. Drug therapy will change in the coming years so that new drugs will be more effective and safer. Today, a physician prescribe a drug knowing only how the average patient will respond, but not if a specific patient will respond to a given drug or suffer side effects.
 
Personalized medicine is offering the potential for revolutionary change in the practice of medicine. It also provides a unique window into the relationship between new medical technologies, new business models for healthcare delivery, and the role of governments in this unique marketplace. The publication of the FDA report created a major inflection point for the industry and its influence continues to be felt today. In fact, the whole industry is treading a critical path as it tries to make sense of the burgeoning genomic data available to it.
 
The first decade of The Biotech Century has set the stage for continuing progress over the next 25 years. Biotech has moved to the forefront of a major shift in healthcare towards predictability—with the development of molecular diagnostics and targeted therapeutics.
 
In order for innovation to progress from the lab to the marketplace it requires investment. Yet, the global financial turmoil from which the industry is just emerging had executives once again wondering whether they would be able to recover one more time to deliver novel products and services. The rules under which the industry has operated since its inception have largely been obliterated. A confluence of forces including global economic trends, policy changes, marketplace demands, and technological advances have transformed the way companies need to operate in order to be successful.
 
The pharmaceutical and biotechnology industry in the United States, Canada, and Europe are facing severe financial constraints, which are expected to worsen in the years ahead. Biopharmaceutical companies are under pressure to reduce expenditures due to the increasing cost of drug development, stiffer regulations, lost revenue to competition from generics, and thinning pipelines. These pressures are driving companies to outsource R&D activities increasingly to low-cost countries such as India and China. Over the last decade, India and China have developed significant capabilities in drug discovery research along with considerable capabilities in early- and mid-stage clinical trials. Both countries are able to provide cost savings in the range of 60 to 70 percent for discovery research and clinical trials.
 
At the same time, emerging markets are striving to become significant players in world trade. Additionally, the growing healthcare demands in emerging markets, coupled with rising income levels, present new opportunities for drugmakers. Biotechnology research is expanding into emerging nations,. China is already the world’s third largest pharmaceutical market and will be number one by 2050. Other Asian nations, such as Singapore and South Korea, are focusing on biotechnology to grow their economies.
 
Although the U.S. biotech industry continues to be the dominant player – leading in market cap, revenue, products, and influence – much of the rest of the world is also embracing biotech in a big way. In today's global playing field, there are more biotechnology companies outside the United States than within. Any country that is prepared to nurture its venture capital and entrepreneurial ecosystem is poised to benefit economically and not necessarily at the expense of another region. This game is one for everyone to win.
 
The established markets of the U.S., Europe and Japan historically represented roughly one-third each of the global pharmaceutical market with the rest of the world representing an insignificant share. However, there is a major market shift underway, and by 2025, what has collectively made up the rest of the world will account for more than half of the market.
 
Emerging markets, particularly China, India, and Brazil, will grow faster than the United States and Europe. Increasing affluence, a growing middle class, and government policies will make healthcare big business in these countries. The global nature of biotech will put pressure on the United States to maintain its dominance and there is increasing evidence of other regions taking the lead in some technologies and business sectors.#p#分頁(yè)標(biāo)題#e#
 
Biotechnology's mission has never been more critical. The challenges confronting our world are enormous. No longer can a nation ignore its environmental footprint while it grows its economy. Climate change and its potential for future devastating effects must be addressed, and biotechnology can help satisfy the increasing demand for food and energy from a growing population and provide solutions that help lead to a low-carbon economy.
 
The long-term prospects for biotech remain strong. Today, there are more than 250 biotechnology healthcare products and vaccines available to patients, many for previously untreatable diseases. The industry continues to innovate at a breathtaking pace, developing medicines that are providing hope where there once was none.
 
The last 25 years has been a remarkable journey. The industry continues to fight many of the same battles–financial, regulatory, and legal—that it has since its earliest days. IPO windows still open and close, the Myriad Genetics case has resurfaced fundamental questions about what it patentable, and the FDA still struggles with striking a balance between ensuring patient safety and making available new therapies to treat unmet medical needs as quickly as possible.
 
Issues get resolved and the industry adjusts. There will be no solutions to old problems. But perhaps the biotech greatest strength is its ability to adapt as new, and old, challenges arise. There is no doubt that it has a long life ahead and the obituary writers anxious to bang out the final word on the industry will have to perpetually wait.