H5N1: Access to Novel Flu Vaccines for Those Who Contribute to Seed Stock

Voo Teck ChuanAssistant Professor

Centre for Biomedical EthicsYong Loo Lin School of MedicineNational University of Singapore

This case highlights how the global burden of diseases, disparity of resources, and power imbalances contributes to different perspectives and experiences of various stakeholders regarding global public health research, surveillance, data sharing, and the fair distribution of benefit and burden.

• First human case – Hong Kong 1997

• > 800 cases, 16 countries

• > 50% of known infected patients died

• Inefficient human to human transmission

http://wordpress.vermontlaw.edu/

http://www.chp.gov.hk/

Indonesia

March 2006 – H5N1 case cluster (7 confirmed, 1 probable)

Sedyaningsih et al, 2008)

Indonesia

• Limited surveillance capacity; received financial assistance from international agencies primarily for capacity building

• Sent specimens to WHO Global Influenza Surveillance Network (GISN, 1952)

• 116 National Influenza Centers and 4 Collaborating Centers• Does epidemiological and virological surveillance of influenza Recommend vaccine strains for seasonal flu & identify emerging

strains of influenza A virus with pandemic potential Dedicated H5 Laboratory Network to monitor H5N1 (2004)Collaborating Centers provide vaccine seed strains to manufacturers

once the decision is made on which is the likely dominant seasonal strain

http://www.influenzacentre.org/

Incidents Leading to Indonesia’s Decision to Stop Virus Sharing

• Lab results disseminated in international meetings and specimens shared with pharmaceutical companies without acknowledgement and notification of Indonesian government & scientists

• Australian vaccine company approached Indonesian government with offer to sell large quantities of vaccine manufactured using a virus strain provided by Indonesia to WHO GISN

WHO Guidance for the Timely Sharing of Influenza Viruses/Specimens with Potential to Cause Human Influenza Pandemics (March 2005)

“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”

“There will be no further distribution of viruses/specimens outside the network of WHO Reference Laboratories without permission from the originating country/laboratory.”

Indonesia’s “No Vaccine, No Virus” Response

• Aug 2006 – decided not to send specimens to WHO GISN for case confirmation

• Dec 2006 – decided to withhold specimens for surveillance and vaccine development so long as WHO followed the “imperialist GISN” system; insisted on a Material Transfer Agreement if it were to share specimens with WHO GISN

“…Indonesia urgently calls for a new transparent, fair and equitable, international mechanism for virus sharing, aimed at ensuring fair and equitable access to H5N1 vaccines and other benefits, taking into account the needs of developing countries… specifically, that vaccines should be available to all countries at risk of being affected at a minimal price that these countries are able to afford.” (Sedyaningsih et al, 2008)

“”…Indonesia would lead other developing countries, which for a long time had been the victims of the greediness of the people of developed countries in the field of health. With spirit burning in my chest, I determined not to step backwards.” (Supari, 2008)

International Health Regulations 2005

• “to prevent, protect against, control and provide a public health response to the international spread of disease in ways that are commensurate with and restricted to public health risks, and which avoid unnecessary interference with international traffic and trade (article 2)

• Require state parties to notify WHO of events that may constitute a public health emergency of international concern (PHEIC)

human influenza caused by new subtype must be notified.

Public health information: Inclusive of biological sample?

Ethical Questions

• To what extent do countries have to share both public health data and biological specimens with the international community? Related to this, to what extent can states retain sovereignty over biological samples (“viral sovereignty” by appeal to Convention on Biological Diversity) isolated within their territories in the face of a potential pandemic?

• How can the rights of the citizens of the affected countries be protected while at the same time ensuring timely development of vaccines and therapeutics? The system seemed to see developing countries as sources of materials which are then manufactured for the protection of citizens of developed countries.

Ethical Questions• How should governments and scientists of less-resourced

countries be involved in the research and development of pandemic planning? Should there be international mandates that scientists from countries affected by emerging infectious diseases be trained or embedded in teams either in-country or out of country that are working on vaccines and therapeutics?

