Gov. Beverly Perdue’s announcement that a California biotech will set up shop in North Carolina’s Research Triangle was a welcome but short-lived diversion Wednesday during the annual meeting of the North Carolina Biosciences Organization in Research Triangle Park.
Sequenom, a San Diego-based diagnostics company, plans to open a lab on Kit Creek Road next year and start analyzing blood samples from a new, prenatal blood test to detect Down Syndrome. The test would replace more invasive measures such as amniocentesis, which employs a long needle to sample amniotic fluid from inside the uterus.
Sequenom will invest $18.7 million and create up to 242 jobs.
The standing-room-only audience in the N.C. Biotechnology Center auditorium gave Paul Maier, Sequenom’s chief financial officer, a round of applause before Maier and Perdue faced the TV cameras and reporters outside.
Then, the biotech executives inside the auditorium went back to the unique chance that presents itself next year to shape the U.S. Food and Drug Administration.
Andrew von Eschenbach, former FDA commissioner and NCBIO’s keynote speaker, left no doubt that nothing short of a radical therapy will do.
“We’re approaching a crisis situation [in the U.S.] as far as being at the forefront of innovation,” Eschenbach said. The FDA is “in need of a systematic, systemic and formal revision. The moment for modernization is now.”
The FDA has been under close public scrutiny since 2004, when Vioxx was linked to thousands of sudden cardiac deaths before Merck pulled the pain killer off the market.
In 2009, a report released by the Government Accountability Office, the investigative arm of Congress, listed the FDA at risk of failing to fulfill its mission. Chronic underfunding, expanding responsibilities and an aging workforce that wasn’t keeping up with the rapidly advancing science hobbled the agency.
In July, FDAImports.com, a blog written by regulatory consultants, published information that suggested FDA Commissioner Dr. Margaret Hamburg was restructuring the agency’s top management tier. As a Washington Post profile pointed out, Hamburg, a Harvard-trained physician and former New York City health commissioner, had no ties to the pharmaceutical industry when President Obama appointed her.
With changes already under way at the FDA, it could become a watershed year.
In 2012, renewal of the Prescription Drug User Fee Act, or PDUFA, is up. Enacted in 1992, PDUFA established a funding mechanism for the FDA to regulate new medical products and make sure they are effective and do no unnecessary harm. The federal law has been subject to changes every five years, when Congress had to renew it to keep the system going.
The potential for significant changes is particularly large in 2012, because PDUFA for the first time is due for renewal during a presidential election year. And what a turbulent election year it promises to be four years into stubbornly high unemployment, ongoing banking crises and steep government budget cuts.
“This is going to create some interesting politics in Congress,” said J.C. Scott, the head lobbyist for AdvaMed, a trade association representing the medical device and technology industry. Scott was one of several NCBIO speakers addressing regulatory policy recommendations for overhauling the FDA.
Lobbyists for the biotech, pharmaceutical and medical device industries are not about to pass up this opportunity.
Young and small companies are getting squeezed by a lack of innovation capital. (More on innovation that isn’t being funded here.) Facing stagnant research and development productivity and the expiration of valuable drug patents in the U.S., large drugmakers have been cutting jobs for years. (More on the lack of big pharma R&D productivity here.)
The Biotechnology Industry Organization, or BIO, has already drawn up a wish list of changes. According to Cartier Esham, BIO’s senior director of emerging companies, health and regulatory affairs, who also spoke at NCBIO’s annual meeting, policy items on the list include:
- a fixed six-year term for the commissioner,
- the use of electronic health records and smart phones in clinical trials,
- faster approval of products for unmet medical needs similar to how European regulators do it,
- improved advisory committees,
- the establishment of chief medical policy officer positions and
- setting up the FDA with an independent budget. (The FDA is now funded under the U.S. Department of Agriculture.)
“It is our intent,” Esham said, “to get as many of these [policy changes] enacted into legislation as possible.”
Construction workers are swarming the two-story building in Research Triangle Park where Medicago plans to start vaccine production in January. In the adjacent greenhouse engineers are testing equipment and some of the first 38 employees are working on trays with 13-day-old wild tobacco plants about 1 inch tall.
Medicago is close to finish building its one-of-a-kind production plant. The French Canadian biotech company, which does its research and development in Quebec City, uses nicotiana benthamiana, a wild tobacco species from Australia, to make influenza vaccine.
The process to extract the vaccine from the leaves of the wild tobacco plants promises to be four times faster than traditional, egg-based vaccine production and require 10 percent of the capital. The RTP production plant will show how well Medicago’s approach is working.
Test runs will start in November and continue in December, said Todd Talarico, senior director of industrial process at the production plant.
