The Honorable Michael O. Leavitt
Secretary of Health and Human Services
Hubert H. Humphrey Building
200 Independence Avenue, SW
Washington, DC 20201
Dear Secretary Leavitt:
The American Society for Microbiology (ASM) welcomes the release of the Department of Health and Human Services (DHHS) Pandemic Influenza Plan which addresses one of the most important public health threats currently facing the nation and the world. The ASM is the largest single life science society in the world with a membership of over 40,000, including researchers who study virology and bacteriology in university laboratories, scientists in clinical and public health laboratories, and microbiologists who work in veterinary medicine, the agriculture, food, environmental, biotechnology and pharmaceutical industries. The Society publishes 11 scientific journals, as well as scientific books, and convenes major scientific meetings, including the annual Interscience Conference on Antimicrobial Agents and Chemotherapy and an annual Biodefense meeting. The ASM membership comprises a large and diverse scientific community, both in the United States and worldwide. The ASM has a long history of concern for infectious diseases, which persist as the third leading cause of death in the United States and the second leading cause of death worldwide. Over the past decade, new and emerging microbial threats have continued to challenge the research community as well as the public health infrastructure.
The ASM Agrees that the Pandemic Influenza Threat is Real and Preparedness is Essential
In the United States, influenza and pneumonia are the leading infectious cause of death and are ranked seventh among all causes of death. On average, 36,000 people in this country die each year and 200,000 are hospitalized due to influenza and influenza-related complications. Influenza viruses steadily mutate and new strains periodically move from animal hosts to humans. Three pandemics have occurred in the twentieth century, including the Spanish influenza in 1918, the Asian influenza in 1957 and the Hong Kong pandemic in 1968. While no single piece of evidence proves that another influenza pandemic is imminent, collectively the evidence is strongly suggestive.
Investigators have shown that the origin of the unusually virulent strains of influenza virus that have appeared in the past century have contained genes derived from avian influenza viruses. Strains of influenza virus known as A/H5N1 have been spreading in wild and domestic birds across Southeast Asia and China since 1996. In recent weeks, the virus has apparently struck poultry in Siberia, Kazakhstan, Turkey and in imported birds in the United Kingdom. Since late 2003, about 100 million domesticated birds, mostly chickens and ducks, either have died of the virus or have been intentionally killed to keep the viruses from spreading. But what has experts so worried are the 133 people reported by the World Health Organization who have been infected with the H5N1 "bird flu," more than half of whom have died. H5N1 to date has not acquired the ability to spread easily from person to person.
While not all experts agree about the timing of an influenza pandemic or whether H5N1 will be responsible for it, all agree that it is inevitable and that preparedness is essential. Based upon the likelihood that a pandemic will begin in countries with very poor disease surveillance and weak public health infrastructure, the rapidity with which it might spread given globalization and widespread travel and commerce, plans for containment must be global and must involve the public and private sectors. The projected global economic devastation from an influenza pandemic is estimated by the World Bank at $800 billion a year. The estimated $40 billion dollar global cost experienced during the recent SARS outbreak, confirms the need for effective planning.
The ASM Supports Funding for the Pandemic Influenza Plan
We commend DHHS for its leadership in planning a federal response to pandemic influenza and support the President’s request of $7.1 billion to implement the plan, including funding for DHHS ($6.7 billion); USDA ($91.4 million); DOD ($130 million); DHS ($47.3 million); Interior ($11.6 million); Department of State ($38.5 million and $131.5 million for international assistance programs); and Veterans Affairs ($27 million). The National Strategy for Pandemic Influenza is designed to address three goals: detecting and containing outbreaks before they spread across the world; stockpiling vaccines and antiviral drugs and accelerating the development of new vaccine technologies and domestic production capacity; and ensuring that federal, state and local communities are prepared for potential domestic outbreaks.
The DHHS Plan Appropriately Targets Vaccine Manufacturing Capacity and Diversity
The most important option for controlling influenza is an efficacious vaccine and the ASM agrees with DHHS that the key weapon against pandemic influenza will be development, rapid production and distribution of mass quantities of an effective vaccine. This effort will require public, private and government collaboration to improve vaccine manufacturing capacity in the United States. We support the goal in the Plan to produce influenza vaccine for the population within the first 6 months of an outbreak and to provide antiviral drugs and medical supplies for treatment. The Plan should also take into account the need for vaccine supply for other parts of the world.
