Gates Foundation’s Yamada: Principles to Guide Global Allocation of Pandemic Vaccine

Perspective
Poverty, Wealth, and Access to Pandemic Influenza Vaccines
Tadataka Yamada, M.D.

New England Journal of Medicine
Volume 361 — September 17, 2009 — Number 12
http://content.nejm.org/current.shtml

On June 11, 2009, Margaret Chan, director general of the World Health Organization (WHO), declared that the status of the influenza A (H1N1) pandemic had reached phase 6 — active transmission on a global scale. Until now, the case fatality rate of this influenza has been quite low, but history teaches us that the situation could take a turn for the worse during the next wave of the pandemic. If a 1918-like pandemic were to occur today, tens of millions of people could die, the vast majority of them in the world’s poorest countries.

Fortunately, the prospects for developing an effective vaccine to prevent infection with the current H1N1 virus are excellent, and the world’s pharmaceutical companies are working diligently at this task. In contemplating equal access to such a vaccine, it is important to consider three key issues: manufacturing capacity, cost, and delivery.

Only a few countries in the world have plants for manufacturing influenza vaccine, and three companies — GlaxoSmithKline, Sanofi-Aventis, and Novartis — account for most of the world’s manufacturing capacity. The number of doses of vaccine against H1N1 influenza that could be produced with the existing capacity is very large, but the sobering truth is that even if production were switched over completely from seasonal influenza vaccine to pandemic influenza vaccine, there would not be nearly enough for everyone in the world. The size of the gap in potential supply depends greatly on the dose that is required, and it may be possible to reduce the necessary dose by as much as 75% with the use of an adjuvant. The challenging problem is that much, if not most, of the manufacturing capacity is already spoken for through purchasing contracts held by many of the world’s wealthy countries.

The second issue is cost. Despite the enormous technological investment required to create a vaccine, the traditional cost of seasonal influenza vaccines even in wealthy countries is quite low. For the pandemic H1N1 influenza vaccine, the major manufacturers have indicated a willingness to offer tiered pricing, with affordable prices for poor countries. Going even further, Sanofi-Aventis has committed to donating 100 million doses of its vaccine to a stockpile for poor countries, and GlaxoSmithKline has committed to donating 50 million doses. Nevertheless, financial commitments from wealthy countries will be needed to help poorer countries purchase vaccines — cost should not be a barrier to access.

Finally, the scope of access to vaccines will in part be determined by the infrastructure required to deliver them to all citizens in mass campaigns. Ironically, poor countries may have an advantage on this front, since many have recent experience with mass campaigns involving vaccines against polio, measles, and hepatitis B; delivery may therefore be less of a challenge for them, provided that the vaccines reach them in a timely fashion. By contrast, in many wealthier countries, such campaigns have not been undertaken for some time. Getting the vaccine to large numbers of young adults, in particular, may be a formidable task for which preparations must surely be made as soon as possible.

Our limited capacity for producing potentially lifesaving vaccines presents a pressing moral challenge. I believe wholeheartedly that all lives have equal value (this is the basic principle motivating the Bill and Melinda Gates Foundation, where I work), and I believe that every stakeholder has a responsibility to ensure that the pandemic does not take a 1918-like toll on the world. We have therefore worked with partner stakeholders to develop a proposed set of principles to guide the global allocation of pandemic vaccine (see Principles to Guide Global Allocation of Pandemic Vaccine below).

Rich countries have a responsibility to stand in line and receive their vaccine allotments alongside poor countries, even if they have paid for their vaccine before others could do so. It would be inexcusable to force poor countries to wait until the rich have been served under their existing contracts with vaccine manufacturers. Moreover, rich countries must also consider how they can provide contributions to offset the cost of vaccines for countries that cannot afford to pay for them. Countries that are home to influenza-vaccine manufacturing plants have a special responsibility to avoid nationalizing those facilities in an effort to reserve their output for their own citizens before others. And all countries must prepare now for the rapid delivery of the vaccines as soon as they become available.

