April 1, 2009 (Vol. 29, No. 7)
South American Country Makes Name for Itself in Clinical Trials and Aquaculture
Chile has set its sights on biotech. Now the question is whether biotech will set its sights on Chile. The South American nation is taking a two-pronged approach—seeking to attract multinational clinical trials by virtue of an accessible population and internationally trained investigators, and bolstering its traditional strengths in aquaculture, agriculture, forestry, and mining with biotech-based enhancements. It is also developing funding mechanisms to help companies become established, and boasts minimal bureaucracy. It is estimated that a Chilean business can be set up and operational in less than one month.
The Chilean Economic Development Agency—(CORFO)—made the case for Chile earlier this year during a University of California at San Francisco seminar.
Chile is a small country, with a population of 16.6 million. “But, population isn’t everything,” insists Graciela Rácero, senior director of Latin America operations for Parexel International. Because 85% of Chile’s population lives in cities, patients are readily available. Retention is increased through a combined public/private healthcare system that results in an average of 4,715 physician visits per 1,000 persons per year, Rácero says.
“Many investigators, trained in the EU and U.S., actively participate in international congresses, and are experienced in multinational trials,” she says. Physicians in Chile are generally eager to participate in trials, she adds.
Most of the trials currently under way in Chile are multinational in scope and focus on cardiology, oncology, infectious disease, pulmonology, obstetrics and gynecology, and neurology. There also is a strong interest in pediatric trials. Traditionally, children were not allowed to participate in clinical trials, with the results that “two of three drugs used for children had never been tested on children. They were treated as small adults. We now know that was a mistake,” emphasizes Pablo Caviedes, Ph.D., CEO, Center for Clinical Research and Pharmacological Studies.
An additional bonus, he says, is that “The Ameri-Indian racial markers are well spread throughout Chile’s population,” but not throughout the traditional testing sites of North America or Europe. That population is, therefore, valuable in testing therapies intended for widespread use.
Currently, more than 30 CROs operate in Chile. There are some 300 research sites and 1,274 clinical trial investigators, 56% of whom are dedicated to Phase III trials. Chile is listed among the top 25 nations in terms of clinical trials for infectious disease and nervous system disorders, according to Jorge Guerra, M.D., senior vp, global clinical operations, Biogen Idec. Globally, of the 66,552 clinical trials conducted in 2008, Chile conducted 415. For comparison, Mexico conducted 782, Rácaro says.
When asked about data reliability, Dr. Guerra, who was at Merck between 1984 and 2008, recalls that “Merck has conducted clinical trials in Chile since 1980. There were no complaints of data unreliability. Merck never had any problems. It was even better than in the U.S.,” he maintains.
Chile currently is working to “strengthen ethical governance and to improve the function of clinical research through the creation of a central office for administering research in a selected number of public sector sites,” according to Rodrigo Salinas, M.D., Ministry of Health. That includes creating a national register for human subjects. Chile is also in the process of writing clinical trial regulatory guidelines for submission to WHO. In addition, the country has a firm policy of ethical review and informed patient consent.
Aside from Chile’s intent to increase its participation in clinical trials, its other biotech interests focus on using biotech to enhance its mainstay industries of agriculture, forestry, mining, and aquaculture. It is doing that through incentives to attract foreign investment and by encouraging Chilean businesses to commercialize their products.
Chile already has a small biotech business sector. For example, Arturo Yudelevick cofounded GrupoBIOS with four companies. The purpose of the organization is to provide infrastructure and services for firms to share. The group also established the Science for Life Foundation to support R&D and tech transfer and to direct science and technology policy at the government level.
Some of the more important results, he says, include the commercialization of blood bank reagents; the development of ncmtRNA oligos for cancer diagnostics; biomedical products including antigens, cytokines and antibodies; and vaccines and diagnostics tests for salmon.
“One program we’re pushing strongly is a project for early detection of cancer,” says Yudelevich, who is also executive vp of BiosChile. Preclinical work indicated that “ncmtRNA kills cancer cells in vitro, without damaging normal cells. The study is in animal trials now at UCSF.”
