No clear outcomes in WHO meeting on avian flu virus sharing

Penang, 9 Aug (Sangeeta Shashikant) -- A meeting organized by the World Health Organisation to review the terms and conditions and oversight mechanism for the sharing of avian flu viruses was held last week in Singapore, and it ended without a clear agreed outcome.

The meeting of an interdisciplinary working group (IDWG) set up by the World Health Assembly (WHA) met on 31 July to 4 August in an attempt to draft revised terms of reference for WHO-linked laboratories and draft standard terms for sharing viruses between originating countries, WHO-designated laboratories and third parties.

Twenty-four member states of the WHO, chosen from the various WHO regions, and representatives of WHO- designated laboratories were invited to take part in the meeting.

The selected countries were Cameroon, Ghana, Nigeria, South Africa, Brazil, Canada, Chile, USA, Bangladesh, India, Indonesia, Thailand, France, Germany, Turkey, United Kingdom, Egypt, Iran, Morocco, Tunisia, Australia, China, Japan and Vietnam.

(The WHO-designated laboratories are national institutions designated by the WHO as "collaborating centres" or "H5 reference laboratories". The centres are based in the US, Australia, UK and Japan, while the H5 reference laboratories comprise the collaborating centres and laboratories in US, Hong Kong, France, and a US naval medical unit in Egypt.)

The IDWG is the result of a resolution at the WHA last May arising from criticisms that avian flu viruses contributed by originating countries (so far, mainly the developing countries) had been commercialized without their knowledge or permission, and from demands that the present WHO-organised system for distributing influenza viruses (the Global Influenza Surveillance Network) be reformed.

Many developing countries had also sought the linkage between the contribution of viruses and the sharing of benefits arising from the use of the viruses (such as vaccines) and other benefits (such as technology transfer to enable local vaccine production).

A draft resolution by over 20 countries, coordinated by Indonesia, at the WHA, reflected the view that the current practices of the WHO Global Influenza Surveillance Network (GISN) do not bring about fair results and that these practices need to be reformed with mechanisms for fairly sharing the benefits resulting from the use of the viruses.

The WHA adopted a resolution setting up the IDWG with a mandate to revise the terms of reference of the WHO Collaborating Centres, H5 Reference Laboratories and other national influenza centres; to formulate draft standard terms and conditions for sharing of viruses between originating countries and WHO Collaborating Centres, the latter and third parties; to devise oversight mechanisms; and to review all other relevant documents.

The resolution also agreed on an inter-governmental meeting (IGM) to consider the IDWG's report as well as consider a report by the WHO Director-General on a benefit-sharing framework, vaccine stockpiling and equitable distribution of vaccines, and a report on patents on viruses and their parts.

The inter-governmental meeting, to which all member states are to be invited as participants, is expected to be held in November.

According to some delegates at the Singapore meeting, the discussions were difficult due to the complexity of the issues, the technicalities involved in formulating terms and conditions (for contribution of viruses and sharing of benefits) and above all, the differences in views, particularly as between several developing and developed countries.

The short notice given to countries about the meeting and the short duration of the meeting itself made it difficult to complete discussions on the many issues on the table.

Among the difficult issues were rights of originating countries over the viruses and their use, the role of the WHO, several intellectual property issues, the sharing of benefits, and the terms of reference and conditions for institutions receiving the viruses and products containing parts of the viruses.

The Chair of the meeting, Dr. Viroj Tangcharoensathien, Director of International Health Policy Program, Ministry of Public Health, Thailand, presented a paper containing draft Standard Terms and Conditions (STC) for discussion on the third day of the meeting.

On the final day, the Chair tabled several documents, including an "Informal Note" on a summary and conclusions of the meeting, a draft text of standard terms and conditions (STC) for the transfer and use of biological materials relating to the GISN, and a document on a list of proposed benefits.

According to several delegates, the meeting concluded without an agreed outcome, with some delegates disagreeing with significant parts of the content of the "Informal note" containing final summary of the discussions, while others insisted that the STC text and other documents presented be all placed in "brackets" i. e. denoting that they were not agreed on by the participants.

Several delegates were not clear as to the status of the documents. It was their understanding that the Chair's summary and conclusions (and possibly other documents) would be revised and sent to participants for their comments.

"We hope it is made clear that the documents were prepared by the Chair and do not reflect the joint views of the participants of the meeting," said one developing-country delegate after the meeting.