The Plan requests $4.7 billion for pandemic influenza vaccine production capacity, stockpiles and research to produce 300 million courses (2 doses of vaccine per person) within 6 months at the onset of an influenza pandemic. The Plan appropriately focuses on working with industry and academia to support advanced development of dose stretching technologies such as the use of adjuvants as well as research on broad spectrum vaccines.
Necessary vaccine surge capacity does not currently exist in the United States or in the world. Vaccine manufacturers had difficulty meeting the demand for influenza vaccine in 2001 and 2002, the mildest influenza years in two decades. Presently, there is only one influenza vaccine manufacturer in the United States. This situation is a major problem in the face of a pandemic when it is unclear if other countries will allow product produced there to be sold for citizens of the United States versus their own. It is absolutely critical for public health to develop vaccine surge capacity and diversity, which is vital to assuring the preparedness of the United States for future epidemics and pandemics of influenza, regardless of whether or not the H5N1 strain of influenza leads to a pandemic.
The DHHS Plan Appropriately Gives Priority to Development of Cell Culture Technology to Eliminate Dependency on Eggs to Produce Vaccines
The Plan would create capacity in the United States for rapidly increasing vaccine production by expanding and accelerating the investment in cell based influenza vaccines. The development of cell culture technologies would enhance the efficiency of vaccine production by obviating the need for embryonated eggs. The ability to vaccinate people en masse against a pandemic influenza depends on the ability to develop cell based culture techniques, and the development of cell culture based methods for large scale influenza vaccine production will also strengthen our ability to produce vaccines against future threats. H5N1 clinical trials sponsored by the NIH/NIAID to investigate the safety of a vaccine against H5N1 avian influenza indicate that the vaccine is effective, although, the dose required is 6 times greater than that needed for the seasonal influenza vaccine (90 micrograms of hemagglutinin versus 15) and 2 doses are needed for a protective immune response. Since the ability to produce two 90 microgram doses of pandemic vaccine against H5N1 virus for each individual to be vaccinated does not currently exist, a strategy is needed to achieve new vaccine production technology.
The DHHS Plan Appropriately Accelerates Development and Production of Antiviral Drugs
The President’s funding request for $1.4 billion for antivirals will accelerate the development of new antiviral drug candidates. Presently, there is no “silver bullet” to protect people against pandemic influenza. Antivirals are the only immediately available strategy which can be used to try to mitigate the spread of pandemic influenza. However, available supplies of these drugs would meet only the current low demand and it could take 18 months or more to manufacture the quantity needed during a pandemic. Anti-influenza drugs should be stockpiled, therefore, in advance of a pandemic and studies made of their most efficacious use. We must support research to determine if and how (timing, dose) antivirals can be used effectively to treat H5N1 cases of influenza after the onset of disease in addition to their use prophylactically. This will provide a factual basis for determining how much antiviral to produce and stockpile, who should receive antivirals, and when they should be administered.
Liability and Compensation Issues Need to be Addressed
We understand that pandemic influenza liability protection is an important issue for industry. The primary goal of the DHHS Plan is to protect people against disease and development of an influenza vaccine is key for realizing that goal. It is important for policy makers to resolve legitimate concerns related to liability and compensation related to injury in order to proceed with the DHHS Plan for pandemic preparedness and the critical objective of producing sufficient quantities of vaccine and antivirals in time to counter the threat of pandemic influenza.
FDA Should be Adequately Resourced to Ensure the Rapid Development, Production and Safety of Antivirals and Vaccines
Only $20 million has been requested for the Food and Drug Administration (FDA). The FDA is already stretched thin by ever increasing demands related to new and emerging infections, SARS, West Nile and Mad Cow Disease and this small increase for additional responsibilities involving increasing manufacturing capacity of the egg based vaccine, the transition to a cell based vaccine, and development of new vaccines and antivirals is inadequate, especially for the Center for Biologics Evaluation and Research (CBER). There has never been a greater need for the FDA to be engaged proactively in establishing new assays and standards for evaluation of safety and efficacy of products. Moving to a cell based vaccine presents unique challenges in screening for adventitious agents. The Critical Product Monitoring Program within the Center for Drug Evaluation and Research (CDER) will be critical to evaluating surge capacity for manufacturing of not only vaccines and antivirals but also antibiotics.