By January, Talarico projected to have another 40 temporary and permanent employees hired to produce the first 10 million doses of flu vaccine in 30 days.
“We’ll be able to tell whether we’re on track,” Talarico said.
Construction of the plant started in October 2010. Medicago received a $21 million grant from the U.S. Department of Defense to prove it can ramp up production to 10 million doses per month. Alexandria Real Estate, which builds facilities for life science companies, invested $13.5 million. Medicago contributed the remaining $7.5 million.
The plant is one of three built in the past 10 years to make commercial vaccines in North Carolina’s Research Triangle.
New Jersey-based Merck operates a $400 million plant north of Durham that has already undergone one expansion. The $500 million Novartis plant in Holly Springs is projected to start making flu vaccines from cell cultures in 2013. The Triangle is also home to most of North Carolina’s more than two dozen companies in vaccine research and development. (More on the Triangle vaccine hub here and here.)
Unlike Merck, Novartis and Pfizer, which acquired a vaccine plant in Sanford with the purchase of Wyeth in 2009, Medicago will grow its flu vaccine.
Flu vaccines are protein vaccines and proteins can be generated by cells, yeast, bacteria or eggs. Medicago uses a combination of agrobacteria and wild tobacco plants. The technology is the brainchild of Louis-Philippe Vézina, the company’s co-founder and chief scientific officer.
Starting with alfalfa and then switching to nicotiana benthamiana, Vézina was able to coax the plants to make virus-like particles, proteins called hemagglutinin, that prevent flu viruses from binding to and consequently infecting cells.
Hemagglutinin comes in 16 different types, including H1, H2 and H3, which are found on human flu viruses such as the H1N1 virus. H5 is part of the avian flu virus, or H5N1.
The virus-like particle, or VLP, the wild tobacco leaves produce is not an inactivated virus. It does not contain genetic material, is unable to replicate and is non-infectious. But in preclinical studies VLPs produced a strong and broad immune response in mice and ferrets.
In 2010, Medicago researchers published a report detailing the benefits of VLPs and their production in wild tobacco plants.
The company has also tested different vaccines in humans, including one for seasonal flu and one for pandemic avian flu. Results from Phase I and II clinical trials, which involved healthy volunteers, suggested the vaccines were safe and effective.
A lot remains to be done before Medicago can gain regulatory approval to produce vaccine for sale. Larger clinical trials to further test how well the VLPs work and whether they cause any side effects are among the requirements.
One step toward regulatory approval is for Medicago to prove that the plant-based process can crank out 10 million doses of vaccine per month. That would amount to about 120 million doses of single-strain pandemic flu vaccine or 40 million doses of triple-strain seasonal flu vaccine per year, a production capacity that comes close to the about 150 million annual doses of flu vaccine Novartis projected to manufacture at its Holly Springs plant.
Medicago’s approach combines botany, biotech and robots used in the Dutch tulip industry.
Talarico explained the production process during a tour of the greenhouse that will be fully automatic once all the equipment is tested and running smoothly. For now, greenhouse specialists like Tanya Blankenship are doing much of the thinning, transplanting and placing of the plants on large growing tables by hand.
In full operation, the greenhouse will be able to accommodate about 90,000 plants.
Each plant will start as a seed that germinates in a plug tray. When the plants are a few days old, they will begin a two-week trip through the greenhouse.
A robot will transplant each little plant with its plug of dirt into a plastic pot filled with soil. A conveyer belt will transport the pots down the line to get watered and then placed on a growing table.
Lined up one after another, the growing tables will slowly move on rollers through the greenhouse. Machines will make sure the plants get watered and fertilized regularly.
“Nobody has to touch plants,” Talarico said.
When the trip through the greenhouse ends, the potted tobacco plants will be transferred into an enclosed chamber or tank and placed into a solution containing agrobacteria that carry the genetic blueprint to make a particular VLP.
A vacuum will suck the air out of the tank, which will prompt the leaves of the tobacco plants to take up the agrobaceria. This infusion will not alter the genetic makeup of the plant, but within an incubation time of about five days the cells in the leaves will start producing VLPs.
Then, machines will strip the leaves off the stalks, cut them in pieces and placed them into a solution to extract the VLPs.
Medicago already used this process at its R&D facility in Canada to make vaccine for the clinical trials. Now, Talarico said, the company is preparing to repeat the accomplishment at its RTP plant, which has the capacity to produce 25 times more and is 50 percent bigger than originally planned.
A month later than originally planned, researchers from Duke University, the University of North Carolina at Chapel Hill, RTI International and N.C. State University gathered Monday at the National Institute of Environmental Health Sciences in Research Triangle Park to talk about the benefits of federally funded research.