Some delegates were also of the view that the issues under discussion were extremely complex and technical, requiring knowledge not only of health and scientific issues, but also an understanding of legal texts and agreements.

Documents put forward for negotiations, let alone as conclusions, had to be carefully scrutinized by experts in the capitals, and the short duration of the meeting did not enable this to take place.

The delegates were also worried that future negotiations on such complicated issues may not conclude in just one inter-governmental meeting, especially since so many countries will be involved.

Among the most detailed of the papers submitted at the meeting was a set of documents prepared by Indonesia, which has been one of the leading countries involved in promoting the issue of linking virus contribution with the sharing of benefits. The paper was given to the Chair and the Secretariat.

The Indonesian paper proposed binding and mandatory commitments on benefit sharing as an exchange for the contributing of bird flu viruses.

It proposed that WHO-designated laboratories (which are based in developed countries) should empower and build the capacity of the laboratories from the countries contributing the viruses. The rationale for this is that the best way to deal with a potential pandemic is to develop the capacity of countries (such as Indonesia, Vietnam, China etc) that are most affected by the bird flu, rather than their having to rely on the foreign-based laboratories.

Indonesia also proposed that vaccine manufacturers that wish to obtain the influenza candidate vaccine virus (for vaccine production and development) should be bound to return multilateral benefits to all developing and least developed countries.

Among the proposals are that the vaccine manufacturers that wish to gain from the GISN should: (1) provide non-exclusive royalty-free access to IP-protected technology to domestic manufacturers from developing countries on request; (2) prioritise the supply of vaccines to countries in need at an affordable price, i. e. at a price no higher than cost per unit plus X% (5%) for developing countries and at "no profit no loss" for least developed countries; (3) provide 60% of the production of every batch of vaccines free of charge to the WHO international stockpile of vaccines, in the event of a pandemic.

The paper also called for access to and transfer of technology and know-how to manufacturers from developing and least developed countries.

The Indonesian paper also proposed to keep all influenza viruses contributed by providing countries and all its components including its genes, sequences, and products/substances derived from the influenza viruses (such as diagnostics) or developed from the influenza viruses (such as influenza candidate vaccine virus or vaccines) free of any IP claims.

The paper is in the format of two agreements containing Standard Terms and Conditions (STC) for the contribution of the influenza viruses and sharing of benefits. The first is between the country contributing the virus and the WHO Collaborating Centre/H5 Reference Laboratory which would use the virus for risk assessment and development of candidate vaccine virus.

The second is between the WHO Collaborating Centres and the vaccine manufacturers and is about the transfer of Influenza Candidate Vaccine Virus from the former to the latter for vaccine development and production.

Both STCs are accompanied by an Implementing Letter, which has to be signed by the Provider and the Recipient when the transfer of the Influenza viruses or candidate vaccine virus is made. The Implementing Letter certifies that the parties accept and agree to the Standard Terms and Conditions unmodified.

The agreements are aimed at ensuring that the recipients are bound, in particular, to share the benefits arising from the use of the influenza viruses and/or candidate vaccine virus. Where the recipient or any party to the agreement fails to fulfill its obligation, the agreement can be terminated. There is also provision for a dispute settlement between parties.

In the first STC, the paper proposes that the material contributed only be used for the research purposes specified in the Terms of Reference (which is also to be revised) of the WHO Collaborating Centre and H5 Reference Laboratory.

Material is defined as "Original Material, isolated viruses, progeny and all of their genetic and other components (modified or unmodified), including genes, sequences (and parts thereof) and polynucleotides as well as the polypeptides they encode . It also includes related information."

According to legal experts, it is important to have specific definitions, as there are an increasing number of patent claims applied for by the private sector on little bits and pieces of the viruses, such as pieces of protein.

Research is defined as "non-commercial, scientific use of the Material for global public health purposes as described" in the Terms of Reference.

The first STC proposed by Indonesia also prevents a WHO Collaborating Centre/H5 Reference Laboratory that received Material (as defined above), from distributing or disclosing it to third parties without the consent of the Providing Country as well as on condition that a separate STC is signed wherein the subsequent recipient agrees to abide by the Standard Terms and Conditions.

It also proposed that the Recipient (the WHO Collaborating Centre/H5 Reference Laboratory), the Recipient Scientist and persons working under the Recipient Scientist's direction or his/her direct supervision "shall not seek or assert intellectual property rights or other rights over the Material or on any derived substances, products or any other substances, processes, products including vaccines, anti-virals, diagnostics developed through the use of or that contain/incorporate the Material."

