TWN Info Service on Intellectual Property Issues (May17/01)
12 May 2017
Third World Network

WHO R&D Blueprint:  Where’s the Benefit Sharing?
- Lessons from the Pandemic Influenza Preparedness Framework -

By Sangeeta Shashikant
Third World Network
(11 May 2017)

The 70th World Health Assembly that will meet in Geneva from 22 to 31 May is set to consider progress on the World Health Organization’s “Blueprint for research and development preparedness and rapid research response”.

The document is a global strategy aimed at facilitating targeted research and development (R&D) for prioritized pathogens, with the overall goal “to reduce delays between the identification of an outbreak and deployment of effective medical interventions to save lives and minimize socioeconomic disruption”, according to the WHO Secretariat’s report to the World Health Assembly (WHA) contained in document A70/10.

The Blueprint followed the Ebola outbreak in West Africa in the spring of 2014, as well as the current Zika virus epidemic wherein the global health community found itself ill-prepared to cope: there were no vaccines, few diagnostics, and insufficient medical teams and trained responders. 

Hence the overall goal of the R&D Blueprint is to improve emergency preparedness and response for prioritized pathogens which as at January 2017 were the viruses causing  renaviral hemorrhagic fevers (including Lassa Fever), Crimean Congo Haemorrhagic Fever; filoviral diseases (including Ebola and Marburg); Middle East Respiratory Syndrome Coronavirus; other highly pathogenic coronaviral diseases (such as Severe Acute Respiratory Syndrome,Nipah and related henipaviral diseases); Rift Valley Fever; Severe Fever with Thrombocytopenia Syndrome; Zika and any disease identified using the Blueprint’s decision instrument.

A cornerstone of the Blueprint is the sharing of data and samples which the WHO report (A70/10) notes is crucial for informed research and development efforts. In what is almost a repeat of the contents of the R&D Blueprint, the report vaguely lists the multiple activities that have been or will be undertaken in relation to sharing of data and samples, such as:

• an initial expert consultation on data sharing (Geneva, 1-2 September 2015);
• developing global norms for sharing data and results;
• elaborating mechanisms for collaboration and data sharing during public health emergencies;
• initiated a process to reach consensus on principles for open access repositories of biological samples (bio-banks) including the development of a virtual resource linking national bio-banks through an information sharing platform;
• elaboration of principles for a shared system of governance and decision-making;
• development of a Material Transfer Agreement (MTA) capacity-building tool to inform negotiations at country level on sharing biological samples.

What the document also reveals is a patchwork of initiatives often in partnership with different external actors and engagement of selected stakeholders. For instance on 16 December 2016, WHO jointly held with the Institute Pasteur in Paris an informal consultation on developing an MTA guidance tool in preparedness for public health emergencies. The participation list obtained by the author shows engagement predominantly with a select group of entities based in developed countries.

This meeting was preceded by several other similar consultations: First WHO Consultation on biobanking (13 May 2015 in Geneva); Second WHO consultation on biobanking (6-7 August in Sierra Leone); WHO consultation on data sharing (1-2 September 2015); Wellcome Trust meeting on biobanking tools (14 January 2016); Wellcome Trust meeting on intellectual property, sample and data sharing and public healthemergencies (9 May 2016).

The most glaring gap in WHO’s approach to handling of biological samples and data is the absence of a transparent and inclusive intergovernmental process driving the development of appropriate norms and standards in a cohesive manner. 

Almost all WHO Member States are party to the Convention on Biological Diversity (CBD), which entered into force in December 1993, and which recognizes a State’s sovereign right over its natural resources, that access to and use of genetic resources (e.g. any pathogen) is subject to prior informed consent and fair and equitable benefit sharing on mutually agreed terms. The Nagoya Protocol on Access and Benefit Sharing, which entered into force in October 2014, further elaborates on these elements.

