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Testimony
Wednesday, January 24, 2007 Mr. Chairman and Members of the Subcommittee, I am honored to be here today to describe for you how the Department of Health and Human Services is working to improve preparedness for a potential human influenza pandemic, specifically by pursuing a strategic and comprehensive approach to the development and acquisition of medical countermeasures including vaccines, antivirals, diagnostics, and through building domestic manufacturing infrastructure for influenza vaccines. We are working cooperatively to leverage resources throughout the Department and with industry to meet the program goals. We recently formalized linkages within HHS through the establishment of the Public Health Emergency Medical Countermeasures Enterprise, led by the leaders of the Office of the Assistant Secretary for Preparedness and Response, the Centers for Disease Control and Prevention, the National Institutes of Health, and the Food and Drug Administration. Thank you for the invitation to testify on this topic which Secretary Mike Leavitt has made a top priority. On November 1, 2005, the President requested $7.1 billion in emergency funding for the National Strategy for Pandemic Influenza, of which $6.7 billion was designated for HHS. Congress appropriated $3.8 billion in December 2005 as the first installment of the President's request to begin these priority activities, and of this amount, $3.3 billion was provided to HHS. The second appropriation in June 2006 provided HHS with $2.3 billion. We appreciate the action of Congress on these appropriations, as it takes us an essential step forward in becoming the first generation in history to be prepared for a possible pandemic. The potential for a human influenza pandemic is a current public health concern with an immense potential impact. We know that the influenza virus has the potential to cause a pandemic but we don't know when a pandemic will occur. We don't know how severe a pandemic might be and we don't know which influenza virus will be the one that develops the ability to spark a pandemic. However, we do know that the H5N1 strain of avian flu has spread to more than 50 countries and has led to the deaths of hundreds of millions of birds, and that more than 260 human cases of avian influenza (so called "bird flu") have occurred in 10 countries. More than half of those persons infected have died. This has heightened global concern about the possibility of a human flu pandemic. To date, H5N1 avian influenza has remained primarily an animal disease, but should the virus mutate further and acquire the ability for sustained transmission among humans, a severe influenza pandemic could result that may have grave consequences for global public health. And while a mild pandemic would be primarily a public health problem, the consequences of a severe pandemic on the global economy and on the functioning of society could be enormous. National and HHS-Specific Pandemic Influenza Plans The day after the release of the President's National Strategy for Pandemic Influenza, Secretary Leavitt announced the HHS Pandemic Influenza Plan - a blueprint for all HHS pandemic influenza preparedness and response planning - and released Parts 1 and 2. Part 1, the HHS Strategic Plan, outlines federal plans and preparation for public health and medical support in the event of a pandemic. It identifies the key roles of HHS and its agencies in a pandemic and provides planning assumptions for federal, state and local governments and public health operations plans. Part 2, Public Health Guidance for State and Local Partners, provides detailed guidance to state and local health departments in 11 key areas. In May 2006, the National Strategy for Pandemic Influenza Implementation Plan was released. It translated the National Strategy for Pandemic Influenza into more than 300 actions, timelines, and metrics for Federal departments and agencies and set clear expectations for State and local governments and other non-Federal entities. One of the Federal priority actions was to "Accelerate the Development of Medical Countermeasures" and included these efforts:
Cascading from the National Strategy and National Implementation Plan, one of the key components of the HHS plan called for increasing capacity to produce pandemic influenza antivirals and vaccines, and increasing stockpiles of these countermeasures. Specific strategic goals for pandemic medical countermeasures are displayed in Table 1. Table 1. HHS Pandemic Medical Countermeasure Goals
The Pandemic Influenza Medical Countermeasure Program now includes 25 contracts obligating over $3 billion. Table 2 illustrates the multi-pronged approach and diversified portfolio of programs that have been established to help us achieve the Implementation Plan's medical countermeasure goals. Table 2. HHS Pandemic Influenza Medical Countermeasure Programs.
I would now like to take this opportunity to provide details about the substantive progress toward meeting our public health emergency preparedness goals in each of these medical countermeasure programs. VACCINES Vaccines - Advanced Development Table 3. HHS Advanced Development Vaccine Projects.
