January 1996
WASHINGTON—Vaccines are a blend of academic creativity, private initiative, federal support, and regulatory oversight. In this world, distinctions between the public and private sectors are blurred by alliances that accentuate each player's unique strengths.
Public and private partnerships are vital to a healthy vaccine research and development (R&D) atmosphere, said R. Gordon Douglas, MD, President, Merck Vaccine Division.
"More than three quarters of all new vaccines licensed in the world have been developed in the United States," Douglas said. "Partnerships already exist; they always have in one form or another. It is not so much about forming something new but encouraging what already has existed. They need to be nurtured and recognized for what they can provide."
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The U.S. government has a long history of involvement in the business of vaccines, from the provision of grants that encourage budding ideas to issuing licenses to market the finished product. The National Institutes of Health (NIH), the Centers for Disease Control and Prevention, the Food and Drug Administration (FDA), the Department of Defense (DOD), and the U.S. Agency for International Development all have an interest in vaccine R&D. The public sector, however, lacks the ability to bring those ideas through the development process; for that, it turns to the private sector.
"NIH funds academic research, which forms the foundation for other ideas," Douglas told Infectious Diseases in Children. "If you do not have that research base, you have nothing. Private industry brings some basic research to the table, but industry is more interested in targeted research and development, both process development and clinical development. Most of the expertise in the world is in private industry."
Recognizing that, the National Vaccine Advisory Committee (NVAC), which advises the Assistant Secretary for Health and Human Services on vaccines and related issues, has taken an interest in fostering public and private partnerships. NVAC's Subcommittee on Future Vaccines, which is headed by Douglas, is exploring ways to strengthen vaccine R&D by facilitating interaction among the players.
NVAC chair Edgar Marcuse, MD, Professor of Pediatrics, University of Washington, Seattle, said the recently completed European acellular pertussis vaccine trials are a model of the interdependence of the public and private sectors.
"The acellular pertussis trials were done under the leadership of...the NIH," Marcuse said. "They coordinated cooperative studies with multiple manufacturers and supplied the funding and expertise in study design and selection of the products. Now we are looking to the manufacturers to bring the products to licensure with the FDA, and then the manufacturers will produce and distribute the vaccines."
Partnerships, although successful, are fragile and subject to outside influences. NVAC noted in its report, The U.S. National Vaccine Plan—1994, that several factors during the last two decades affected private sector vaccine development and made public sector involvement more beneficial.
During the 1970s, the FDA not only took responsibility for the regulation of vaccines but it also established new procedures for the review of safety and efficacy data. Toward the end of that decade, growing liability concerns over vaccine-associated adverse events coupled with low profitability forced some companies to abandon the vaccine industry. By the 1980s, only a handful of vaccine developers were left in the United States.
The Omnibus Budget Reconciliation Act of 1993 (OBRA '93) dealt those companies another blow. In its authorization of a federal vaccine purchase program, OBRA '93 set a price cap on the vaccines purchased by the federal government and gave states the option to purchase vaccines at the government's discounted price. Whereas the public sector had previously purchased about 55% of vaccine, its share could now theoretically reach 80% or more—another type of public and private partnership, but one that skeptics suspect may threaten R&D.
Because larger developers typically use the profits from licensed products to fund R&D, any shift in the equation is feared to have a devastating affect on private industry, making government resources even more crucial.
"A few years ago, when the administration was attacking the vaccine industry, the network that existed became dysfunctional," Douglas said. "When any part is attacked—now it is NIH being attacked by Republican budget cuts—the whole enterprise suffers."
Overall, private sector R&D activity is apparently rebounding during the 1990s, according to the NVAC report. Part of this recovery may be attributed to the smaller, so-called "biotech" companies. Funded by venture capitalists, these relatively new companies are an important source of innovative research.
Many of these small companies, however, "do not have the resources or experience for pilot manufacturing of candidate vaccines to standards required by the FDA for efficacy trials or for the conduct of trials themselves," according to the NVAC report. Because those resources are within the realm of the public sector, that observation underscores the continued importance of public and private partnerships for vaccine development not only in the United States but also globally.
Vaccines are a business, and development decisions have economic undertones. A single vaccine may take a decade or more to develop at a cost that may soar into the hundreds of millions of dollars—all for a product that may never be licensed.
Developers, therefore, may be reluctant to sink resources into products that are unlikely to recoup the initial investment; for example, vaccines for diseases that are mostly limited to developing countries.
The Children's Vaccine Initiative (CVI), a global concern under the aegis of the World Health Organization (WHO), suggested that, in the interest of worldwide public health, the U.S. government become a more active partner, encouraging development of vaccines with limited market potential through grants and other types of support.
A number of the items on the CVI's wish list—such as a "super vaccine" that would provide complete protection against a number of diseases after a single dose—sell themselves.
"If there is a market in the United States, the big players will get involved," Douglas said. "The push for combination vaccines really came from WHO. They need combination vaccines in developing countries to make it easier to vaccinate children, but it is something that is also valuable in the United States. Tuberculosis vaccine is something that is big in the United States, and malaria [vaccine] because of travelers. These vaccines will be developed by large companies.
Some [vaccines for] diseases that occur only in Africa, such as onchocerciasis, may not be [developed]. That is where the public sector has to jump in and take the lead. Then there are the diseases that are important to the military; these vaccines will be developed by the DOD or through grants issued by the DOD."
Fostering public and private partnerships, then, is essential to the global vaccine industry. If one link weakens, the others in the chain could suffer as a result.
"It is terribly important that people realize that the various components are all needed," Douglas said. "We need WHO for vaccines for developing countries; the DOD to develop vaccines that are important to the military; NIH for the basic research; large companies for development expertise; and small companies for creative new ideas. A healthy respect for each party is important, and we need to nurture these relationships."
For more information, see:
Institute of Medicine. The Children's Vaccine Initiative: Achieving the Vision. Washington, D.C.: National Academy Press; 1993.
National Vaccine Program Office. Disease Prevention Through Vaccine Development and Immunization: The U.S. National Vaccine Plan—1994. Washington, D.C.: Department of Health and Human Services/Public Health Service; 1994.
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