Jun 19, 2007 TORONTO (CIDRAP News) The continuing debate over developing countries' ability to afford pandemic-influenza vaccines has produced a disturbing complication: the possibility that Indonesia and other countries affected by H5N1 avian flu will assert legal ownership of the viral isolates on which the vaccines would be based.
The prospect of a territorial or intellectual-property claim on the isolateswhich are used both to track the movement and evolution of the virus and to develop vaccines against itis roiling senior members of the international flu community, who are meeting in Toronto this week at the International Conference on Options for the Control of Influenza. About 1,400 experts from 65 countries are attending.
If such a claim were successfulwhich legal experts say is far from guaranteedit could both disrupt the fragile and relatively low-profit flu vaccine system and potentially threaten the legal standing of other biological products as well.
In speeches and interviews here, international public-health figures are stressing their desire to avoid a confrontation.
"The need to balance the sharing of viruses through global surveillance and the need to make the access to vaccines and those sorts of technologies broadly available should not come as a surprise," Dr. Keiji Fukuda of the World Health Organization's (WHO's) Global Influenza Programme said in a speech yesterday. "We see there is a need to increase the access of the developing world to vaccine."
An ongoing series of international meetings extending into next autumn has been set up in hopes of defusing the situation, Fukuda and other WHO officials said.
"We have some hard things to deal with," Fukuda said in an interview. "We do not know whether we will face a pandemic in a short time or a long time. Given that kind of uncertainty . . . I think there is a real practical want on the part of all of the parties involved not to have a long discussion and to come up with practical solutions."
New twist in an ongoing dispute
The fear of a legal claim that could disrupt flu surveillance and vaccine manufacturing is the latest chapter in a dispute that began late last year when the government of Indonesia withdrew from the 55-year-old system by which flu viruses are shared around the world.
Under that system, which was developed for tracking and controlling seasonal flu and has now been extended to flu strains that could spark a pandemic, viruses are isolated in a country and analyzed to increasing levels of sophistication by a national lab, regional lab, and WHO Influenza Collaborating Centers in Tokyo, Melbourne, London, and the US Centers for Disease Control and Prevention in Atlanta. Gene sequences from the analyses are used to identify emerging strains of flu and then passed free of charge to pharmaceutical companies to be commercialized as vaccines.
Developing countries paid little heed to the system for most of its existence because they do not manufacture vaccine and typically do not vaccinate their populations against seasonal flu. However, the Southeast Asian countries where H5N1 is concentrated have a strong interest in protecting their populations against a potential pandemicbut they would be unable to afford the pandemic-flu vaccines that Northern Hemisphere manufacturers might produce.
Indonesia ceased sending isolates to the WHO at the end of 2006 as a protest, triggering intensive international negotiations. Its government and several other Southeast Asian countries, including Thailand, lodged their objections in front of the WHO's executive board in January, casting the impasse as an issue of human rights and equity.
But at last month's World Health Assembly, the voting gathering of the WHO's 193 member states, the countries restated their case as an issue of sovereignty. A group of more than 20 countries asserted that they retain rights to isolates from their territories under the 1991 International Convention on Biological Diversity, which protects unique genetic resources.
And in a resolution passed by the WHA after almost a week of negotiation, the group asked for international reconsideration of the virus-sharing system, increased investment in developing-world research, and a guarantee of "fair and equitable [vaccine] distribution" as the price of continuing to send isolates to the WHO.
Since then, the WHO has promised to create a stockpile of pandemic vaccines for developing-world use, given contracts to support flu manufacturing in countries that lack the capacity, and set up meetings in August and November to continue to negotiate virus-sharing. Indonesia has meanwhile released only a few isolates.
Defensibility of property claims unclear
It is not clear whether Indonesia and its partners could assert enforceable property rights over isolates from their territories, according to several intellectual-property experts.
Under US law and the voluntary International Patent Cooperation Treaty, natural organisms such as wild-type viruses cannot be patented, said Gerry Norton, PhD, a flu virologist who heads the intellectual-property group at the Philadelphia law firm Fox Rothschild.
"There has to have been an 'act of man' to have changed the thing found in nature," he said. "To be patentable, it has to be new, it has to be useful and it has to be something that didn't exist before."
Moreover, patent laws that protect intellectual property cannot be enforced outside a country's borders, even if the country subscribes to the patent treaty, said Larry S. Millstein, PhD, a molecular biologist and partner with the Washington-area law firm Holland + Knight.
"But they could say you can't export our strains, or they could exert government control over how and when people can handle them within Indonesiaand they could do that by just passing a law, not seeking a patent," he said.
The countries probably can assert a claim to their isolates as real property rather than intellectual property under the Convention on Biological Diversity, said Elizabeth Haanes, PhD, a microbiologist and director in the biotechnology practice of the Washington, DC, law firm Sterne, Kessler, Goldstein & Fox. Article 15 of the Convention specifies that "the authority to determine access to genetic resources rests with the national governments."
However, the United States is not a signatory to the Convention, indicating that it does not consider its provisions binding. The European Union, where most vaccine manufacturers are based, is a signatory to the treaty but has not ratified it.
Experts worry about ripple effects
"A developing-world country's remedy, if their resources were used in the commercial development of vaccine, would probably be through the international courts, but that would be very difficult to enforce," Haanes said. "On the other hand, the countries hold the trump card because they have the virusesand I think they realize that not sharing this material will be bad for them as well as bad for everyone else. Hopefully, there will be a negotiated settlement."
Intellectual property concerns have already touched pandemic-flu vaccine research. The reverse genetics process that mutes H5N1's highly pathogenic aspects, producing a vaccine seed strain that will reproduce in chicken eggs, is owned by MedImmune Inc. That company has agreed to suspend licensing fees during the pandemic-vaccine research phase and will begin charging only when the vaccines go into commercial production.
But the potential effect of Indonesia's property claimregardless of the country's ability to recover in courtis so much wider, and the ripple effect it could trigger so uncertain, that it is provoking significant anxiety in the international flu community.
Doris Bucher, PhD, of New York Medical College, who is attending the Toronto meeting, runs the lab that makes most of the seed strains for seasonal flu vaccine production. The strains are distributed to manufacturers for free. Introducing fees or royalties into the virus-sharing system could have a dramatic effect, she said in an interview: "It would slow down the process. It would raise the price of vaccine," she said.
If rights were asserted over isolates of potentially pandemic strains, they could equally be sought for the seasonal flu strains used to make millions of doses of vaccine each year.
"It does worry me, because it makes the whole thing murkier, and it is difficult enough already," said Dr. John Wood, a conference speaker and principal scientist at the United Kingdom's National Institute of Biological Standards and Control. "It could also spread to seasonal [vaccine], I agree."
May 23 CIDRAP News story "WHO adopts resolution on flu virus sharing"
Feb 6 CIDRAP News story "System for global pandemic vaccine development challenged"
Convention on Biological Diversity