The NIEHS, one of 21 institutes under the National Institutes of Health and the only one outside Bethesda, Md., had planned the roundtable discussion in July, because support for research is under fundamental review. But then the date coincided with the debate that a month ago was raging in Congress over raising the national debt ceiling.
For roundtable member David Price, a Democratic Congressman who has represented North Carolina’s Research Triangle since 1987, the debt ceiling debate signaled the sentiment shift in Washington, D.C. that also affects research funding.
“There’s nothing in the world that comes close to the NIH’s 100-year history, though other countries aspire,” Price said, talking about the role the NIH have played in supporting health-related research at universities and institutes nationwide with federal tax dollars.
Federal funding for research in disciplines from medicine to engineering has been the foundation onto which Research Triangle Park and its more than 40,000 jobs were built over the past 50 years.
But, Price said, “things we might have taken for granted, parts of the RTP success story, may have to be redefined.”
In 2009, UNC-CH, Duke, NCSU and RTI spent about $2.5 billion on research, according to the latest figures from the National Science Foundation and RTI’s 2009 annual report. Federal tax dollars made up more than two-thirds of the money spent.
The expenditures represented nearly 2.9 percent of the Research Triangle’s gross product that year. In 2009, the metropolitan areas surrounding Raleigh and Durham generated services and goods worth about $86.9 billion, according to figures of the U.S. Bureau of Economic Analysis.
Sponsored research is a formidable economic engine in the Research Triangle, paying salaries and creating jobs when startup companies are formed around technologies that were developed at area universities or research institutes. (More on sponsored research in the Research Triangle here and here.)
NIEHS injects about $200 million in federal tax dollars into the local economy per year, said Linda Birnbaum, NIEHS director and member of the roundtable discussion. About 1,400 employees work on the sprawling NIEHS campus in RTP.
“We’re really making an impact, not only economically, but scientifically,” Birnbaum said.
As proof, NIEHS had invited researchers from RTI, NCSU, UNC-CH and Duke to participate in the roundtable discussion. NIEHS has awarded grants to researchers at the three universities anchoring RTP and the research institute that started operations shortly after RTP was established in 1958.
Dr. John Hollingsworth, an associate professor of medicine at Duke, receives funding from the NIEHS to study whether environmental pollutants such as diesel exhaust and ozone cause genetic changes that affect how the immune system works.
His research is tracking the interaction of genetic and environmental factors behind inflammatory diseases such as asthma, especially during vulnerable periods like pregnancy. About 8 percent of the U.S. population suffers from asthma, Hollingsworth said, and his research could lead to new, innovative therapies.
Heather Patisaul, an assistant biology professor at NCSU, studies the effects of hormone-like substances on the developing brain. Among the environmental estrogens she’s tracking are genistein, which is in soy-based foods including soy baby formula, and bisphenol A, a chemical that is in metal food can linings and many plastic containers.
Genistein and BPA are suspected to impair fertility and trigger early puberty in girls.
At RTI, researcher have received NIEHS grants to study air quality inside and outside of homes and diseases associated with poor air quality, said Charles Rhodes, a senior fellow at RTI.
Rhodes brought a sensor that RTI developed to run the air quality tests. Similar sensors will be used in a study that is scheduled to start next year in areas devastated by hurricane Katrina six years ago. The sensors will measure the air quality in trailers the Federal Emergency Management Agency provided residents whom Katrina rendered homeless. The trailers have been called “toxic tin cans,” for high formaldehyde levels in the air inside and health problems that have plagued many who have lived in the temporary housing.
UNC has worked with the NIEHS for a long time, training more than 500 researchers, looking for ways to determine susceptibility to environmental diseases, tracking how carcinogens and toxicants make people sick and how environmental toxins interact with human genes.
In the past decade, UNC has received about $112 million in research funding from the NIEHS, said James Swenberg, a UNC professor in environmental sciences and engineering.
Swenberg said he’s been trekking to Washington for 25 years to talk to federal lawmakers and lobby for research funding. In the past, lawmakers were generally eager to learn regardless of their politics.
“Research had never been a partisan issue,” he said. “It’s not going to be the same this time around. That’s really sad.
Republicans, especially in the House, and candidates running for President in next year’s election are “catering to extreme antigovernment views,” Price said. “We have to leave no doubt, that we’re good stewards of our tax dollars and that [research funding] is not some academic pork barrel.”
As a molecular biologist, Niels van der Lelie has researched microorganisms in different settings – in cheese making, in cleaning up contaminated water and soil and in growing crops on marginal lands. As the director of RTI International’s newest research center, van der Lelie plans to expand on these experiences and help develop technologies that aim at being greener and cleaner.
