"Sharing" of avian flu virus to be a major issue at WHA

Geneva, 7 May (Martin Khor and Sangeeta Shashikant) -- Among the key issues that are expected to be discussed at the World Health Assembly starting 14 May is the stark inequity between developed and developing countries in their access to vaccines in the event of a pandemic of avian influenza.

Many developed countries have already placed orders and paid drug companies to stockpile pre-pandemic vaccines and made advance purchase orders to have pandemic vaccines delivered to them in the event of a pandemic. There is a rush to place the orders and stockpile because vaccines are scarce and there is only a limited amount that drug companies can produce in a year, which is far exceeded by demand if a pandemic emerges.

According to a 2006 WHO report on an action plan to increase vaccine supply, the global production capacity was only 350 million doses, which could rise to 500 million doses at full capacity. But as two doses may be needed a year per person, the global vaccine output would not be enough for the world population in the event of an avian flu pandemic.

Even with technological advances, in 2008-9 flu vaccine production would be at most 2.3 billion doses a year, "still several billion doses short of the expected demand if there were to be a pandemic," said the report.

As the vaccines are patented and expensive, most developing countries cannot afford to order or buy them in the amounts required. If a pandemic strikes, they fear their populations will be unprotected, as much of the vaccine stocks will be located in and channeled to people in the developed world.

Adding to this imbalance is the fact that a crucial component - the avian flu viruses - in the research and development, and the manufacture, of the vaccines comes overwhelmingly from the developing countries, where the human cases of avian influenza are located.

Under a WHO scheme, countries affected by avian flu send samples of the viruses to the WHO's collaborating research centres and laboratories, almost all of which are national institutions located in developed countries.

Under the WHO's 2005 and 2006 guidelines, these WHO-linked centres are not supposed to pass on the viruses to third parties such as companies or to publish papers or make known the gene sequences of the viruses without the prior permission of the countries contributing the viruses.

However, officials of some developing countries have discovered that their viruses have been made use of in activities such as patenting, commercial development and production of vaccines and publication of research materials, without their permission or even their knowledge.

The countries are being approached by drug companies to make orders for vaccines that were developed or made with the use of the viruses they supplied freely under the WHO scheme. The prices quoted by the companies are too high for the countries to afford, especially since they need vaccines in very large quantities in the event of a pandemic.

World public attention was focused on this issue when the Indonesian Health Ministry announced a few months ago that it would no longer provide bird flu viruses to the WHO's collaborating centres as it believed the centres and the system had betrayed its trust.

Some viruses contributed by Indonesia under the WHO system were being used not only for the research activities that the centres were supposed to perform, but also passed on to companies for commercial activities without Indonesia's knowledge or permission, while there was no international system in place to ensure that Indonesia or other developing countries would be supplied with sufficient vaccines, and at affordable prices.

When announcing her country's move to suspend the sharing of viruses, Indonesia's Minister of Health Siti Fadilah Supari called the current system "unfair".

Indonesia, supported by other developing countries, is expected to highlight this issue during the WHA starting next Monday.

Indonesia, some other countries and the WHO secretariat have been discussing how to ensure that the donated viruses are not misused or misappropriated, and that a framework is established to ensure benefits to developing countries.

The H5N1 influenza virus is highly pathogenic i. e. able to cause severe disease and deaths in humans. It has caused widespread sickness and death in domestic and wild bird populations globally in the last decade. And as the infection among birds increases, so does the opportunity for H5N1 to be transmitted directly from birds to humans.

If avian and human influenza viruses were to simultaneously infect a person or animal, the two viruses might swap genes. The result could be a new virus that can be transmitted between humans, which could lead to a worldwide pandemic.

From 2003 to April 2007, 291 confirmed human cases (including 172 deaths) of Avian Influenza A/(H5N1) were reported to the WHO.

The most affected countries are Vietnam (93 confirmed human cases and 42 deaths in 2003-5), Indonesia (81 cases, 63 deaths in 2005-2007), Egypt (34 cases, 14 deaths in 2006-2007), Thailand (25 cases, 17 deaths in 2004-2006), China (24 cases, 15 deaths in 2005-2007), Turkey (12 cases, 4 deaths in 2006), Azerbaijan (8 cases, 5 deaths in 2006), Cambodia (7 deaths in 2005-7), Iraq (3 cases, 2 deaths in 2006), Laos (2 deaths in 2007), Nigeria (1 death in 2007) and Djibouti (1 case in 2006).

Many of these countries have been contributing their viruses to the WHO Global Influenza Surveillance Network (GISN), made up of the National Influenza Centres (NICs) which annually submit around 2,000 viruses to the WHO centres. In 2004, WHO H5 Reference Laboratories were also established as an ad hoc component of the GISN.

Twice each year, the GISN recommends the content of the influenza vaccine for the subsequent influenza season.

There are four WHO Collaborating Centres, all based in developed countries (i. e. in Australia, Japan, United Kingdom, and United States) and three H5 Reference Laboratories (in Australia, UK and US) that participate in the WHO GISN.

