Innovation spurs access

The international community has launched a massive campaign to combat the AIDS epidemic and other major diseases raging throughout the third world. Last year, numerous international conferences highlighted the need for a huge investment in the development of new vaccines and medicines to combat AIDS, malaria and tuberculosis (TB). At the World AIDS Conference in Barcelona, Spain (July 2002), pharmaceutical manufacturers announced additional price reductions for AIDS therapies and increased support for research into new treatments. Further discussion of these issues took place at the Johannesburg World Summit on Sustainable Development in September. World AIDS Day in December generated pledges from the West to increase support for international disease prevention and treatment programmes.

Manufacturing gains attention Up until now, efforts to combat AIDS and other diseases have focussed largely on increasing public access to existing therapies, and investing in research into new compounds and biomedical approaches that are likely to lead to new vaccines and disease treatments. Donor organizations and health foundations have been expanding research and development (R&D) programmes and establishing international clinical trial networks to study promising therapies. Pharmaceutical companies are involved in tests of 14 vaccine candidates, including one that has begun Phase III clinical trials in Thailand, the US and Europe.

As programmes to develop new vaccines and therapies show promise, health experts are recognizing the need to plan to manufacture any new treatments on a global scale. To be able to produce a vaccine as soon as it is licensed, plant construction has to begin before sponsors have assurance that a test product will work. Construction of a vaccine manufacturing plant that meets GMP (good manufacturing practice) standards normally requires several years and at least $50 million to build. However, the numbers are much higher for an AIDS vaccine that would be needed by much of the world.

Many of the difficulties related to new vaccine production have been apparent for years, as international health organizations have struggled with vaccine production, distribution and safe administration challenges involved in expanding third-world access to existing vaccines and medicines (see sidebar "Innovation spurs access"). Drug manufacturing capability still barely exists in most third-world nations, and vaccine shipping and storage often requires rigid monitoring. The need to find ways to produce billions of vaccine doses that will be affordable in Africa and Asia is nothing short of overwhelming.

Formulation changes threaten vaccine access

Consequently, sponsoring organizations are launching programmes to map out manufacturing approaches and investment requirements. Process development challenges dwarf the difficulties of getting a test product into clinical trials, observed Edward Pollock, director of business development and strategic planning of the International AIDS Vaccines Initiative (IAVI). "We can't just focus on clinical candidates," but need to follow up with "real manufacturing capability to go along with it," he commented at the Partnering for Global Health Forum (2002) sponsored by the Biotechnology Industry Organization (BIO) and the Bill & Melinda Gates Foundation in Washington DC in December. The Forum brought together funding organizations, such as Gates and groups associated with the World Bank and the United Nations, with biotech companies seeking support for R&D programmes for AIDS and other third-world diseases.

Whereas most presentations discussed R&D, several addressed issues related to manufacturing and product development:

• The Global Alliance for TB Drug Development is paying more attention to whether potential test products will lend themselves to affordable manufacturing in deciding what new technologies to fund.
• The International Financial Institution, a member of the World Bank Group, is funding large-scale private sector drug manufacturing projects in India, South Africa and other countries to enhance third-world production capacity.
• California-based VaxGen has formed a $120 million joint venture with South Korean investors to build manufacturing facilities for AIDS and anthrax vaccines and other cell culture products. A plant in

San Francisco (California, USA) will be able to produce up to 10 million vaccine doses per year by 2005. A South Korean facility (Celltrion) will produce 200 million doses annually and will eventually have eight 12000 litre bioreactors that are capable of a much greater production volume.

Link to manufacturing IAVI is devoting considerable resources to formulating a plan for massive AIDS vaccine production as part of its "virtual company" model for managing vaccine R&D projects. The non-profit organization was founded in 1996 to spur AIDS vaccine development and is funded by Gates and other foundations, the World Bank, industry and Western governments. A prime goal is to link academic research efforts with networks that are able to conduct clinical trials in developing nations and have the product development skills found in the vaccine industry. To speed vaccines to Phase I trials, IAVI uses contract manufacturers to produce pilot lots for preclinical testing and for early clinical studies.

Recently, the organization hired Don Gerson, who has led vaccine manufacturing programmes at Wyeth and Acambis, to move to the next step: large-scale development and manufacturing partnerships. As IAVI's managing director for manufacturing, Gerson's task is to formulate a programme for producing a vaccine to meet the needs of 5 billion people in the Third World. He estimates that it will take 6–7 years to build and validate the necessary production facilities, which coincides with the time frame that scientists estimate will be needed to fully test and license an effective product.

Gerson has begun by preparing a preliminary engineering study for meeting such an enormous goal. The initial plan is to establish five regional plants, each able to serve 1 billion people and to produce 150 million doses a year. Each plant will be able to accommodate a variety of vaccine products in three production areas for egg or cell production of viral vectors and bacterial plasmid production. Each plant will cost approximately $300 million to build, for a total manufacturing construction budget of $1.5 billion. That amount will get the facilities built in compliance with GMPs, but does not cover actual production costs.