ASIL Insights

 

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On October 5, 2004, the United States lost half of its anticipated influenza vaccine supply when the United Kingdom suspended the manufacturing license of the Liverpool, England facility of California-based Chiron Corporation. Chiron was to produce between 46-48 million doses of influenza vaccine for the United States. [1] The U.K. government stopped production because it identified bacterial contamination in vaccine doses. [2] This development triggered a crisis for U.S. federal and state public health officials, who are trying to direct the remaining supply of influenza vaccine to people most in need. [3]   Events like this, involving influenza vaccine supplies, raise potential issues under international law.  

Global Fears Concerning Influenza and the Importance of Vaccines  

Influenza poses a public health problem for developed and developing countries. Influenza annually kills approximately 36,000 people in the United States and between 250,000 and 500,000 worldwide. [4] In addition to the seasonal threat, health officials have warned about the emergence of a pandemic of virulent influenza that could kill millions worldwide. [5] The 2004 epidemic of avian influenza A (H5N1) in Asia again rang alarms about the dangers influenza poses to global public health. [6] As the Director of the U.S. Centers for Disease Control and Prevention put it, "A time bomb is ticking." [7]  

Vaccines are one of the most effective and cost-efficient interventions against influenza. [8] As a result, public health experts advocate greater vaccine use in all regions of the world. In the absence of adequate supplies, governments would have to ration vaccine, bear the increased costs and burdens of treating influenza patients in health care facilities, and perhaps utilize non-medical interventions (e.g., isolation of patients and increasing "social distance" by suspending public gatherings and schools).  

According to the World Health Organization (WHO), current global manufacturing capacity for influenza vaccines "is finite and inadequate." [9] Over 90% of world production of influenza vaccines is located in North American and Europe, home to less than 10% of the world's population. [10] This situation creates problems for maintaining or increasing vaccine use to address seasonal epidemics and represents a dangerous context in the event of pandemic influenza. The crisis in the United States caused by the suspension of Chiron's license demonstrates the fragility of global vaccine production capabilities even for developed countries. [11]  

Influenza and International Law  

Historically, international law norms and processes created directly for control of infectious diseases did not apply to influenza. The main international legal framework for infectious disease control, the International Health Regulations (IHR), originally promulgated by WHO in 1951, has never included influenza as a disease subject to its rules. Instead, WHO established in 1952 a WHO Influenza Surveillance Network to identify influenza strains that would most likely spread in the next influenza season. The identified strains then become the basis for the production of influenza vaccines by pharmaceutical companies.  

Concerns about the inadequacy of global vaccine production capacities for seasonal epidemics or a pandemic have stimulated proposals for building a global regime to ensure increased vaccine supplies, more stable vaccine production, and more equitable distribution of vaccines in time of need.  As a result, issues are raised that implicate international law. These issues divide into measures to increase global vaccine supplies and responses to influenza epidemics or pandemics when vaccine supplies are inadequate.  

Increasing global vaccine supplies  

Public health experts have warned for years that efforts to increase the scale and stability of influenza vaccine production are needed. Presently, global "manufacturing capacity is sufficient to cover less than 5% of the world's population." [12] Increasing vaccine supplies involves action at the national level to increase demand for influenza vaccines (e.g., by educating people of the importance of vaccination) and incentives for more pharmaceutical companies to produce vaccines (e.g., reducing the costs companies have to bear from regulatory approvals and vaccine-related lawsuits).  Many experts believe, however, that ad hoc, uncoordinated national efforts will not adequately address the problem. Thus, a global strategy is required.  

Through binding and non-binding international instruments, the tasks of increasing and stabilizing global vaccine supplies have to address a number of challenges, which include:  

. Greater incentives for pharmaceutical companies to manufacture more influenza vaccine are needed, which could involve commitments to increase national demand through vaccine awareness campaigns and to contribute to regional [13] or global [14] influenza vaccine purchasing funds. Boosting demand and providing credible, stable purchasing commitments would increase the financial attractiveness of influenza vaccine manufacturing to existing pharmaceutical companies and perhaps attract new manufacturers to the market.  