Given this, the approach taken by the R&D Blueprint raises concerns and hence important questions such as: how will these fundamental rights of WHO Member States be implemented; what will be the terms for accessing biological samples and related data; what is the mechanism for recording and tracking biological materials that have been shared, who will have ownership over the biological material, how is intellectual property dealt with; what forms of benefit sharing will be realized, and how will it be ensured that such benefit sharing is fair and equitable.

Further, will an assortment of bilateral MTAs (presumably maintained confidentially) withdifferent terms and conditions among different parties be able to secure access to knowledge, technology and affordable treatments arising from the use of the samples and data (e.g. by multinational companies) in a prompt and timely manner during an emergency?   How will such MTAs ensure affordability and timely availability of medical interventions, in particular that the manufacturers will prioritize the needs of the global health community (especially vulnerable or affected communities) over the special interests of particular countries, especially developed countries that often enter into exclusive licenses and advance purchase agreements with manufacturers. 

In addition, what are the rules, systems and mechanisms in place to ensure that the activities of the R&D Blueprint are transparent, accountable, and will deliver and fair and equitable outcomes.

Pathogens & Controversies

Over the years, several controversies over access and benefit sharing for pathogens, patents and other intellectual property, and timely access to affordable medical interventions have erupted.

In 2003, following the outbreak of severe acute respiratory syndrome (SARS), teams of scientists in Canada, Hong Kong, and the United States, brought together by WHO to address the outbreak, filed patent applications on all or part of the SARS virus genome and on the virus itself which were reported to be sufficiently broad to allow their holders to claim rights over most diagnostic tests, drugs, or vaccines that have been or would be developed to cope with the outbreak. Several of the applicants were reported to be in negotiations with commercial partners to develop diagnostic tests and other products.

This prompted WHO to issue a notice in May 2003 stating that it “intends to monitor the effects of patents (and patent applications) on the speed with which SARS diagnostic tests, treatments, and vaccines are developed and made available for use and on the manner in which prices are set for these technologies”, adding that “In the longer term, the manner in which SARS patent rights are pursued could have a profound effect on the willingness of researchers and public health officials to collaborate regarding future outbreaks of new infectious diseases”.

In 2007, another controversy erupted as Indonesia, severely affected by the highly pathogenic H5N1 influenza virus, suspended the sharing those viruses, asserting that the then WHO virus-sharing scheme (Global InfluenzaSurveillance Network - GISN) was “unfair”.  Under this system, affected countries would send influenza virus samples to certain laboratories designated as WHO's Collaborating Centres located in developed countries. These laboratories would characterize the viruses, develop candidate vaccine strains and in violation of WHO guidelines, send viruses to the commercial sector for vaccine development, without the consent of the contributing country. Worse still, the vaccines developed by the private sector using viruses obtained from the GISN were unavailable and/or not affordable for developing countries.

Moreover, patent claims were filed by WHO designated laboratories and companies alike, over influenza viruses and virus parts, i.e. viral gene segments and their sequences, shared in good faith with the GISN by avian influenza affected countries such as Indonesia, Vietnam, China and Thailand.

Thus the GISN virus sharing system had a clear set of winners: the vaccine companies thatgained access to flu viruses, and developed proprietary flu vaccines that are sold at high prices; developed countries that enter into advance purchase agreements with vaccine manufacturers for the supply and stockpile of vaccines, and laboratories in those countries that gain access to flu vaccines, sometimes claiming patents. On the other hand, losers were especially developing countries facing dangerous outbreaks, astronomical bills for the purchase of vaccines and other treatments, and even difficulty in accessing such supplies at all, due to their limited availability. Technologies and know-how used in vaccine development and production are also largely based in developed countries and protected by intellectual property.

In 2014, another dispute exploded, this time over the Middle East Respiratory Syndrome (MERS) as it emerged that Erasmus University in the Netherlands had filed patent applications over the MERS virus which had sent to the Netherlands without permission from the country of origin, Saudi Arabia. An nternational patent application, WO2014045254, claimed the MERS virus as a whole, and its genetic material, particularly the unique variations that differentiate the MERS virus from related viruses and appear to enable it to infect humans. Erasmus’ patent claims then go on to include any MERS diagnostics, as well as use of the virus in a vaccine.