Cell-based Projects Accelerating the development of this vaccine technology and enhancing domestic production capacity are critical enhancements of our public health emergency preparedness efforts. Cell-based vaccine manufacturing -- a technology that is used for the manufacturing of many other modern vaccines -- holds the potential of a reliable, flexible, and scalable method of producing influenza vaccines. Using a cell culture approach to produce influenza vaccines offers a number of benefits. Currently licensed influenza vaccines are produced in embryonated hens' eggs in a technique that has changed little in the past 50 years. With increasing demand for seasonal influenza vaccine and with the looming threat of a pandemic, a system that allows surge capacity in an emergency is needed. Vaccine manufacturers utilizing cell-culture technology may be able to bypass the steps needed to adapt the virus strains to grow in eggs, which may save weeks in vaccine production during a pandemic. Since cell-culture technology is used to produce other licensed biologicals, emergency usage of such facilities for pandemic vaccine production is more feasible than with egg-based vaccine manufacturing, which requires highly specialized equipment for egg handling. Further, manufacture of influenza vaccines produced by cell culture also will provide security against risks associated with egg-based production, such as the potential for egg supplies to be unavailable as a result of various poultry-based diseases. Finally, the new cell-based influenza vaccines will provide an option for people who are allergic to eggs and therefore unable to receive the currently licensed vaccines. Currently, six manufacturers are in Phase 1 clinical studies in the U.S. to determine the safety and immunogenicity of these cell-based products; however, several of these seasonal influenza vaccine products have already been evaluated clinically in Europe and have been shown to be well-tolerated, immunogenic, and efficacious. H5N1 vaccine products under development in these contracts include inactivated split and whole virion vaccine candidates formulated with adjuvants and live, attenuated virus vaccine candidates. In pursuit of Pandemic Vaccine Goal 2, the impact of these contracts on domestic surge capacity is forecasted to begin by 2009, and will grow through 2013. Antigen-Sparing Projects The contracts provide support for advanced development of antigen-sparing pandemic vaccine with adjuvants through U.S. clinical trials towards U.S-licensure. Further, these contracts facilitate the establishment of manufacturing capabilities for these adjuvants and development of delivery devices, including adjuvant containing patches which could similarly extend a limited vaccine supply. Under the contracts, each company will build up to a capacity to produce, within six months after the onset of an influenza pandemic, either 150 million doses of an adjuvant-based pandemic influenza vaccine or enough adjuvant to be stockpiled for 150 million doses of a pandemic influenza vaccine. In addition to supporting the development of each company's antigen-sparing vaccine candidate, the contracts also require each company to provide its proprietary adjuvant for U.S. Government-sponsored, independent evaluation with influenza vaccines from other manufacturers. Initial clinical studies conducted by NIH on antigen-alone H5N1 vaccine candidates in humans have shown that two 90-microgram doses of the vaccine are required to stimulate a level of immune response that researchers anticipate would provide protection for an individual against the H5N1 strains that have been spreading among birds in Asia. However, the addition of adjuvant to these candidate vaccines has been shown, in initial European clinical studies, to reduce by 10-to-20-fold the amount of antigen per dose needed to achieve effective individual protection. Phase 1 and 2 clinical studies for safety, immunogenicity, and cross protection are planned in 2007 for the H5N1 vaccine products with the each of the three new adjuvants. If these results are confirmed in larger clinical studies, then these adjuvants may make reaching the goal of U.S. and global pandemic vaccine preparedness faster and more feasible, and help to achieve Pandemic Vaccine Goals 1 and 2. Egg-based Supply Vaccines - Acquisitions Table 4. HHS H5N1 vaccine acquisition projects.
Manufacturing these pre-pandemic vaccines not only provides the industry experience in producing novel influenza vaccine candidates at a commercial scale, but also provides a foundation for pre-pandemic vaccine stockpiles. In the early stages of a severe pandemic, and before a well-matched vaccine is available, pre-pandemic vaccines may be used in selected populations to mitigate disease, support essential operations, and maintain social and economic systems. Currently, 1.3 million doses of H5N1 Clade 1 vaccine (90 ug/dose) have been filled in vials. More than 6 million doses (90ug/dose) of H5N1 Clade 1 vaccine remain in bulk form and await instructions for formulation into final vaccine vials. Additionally, approximately 5 million doses of H5N1 Clade 2 vaccine are currently under production. Vaccines - Infrastructure Building To further capitalize on the promise of cell-based influenza vaccines, HHS plans to issue an RFP later this year to assist in the establishment of new U.S.-based vaccine manufacturing facilities for the production of cell-based seasonal and pandemic influenza vaccines (Table 5), helping us achieve Pandemic Vaccine Goal 1. Table 5. HHS influenza vaccine manufacturing infrastructure building projects.
