The Current Vaccine Wave and Global Health
Production, Policy, Pricing, and Promising Technologies

You served as president of Merck Vaccines from 1999 to 2005, a period marked by exceptional productivity in vaccine production and manufacturing, not only for Merck, but industry-wide. Looking back from an industry perspective, how would you sum up the major shifts that have taken place over the past two decades?

During the last decade of the previous century, only four of the major multinational pharmaceutical companies had vaccine research and production programs. Today the top ten global pharmaceutical companies are involved in the vaccine field. Similarly, emerging market manufacturers used to contribute a minor role to the total vaccine production capability, but today approximately 50% of vaccines procured by the GAVI Alliance [1] come from emerging markets.

What developments in the vaccines field were behind this profound transformation?

The global vaccine scene has changed drastically during the past decade for several reasons. The most obvious sign of change is a wave of production of new vaccines that began towards the end of the last decade of the 20th century and continued for several years thereafter. The new vaccines represent a major advance in the science of discovery as well as in production technologies.

For example, this period witnessed the production of several conjugate vaccines [2] for Haemophilus influenza type B (Hib) and pneumococcal and meningococcal infections. These vaccines, which established a new approach for the protection of young children, are now being used as part of the effort to produce combination vaccines that will reduce the necessity of administering multiple injections. The next step forward was utilization of a new technology—reassortment of viruses, which mixes genetic material into new combinations—to produce a rotavirus vaccine. In addition, a major discovery of the self-assembly characteristic of one of the components of human papillomavirus (HPV) resulted in the production of two new vaccines using recombinant technology. [3]

This wave of new vaccines also correlated with new pricing policies, such as tiered pricing to make vaccines more affordable for developing countries without interfering with pricing in developed markets. With these new policies, major vaccine manufacturers were able to both complete the production of over a dozen new vaccines in the span of one decade and develop a business model that made the vaccine industry an attractive economic pursuit for private as well as emerging markets, such as China and India.

Along with these changes, the formation of the GAVI Alliance and the dedication of new streams of funding led to a new emphasis on global vaccination efforts and a more robust market. Sensing new opportunities, several other multinational pharmaceutical and emerging market manufacturers committed more attention to vaccines.

Looking ahead, and drawing on your experience with the R&D process, do you think the rate of productivity during this last period will be sustainable going forward? What kind of future do you see for the innovation in development of preventive tools for the complex diseases of the 21st century?

Vaccine discovery and development is a long and protracted process. A new vaccine is usually the result of a research discovery emerging from an academic institution or government laboratory. Traditionally, the next step has been the acquisition of rights to these fundamental research observations by pharmaceutical companies or biotechnology establishments, which then initiate a development process that will typically take a decade or so.

The unprecedented rate of productivity over the past two decades may be partly responsible for enhanced interest in the discovery of new vaccines. But we must have realistic expectations for the future, recognizing that much of the vaccine discovery to date has not come from a systematic or rational search. Vaccine discovery has often resulted from one form of serendipity or another that pointed to a rewarding outcome. Nevertheless, the future holds promise for continued development because of the many new scientific capabilities available to the scientific community today and the reality of the global challenge of infectious diseases.

Your research [at the Woodrow Wilson School of Public and International Affairs at Princeton University] focuses on global health and policy issues, including the means by which vaccines are introduced into developing countries. What are the industry realities that must be considered, particularly with regard to demands for lower pricing?

Vaccine pricing will always be a subject of intense debate for multiple practical, theoretical, and political reasons. The problem stems from little understanding among donors and international organizations of the dynamics of vaccine discovery and development, both of which are long and protracted processes. Most vaccine development takes place in private enterprises that have to assume total risk until a product is launched. The development process can take a decade or longer to complete. If investors (usually private capital) consider the vaccine field to be too risky, they will flee, and the alternatives to private capital are still a work in progress. Government efforts, as well as public-private partnerships, have still to prove they can discover and develop innovative, new vaccines.

The global community is right to demand new products and to try to see that their pricing is within the reach of the majority of consumers—this is a common goal among NGOs, donors, country leaders, and companies alike. No one has an interest in vaccines that are priced too high to be used, but companies are also wary of expectations that vaccines should be free, given the extraordinary amounts of time and financial and infrastructure resources needed to bring a new or improved vaccine to market.

What is the best path forward for increasing access to vaccines in developing countries?

This difficult issue will require a broader debate about the impact of differential or “tiered” pricing (selling the product at different prices in different markets) and other sources of financing and other financial innovations, such as Advance Market Commitments. [4] More importantly, there needs to be a demonstration of political will in developing countries about budgetary priorities.