Thus, the WHO Blueprint, if it does not take on board the lessons from such past controversies by ensuring fair and equitable benefitsharing in harmony with the CBD, will run a high risk of repeating past mistakes and generating future controversies.

More recently, several civil society organisations, e.g. Knowledge Ecology International and Médecins Sans Frontières (MSF) have opposed the United States Army’s proposed grant of exclusive royalty bearing licenses to Sanofi Pasteur on the US Army’s pending patent on a Zika vaccine (US applications 62/343,315, “Zika Virus Vaccine and Methods of Production” and 62/370,260, “Zika Vaccine and Methods of Preparation”).

MSF urged the US government to consider the negative impact an exclusive agreement will have on the development, affordability and availability of a Zika vaccine, which is urgently needed for people affected by the Zika virus in the US and worldwide. MSF requested the US government to consider instead granting an open non-exclusive patent license with appropriate and publicly available terms and conditions to help ensure that further development of this US government funded-technology will prioritize all health needs and ensure sustainable and affordable access of any resulting vaccine.

There is no requirement on Sanofi to make the vaccine available at an affordable price and to all that need it, both in the US and other countries.

In its response, the US army rejected the objections, and expressed its intent to grant the exclusive license, expressing belief that market competition among the Zika solutions can fairly determine the availability and market for products.

These disputes point to the need for clear rules in the WHO with regard to use ofpathogens and related data that have been shared and accessed, and securing of fair and equitable benefit sharing that will allow the WHO to promptly respond, in times of emergencies, with adequate supplies of affordable diagnostics, vaccines and treatments. And here lessons may be learned from the Pandemic Influenza Preparedness (PIP) Framework.

Lessons from PIP Framework

The PIP Framework is a historic landmark agreement adopted in May 2011 by the WHA Resolution 64.5 that sets out international rules in the WHO with regard toaccess to influenza viruses of pandemic potential, and fair and equitable sharing of benefits arising from their use. Its adoption was preceded by intense intergovernmental negotiations beginning in 2007.

It emerged from outrage over the WHO’s flu virus sharing scheme, i.e. that the GISN system was inequitable and especially harmful to the interests and needs of developing countries, while its operations were inconsistent with the legal rights of WHO Member States that are also Parties to the CBD.

The Framework overhauled the WHO’s approach to sharing of influenza viruses of pandemic potential (IVPP). For the first time, in the WHO, access to such viruses was linked to access to vaccines and other benefits on an “equal footing”.  The Framework also substituted the WHO GISN scheme with a WHO Global Influenza Surveillance and Response System (also known as “WHO GISRS”).

It set up a transparent traceability mechanism that track in real time the movement of IVPP biological material shared by WHO Members known as the “Influenza Virus Tracking Mechanism” (IVTM).

All sharing of IVPP biological material among WHO-designated GISRS laboratories (e.g. national influenza centres, WHO Collaborating Centres) and with entities outside the GISRS (e.g. pharmaceutical companies) is subject to Standard Material Transfer Agreements (SMTAs), These agreements negotiated by WHO Member States, form part of the Framework.

A specific agreement (SMTA 1) governs the sharing of IVPP biological material among WHO-designated laboratories. This SMTA requires inter alia that the receiving laboratory comply with its Terms of Reference; any shipments of IVPP biological materials be recorded in the tracking mechanism; actively involve scientists from the originating laboratories especially those from developing countries in scientific projects on clinical specimens or the influenza viruses and to actively engage them in preparation of manuscripts for presentation and publication and acknowledge their contributions. SMTA 1 also makes clear that neither the provider nor the recipient laboratory should seek to obtain any intellectual property on the IVPP biological materials.

Another agreement, known as SMTA 2, list benefit-sharing options that non-GISRS entities (e.g. influenza vaccines, diagnostic, pharmaceutical manufacturers, academic institutions) receiving IVPP biological material have to commit to.  The options include donation of real-time pandemic vaccine and/or anti-virals to the WHO; reservation of real time pandemic vaccine and/or anti-virals for supply at affordable prices; and the grant of royalty free licenses to manufacturers in developing countries or to the WHO (which can be sub-licensed), for the production of pandemic influenza vaccines, adjuvants, antivirals products and diagnostics needed in a pandemic.