ANTIVIRAL DRUGS HHS funding was therefore allocated to acquire antiviral drugs. Currently two drugs, oseltamivir (Tamiflu�) and zanamivir (Relenza�) may provide clinical benefit against most H5N1 virus strains currently circulating in Asia; however, several cases of drug-resistant H5N1 viruses in humans have been identified. Accordingly HHS is stimulating the development of new and more promising influenza antivirals and establishing antiviral drug stockpiles to achieve antiviral goals #1 and #2. ANTIVIRAL DRUGS: ADVANCED DEVELOPMENT Table 6. HHS influenza antiviral drug advanced development project.
Funding in this contract over the next 4 years will support manufacturing of clinical investigational and consistency lots; Phase 2 and 3 clinical studies to evaluate safety and efficacy in support of product approval in the U.S.; manufacturing process validation; and other product approval requirements. ANTIVIRAL DRUGS: FEDERAL AND STATE ACQUISITIONS Table 7. HHS influenza antiviral drug stockpile projects.
Additionally, the Implementation Plan calls for States to purchase 31 million antiviral treatment courses, for which the Federal government subsidizes at 25 percent of the cost ($170 M total). In summer 2006, HHS announced two-year contract awards totaling $166 million that provided discounted prices for all 50 states, the District of Columbia, five U.S. territories, and the three Freely Associated States of the Pacific to purchase influenza antiviral drugs for State pandemic stockpiles. At the time, Secretary Leavitt commented, "Our ultimate goal is to stockpile sufficient quantities of antiviral drugs to treat 25 percent of the U.S. population. Helping the states develop their own medical stockpiles will facilitate quicker distribution of antiviral drugs in the event of a pandemic influenza outbreak." To date 43 States have ordered ~11 million treatment courses and are committed to purchasing 30.6 million treatment courses by 2008. A complete table of projected antiviral purchases and subsidized allocations for all jurisdictions is posted online at http://www.pandemicflu.gov/state/antivirals.html. DIAGNOSTICS Table 8. HHS pandemic rapid diagnostics development projects.
In December 2006, HHS announced $11.4 million in new contracts to four companies working to develop new point of care diagnostic tests that doctors and field epidemiologists could eventually use to quickly and accurately test patients for avian influenza H5N1, other emerging influenza viruses, as well as more common influenza viruses. The tests could provide public health experts worldwide with critical information on the influenza viruses circulating and help monitor for viruses that could cause a global influenza pandemic. During the next year, the four companies will work to create tests that would detect seasonal human influenza viruses and differentiate within 30 minutes influenza A H5N1 from seasonal human influenza viruses. These contracts, in support of diagnostics goal #1, will stimulate development of promising technology that could help doctors treat their patients faster and help public health authorities track influenza viruses that could spur a pandemic, and may be used at points of entry for screening. In addition to these contracts, CDC will provide funding for a repository of influenza reagents and other materials to aid with the advanced development of these point-of-care diagnostics. NON-PHARMACEUTICAL MEDICAL SUPPLIES and RESPONSE CAPACITY HHS has also directed funding to increase State and local capacity, enhance international surveillance, expand clinical research capacity Southeast Asia, and implement rapid outbreak response in currently affected countries. HHS has also allocated funds for risk communication strategies and other domestic preparedness activities. Lastly, ASPR has provided grants in 2006 for $11 million to Vietnam and the World Health Organization for in-country development of H5N1 vaccine candidates. CONCLUSION
Although much has been accomplished, continued vigilance and preparation are needed for us to be ready for Influenza - seasonal epidemics and Pandemics Thank you for the opportunity to share this information with you. I am happy to answer any questions.
Last Revised: January 25, 2007 |
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