• If data sharing is for global public health benefit, how should the international community ensure that the benefit is truly global? What are various parties’ (e.g., wealthier nations, NGOs, pharmaceutical companies) ethical obligations towards people in poorer regions vis a vis the people in their own countries of domicile?

Meeting the Challenges• International meetings were convened to promote equitable

and transparent processes of data and benefit sharing Jakarta Declaration on Responsible Practices for Sharing of

Avian Influenza Viruses and Resulting Benefits (Mar 2007)

• In 2011 at the World Health Assembly, a framework was created by which viruses were shared with WHO in return for small amounts of vaccine being reserved for developing countries as well as provisions for compulsory licensing of pandemic vaccines for manufacturers in developing countries.

PANDEMIC INFLUENZA PREPAREDNESS (PIP) FRAMEWORK

• Applies to the sharing of H5N1 and other influenza viruses with human pandemic potential and the sharing of benefits

• “Member States should urge vaccine manufacturers to set aside a portion of each production cycle of pandemic influenza vaccine for use by developing countries” (6.11 Access to pandemic influenza vaccines)

• “Member States should urge influenza vaccine and antiviral manufacturers individually to implement tiered pricing for these vaccines and antivirals. As part of this approach, influenza vaccine and antiviral manufacturers individually should be urged to consider the income level of the country, and negotiate with the national authorities of the recipient country, in arriving at the price to be applied in the private and public markets of each country.” (6.12 Tiered pricing)

PIP FrameworkStandard Materials Transfer Agreement (SMTA) 1

Article 5. Rights and obligations of the RecipientThe Recipient shall actively seek the participation of scientists to the fullest extent possible from originating laboratories and other authorized laboratories, especially those from developing countries, in scientific projects associated with research on clinical specimens and/or influenza virus from their countries and actively engage them in preparation of manuscripts for presentation and publication.

Article 6 Intellectual Property RightsNeither the Provider nor the Recipient should seek to obtain any Intellectual property rights (IPRs) on the Materials.

PIP FrameworkSMTA 2

Non-GISN institutions that receives PIP biological materials from a GISRN laboratory are required to sign an SMTA 2 with WHO.

Key Questions Unanswered

• With the ongoing global disparity in resources as the backdrop, how may the international community create a systematic framework or global operational guidelines for public health data and sample sharing that will be fair to all stakeholders?

• How can the international public health and research communities (re)build trust in an unequal global context?

• What are various ways to promote more equitable access to production of vaccines, diagnostics and therapeutics?

Key Questions Unanswered

• Is obligatory benefit sharing in return for specimen sharing ethical defensible and economically feasible? What systemic, ideological, and cultural changes would be required for such paradigm shift? (e.g., humanitarian or charity-based versus justice-based arguments)

• How can we ensure that discussions about surveillance are not separated from considerations of equitable access to benefits? To what extent should this be ensured?

Case Writers

• Anita Ho, Associate Professor, Centre for Biomedical Ethics, National University of Singapore, Yong Loo Lin School of Medicine, medatsho@nus.edu.sg

•  • Paul Anantharajah Tambyah, Professor, Department of

Medicine National University of Singapore, Yong Loo Lin School of Medicine; Senior Consultant, Division of Infectious Diseases, National University Health System, mdcpat@nus.edu.sg

With thanks to Joseph Millum, NIH ,Department of Bioethics

ReferencesE. R. Sedyaningsih et al. “Towards Mutual Trust, Transparency, and Equity in Virus Sharing Mechanism: The Avian Flu Mechanism”. Ann Acad Med Singapore 2008;37:482-8.

S.F. Supari. It's Time for the World to Change in the Spirit of Dignity, Equity and Transparency. Penerbit Lentera, 2008.

D.P. Fidler. “Negotiating Equitable Access to Influenza Vaccines: Global Health Diplomacy and the Controversies Surrounding Avian Influenza H5N1 and Pandemic Influenza H1N1.”PLOS Med 2010;7:e1000247.

L.O. Gostin, Global Health Law, Harvard University Press, 2014.