The Center for Agricultural and Environmental Biotechnology will be operational on RTI’s campus in Research Triangle Park in about two months. Initially, about 15 researchers will work at the center. Construction of a greenhouse, measuring 3,000 square feet to 4,000 square feet, is planned, with room for expansions.
Within a year, the number of researchers working for the center is projected to double to 30 and Lelie plans to establish a computational biology group.
The center will target research that deals with beneficial microorganisms that help clean up persistent contamination and digest municipal or animal wastes into biofuels, as well as with harmful microorganisms, such as bacteria that cause food-borne illnesses. The center also wants to work on making crop plants more drought resistant and produce better tasting. And it will look into domesticating medicinal plants, so natural resources can be protected.
Lelie expects the work to come from government research contracts and collaborations with industry. He has good chances of finding potential research and business partners in or near RTP. North Carolina’s Research Triangle is a hub for agricultural biotechnology. Companies such as Bayer CropScience, Syngenta and BASF CropScience have operations here. (More about agricultural biotech in the RTP area here.)
Lelie talked to Science in the Triangle about setting up the center and getting started:
Forget about the Bay Area and Boston. North Carolina’s Research Triangle, anchor of the third largest U.S. biotech hub, needs to look beyond continental shores if it wants to measure itself against some of the most innovative regions in the world. In China, India and Brazil, emerging biotech industries are stirring restlessly.
This came across so loud and clear at BIO 2011, the international biotechnology convention that from June 27 to June 30 brought companies, economic development recruiters, lobbyists and analysts from across the world to Washington, D.C., the message took on a measure of self-evidence.
The annual state-of-the-industry report, which Ernst & Young presented at the convention, provided supporting numbers:
- $61 billion, China’s drug market, which ranked second behind the U.S. last year and is projected to double in size by 2015.
- $1.8 billion, Brazil’s share of global investments in biofuel production last year. The U.S. ranked second and Europe was third.
- 70 percent to 75 percent, developing countries’ projected share of worldwide deaths from heart disease, stroke and diabetes in 2020.
- 25 percent, amount by which research and development investments in U.S., Europe, Canada and Australia decreased in the past two years.
What is happening, commentator and book author Fareed Zakariah said, is that “the landscape of innovation is shifting around the world.” Zakariah moderated a panel discussion with experts from India, Malaysia and China at BIO to explore the situation in those countries. Hundreds of BIO attendees came to listen.
To set the stage, Zakariah explained how the U.S. became the nation that sent the first man to the moon, developed vaccinations for childhood diseases such as polio and invented the personal computer.
In the 1920s and 1930s, Germany was the most innovative country, he said. During and after World War II, some of the brightest and most talented German scientists, many of them Jews, were part of a mass exodus that headed for the U.S.
“The U.S. benefited enormously from this inflow of talent,” Zakariah said.
The Immigration and Nationality Act of 1965 opened America’s gates to a similar mass inflow of talent from Asia. Buoyed by generous funding of basic sciences, nascent companies and public university systems during the Cold War, the U.S. became a worldwide dominating innovation power. But in the 1980s, the rest of the world started to catch up, Zakariah said. Economies developed, incomes and living standards rose – first in Japan, then in Singapore, Hongkong, South Korea and Taiwan, also known as the four Asian tigers, and most recently in India and China.
In the U.S., the housing market collapsed and the banking industry faltered. Research and development jobs started to move to low-cost countries, where many U.S. manufacturing jobs had already gone. Rising incomes and demand in developing countries convinced companies to pay more attention to consumers there.
“Now we face the question: Where does the U.S. go,” Zakariah said.
Companies like the manufacturer that sells its portable EKG machine in India for a fraction of the price General Electric charges for its EKG machines is driving frugal innovation, said Anula Jayasuriya, an Indian life science investor and a member on Zakariah’s panel.
The Indian manufacturer is considering bringing its portable EKG machine to the U.S., Jayasuriya said.
Health care problems will be solved where the need is biggest, which is in developing countries, said Georg Baeder, Asia life science business leader of the strategic consulting group Monitor and also a member on Zakariah’s panel. And at costs that are customary in developing countries.
The Chinese government is spending about $125 billion to upgrade and stimulate life science research. In India, the government is trying to help early stage companies. In Singapore, the government is expected to invest $12.5 billion on life science research innovation over the next five years, according to the Ernst & Young report.
And about 80,000 researchers and entrepreneurs who left China for a college education in the U.S. and Europe are returning to China, Baeder said.
A score card that Scientific American magazine developed for BIO in concert with the biotech industry’s trade organization showed that China, India, Brazil still have some catching up to do before they become serious challengers to a still dominant U.S. But a ranking of the top 48 countries capable to generate innovation in biotech worldwide, the score card lists Singapore ninth, Malaysia 28th, China 30th, Brazil 42nd, and India 44th.