Manufacturers have a responsibility to apply their full capabilities to creating the greatest possible quantity of vaccine doses. Despite contractual obligations to supply many wealthy countries with their vaccines, manufacturers must resist the temptation to commit all their capacity to those who can pay the most. This is not a time to adhere to the “first come, first served” model of business, since we may be facing a health crisis of global proportions in which all people and countries are equally at risk. To ensure fairness, full adherence to a tiered pricing scheme in which the cost to the purchaser is proportionate to its ability to pay is essential. The generous donations made by Sanofi-Aventis and GlaxoSmithKline set an example that all manufacturers should emulate. In return for their responsible actions, it would be reasonable for manufacturers to be indemnified against liability from potential adverse reactions to their vaccines.

Regulatory agencies have an important responsibility in this impending crisis because they stand between the manufacturers of pandemic influenza vaccines and the people who will benefit from them. It is critically important that regulators apply their usual rigorous standards in approving the new vaccines — but also that they do so in a timely fashion. A special task facing them is the rapid review and consideration of the safety and efficacy of adjuvants, whose use could greatly reduce the required dose of vaccine and thereby expand the number of doses that could be manufactured.

The WHO has provided strong leadership as the world has contemplated the prospect of an influenza pandemic. We are counting on the organization to guide us, wisely and fairly, through the complex challenges that lie ahead.

The prospect of a worsening global influenza pandemic is real and will not go away anytime soon. I cannot imagine standing by and watching if, at the time of crisis, the rich live and the poor die. It will take collective commitment and action by all of us to prevent this from happening.

Principles to Guide Global Allocation of Pandemic Vaccine.

1. The global community should take steps to protect all populations, including those without resources to protect themselves.

2. Vaccination should be considered in the context of comprehensive pandemic preparedness and response efforts in all nations.

3. Developed countries and vaccine manufacturers should urgently agree upon a mechanism to ensure access to vaccine by developing countries.

4. Influenza vaccine manufacturers should identify strategies such as tiered pricing and donations to make pandemic vaccine more accessible to developing nations.

5. Pandemic vaccines allocated to developing nations should become available in the same time frame as vaccines for developed nations.

6. The global community should obtain data to help establish a consensus on the safety and efficacy of adjuvants, and efforts should be made to ensure the fullest use of this and other dose-sparing strategies.

7. All countries obtaining pandemic vaccine should ensure that mechanisms are in place to provide the vaccine to their populations, to ensure that this scarce resource is not wasted, and donors should be prepared to provide resources and technical assistance to help countries bolster these mechanisms.

8. The World Health Organization is uniquely positioned to lead the global response to a pandemic virus and should support governments and industry in their efforts to implement these principles.

* From the Pneumonia and Flu Web site of the Bill and Melinda Gates Foundation (www.gatesfoundation.org/topics/Pages/pneumonia-flu.aspx).

Dr. Yamada reports holding equity in GlaxoSmithKline. No other potential conflict of interest relevant to this article was reported.

President Obama Announces H1N1 Pandemic Vaccine Donation

September 17, 2009

President Announces Plan to Expand Fight Against Global H1N1 Pandemic

Today, President Obama announced the United States will continue to act aggressively to stop the global spread of the pandemic 2009-H1N1 influenza virus and is prepared to make 10 percent of its H1N1 vaccine supply available to other countries through the World Health Organization (WHO). In recognition that diseases know no borders and that the health of the American people is inseparable from the health of people around the world, the United States is taking this action in concert with Australia, Brazil, France, Italy, New Zealand, Norway, Switzerland, and the United Kingdom. The United States will make the H1N1 vaccine available to the WHO on a rolling basis as vaccine supplies become available, in order to assist countries that will not otherwise have direct access to the vaccine.

This week, the Food and Drug Administration officially licensed the 2009-H1N1 influenza vaccine. Last week, the Department of Health and Human Services and the National Institutes of Health announced that one dose of the vaccine – instead of two doses – will be effective in developing immunity in most adults, and HHS Secretary Sebelius announced the vaccine would be available in the coming weeks, earlier than originally anticipated. We remain confident that the United States will have sufficient doses of the vaccine to ensure that every American who wants a vaccine is able to receive one. We continue to recommend that early priority at home and abroad should be given to pregnant women, health care workers, individuals caring for infants less than 6 months of age, and other high-risk populations.

