Regulation of vaccines: strengthening the science base.

This paper aims to review the history of development of vaccine regulatory approaches, to assess practices that may be barriers to access to innovative products, and to suggest possible approaches to address these practices. Despite the appearance of new vaccines in the past few years, many vaccines are based on old technologies, and are still subject to regulatory practices devised many years ago. Vaccine regulation began with a foundation on vaccine testing, and only in response to tragedies associated with vaccine use did new concepts begin to be defined. Vaccine regulation now includes a range of functions that cover the entire continuum of vaccine development and use. However, some regulatory practices, such as the continuing dependence on outdated animal tests, have not kept pace with these changes. Other practices, such as the continual raising of the standard of Good Manufacturing Practice (GMP) compliance, or the move to increasingly larger phase 3 clinical trials, appear to be based more on perceived risks than on firm scientific principles. The future of effective regulation for vaccines that will allow innovation while protecting the public health must be based on three guiding principles: a firm science base for policies and decisions, a risk-based approach to implementation of regulatory oversight, and support for regulatory research to inform these activities. These should be implemented in a setting of international harmonization.

The role of emerging manufacturers in access to innovative vaccines of public health importance.

The role of developing country manufacturers in assuring global access to innovative vaccines was compared to the situation in 2005. These producers now supply over 60% of traditional vaccines doses globally and an increasing value (up to 15% in 2007) of innovative products. More suppliers are now strong players in global market, and an even larger group has potential to do so. These manufacturers are not a homogeneous group and most of them are now at a crossroads. Decisions made by their management and governments as well as by the international community will have a large impact on their existence and future and their ability to manufacture innovative vaccines at affordable prices.

The GO License: only part of the solution.

The Generic Open (GO) License is a proposal to make patents more accessible for vaccines and drugs in low- and middle-income countries. However, for some health-related products, such as vaccines, intellectual property is frequently not the primary constraint. Technical know-how and assurance of a viable market built on reliable demand at prices that cover costs are the most critical factors for vaccine access. Together with innovative efforts to reduce product development risks and costs and to assure credible markets at profitable prices, the GO License may yet play a role in assuring access for drugs and vaccines for poor countries.

The GAVI Financing Task Force: one model of partner collaboration.

The Global Alliance for Vaccines and Immunization, now called the GAVI Alliance, was launched in 2000 as a coalition of partners, including countries, international organizations, bilateral donors, the vaccine production industry, and nongovernmental organizations; most activities were to be implemented through these partner organizations. Four task forces were established at the outset to define issues relevant to GAVI Alliance goals and to recommend actions. This paper describes the innovations and outputs of the Financing Task Force (FTF), which worked in three areas: country support to sustainably finance vaccines and immunization programs in the context of introducing new vaccines; vaccine supply and demand issues as they impact vaccine choice, production costs and price/dose; innovative financing mechanisms for vaccines and immunization programs through, for example, capital markets. This analysis particularly focuses on the FTF's work on financial sustainability. Through its partnership, the FIF was able to leverage organizational change in its participating organizations, in the countries supported by the GAVI Alliance, and in the policies of GAVI itself. These achievements, along with areas where the desired outcome was not achieved, are summarized with lessons that may be useful to other multi-partner health alliances.

Strategies for financial sustainability of immunization programs: a review of the strategies from 50 national immunization program financial sustainability plans.

Financial sustainability plans (FSPs) were developed by over 50 of the world's poorest countries receiving funding support from the Global Alliance for Vaccines and Immunization (GAVI) to introduce new and underused vaccines, injection safety and immunization service support between 2000 and 2006. These plans were analysed with respect to the strategies selected to promote financial sustainability, allowing classification of FSP strategies in three areas: (1) mobilizing additional resources, (2) increasing the reliability of resources, and (3) improving program efficiency. Despite some country successes and the magnitude of planned financial sustainability strategies, huge funding gaps remain for these countries due to the initial underlying assumptions of the GAVI and financial sustainability plan model.

Access to vaccine technologies in developing countries: Brazil and India.

This study, conducted by visits, interviews, and literature search, analyzes how vaccine manufacturers in Brazil and India access technologies for innovative vaccines: through collaborations with academia and research institutions, technology transfer agreements with multinational corporations, public sector, or developing country organizations, or by importation and finishing of bulk products. Each has advantages and disadvantages in terms of speed, market, and ability to independently produce the product. Most manufacturers visited are very concerned about avoiding patent infringement, which might result in undeveloped or delayed products because of a lack of mastery of the patent landscape. Disregarding the patent picture could also threaten the market of a potential product. Although it is too soon to assess the effects of TRIPS on vaccine technology access in Brazil and India, a good understanding of intellectual property management will be useful. A case study on development of a new combination vaccine illustrates these findings.

The impact of globalization on vaccine development and availability.

Globalization is likely to affect many aspects of public health, one of which is vaccine-preventable communicable diseases. Important forces include increased funding initiatives supporting immunization at the global level; regulatory harmonization; widespread intellectual property rights provisions through the World Trade Organization agreements; the emergence of developing-country manufacturers as major players in vaccine supply; and the appearance of new communicable disease threats, including those potentially linked to bioterrorism. All of these forces can affect, either positively and negatively, the development and availability of vaccines. Harnessing these will be a challenge for policymakers and immunization stakeholders.