Innovation capital, money to turn some of today’s most innovative discoveries into tomorrow’s medical treatments, is getting so scarce in the U.S., politicians, economic developers and entrepreneurs in regions specializing in early stage biotech research and development are scrambling.
North Carolina’s Research Triangle, the third largest U.S. biotech hub, is one of those regions.
Some of the world’s largest R&D companies have operations in the Triangle, including GlaxoSmithKline, Novartis and Bayer. But the lifeblood of the area has long been young, early stage companies in pursuit of ideas developed at local research universities such as Duke University, the University of North Carolina at Chapel Hill and N.C. State University or hatched by researchers who used to work in corporate labs in Research Triangle Park.
A little more than two years after a deregulated U.S. banking industry stumbled in the fall of 2008, investors are increasingly shying away from early stage biotech companies, a high-stakes, high-rewards gamble in the best of times. Innovation capital is drying up in the U.S., according to a 2011 report the U.S. accounting firm Ernst & Young published this month.
One consequence, a Research Triangle venture capital investor said, is “deals are dying on the vine.”
“More and more small, really good startups are having problems finding money,” said Norris Tolson, chief executive of the N.C. Biotechnology Center. “We’re about the only game in town for early stage biotech companies.”
The biotech center, which offers grants and loans up to $250,000, has seen the number of funding requests increase by about 10 percent, Tolson said. In the past year, about 280 applicants asked for financial support. About 130 were approved.
Traditionally, young biotech companies have relied on private investors, often venture capital investors, to kick their R&D into gear.
U.S. biotech companies raised $5.5 billion in venture capital in 2007, about twice as much as in 2000, according to Ernst & Young. But in the past three years, the amount has stagnated at about $4.5 billion annually and venture capitalists have begun to hold money back until companies reach certain milestones.
Total capital raised by biotech companies in the U.S. bounced back to $20.7 billion last year, from about $13 billion in 2008, according to Ernst & Young. But much of that capital went to mature companies. Young, early stage companies, which work on the most innovative technologies and generate more jobs than large, established companies, actually received about 20 percent less in capital than the year before.
In Europe, capital raised was more evenly distributed among startups and mature companies. In Singapore, China and India, governments are ratcheting up efforts to bolster biotech innovation. And in Latin America, Brazil’s already strong agricultural biotechnology sector is gaining attention.
But politicians, economic developers and university administrators in the Research Triangle have come up with ideas to encourage the formation of R&D startups despite the early stage funding crunch
The biotech center teamed up with Alexandria Real Estate Equities, a Pasadena, Calif.-based real estate investment trust, to attract young companies working in agricultural biotech research. Alexandria, which already owns lab buildings in the Triangle, will build a $13.5 million business incubator with about 18,000-square-feet of greenhouse space near RTP.
Several universities and the Council for Entrepreneurial Development are working with the charitable arm of the Blackstone Group, a global investment firm, to turn more technologies developed at universities into companies and bolster the Triangle’s existing entrepreneurial network.
The chancellors at UNC-CH and NCSU have set up innovation funds to further support spinoffs.
And state legislators are again considering establishing a nonprofit that can loan young companies money. The legislation has come up twice before and would use about $100 million an out-of-state investor is willing to provide, Tolson said. Initially, only life science companies could benefit, but recently state lawmakers suggested that information technology and green technology companies should also be included.
“There’s a huge need for startup capital across the U.S.,” Tolson said. In North Carolina, “a lot of people are understanding the need.”
On his visit Monday to Cree’s Durham manufacturing plant President Obama brought his advisors from the Council on Jobs and Competitiveness along to impress on North Carolinians that his administration is focused on lowering the stubbornly high U.S. unemployment rate, which in May was 9.1 percent.
Jobs council members, which come from the business sector, labor and universities, are dedicating their time and energy to one singular task, Obama told Cree workers. “How do we create more jobs in America?”
Not far from where Obama was talking about getting out of the Great Recession, a job creation effort was under way to lower the state unemployment rate, which in April was 9.7 percent, and particularly the unemployment rate in the Research Triangle, which in April was at 7 percent in the Durham-Chapel Hill area and at 7.7 percent in the Raleigh-Cary area.
NCSU, Duke University and the University of North Carolina at Chapel Hill have long been engines of economic development in the region. They drove the formation of Research Triangle Park in the 1950s and educated the work force that attracted corporate research and development operations to RTP in the following three decades. The three universities that anchor RTP have also brought about technologies that started many an R&D company in the area.
Cree itself is a NCSU spinoff. The RTP company that makes light-emitting diodes, or LEDs, was formed in 1987 based on technology developed at NCSU.