There is broad international recognition that the 2009-H1N1 pandemic presents a global health risk. Millions of people around the world have been affected, thousands have died and the virus continues to spread across international borders. The United States recognizes that just as this challenge transcends borders, so must our response.      We invite other nations to join in this urgent global health effort. Working together, we can ensure that this vaccine limits the spread of the disease, reduces the burden on health care systems, reduces the risk of an even more virulent strain emerging and, most importantly, saves lives—in the United States and around the world.

http://www.whitehouse.gov/the_press_office/President-Announces-Plan-to-Expand-Fight-Against-Global-H1N1-Pandemic/

WHO Director-General Dr Margaret Chan on pandemic vaccine donations for the developing world

18 September 2009

Statement by WHO Director-General Dr Margaret Chan on Pandemic vaccine donations for the developing world

WHO applauds and welcomes the announcement of donations of pandemic vaccine made today by the United States of America, in concert with Australia, Brazil, France, Italy, New Zealand, Norway, Switzerland, and the United Kingdom.

The announcement demonstrates the commitment of these countries to fairness in sharing of scarce resources as the 2009 H1N1 influenza pandemic continues to evolve.

Current supplies of pandemic vaccine are inadequate for a world population in which virtually everyone is susceptible to infection by a new and readily contagious virus.

Given that current demand outstrips supply, these donations, together with the doses pledged by manufacturers, will help increase supplies of pandemic vaccines to populations that would otherwise not have access.

WHO continues to support developing countries to ensure donated vaccines are distributed where they are most needed. http://www.who.int/mediacentre/news/statements/2009/pandemic_vaccine_donations_20090918/en/index.html

Gates Foundation Statement on H1N1 Vaccine Donations to Developing Countries

September 18, 2009

Gates Foundation Statement on Global Agreement to Supply H1N1 Vaccine to Developing Countries by Dr. Tachi Yamada, president of the Global Health Program of the Bill & Melinda Gates Foundation.

We heartily applaud the commitment by nine nations to donate a portion of their H1N1 vaccine supply on a rolling basis to the World Health Organization for distribution to countries that would otherwise not have direct access.
Australia, Brazil, France, Italy, New Zealand, Norway, Switzerland, the United Kingdom, and the United States have all shown tremendous leadership. Wealthier countries have an obligation to ensure more equitable access to vaccines in this global pandemic. This issue is surely one of the most pressing moral challenges of our time.
This announcement underscores the interdependency of all people when it comes to matters of health. As important as the announced generosity is, we must keep in mind that the needs are great, and more must be done to ensure that all nations have access to vaccines and other tools.
We understand that these are hard decisions to make right now. We hope and expect that more nations will join this effort.”

http://www.gatesfoundation.org/press-releases/Pages/gates-foundation-statement-on-global-agreement-h1n1-vaccine-090918.aspx

Pandemic (H1N1) 2009 – update 66: 18 September 2009

The WHO continues to issue weekly “updates” and briefing notes as below:
Pandemic (H1N1) 2009 – update 66: 18 September 2009

Weekly update
In the temperate regions* of the northern hemisphere, influenza activity remains widely variable. In North America, the United States is reporting increases in influenza-like-illness activity above the seasonal baseline, most notably in the southern, southeastern, and parts of the northeastern United States.

In Canada, influenza activity remains low. In Europe and Central Asia influenza activity remains low overall, except in France, which is reporting increases in influenza-like-illness activity (for week 37) above the seasonal epidemic threshold. Geographically localized influenza activity is being reported in several countries (Austria, Georgia, Ireland, Luxembourg, Norway, Portugal, the Czech Republic, Cyprus, and Israel). In Japan, influenza activity remains stably increased above the seasonal epidemic threshold with the most notable increases being reported on the southern island of Okinawa.

In the tropical regions of the Americas and Asia, influenza transmission remains active. Geographically regional to widespread influenza activity continues to be reported throughout much of South and Southeast Asia, with increasing trends in respiratory diseases being reported in India and Bangladesh. Geographically regional to widespread influenza activity continues to be reported for the tropical regions of Central and South America without a consistent pattern in the trend of respiratory diseases (continued increases are being reported in Bolivia and Venezuela).

In the temperate regions* of the southern hemisphere, influenza activity continues to decrease or has returned to the seasonal baseline in most countries. In Australia, later affected areas are also now reporting declining levels of influenza-like-illness. In South Africa, influenza activity appears to have recently passed over the second peak (the first peak was due to seasonal influenza A (H3N2) and second peak was due to pandemic (H1N1) 2009).

