A Fresh Injection of Optimism: New funds and expanding partnerships spur global vaccination campaigns

A Fresh Injection of Optimism
New funds and expanding partnerships spur global vaccination campaigns

By Margot Cohen
 
Vital campaigns to immunize children worldwide are slated for a major boost from new financing mechanisms and more scientific collaboration among researchers from developing and industrialized countries. These developments are especially welcome given the severe vaccine shortages that plagued the world from 1999 to 2001.

"We're confident that as countries scale up and try to reach every child, the vaccines will be there," says Shanelle Hall, director of the supply division at UNICEF, which procures 3 billion doses of pediatric vaccines annually and remains the key supplier to the world's poorest countries. "UNICEF is very optimistic about the vaccine market."
 
That optimism is currently shared by a number of public and private players in the complex, competitive world of vaccine research and development. The last four months have witnessed a flurry of good news. November 2006 marked the debut of the International Finance Facility for Immunisation (IFFIm) with a landmark $1 billion, five-year bond issue aimed at generating more resources to purchase vaccines and strengthen health systems in the developing world. The new financing is meant to help address the estimated 27 million children who are still deprived of vaccinations against common diseases like measles and tetanus. The IFFIm bond issue was oversubscribed by 75 percent, with many subscribers citing ethical concerns as a key factor in their decision to buy the bonds.
 
Over the next decade, IFFIm intends to raise a total of $4 billion in capital markets, with the United Kingdom, France, Italy, Spain, Sweden, and Norway serving as sovereign government sponsors. According to Michel Zaffran, deputy executive secretary of the Geneva-based GAVI Alliance (formerly known as the Global Alliance for Vaccines and Immunisation), approximately 60 percent of the funds are being spent on vaccine procurement and the remainder on bolstering the ability of developing nations to plug gaps in their immunization campaigns. A separate GAVI fund of $500 million, “Health Systems Strengthening,” announced in January 2007 at the World Economic Forum meeting in Davos, will target training and management to ease health system bottlenecks that affect local immunization programs, says Zaffran.

Most recently, a group of developed nations led by Italy banded together to provide incentives for companies to create vaccines specifically required by developing countries, and to increase their production capacity. Most companies in the United States and Europe had previously avoided investing in such efforts for fear of low profit margins and uncertain markets. The first phase of the $1.5 billion program, called Advance Market Commitment (AMC), will be devoted to enhancing access to a vaccine against pneumococcal disease, which claims nearly a million lives of children under age 5 each year, according to the World Health Organization (WHO). The advent of AMC even won praise from Pope Benedict XVI as a "creative and promising initiative" at the Rome launch on Feb. 9, 2007.
           
"In this era of globalized markets, we are all concerned about the growing gap between the standard of living in countries that enjoy great wealth and a high level of technological development, and that of underdeveloped countries where poverty persists and is even increasing," said the Pope.

That gap helps explain the vaccine shortages experienced between 1999 and 2001. As industrialized nations shifted to more complex and costly vaccines, the top Western manufacturers largely abandoned production of the basic monovalent, or one-disease-specific, vaccines needed in developing countries—leaving public health experts scrambling.
           
Luckily, some manufacturers in developing countries, notably India, stepped up to the plate. But the Indian efforts behind vaccine production have been far less visible than India's widely celebrated role in churning out low-cost generic drugs in the fight against HIV/AIDS.
 
Measles offers one example. In mid-January, officials from UNICEF and the WHO proudly announced that a global campaign against measles had saved 2.3 million lives since 1999. Worldwide deaths from measles fell 60 percent; the reduction was even more dramatic in Africa, at 75 percent.  But one astonishing fact went unreported: At least 70 percent of the measles vaccine used in those global immunization campaigns was produced by just one private Indian company, the Serum Institute of India Ltd.
           
"We are trying to ensure that people from developing countries get products at the most affordable price," says Suresh Jadhav, executive director of the Pune-based Serum Institute. The company sold the vaccine for just 11 to 14 cents a dose between 1994 and 2007. At UNICEF, Hall also praises Serum Institute for its high-quality supply and flexible production schedules.
           
Aside from polio vaccine, which mainly comes from Europe and the United States, UNICEF now sources 80 percent of its supply of pediatric vaccines from alternative producers in India, Indonesia, Brazil, and South Korea. India alone provides 60 percent of these pediatric vaccines, up from 25 percent just five years ago. "If today we can vaccinate children in the world, it's thanks to the manufacturers in India," says Stephane Guichard, technical officer for Immunization and Vaccine Development in the WHO office in New Delhi. "I've seen a very impressive evolution, both on the side of the private sector, and in regulatory activity at the government level," says GAVI's Zaffran, who travels regularly to India.
           
Moreover, India's private vaccine producers are moving forward to expand their facilities and develop more complicated vaccines. "Over the next 10 years, India will provide a substantial amount of combination vaccines to the developing world," predicts Guichard. "It's a good example of developing countries taking an active part in the global agenda."
But the measles story also illustrates the unfortunate irony of a government immunization program that has not kept pace with dynamic private producers. Despite the success of the Serum Institute in reducing measles deaths worldwide, the Indian government's own outreach efforts have fallen far short of targets. Most Indian children still do not get a second dose of measles vaccine, as recommended by UNICEF and WHO. Some analysts explain that India's focus on eradicating polio has sapped the energy the health bureaucracy needs to pursue vaccination campaigns against measles and other diseases. Public health specialists estimate that India has the world's largest number of children who die annually from measles complications, charting some 100,000 deaths.
 
