If a successful vaccine is developed, large-scale investment will be needed to make it available on a global scale. IAVI has made five recommendations to secure that investment and general access, especially if any reliance is placed on private sector involvement in the process. (IAVI 2000a):

• Effective pricing and global financing mechanisms must be developed to assure [ensure] that vaccines are promptly available for use where they are needed.
• Mechanisms must be developed to make reliable estimates of demand for specific vaccines and to ensure creation of production capacity to permit accelerated worldwide access.
• Appropriate delivery systems, policies, and procedures must be developed for adolescents, sexually active adults and other at-risk populations.
• National regulations and international guidelines governing vaccine approval and use must be harmonised.
• To demonstrate global commitment to effective worldwide deployment of important vaccines, immediate efforts should be undertaken … building on existing mechanisms, such as the Global Alliance for Vaccines and Immunization (GAVI) and the Global Fund for Children’s Vaccines (GFCV) – to achieve maximum use in developing countries of one or more currently under-utilised non-AIDS vaccines.

Tiered or 'equity' pricing – where prices reflect what countries can afford – will be needed from the moment an HIV vaccine is launched. This implies safeguards, including political support in wealthier countries, against the international trading of cheaper vaccines from developing countries into wealthier countries.

The traditional pattern is that new products are introduced first into wealthy countries, sold at premium prices which enable the manufacturers to recoup their costs in developing the vaccine. Fifteen or more years later, when development costs have been written off and patents have expired, prices can be reduced sufficiently for international agencies to purchase them for use in developing countries. IAVI is saying that this traditional pattern is unacceptable for HIV, and in fact should be unacceptable for any vaccine or treatment.

There are encouraging signs that this thinking is now being adopted by some of the larger companies in the field, in respect of a range of new vaccines that are being developed against diseases that are either confined to countries with limited resources or present far greater public health problems in those countries than in wealthier, industrialised countries. (A rotavirus vaccine, against infant diarrhoea, currently being developed by GSK Biologicals may be the test-case for this approach.)

Financing refers to the need for both ‘push’ and ‘pull’ mechanisms to overcome the perception that there are no profits in making vaccines. Direct public investment in vaccine development by private companies is one form that ‘push’ mechanisms can take. The French and American governments, and the European Commission, are already doing this. Purchase funds, underwritten by international development agencies such as the World Bank, or by individual governments committing themselves to purchase future vaccines meeting set criteria, are examples of ‘pull’ mechanisms. Many years ago, the State of California enacted specific legislation limiting liability and guaranteeing purchase of any effective vaccine, and this seems to have helped Californian biotechnology companies (Chiron and Genentech, later VaxGen) take an early lead in this area.

It may never be possible to make an accurate assessment of the demand for any HIV vaccine until it is in widespread use. Nonetheless, it is important to realise that companies will be unlikely to risk large sums of money building manufacturing facilities on a global scale, unless there is some assurance for them that their money will not be wasted.

To produce a potential vaccine on a small scale, to test out an idea in a very few animals, is well within the capability of a well–equipped academic laboratory. However, to produce a vaccine in bulk, to the high industrial standards required by regulatory bodies for any product given to humans, is a very different matter. Expertise in this area is almost entirely located in the pharmaceutical industry, and indeed four large companies produce most of the world's commercial vaccines. These are Merck, Aventis Pasteur, American Home Products (Wyeth Lederle), and GlaxoSmithKline, all of which have had some level of involvement in HIV vaccine development.

A new and interesting model that is emerging in the UK is represented by Cobra Pharmaceuticals, a company that makes vaccines on behalf of developers, owning some of the delivery technology (in particular for DNA vaccines) but not seeking to produce or market vaccines for end-users. While they currently make vaccines primarily on a pilot scale, they plan to expand facilities to produce in larger quantities. Such facilities might be developed in public-private partnerships, with public investment to enhance the scale of multi-purpose manufacturing facilities.

Delivery systems to administer vaccines to adults are not widespread. Most vaccines are given to young children, and in many countries it would require new systems of medical records and administrative measures to identify and invite adults or even adolescents to be vaccinated.

There is a need to standardise procedures and criteria across different countries’ regulatory agencies. Within Europe, there is now a system which provides both for mutual recognition of decisions to license pharmaceutical products and for Europe-wide registration through the European Medicines Evaluation Agency (EMEA). However, drug regulation is more variable in other countries: South Africa has a professional regulatory agency, but many others do not. A related issue is the absence of any fast-tracking procedure for vaccines, to prioritise those where the safety concerns are minimal and the disease against which they are directed is most serious as a public health problem.

Liability issues may be real. Vaccines are given to people who are well, including young children, often at an age or in circumstances where they may, perhaps coincidentally, be diagnosed with other conditions. In the United States, lawsuits about such cases led most pharmaceutical companies to stop manufacturing vaccines, until legislation was passed setting a ceiling on such liabilities. However, the damage had been done.

As vaccines succeed in eradicating a feared disease, the real adverse effects of the vaccines may match or outweigh the immediate threat to individuals from the disease itself. Public health authorities have not always been effective in dealing with this issue, with an ever-present temptation to deny that these effects occur and to resist compensating those who suffer for a very real public benefit.

The UK government's Policy and Innovation Unit, part of the Cabinet Office, recently published a detailed review of incentives for private investment in meeting global public health needs, with particular reference to HIV, TB and malaria.