. According to WHO, increasing the number of vaccine manufacturers, particularly in the developing world, will require "[a] global approach to the sharing of intellectual property rights." [15]   Formal or informal international instruments would be needed to create global access to patented technologies that are important to new ways to develop vaccines, such as reverse genetics.  

. Internationally coordinated research and development efforts are needed to advance vaccine-production methods from current egg-based techniques to more modern approaches, such as cell-culture technology, that may shorten production times, increase doses produced, and reduce manufacturing costs.    

. Global harmonization of biosafety requirements for vaccine development and manufacture will facilitate safer and more rapid vaccine production, particularly when influenza creates public health crises, as would occur with pandemic influenza.  

The construction of a global regime to increase and stabilize influenza vaccine production would be an unprecedented public health undertaking. Non-binding instruments, such as WHO recommendations, may suffice for encouraging countries to increase national demand for influenza vaccine. [16]   But creating purchase funds, establishing a global approach to intellectual property issues, and harmonizing biosafety regulations involve tasks that might require the negotiation of treaties at regional and/or international levels. [17] Increasing global vaccine supplies would also face political and economic obstacles, including competition for attention and resources created by other infectious disease problems, such as fighting HIV/AIDS and defending against bioterrorism.  

Responding to influenza when vaccine supplies are inadequate  

Public health officials stress the importance of countries preparing for influenza epidemics and pandemics when vaccine supplies are insufficient. Responding to influenza epidemics or pandemics in the context of vaccine shortages implicates international law in various ways.  

Influenza vaccine shortages and the revision of the IHR  

In November 2004, intergovernmental negotiations will begin on WHO's proposed revision of the IHR. [18] WHO has proposed changes to the international legal framework on infectious disease control that would bring serious influenza epidemics or pandemics within the scope of the new rules. WHO's proposal includes authority for WHO to issue recommendations with respect to public health emergencies of international concern. [19] Disruption or shortages of influenza vaccine during seasonal epidemics or pandemics could contribute to, or itself constitute, a public health emergency of international concern, triggering WHO's recommendatory authority on what measures WHO member states should take to address the consequences of restricted vaccine supplies.  

Further, the IHR revision would obligate WHO member states to develop and maintain adequate public health capabilities to identify and address public health emergencies of international concern; [20] these obligations would cover epidemic and pandemic influenza preparedness and response capacities. Failure to engage in influenza planning, particularly for scenarios when vaccine supplies might be scarce, could constitute a breach of obligations under the revised IHR.  

Exchange of information concerning influenza vaccine production problems  

According to the U.S. Food and Drug Administration, the U.K. government's suspension of Chiron's manufacturing license came as a surprise. [21] The U.K. government acted to locate other sources of vaccine supplies before it suspended Chiron's license. [22]   Advance notice of the seriousness of the problems at Chiron's facilities may have provided the U.S. government more time to craft a strategy for addressing influenza with reduced vaccine supplies. Establishing procedures to facilitate improved information flows between vaccine-exporting and vaccine-importing countries through non-binding memoranda of understanding or binding agreements could enhance importing countries' efforts to address vaccine shortages caused by production-related problems. [23]  

Vaccine rationing among countries when shortages occur  

International public health experts are worried that influenza vaccine shortages may trigger a process of rationing supplies among countries that is inequitable, particularly for developing countries that have no vaccine production facilities. In the context of pandemic influenza, WHO has warned that "[c]ountries without manufacturing capability will face the most acute vaccine shortages, as countries with manufacturing capacity can be expected to reserve scarce supplies for their own populations." [24]   Agreements or arrangements between vaccine-exporting countries and vaccine-importing countries may be needed to ensure that, in contexts of vaccine shortages, rationing of available stocks takes into account the needs of all affected nations, not just those states in whose territory production facilities are located.  