In contrast, domestic needs have been given top priority in Brazil and China. Both countries have emerged as powerhouses in producing low-cost vaccines. For now, Brazil is expected to continue to concentrate on its domestic market while increasing exports elsewhere in South America. But China appears to be preparing to export a wide variety of inexpensive vaccines to the developing world, which could have a major impact on expanding global supply.
 
Quality assurance is a key concern. China's top Communist Party officials recently launched a crackdown on fake drugs amidst a public outcry over health risks and corruption within regulatory agencies. But in the field of vaccines, public health experts see rapid progress in regulatory controls and expect China to become a major vaccine exporter within two to four years. "We are working in China quite a bit. It's been very encouraging," says Dr. Rajat Goyal, the New Delhi-based project director for the rotavirus vaccine program at PATH, a nongovernmental organization. "I think they are making significant investments in factories now to make them WHO-compliant."
 
Rotavirus is also an area where India and China have begun to share information, as part of a global trend toward more collaboration between developing countries. Various commercial tie-ups between companies in India, Indonesia, and Cuba are stimulating research and production. Such exchanges are also beginning to pick up steam through the Developing Country Vaccines Manufacturing Network, whose most active members include India, Brazil, Indonesia, Egypt, Mexico, China, and Vietnam. The network aims to bring low-cost vaccines more quickly to market, enhance the quality of clinical trials, and apply pressure on industrialized manufacturers to reduce prices.
 
But global flows of investment are also breaking down traditional barriers between companies in industrialized and developing countries. Many multinationals are looking to use India as a supply base to Asian markets, expand their access to India's booming private domestic market and carry out clinical trials at lower cost.
 
For example, GlaxoSmithKline PLC will open a large new vaccine facility in Maharashtra state in mid-2007. And last November, the French health-care company Merieux Alliance acquired a 60 percent stake in one of India's most dynamic vaccine producers, the Hyderabad-based Shantha Biotechnics Ltd. Shantha's new executive chairman, Georges Hibon, says that the company is exploring "synergies" between its affiliated research units in France and the United States. "With India, I think we have a cost advantage and a speed advantage," says Hibon. "We hope to develop the R&D activities of Shantha in its core businesses, namely vaccines and clinical research."
 
However, costs are going up even in developing countries like India and China. As companies strive to meet international standards and hire the best talent, production costs are rising along with wages.

Perhaps the most ambitious form of collaboration on vaccines can be found in public-private partnerships, known as PPPs. The urgent quest to create low-cost vaccines against malaria, meningitis, rotavirus, tuberculosis, and HIV is taking place in multiple laboratories around the world and drawing increased support from multiple donors. In addition to creating innovative vaccines, some partnerships are also working on thermostable products that can overcome the vast problems with preserving a cold chain in developing countries.
 
By promoting the interaction of top scientists and increasing training opportunities for researchers in developing countries, such partnerships are encouraging. "The challenge, however, lies in sustaining their funding and ensuring their ability to proceed from discovery to development and manufacturing," notes the second edition of a comprehensive public health guide, Disease Control Priorities in Developing Countries.
 
One key element is winning the political support of the host country. In India, where 5.7 million people are infected with HIV, politicians and technocrats have demonstrated their commitment to the International AIDS Vaccine Initiative. Under the broader PPP umbrella, the work involves India's Department of Biotechnology, the Council of Scientific and Industrial Research, and the Indian Council of Medical Research. Clinical trials of two different vaccine candidates are underway in Pune and Chennai. The project has certainly transcended national boundaries: An Indian scientist from a government institute in Kolkata assisted an American company, Therion Biologics Corporation, in designing the candidate vaccine now being tested in Chennai.
 
It's a good start. But many players are eager to see India's cabinet approve an ambitious national biotechnology development strategy that would invest heavily in basic scientific research and pump funds into private companies to develop priority vaccines. The policy would be in line with India's goal to gradually increase spending on science and technology from less than half of 1 percent of GDP to 2 percent of GDP. According to one official at the Department of Biotechnology, the cabinet will "hopefully" approve the policy within the next several months.
 
"Indian companies have limited resources in investing in basic research. This has to be done by the public sector," says K.K. Narayanan, president of the Bangalore-based Association of Biotechnology Led Enterprises. Indeed, some Indian companies are doubtful that they will benefit from the Advanced Market Commitment program, since their development programs for new vaccines against diseases like pneumococcal are at least six years behind their Western counterparts.
 
Within the global community, there is also a keen desire to see the Indian government do more to spur research tailored to the disease profile of poor communities inside its borders. Public health advocates argue that if India helps itself, it will help the rest of the globe. "The central government and the local governments have an important role to play in providing incentives to support the industry," says Bernard Pecoul, executive director of the Drugs for Neglected Diseases Initiative. "If you improve the situation of hundreds of millions of poor inhabitants of India, this will have consequences for most of the world."
 
Margot Cohen has worked as a journalist in Asia for two decades, including stints in the Philippines, Indonesia, Vietnam, and India. She is currently based in Bangalore, and may be reached via email at Margot.Cohen@gmail.com.