Vaccines, public health, and prevention of disease have to be the top priorities of political leaders in developing countries. The way they plan their budgets, however limited their resources, must reflect a clear sense of prioritization and clear commitments. Dependence on outside sources may be needed as a supplement, but external financing should not be the main source for funding of immunization programs.

So, what are the main vaccine challenges for the global community in the foreseeable decade or two?

The most acute need is an appreciation for the necessity of a new scientific approach to vaccine discovery based on the basic understanding of microbial genomes—their organization and their interaction with host defense mechanisms. Most vaccine discovery to date has been based on the scientific discoveries of the past two centuries. While those achievements are remarkable, we have to admit that without new and enhanced scientific capabilities, we would be searching in the dark. New pursuits using genomics, metabolomics, structural biology, and computational sciences will necessitate the engagement of a new generation of scientific talent deeply trained in these sciences; most scientists and researchers with these specialties are currently not involved in vaccine discovery. The challenge for scientific and global leadership is to devise attractive mechanisms to recruit a new generation, and that new generation should include scientific talent from both developing and developed countries.

The second challenge that our total moral and social commitment faces is the delay in availability of new vaccines. The fundamental principle for an enhanced global effort in 2000 to introduce new vaccines resulted in the initiation of the GAVI Alliance and remarkable success with the Hepatitis B vaccine introduction. By contrast, a decade later, and with several new vaccines newly available in the developed world, the introduction of any new vaccines in developing countries is fragmented, and access is far from optimal. The only current effort to expand access is around the introduction of pneumococcal conjugate vaccine, yet the list of available new vaccines includes at least five or six equally important vaccines in need of global introduction efforts. There is no clear pathway for planning, nor is there a systematic approach in place. Originally, the complaint about delayed vaccine introduction in developing countries was loud and clear. Currently, this same scenario is playing out again, yet the road ahead is unpaved.

Endnotes

[1] The GAVI Alliance is a public-private partnership focused on increasing access to vaccines in poor countries. Partners include national governments in developing and developed countries, UNICEF, WHO, the World Bank, the Bill & Melinda Gates Foundation, the vaccine industry in developing and developed countries, public health institutions, and civil society organizations (CSOs). Since its inception in 2000, the GAVI Alliance has made available more than USD $2.5 billion for immunization in GAVI-eligible countries. As a result, vaccination coverage levels have increased dramatically. See http://www.gavialliance.org for more information.

[2] A conjugate vaccine is “a vaccine formulated by chemically linking sugar chains derived from the pathogen to a protein backbone, created with improved ability to stimulate the immune system providing protection for a longer period of time and is aimed at giving better immune responses for those exposed to the bacteria or requires a repeat booster dose at a later stage.” Conjugate vaccines are more effective than other types of vaccines for young children under the age of two, who do not yet possess the ability to develop antibodies. (Source: “GAVI Partners Mobilise to Counter Meningitis Outbreaks,” The GAVI Alliance, Press Release, April 9, 2009, http://www.gavialliance.org/media_centre/press_releases/2009_04_09_Meningitis_A.php.)

[3] Recombinant vaccines are “engineered viruses or bacteria into which harmless genetic material and other disease-causing organisms are inserted.” (Source: Crucell Glossary, s.v. “recombinant vaccines,” http://www.crucell.com/glossary/item/recombinant+vaccines.)

[4] An Advance Market Commitment (AMC) is “a legally-binding agreement for an amount of funds to subsidize the purchase, at a given price, of an as yet unavailable vaccine against a specific disease causing high morbidity and mortality in developing countries. . . . The purpose of an AMC is to provide incentives to vaccine manufacturers to invest in the necessary research and manufacturing capacity needed to bring a vaccine for the developing world to market. . . . Concretely, through the AMC mechanism, donors would subsidize the purchase of vaccines by developing countries, up to a fixed number of sales or a fixed total amount. Once this fixed number of sales or total amount has been reached, manufacturers having benefited from the subsidy would be contractually obliged to either sell to developing countries at a price affordable over the long term or to license their technology to other manufacturers. . . . Donor pledges would be underpinned by national financial commitments and would complement existing public funds for research.” (Source: “Advanced Market Commitments to Vaccines,” World Health Organization, Press Release, July 19, 2006, http://www.who.int/immunization/newsroom/amcs/en/index.html.)

This interview was conducted by Claire Topal and Karuna Luthra for the NBR Center for Health and Aging (CHA).