Shortages, or the threat of pandemic influenza, may force governments to nationalize foreign-owned manufacturing facilities in their territories, [25] perhaps triggering consequences under expropriation provisions of regional or bilateral investment treaties.  

Vaccine shortages may cause other transnational effects that potentially implicate international law. Some U.S. citizens have attempted to obtain influenza vaccine in Canada; many have been turned away because they are not Canadian residents, without regard to whether they may be more in need of the vaccine than many Canadians. [26] Vermont asked the Province of Quebec whether it could supply Vermont with some vaccine because of the shortage in the United States, and Quebec responded that such an arrangement would have to be negotiated between the two federal governments. [27] This situation raises the question whether countries should negotiate arrangements under which vaccine supplies are shared in situations of unexpected shortages to ensure that people most in need get vaccinated. [28]  

Vaccine rationing among individuals within states  

The suspension of Chiron's manufacturing license forced the United States to devise a strategy under which the available vaccine is directed toward those most at risk from influenza. In countries that recognize the international human right to health (e.g., states parties to the International Covenant on Economic, Social, and Cultural Rights), rationing could implicate this right because it might impede the prevention of epidemic disease by restricting access to vaccine. [29]   Moreover, distribution of scarce vaccine supplies would need to comply with internationally-recognized disciplines applicable to the right to health. [30]  

Depending on the shortage's severity, governments may need to seize vaccine supplies owned by private entities (e.g., pharmaceutical companies, vaccine distributors, or health care facilities) in order to distribute vaccine effectively to those most in need. Government takings of privately owned vaccine supplies would implicate the international human right to property in jurisdictions recognizing the right [31] because the takings would deprive owners of their property. The right to property does not preclude government seizures of vaccine supplies, but it would require public-interest seizures to follow legally prescribed procedures and could trigger a government's duty to compensate affected property owners. [32] Tension between rationing and human rights could also appear in connection with limited supplies of anti-virals used to treat sick patients. [33]  

Vaccine shortages may also force governments to utilize non-medical interventions that have human rights implications, including measures to increase "social distance" (e.g., closing schools and suspending public events), restrict travel, or prevent infected persons from transmitting the virus (e.g., confinement or isolation).  

Conclusion  

Some experts have described the disruption of the supply of influenza vaccine to the United States in October 2004 as a "wake up call" [34] concerning the fragility of influenza vaccine supplies, the vulnerability of strong and weak countries to the inadequate nature of global influenza vaccine production, and the dangerous lack of preparedness in many countries concerning the prospect of pandemic influenza. Whether governments take this "wake up call" seriously remains to be seen.  

About the author:

David P. Fidler is Professor of Law and Harry T. Ice Faculty Fellow at Indiana University School of Law, Bloomington and Senior Scholar at the Center for Law and the Public's Health at Georgetown and Johns Hopkins Universities.  

[1] David Brown, Half of U.S. Flu Vaccine Withheld; Supply Due from British Firm Tainted, Washington Post, Oct. 6, 2004, at A01.

[2] Id.

[3] See U.S. Centers for Disease Control and Prevention, 2004-05 Flu Vaccine Shortage, at www.cdc.gov/flu/protect/vaccineshortage.htm; and U.S. Centers for Disease Control and Prevention, Fact Sheet: 2004-05 Flu Vaccine Shortage: Who Should Get Vaccinated, Oct. 7, 2004.

[4] Jeanne Whalen, Betsy McKay, and Sarah Lueck, U.S. Flu Vaccines Face Rationing as Plant is Shut, Wall Street Journal, Oct. 6, 2004, at A1.

[5] World Health Organization, Pandemic Preparedness, at www.who.int/csr/disease/influenza/pandemic/en/ (“In the past, new [influenza] strains have generated pandemics causing high death rates and great social disruption. In the 20^th century, the greatest influenza pandemic occurred in 1918-1919 and caused an estimated 40-50 million deaths world wide. Although health care has improved in the last decades, epidemiological models from the Centers for Disease Control and Prevention, Atlanta, USA project that today a pandemic is likely to result in 2 to 7.4 million deaths globally.”)