This proposed provision is a response to the increasing number of patent claims on the materials already supplied by providing countries. The paper also wants to keep any products/substances that are derived from the Material or that use the Material free from any IP claims.

The paper also proposes that all gene sequences (of the virus) should be placed in databases that are to be governed by terms and conditions, to ensure that misappropriation, such as patenting of the sequences does not take place. The terms and conditions will also ensure that fair and equitable benefit sharing arising from the use of the sequences will be shared with the developing countries.

In relation to benefit sharing, Indonesia proposes that the Recipient (in this case, the WHO Collaborating Centre/H5 Reference laboratory) "empower and build capacity" of the country providing the virus, in particular, by conducting the research in the facilities of the Provider Country. The Recipient should also allow scientists from the provider countries to participate in its activities.

Regarding the second STC (on the transfer of influenza Candidate Vaccine Virus developed by the WHO Collaborating Centres, using the viruses provided by the Provider Country, to vaccine manufacturers), Indonesia proposed that the Candidate Vaccine Virus only be used for vaccine development and production.

Key elements of the second STC are that the vaccine manufacturer: (1) agrees to keep Material Received in confidence ensuring that any part of it is not transferred, distributed or disclosed to any third party; and (2) that the manufacturer will not seek or assert IPRs or other rights on Material Received (i. e. candidate influenza vaccine virus) or on any derived substances, products or any other substances, processes, products including vaccines, developed through the use of or that contains/incorporates the Material Received (i. e. candidate influenza vaccine virus).

The Indonesia paper also proposed that the vaccine manufacturers agree to the following multilateral benefits:

(I) to grant on request, a non-exclusive, royalty-free license to any domestic influenza vaccine manufacturer from developing and least developed countries to use its intellectual property and other protected substances, products (including technology), know-how, information used in the process of influenza vaccine development and production;

(ii) on request, to allow access to and transfer of, its technology and related know-how particularly to domestic influenza vaccine manufacturers from developing and least developed countries especially to the Providing Country and other countries in need;

(iii) to set aside X% of vaccines for developing and least developed countries especially to those in need and particularly during the pandemic period. These vaccines will be made available at an affordable price for developing countries and least developed countries. The manufacturer, in pricing its products, should consider "affordable price" for developing countries as a price no higher than cost per unit + X% (e. g. 5%), while for least developed countries, as "no profit no loss", particularly during the pandemic period;

(iv) to transfer at least 60% of every production batch of vaccines developed free of charge to the WHO international stockpile prior to commercialization in the event of a pandemic;

(v) to transfer at least 40% of every production batch of vaccines developed free of charge to the WHO international stockpile prior to commercialization during the pre-pandemic period.

Some Indonesian delegates expressed disappointment that many of the paper's important elements, such as its proposed format, elements on IPRs and mandatory benefit sharing elements, were either not featured in the text on STCs presented by the Chair or were featured in a manner that diluted Indonesia's proposed elements.

In fact, the delegates mentioned that despite Indonesia's attempts to insert language from Indonesia's elements into the STC text presented by the Chair, the text failed to reflect these elements.

The controversy over the sharing of avian flu viruses arose when Indonesia earlier this year announced that it would slow down its contribution of influenza viruses because the vaccines (which contain part of the viruses) are too costly for developing countries.

The capacity to do adequate risk assessment of the H5N1 influenza virus is primarily with the WHO-designated laboratories which are based or owned by developed countries.

There is a limited supply of vaccines globally, and production is concentrated in 9 industrialized countries. Many developed countries have already booked supplies of vaccines with manufacturers, in the event of a pandemic, but developing countries are unable to afford to do so.

According to WHO data, the global vaccine production capacity is only 350 million doses, which could rise to 500 million doses at full capacity. 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 a WHO report.

Developing countries have also been anxious about an increasing number of patent claims by the private sector (and even from a WHO-designated laboratory) on many of the viruses and its genes and sequences.

Developing countries, especially those which have already suffered human deaths from the avian flu, are worried that in the event of a pandemic, the limited supply of vaccines are already reserved for developed countries, and little of it may trickle to the developing countries.

They are therefore looking towards a global framework which will better ensure the supply of affordable vaccines to countries on the basis of need, and that transfers vaccine production technology to developing countries.