With budget cuts for higher education looming, Triangle universities are stepping up and retooling their economic development efforts.
At NCSU, Terri Lomax, vice chancellor for research and innovation, is taking on responsibilities starting July 1 to help the state recruit companies and jobs, and the university is trying to boost the formation of spinoffs and their chances to survive and expand, be acquired or go public.
William Woodson, who was named NCSU chancellor in January 2010, established an innovation fund that will provide $2.5 million over the next five years to NCSU researchers to work on technologies that could be licensed or spun out as a company. To get off the ground, the young companies could tap into expertise at the university through a so-called proof-of-concept center on NCSU’s Centennial Campus.
To further accelerate startup formation, NCSU has joined forces with UNC, Duke, the Council for Entrepreneurial Development and N.C. Central University. The consortium is getting involved in the Blackstone Entrepreneurs Center, which has $3.6 million available over three years to evaluate technologies and tutor new companies.
“Most new jobs come from companies less than five years old,” Lomax said in an interview with Science in the Triangle. “We want to do everything we can to help these companies be successful. Especially after a recession that’s extremely important.”
She suggested that the efforts could double the number of successful startups that NCSU spins out per year to 10 to 12 by 2015.
“What we want is sustained economic development,” Lomax said.
Watch the entire Science in the Triangle interview with Terri Lomax here:
North Carolina’s Research Triangle is one of several research hubs in the U.S., Canada and the United Kingdom, where large drugmakers have hooked up with universities in the past year to boost drug discovery and shore up dwindling product lineups.
Pfizer signed a research collaboration with the University of California, San Francisco. Sanofi-Aventis has done the same with Harvard University, UCSF and Stanford University. GlaxoSmithKline and AstraZeneca called on the British University of Manchester. GSK, which is based in London and has its U.S. headquarters in Research Triangle Park, also struck up a strategic partnership with 16 academic institutions in Toronto.
In the Research Triangle, Novartis went to Duke University.
“We had the right infrastructure,” said Tom Denny, chief operating officer of the Duke Human Vaccine Institute. Duke and Novartis will be working together on pandemic flu vaccines.
Big pharma companies have begun to troll for marketable innovation at universities – places where science and research are a taxpayer- and tuition-funded way of life – after spending increasing amounts of money on their own and other companies’ research and development with meager results.
Consolidation, R&D reorganizations, acquisitions of technologies and whole companies – large drugmakers have tried many strategies in the past decade to rejuvenate aging product lineups and plump up drug development pipelines. But the average number of innovative new medicines that came to market in the U.S. decreased to 22 in the second half of the decade from 28 in the first half, and that despite annually rising R&D expenses.
With R&D productivity stalled and valuable drug patents about to expire, big pharma three years ago began to cut R&D jobs and lay off thousands. The restructuring is still ongoing with a focus on reducing R&D expenses and boosting sales in emerging markets such as Asia and Latin America.
The driver behind the cost cutting is the U.S. “patent cliff.”
By 2015, cheaper generics are projected to replace prescription drugs worth more than $100 billion in U.S. sales. The losses are expected to send sales on a sharp decline that, drawn as a line, looks like a cliff.
After trying everything else with insufficient success, large pharma companies are now betting on universities for inspiration.
Pfizer agreed to pay UCSF $85 million over five years. Under the agreement, researchers from Pfizer and UCSF will work at UCSF labs to turn research into potential biological medicines.
The University of Manchester will receive about $16 million from GSK and AstraZeneca. The investment will establish a translational research center and recruit scientists who will look for novel treatments for inflammatory diseases, such as asthma and rheumatoid arthritis.
The pharma industry has long had relationships with individual university professors. It’s also not uncommon that university medical school faculty work with industry to test new treatments or that an academic research project attracts the interest of pharma companies. What’s new is that big pharma companies are outsourcing R&D to universities.
The seed for the pandemic flu vaccine collaboration grew out of an HIV/AIDS collaboration between Novartis and Duke, Denny said.
One of the Novartis HIV/AIDS researchers was a Duke alumnus who knew his alma mater was just 30 miles from the state-of-the-art flu vaccine manufacturing plant Novartis opened in 2009 in Holly Springs. (More on the Novartis plant here.)
Flu viruses can change from year to year and vaccines have to be made to match the anticipated changes in the virus. But it’s only safe for researchers to work with highly contagious, maybe even deadly, flu virus strains in a specially equipped biocontainment lab. Duke has such a lab and the ability to test pandemic flu vaccines on animals.The vaccine manufacturing plant, which Novartis build in Holly Springs precisely because of the site’s proximity to RTP and its three anchor universities, has neither.