[6] World Health Organization, WHO Consultation on Priority Public Health Interventions Before and During an Influenza Pandemic, 16-18 March 2004 (WHO: Geneva, 2004), at 1 (noting that one of the most important dangers arising from the avian influenza outbreak in Asia “is the risk that conditions present in Asia could give rise to an influenza pandemic.”) For a previous Insight on avian influenza, see David P. Fidler, Global Outbreak of Avian Influenza A (H5N1) and International Law, January 2004, at www.asil.org/insights/insigh125.htm.

[7] Bernard Wysocki, Jr. and Betsy McKay, Flu-Vaccine Shortage Signals U.S. Vulnerability to Pandemic, Wall Street Journal, Oct. 8, 2004, at B1.

[8] “Vaccines are the single most important intervention for preventing influenza-associated morbidity and mortality during both seasonal epidemics and pandemics.” WHO, supra note 6, at 41.

[9] Id.

[10] Id.

[11] David Brown, Fixing Vaccine Supply System; Task Will Not Be Easy, Say Health and Drug Industry Officials, Washington Post, Oct. 9, 2004, at A05 (quoting Julie Gerberding, Director of the U.S. Centers for Disease Control and Prevention: “We continue to have a completely fragile vaccine production system in this country—and it is getting more fragile daily.”).

[12] WHO, supra note 6, at 37.

[13] “One example of a regional purchasing scheme is a revolving fund maintained by PAHO [Pan American Health Organization] for bulk purchasing of influenza vaccines, with local filling, for some Latin American countries.” Id. at 40.

[14] Influenza expert David S. Fedson raised the possibility of creating a “Global Influenza Vaccine Fund . . . to facilitate multinational vaccine purchases and distribution, especially for countries with limited resources.” David S. Fedson, Pandemic Influenza and the Global Vaccine Supply, 36 Clinical Infectious Diseases 1552, 1561 (2003).

[15] WHO, supra note 6, at 39.

[16] See, e.g., World Health Assembly, Prevention and Control of Influenza Pandemics and Annual Epidemics, WHA56.19, May 2003, at ¶1 (urging WHO member states to increase vaccination coverage of all people at high risk).

[17] Fedson also raised the potential need for the negotiation of a WHO Framework Convention for Influenza Pandemic Preparedness and Vaccine Supply. Fedson, supra note 14, at 1561.

[18] See David P. Fidler, Revision of the World Health Organization’s International Health Regulations, ASIL Insight, April 2004, at www.asil.org/insights/insigh132.htm.

[19] World Health Organization, Review and Approval of Proposed Amendments to the International Health Regulations: Draft Revision, A/IHR/IGWG/3, Sept. 30, 2004, Article 13.

[20] Id. at Article 4.1 (“Each State Party shall develop, as soon as possible but no later than five years from the date of entry into force of these Regulations for that State Party, the capacity to detect, assess, notify and report events in accordance with these Regulations, as specified in Annex 1.”) and Article 11.1 (“Each State Party shall develop, as soon as possible but no later than five years from the date of entry into force of these Regulations for that State Party, the capacity to respond promptly and effectively to public health threats and public health emergencies of international concern as set out in Annex 1.”).

[21] Whalen, McKay, and Lueck, supra note 4, at A1; Jeanne Whalen, Sarah Lueck, and Besty McKay, Closing of Flu-Vaccine Plant by British Regulators Took Chiron, U.S. by Surprise, Wall Street Journal, Oct. 7, 2004, at B1; Glenn Frankel and Glenda Cooper, Britain: U.S. Told of Vaccine Shortage; Flu Shot Records Contradict FDA, Washington Post, Oct. 9, 2004, at A01; Sarah Lueck and Pui-Wing Tam, U.S. Uncovered Problems at Chiron Plant in 2003, Wall Street Journal, Oct. 11, 2004, at A3; Rob Stein, FDA Denies It Had Alert on Flu Vaccine, Washington Post, Oct. 12, 2004, at A03; Betsy McKay and Sarah Lueck, Florida Sues Flu-Vaccine Supplier, Wall Street Journal, Oct. 14, 2004, at A3.