As at March 2017, the WHO has signed 9 agreements with vaccine and antiviral manufacturers, which according to the WHO provides real-time access to an estimated 400 million doses of pandemic vaccine during the next flu pandemic. However, none of the agreements have yet committed the manufacturers to the technology transfer options.

The WHO has also concluded 50 SMTA 2 with academic and research institutions and received 22 benefit sharing offers. While the specific details of these offers are unknown, according to the WHO, most of these institutions have offered to provide laboratory and surveillance capacity building as a benefit contribution.

In addition to SMTA 2 commitments, influenza vaccine, diagnostic and pharmaceutical manufacturers also have to commit to payment of partnership contribution.

The Framework requires influenza vaccine, diagnostic and pharmaceutical manufacturers to make an annual partnership contribution to the WHO set at “50% of the running costs of the WHO GISRS”, with the understanding that costs may change over time and the partnership contribution will change accordingly. At the point of the Framework’s adoption, these running costs were estimated to be US$56.5 million.

Hence, companies that use the GISRS system (i.e. access the IVPP biological materials and data) are collectively responsible for contributing US$28 million annually. How much each company pays is based on a formula agreed among the industry representatives. As at 31 January 2017, the total partnership contribution collected, beginning from 2012, from 47 contributors amounted to US$117,758,149. Presently 30% of this amount is reserved for response activities in the event of a pandemic, while 70% is allocated for preparedness activities in different regions.

The Framework also builds in certain checks and balances for its implementation. For example, an Advisory Group has been set up to specifically monitor implementation of the PIP Framework, and there is detailed reporting to the Executive Board and the WHA. Information on IVPP biological material shared, SMTAs signed, benefitssecured, partnership contributions collected and spent, is publicly available on the WHO website.

Implementation of the Framework has not been without challenges as has been revealed by the findings of an expert team that reviewed implementation of the Framework in2016. It faces issues such as rapid technological developments, which has brought to the forefront, the importance of treating genetic sequence data in a manner equivalent to viral isolates, its use linked to fair and equitable benefit sharing and other obligations of the Framework.

The same Expert Review team, however, also unequivocally confirms that the Framework is a “bold and innovative tool for pandemic influenza preparedness”, and “its implementation has led to greater confidence and predictability in the global capacity to respond to an influenza pandemic”.

Noteworthy also is the review’s conclusion that “the principle of the Framework of placing virus sharing and benefit sharing on an equal footing remains relevant today,” and that the Framework “is a foundational model of reciprocity for global public health that could be applied to other pathogens”.

On a similar note, the Review Committee on the Role of the International Health Regulations (2005) in the Ebola Outbreak and Response found that a number of State Parties continue to be concerned that data-sharing would not be balanced by benefit-sharing and concluded that the PIP Framework serves as an example of an agreement that facilitates sample and, potentially, gene sequence data-sharing, with benefit-sharing on an equal footing.  Accordingly the Review Committee concluded that the WHO and State Parties should ensure that sharing of samples and sequence data is balanced with benefit-sharing on an equal footing.

WHO Member States are thus faced with a choice.  The continued development of the Blueprint, and so-called “open access” bio-banks for samples and data, without sufficient attention paid to national sovereignty over genetic resources and fair and equitable benefit sharing, will lead tofuture controversies over patents and access to vaccines for developing countries like those that have come before, e.g. with H5N1 influenza.

But instead of repeating past mistakes and reliving past controversies, Member States should ensure that the Blueprint sets clear rules for access to pathogens that include restrictions on intellectual property and requirements for benefit sharing by users that utilize and derive commercial benefit from viral genetic resources (e.g. vaccine companies). These rules uphold the principles and requirements of the CBD and can improve timely access to and affordability of vaccines, diagnostics, and antiviral drugs in developing countries.