WHO Collaborating Centres and other laboratories continue to report sporadic isolates of oseltamivir resistant influenza virus. Twenty six such virus isolates have now been described from around the world, all of which carry the same H275Y mutation that confers resistance to the antiviral oseltamivir but not to the antiviral zanamivir. Of these, 12 have been associated with post-exposure prophylaxis, five with long term oseltamivir treatment in patients with immunosuppression. Worldwide, over 10,000 clinical samples and isolates of the pandemic (H1N1) 2009 virus have been tested and found to be sensitive to oseltamivir. WHO will continue to monitor the situation closely in collaboration with its partners.

Pandemic (H1N1) influenza virus continues to be the predominant circulating influenza virus, both in the northern and southern hemisphere. See below for detailed laboratory surveillance update.

*Countries in temperate regions are defined as those north of the Tropic of Cancer or south of the Tropic of Capricorn, while countries in tropical regions are defined as those between these two latitudes.

Weekly update (Virological surveillance data)

http://www.who.int/csr/don/2009_09_18/en/index.html

FDA approves four vaccines against 2009 H1N1 influenza virus

The U.S. Food and Drug Administration approved four vaccines against the 2009 H1N1 influenza virus. The vaccines are made by CSL Limited, MedImmune LLC, Novartis Vaccines and Diagnostics Limited, and sanofi pasteur. All four firms manufacture the H1N1 vaccines using the same processes. Jesse Goodman, M.D., FDA acting chief scientist, commented, “The H1N1 vaccines approved today undergo the same rigorous FDA manufacturing oversight, product quality testing and lot release procedures that apply to seasonal influenza vaccines.” The FDA said that, as with the seasonal influenza vaccines, the 2009 H1N1 vaccines are being produced in formulations that contain thimerosal, a mercury-containing preservative, and in formulations that do not contain thimerosal.

http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm182399.htm

Wellcome Trust and Merck form MSD Wellcome Trust Hilleman Laboratories

The Wellcome Trust and Merck announced the creation of the MSD Wellcome Trust Hilleman Laboratories (www.hillemanlaboratories.in), described as “the first of its kind research and development joint venture with a not-for-profit mission to focus on developing affordable vaccines to prevent diseases that commonly affect low-income countries.” The joint venture “marks the first time a research charity and a pharmaceutical company have partnered to form a separate entity with equally shared funding and decision-making rights. Pairing two of the world’s preeminent healthcare institutions provides an opportunity to integrate the best of both to drive the investment and expertise needed to develop and deliver vaccines to low-income countries.”

The organizations described the vision as “a sustainable, not-for-profit operating model to turn innovative science into practical solutions for those in greatest need.”

The new Hilleman Laboratories “will also work on optimizing existing vaccines, an important and powerful way of increasing the impact of vaccination in resource-limited settings. By working in partnership, the Wellcome Trust and Merck seek to achieve what neither can do alone.”

Merck and the Wellcome Trust will invest equally in the R&D joint venture, which will be primed with a combined cash contribution of 90 million GBP (approximately US$130 million) over the next seven years, and will support a staff of approximately 60 researchers and developers. The venture will be based in India to facilitate engagement and partnership with a broad range of experts in vaccine research, policy and manufacturing to develop and mature its R&D pipeline. The Hilleman Laboratories will work to advance projects to ‘proof of concept’ by providing key expertise in product development and optimization that is typically available only within large vaccine companies. The Hilleman Laboratories will also work with vaccine manufacturers to ensure production can be scaled and that the vaccines are affordable. Through this model, the Hilleman Laboratories “will help deliver vaccines to registration that are specifically designed to meet the needs and practical realities in developing countries.”

Altaf A. Lal, Ph.D., was named CEO of the Hilleman Laboratories. Dr. Lal spent 20 years working for the National Center for Infectious Diseases at the U.S. Centers for Disease Control and Prevention (CDC) and was the Chief of the Molecular Vaccine Section in the Division of Parasitic Diseases. Dr. Lal is currently Health Attaché and Department of Health and Human Services Regional Representative for South Asia at the Embassy of the United States of America, New Delhi, India. His extensive experience in global public health gives him the expertise needed to lead this new public-private research partnership.

http://www.businesswire.com/portal/site/home/permalink/?ndmViewId=news_view&newsId=20090917005186&newsLang=en