In case a new flu virus starts spreading around the world and the Centers for Disease Control and Prevention and the World Health Organization call a pandemic emergency, the agreement gains Novartis priority access to the Duke biocontainment lab within 24 hours for a daily fee.
The agreement also allows researchers from Duke and Novartis to collaborate on longer-term projects paid for by grants from the National Institutes of Health. The rights to any technology would be jointly owned by each partner, Denny said.
“This is, what we would hope, a long-term collaboration,” he said.
Nanotechnology promises to make medicines more effective, reduce side effects and allow earlier diagnoses of diseases. But nanotechnology also raises multiple questions most of which, for now, remain unanswered.
When the N.C. Center of Innovation for Nanobiotechnology, also known as COIN, brought together a panel of regulatory experts in Research Triangle Park, several entrepreneurs and developers sought guidance on how to develop safe and effective nanotechnology products, especially from panel member Katherine Tyner, a chemist who heads a small nanotechnology research group at the Food and Drug Administration’s Center for Drug Evaluation and Research.
Understanding FDA requirements is crucial to get new drugs and medical devices approved for sale, but the FDA doesn’t have specific guidelines for nanotechnology. The agency doesn’t even have an official definition for nanotechnology, Tyner said. To assess safety risks of a nanotechnology product and whether it works, regulators apply existing guidelines for products without nanotechnology on a case-by-case basis.
It’s a system that works, said Lawrence Tamarkin, chief executive of CytImmune, a Rockville, Md.-based nanomedicine company, who also sat on the COIN panel on May 17.
Tamarkin suggested the great variety in nanotechnologies doesn’t lend itself to common guidelines. “It’s better the way we do it now,” he said.
Tyner, who researches drug safety but doesn’t review requests to approve nanotechnology products for sale, listed about two dozen medicines, cosmetic products and contrast agents for diagnostic tools that use nanotechnology and have passed muster with the FDA in the past 15 years.
But the list didn’t go over well with Jamie Oliver, a pharmacist and the chief executive of Peptagen, a Raleigh startup working on a nasal spray that delivers nanoparticle vaccines. Oliver, who sat in the audience during the COIN panel, shook his head when asked about Tyner’s FDA-approved nanomedicines list.
“No true nanoparticle [drug] is on the market,” he said.
Nanotechnology has been used for years in material science, electronics and cosmetic products, according to the National Nanotechnology Initiative. Nanoparticles make tennis rackets stronger, fabric wrinkle-free and camera lenses self-cleaning. Engineers have shrunk resistors to nanoscale to make computers smaller and more powerful.
Nanotechnology is also used to make batteries more efficient and to power mobile devices. A nanofabric paper towel cleans up 20 percent more spilled crude oil in an environmental cleanup. Many sunscreens, shampoos and lotions contain nanoparticles.
Though the applications are diverse, they all have one thing in common: The technology is generally only called nano when it measures between 1 nanometer and 100 nanometer.
One nanometer is about 100,000 times smaller than a hair is thick. Hemoglobin, the oxygen-transporting protein in red blood cells, fits the official nanoscale, so does HIV, the virus that causes AIDS, and the width of a cell membrane. Single-walled carbon nanotubes and nanosilver are also true nanoparticles.
XinRay Systems, a medical device startup in RTP, uses carbon nanotubes-studded film to develop X-ray machines that are faster and more accurate. (More about XinRay Systems here.)
Nanosilver is a natural germ killer and is used in anything from pacifiers to sunscreen.
Lacking a definition for nanotechnology, the FDA considers even structures ten times larger than 100 nanometer as nanoparticles, such as liposomes, man-made vessels that are filled with drugs. Liposomes tend to measure more than 1,000 nanometers.
But size is crucial to nanotechnology. Richard Feynman, the father of nanotechnology, pointed that out in 1959. In “There’s Plenty of Room at the Bottom,” Feynman wrote that in a very, very small world, “we are working with different laws, …, we have new kinds of forces and new kinds of possibilities, new kinds of effects.”
Half a century later, researchers have just begun to look into some of those forces and effects that only occur on a true nanoscale.
Case in point: nanosilver.
Products that use nanosilver as an antibacterial contain silver particles that are 10 nanometers and 50 nanometers, but also silver particles that are much larger. Nanosilver was considered safe enough to be used in baby products, such as blankets, pacifiers and bottles.
But a 2008 study by researchers from the University of Connecticut’s Center for Environmental Sciences and Engineering raised concerns that loose nanosilver could compromise the human immune system. The smaller particles had that effect but not the larger ones, according to a ScienceNews report.
Since then, the Environmental Protection Agency has started to study the effects loose nanosilver has on the environment. (More on a petition to have nanosilver declared a pesticide here.)