The Plan Should Address Treatment of Secondary Bacterial Infections in Influenza Patients and the Critical Need to Ensure Biopharmaceuticals In the Event of a Pandemic
The Plan should include provision for responding to secondary bacterial infections that in the past have been major causes of mortality during an influenza pandemic. Increasing bacterial resistance to antibiotics, the significant reduction in available new antibiotics, and the reduced manufacturing capacity of existing antibiotics raises questions about the ability to deal effectively with secondary bacterial pneumonia, a common cause of influenza deaths. Given this potential vulnerability, there is need to ensure surge capacity within the United States for manufacturing those antibiotics that would be needed in an influenza pandemic. During a pandemic it will be important to have current antimicrobial resistance trends in different geographical areas. Attention should also be paid to prevention of secondary bacterial infections by assuring appropriate child and adult vaccination against bacteria that cause pneumonia.
A related issue that deserves attention is the unique challenge posed to the biopharmaceutical industry by an influenza pandemic and the need to ensure production and a continual supply of life-saving drugs and vaccines over and above those critical for treating and preventing influenza and its related complications.
DHHS Plan Must Include Adequate Resources for Critical International Surveillance and Response
The ASM stresses the importance of international preparedness and work with international organizations to mitigate the potential for an influenza pandemic and appreciates the support designated for these efforts in the Plan. A pandemic influenza outbreak will have a devastating effect on global health and the economy. Global cooperation in research, containment and surveillance is critical. The best defense against an influenza pandemic is a heightened global surveillance system. We must assure that funding is adequate for this critical area.
The DHHS Plan Needs Further Attention to State and Local Planning and Resources
The DHHS Plan requests $100 million for state preparedness and planning and a 25 percent subsidy to states to purchase antivirals. We recognize that it is vital for state and local governments to plan for pandemic influenza and to make preparedness efforts a priority. This level of funding does not appear adequate for state and local pandemic preparedness. Plans and cost estimates for preparedness at the state and local levels are needed. Even in this period of difficult fiscal constraints, it will be necessary to give high priority to planning for a pandemic given the potential magnitude of the problem. Strategies for hospital surge capacity, mass casualty care, implementation of disease control measures, including distribution of drugs, vaccines or other supplies require greater attention, planning and resources. Plans for public health measures and dissemination of drugs and vaccines at the local level are needed to assure a rapid workable and efficient response to a public health emergency.
The DHHS Plan Needs to Address Additional Gaps Related to Diagnostic Testing of Influenza Critical for Early Detection and Zoonotic Diseases Research
Definitive diagnostic testing of influenza cases is of paramount value in recognizing epidemics and is of utmost importance for early detection of an influenza pandemic. The demand for diagnostic testing during an epidemic will be challenging. Adequate supplies of reagents necessary for avian influenza should be stockpiled as a part of preparedness planning. In addition to preparing for large scale diagnostic testing at appropriate sites, key regional sites should be provided the reagents necessary for recognizing avian influenza. The NIH-supported Regional Centers of Excellence in Biodefense and Emerging Infections would be an appropriate group of academic health centers to be considered for expanding their influenza diagnostic capabilities. The capacity to recognize these strains should not be limited to public health laboratories.
Most of the emerging infectious health threats are zoonotic diseases. Research on the human-animal interface has been neglected for many years and increased research is needed.
The DHHS Plan Needs to Clearly Define Leadership, Accountability, and Coordination
It is unclear which government entity will be the lead in coordinating the pandemic influenza preparation efforts with industry. At least three components of DHHS are responsible for coordinating and communicating with industry. It is vital that those agencies and offices responsible for coordination with industry have the necessary support and expertise to work effectively with industry on manufacturing capacity, the development of new vaccine production technologies, stockpiles and other related issues. Public health expertise will be critical for a pandemic influenza response and the DHHS should be the lead agency to coordinate public health efforts.
It is our expectation that the Plan will evolve as new information and events unfold. The ASM will continue to monitor and review DHHS plans and activities related to pandemic influenza. We greatly appreciate your leadership and responsiveness to biomedical research and public health and stand ready to assist you in any way possible.
Stanley Maloy, Ph.D., President, ASM
Ruth L. Berkelman, M.D., Chair, Public and Scientific Affairs Board
Gail H. Cassell, Ph.D., Chair, Committee on Biomedical Research
Michael T. Osterholm, Ph.D., M.P.H., Chair, Committee on Public Health
Margaret A. Hamburg, M.D., Chair, Committee on Global Health
Kenneth I. Berns, M.D., Ph.D., Co-Chair, Task Force on Biological Weapons Control
Ronald M. Atlas, Ph.D., Co-Chair, Task Force on Biological Weapons Control
Joseph M. Campos, Ph.D., Chair, Committee on Laboratory Practices