[22] Frankel and Cooper, supra note 21, at A01.

[23] Stein, supra note 21, at A03 (quoting FDA acting commissioner Lester M. Crawford: “We do not have a data-sharing agreement [with the British] . . . that would tend to force them to inform us of this kind of thing.”).

[24] WHO, supra note 6, at 41. See also Wysocki and McKay, supra note 7, at B1 (quoting Chiron executive warning a U.S. Senate subcommittee that the United Kingdom could require Chiron to fulfill U.K. vaccine needs first followed by vaccine needs in Europe before vaccine would be made available to the rest of the world).

[25] WHO has stated that “while governments are not urged to nationalize manufacturing capacity during a pandemic, governments are likely to face great pressure to do so.” WHO, supra note 6, at 40.

[26] Graeme Smith and David Ebner, Canada Shuts Out Vaccine Seekers: Demand from U.S. Prompts Provinces to Implement Restrictions for Flu Shots, Toronto Globe and Mail, Oct. 16, at A1.

[27] Id.

[28] The Associate Medical Officer of Health for the Niagara Region observed that “[t]he lessons of SARS and other recent outbreaks have been that viruses can pass quickly across political boundaries . . . so the best way to protect Ontarians would be to share vaccines with the most needy people on the other side of the Niagara River.” Id.

Addendum: Conclusions from Influenza Vaccine Summit

By David P. Fidler

November 2004

In response to growing concerns about the inadequacy of global capabilities to produce a vaccine for an influenza pandemic, the World Health Organization (WHO) hosted on November 11-12, 2004, a meeting involving influenza vaccine manufacturers, national licensing agencies, and governmental representatives to discuss influenza pandemic vaccines. The participating experts agreed that “[a]n influenza pandemic, when it arrives, will be an immediate threat to the health of nearly everyone on Earth, but very little is being done to prevent its potential devastation[.]” The main objectives of the meeting were to review the existing capabilities for producing vaccine for pandemic influenza, identify the obstacles to developing a vaccine for an influenza pandemic, and formulate solutions to such problems.

According to WHO, participants agreed that the threat of pandemic influenza was real and growing, but that the existing structure and dynamics of influenza vaccine development and manufacturing are inadequate to respond to the emergence of pandemic influenza. The participants identified as pressing concerns the need for: good scientific data on pandemic vaccine formulation; studies to determine the feasibility of techniques to stretch limited vaccine supplies; funding for clinical trials; addressing vaccine liability concerns; and work on licensing and regulatory issues. On a positive note, industry representatives “announced that intellectual property issues for patented technologies, including reverse genetics, would not affect either the development of a prototype strain or clinical trials of a candidate vaccine.”

The meeting also stressed the importance of scaling up the use of influenza vaccine for seasonal epidemics because such increasing vaccine use contributes to creating incentives for companies to engage in influenza vaccine development and production, building vaccine manufacturing capacity, and priming licensing and regulatory systems for pandemic contexts. Participants called for governments to increase their engagement in pandemic vaccine development and for WHO to play a stronger role in coordinating activities related to pandemic vaccine development, such as testing.

WHO, Main Conclusions from the Informal Meeting of WHO, Influenza Vaccine Manufacturers, National Licensing Agencies, and Governmental Representatives on Influenza Pandemic Vaccines, Nov. 12, 2004, at http://www.who.int/csr/disease/influenza/summary2004_11_08/en/index.html.

David Brown, WHO Meeting Warns of Flu Pandemic; Experts Say Countries Have Not Done Enough to Prevent the Spread of Virus, Washington Post, Nov. 13, at A04.

WHO, supra note 1.