So without a definition for nanotechnology in place, will the FDA catch potential safety risks that are specific to particle size?
Tyner presented an FDA that is very confident in the way it regulates nanotechnology products. But research projects under way at the FDA suggest regulators worry about missing clues for potential risk factors. Researchers at the agency are working on improved methods and tools to detect and measure nanomaterials and assess their safety and efficacy. And they’re developing class-based approaches to risk assessment of nanotechnology products.
North Carolina is on the way to become a state with one of the largest photovoltaic solar farms and one of the largest wind farms in the U.S.
The N.C. Utilities Commission Tuesday approved plans of a Spanish company to build up to 150 turbines, each about 400 feet tall, near Elizabeth City in the northeastern corner of the state. If the $600 million project gets the necessary federal, state and local permits, it will be another large source of renewable energy that is produced in North Carolina.
About 270 miles west of Elizabeth City, near High Point, construction of the final phase of a $173 million solar farm with 63,000 photovoltaic panels is under way on about 200 acres.
The electricity the two projects are expected to generate – enough to provide power to about 62,000 homes per year – would become part of the energy blend that residential, commercial and industrial consumers in the state already receive from the power grid. The utilities commission has been goosing North Carolina power companies and cooperatives for three years to add energy generated from renewables to the mix.
This regulatory pressure and industry incentives are key to successfully reduce America’s dependence on oil and lower the amount of harmful greenhouse gas emissions, Steve Kalland, executive director of the N.C. Solar Center, said during a recent meeting of the Triangle Area Research Directors Council in Research Triangle Park.
“It’s not a technology question anymore,” Kalland said. “Financing and regulatory are the two biggest barriers to move technologies forward.”
Energy from renewables is still more expensive than energy from traditional sources, such as oil and coal, Kalland said, but oil prices are going up and the price for green technology is coming down. “The trendlines say time is working in our favor.”
For the second time in three years, crude oil prices are above $100 a barrel and gas prices at the pump are closing in on $4 per gallon. Meanwhile, the cost to get solar panels installed in North Carolina has dropped 49 percent since 2007.
“Everytime oil goes up, we get a policy opportunity,” Kalland said. What he means by that is legislation that supports renewable energies, particularly federal legislation that deals with the differences in regulations from state to state. “Fifty states have 50 regulatory commissions, it’s something that cries out for federal intervention,” he said. But an array of special interests have so far foiled attempts to get anything done nationally.
The North Carolina legislature has done more for renewable energy supporters.
In 2007, state lawmakers established renewable portfolio standards that the utilities commission tracks by making power suppliers file compliance reports. The standards say that by 2021, 12.5 percent of the energy that investor-owned utilities like Duke Energy supply must be generated from renewable sources. Solar, wind, biomass, tidal energy, landfill gas, swine and poultry waste all qualify and consumers must pay for part of the costs.
North Carolina is one of 32 states with such standards, according to information collected by the U.S. Department of Energy.
For several years, the state has also offered a 35 percent renewable energy investment tax credit as an incentive to install solar, wind, geothermal and other renewable energy technology. Last year, the legislature added a tax credit for businesses and homeowners who install combined heat-and-power systems. CHP systems are up to twice as efficient than traditional heating and cooling systems.
If 20 percent of U.S. households installed CHP systems by 2030, the amount of energy consumed by U.S. households would be cut in half, the U.S. Department of Energy estimated.
The carrot-and-stick approach has boosted the number of solar water heating installations and photovoltaic installations in North Carolina, ranking the state in the top 10 nationwide. In 2010, more than 100 solar energy companies operated in the state, employing more than 1,500, according to a report by the N.C. Solar Center.
The N.C. Sustainable Energy Association estimated that last year about 12,500 job in North Carolina were green.
SunEdison completed construction of the photovoltaic farm near High Point in January. Duke Energy has a 20-year contract to buy all of the power generated by the farm – about 17 megawatt, or enough to supply 2,600 homes per year.
The wind farm that the U.S. subsidiary of the Spanish Iberdrola Renewables wants to build on about 20,000 acres in northeastern North Carolina is projected to produce up to 300 megawatt, or enough to supply 60,000 homes per year. The wind farm could start operations as soon as January 2013.
There’s potential for more to come off the coast.
A 9-month feasibility study that the University of North Carolina published in 2009 recommended that North Carolina pursue wind energy production aggressively. The study looked at locations offshore and in the Pamlico and Albermarle sounds and found 2,800 square miles within 50 miles of the coastline particularly well suited and worthy of further investigation.
Hurricanes are a threat to offshore wind farms, Kalland acknowledged during his TARDC talk. But insurance companies have no problem insuring the turbines.