Indonesia found its viruses had been used to make vaccines without its permission when it was approached by an Australian drug company wanting to sell it a vaccine for $20 a dose. As the country may need to vaccinate its entire population of over 200 million should a pandemic occur, the cost at this price level would be astronomical.

Shocked and angered at this situation, Indonesia suspended sending further virus samples to the WHO centres. This raised an international storm of controversy, with some countries accusing Indonesia of holding back research activities, while many others (including some mainstream media such as New York Times and New Scientist) expressed sympathy for Indonesia's position.

A few weeks ago, Indonesia announced it would resume sharing the viruses in the understanding that the WHO would set up a more equitable system.

Indonesia's strong response was partly due to its belief that the WHO and its collaborating centres have been violating the WHO's own guidelines on virus sharing. Though the guidelines state that the viruses received would not be given to third parties, in fact the centres have been providing viruses and data on them to companies and other institutions without the permission of Indonesia.

The WHO's March 2005 "Guidance for the timely sharing of influenza viruses/specimens with potential to cause human influenza pandemics" states: "There shall be no further distribution of viruses/specimens outside the network of WHO Reference Laboratories without the permission from the originating country/laboratory".

It also states that the "The designated WHO Reference Laboratories will seek permission from the originating country/laboratory to co-author and/or publish results obtained from the analyses of relevant viruses/samples".

It is learnt that Indonesian health officials recently asked WHO Secretariat senior official why the guidelines were not being adhered to. A few weeks ago, the Guidance document appears to have been removed from the WHO website.

Various WHO notices reveal that the WHO centres have been commonly passing seed viruses developed from the viruses provided by affected countries to companies and institutions outside the GISN. The centres are even signing "material transfer agreements" with companies and institutions.

For example, a WHO notification dated March 2006 stated that "An H5N1 recombinant vaccine strain developed from A/Indonesia/5/2005, by the WHO Collaborating Centres for Disease Control and Prevention, Atlanta USA is available for distribution under a Material Transfer Agreement".

The notice invites "Institutions, companies and others interested in pandemic vaccine development, who wish to receive the prototype strain" to "contact either the WHO Global Influenza Programme at or WHOCC CDC" in Atlanta, USA.

Similar WHO notifications are also available in relation to recombinant H5N1 prototype vaccine strains A/Vietnam/1194/04, A/Vietnam/1203/04, A/Hongkong/213/03, A/turkey/Turkey/1/2005, A/Bar headed goose/Qinghai/1A/2005 and A/Whooping swan/Mongolia/244/2005.

Some notifications also state that several of the "H5N1 influenza pandemic vaccine prototype strains have already been made available to a number of institutions and companies and several different vaccines have been produced for clinical testing".

The notices do not provide information whether the consent of the countries contributing the viruses had been obtained prior to providing the viruses to institutions outside the WHO GISN, or whether there were benefit-sharing arrangements made with countries contributing the viruses.

According to Indonesian officials, their permission was neither sought nor granted. Dr. Triono Soendoro, Director General of Indonesia's National Institute of Health Research told the Jakarta Post: "We screamed when we heard that an international company wanted to sell us the vaccine which was developed from our strain without our permission."

The Convention on Biological Diversity clearly establishes the right of a sovereign state over its own biological resources including genetic resources. Access by foreigners to such resources is contingent on prior informed consent of the country of origin, which can also negotiate benefit sharing arrangements.

Indonesian health officials have explained that their country shared the avian flu viruses on good faith with WHO centres (which were only supposed to conduct scientific analysis on the viruses), but this faith has been broken by their passing on the viruses or its parts to third parties conducting commercial activities.

According to the officials, this violates Indonesian law (that requires that transfers of genetic materials for commercial activities must be accompanied by an agreement), the Convention on Biological Diversity principles, as well as the WHO's own guidelines.

The apparent change in positions by the WHO Secretariat on respecting the rights of countries of origin can also be seen from a recent 12 March 2007 WHO document on best practices for sharing viruses.

The document favours the current practice (which is in violation of the March 2005 WHO Guidance) as it describes as a "best practice" for virus sharing that the "Global Influenza Surveillance Network Collaborating Centres and H5 Reference Laboratories should provide candidate influenza vaccine strains to any requesting vaccine producer meeting all applicable regulatory biosafety standards and requirements, for the sole purpose of developing a safe and effective vaccines."

This "best practice" conflicts with the provision in the WHO Guidance that "There shall be no further distribution of viruses/specimens outside the network of WHO Reference Laboratories without the permission from the originating country/laboratory."

Such a "best practice" would benefit developed countries' vaccine manufacturers; it would however violate the "prior informed consent" right of countries contributing the virus and make it even more difficult for these countries to request a benefit sharing arrangement with researchers and manufacturers undertaking commercial activities.

Perhaps the removal from the WHO website of its 2005 Guidance is linked to its being in conflict with this latest "best practice" document - both of which were issued by the WHO secretariat.

(This is part of a SUNS series on the avian flu virus sharing controversy. The second article in this series will be published in the next issue of SUNS.)