Other notable Chilean efforts include those of Phytotox, a newly formed biotech company, which is focused on the purification of a toxin found in red tide to relax muscles. Medivation has an Alzheimer’s disease therapy in Phase III trials in Chile. The Tree Lab, incorporated in Chile earlier this year, is developing micropropagation for biodiesel and ornamental plants.
As one of the world’s top exporters of salmon, Chile has developed a battery of PCI, ELISA, and immunofluorescent tests to detect fish pathogens, including the infective anemia virus that became a great concern last year. Chilean companies developed a vaccine for that disease, as well as treatments for Pisciricketsia salmonis and Aeromonae salmonicida, stemming considerable losses in the salmon export business.
Centrovet, founded in 1979 as a diagnostics lab, has become a leading veterinary pharmaceutical company. It produced 65 million doses of vaccine in 2008 with no trace of cross contamination, according to David Farcas, CEO. “This is larger than the human pharmaceutical industry in Chile,” he says. Centrovet exports to 40 countries. “The country doesn’t apply barriers to the market and gives incentives to make business a reality,” he stresses.
The firm’s accomplishments include a line of therapeutics that animals can drink because sick animals won’t eat, he explains. Centrovet has developed injectable, immersion, and oral vaccines for salmon, chicken, and swine. “We are the first lab offering immunological follow-up, so users can tell how long a vaccine lasts,” he says.
Synthon Holding, a fully integrated specialty pharmaceutical company that specializes in follow-on biologics and generics, opened facilities in Chile “to increase our South American presence,” according to Jack Nijssen, evp and COO. “To be as close to the market as possible, we established a hub to develop and manufacture for that market and for international markets.”
Before choosing Chile, “we looked at several possibilities,” Nijssen continues. Chile has economic and social stability, a skilled workforce, a simple and favorable tax system, multiple trade agreements, and CORFO.” Synthon currently is building an approximately $24 million facility that is expected to be operational by the second quarter of 2011 and employ 50 to 70 full-time-equivalent personnel.
Monsanto also has a history in Chile. More than 500 of its 22,000 employees are located there, according to Rashmir Nair, Ph.D., team leader, international cultivation, global regulatory affairs. Dr. Nair says Chile was Monsanto’s springboard for Latin America.
“It has an advanced information technology infrastructure, low overall labor costs, and “the business ethics are pretty great.” Monsanto does its multiseason seed production for the world there, and the winter seed production for corn and soybeans. And, as home to the Atacama Desert, “it’s great for drought research.” (Some parts of that desert haven’t seen rain for at least 20 million years.)
Chile relies upon public and private collaboration to incorporate biotech into its economy. “InnovaChile funds applied research under the National Innovation Council, which advises the President where to invest in R&D,” according to Gloria Maldonado, deputy director of InnovaChile and head of its biotechnology, energy, and environment division. Awards criteria are risk, innovation, economic potential, and the design of the collaborative effort. In 2008, InnovaChile’s $93 million budget funded 916 projects. “Some 55 percent of the total costs of projects are privately funded,” she says.
CORFO’s main innovation incentives provide up to $6 million for process or product development, up to $600,000 for tech diffusion and transfer from abroad, up to $1 million for precompetitive innovation that serves the public interest or builds regional capacity, and up to $600,000 for seed capital, incubators, and a network of angel investors to foster entrepreneurship.
Its high-technology investment program provides a wide range of assistance that includes investment incentives. That program, for example, will refund up to 60% of the pre-investment study costs, up to $30,000 for start-up activities, up to 50% of annual salaries for on-the-job training, up to 40% of the total investment in fixed assets, up to 40% of the total lease value for long-term property leases, up to 100% of the lease value for long terms leases of CORFO property, and up to 50% of the training for recruitment expenses.
Benefits to doing business in Chile include strong protections for intellectual property and foreign institutions. For example, the new intellectual property laws allow for the patenting of genes and microorganisms. Chile also has the largest network of Free Trade Agreements in Latin America, which provide tariff benefits and other incentives to business deals.
Some 57 nations have free-trade agreements with Chile, including the U.S., European Union, Canada, India, China, Japan, Central America, Mexico, and New Zealand, according to Nicolo Gligo, executive director, U.S. region, InvestChile. Notably, there are no joint venture requirements, and foreign companies may have wholly owned subsidiaries.