Mr. Chairman and Members of the Subcommittee, thank you for inviting me here today. The Department of Health and Human Services (HHS) welcomes your interest in our efforts to respond to terrorist events, including uses of biological weapons against the civilian population. To that end, I am happy to discuss HHS's readiness to protect the American people from acts of biological terrorism and our role in vaccine research and development.
HHS READINESS TO RESPOND TO MASS CASUALTY EVENTS
Although the Department of Defense (DOD) has developed defenses for biological warfare, there are additional concerns that need to be addressed to provide an adequate civilian defense from a bioterrorist attack. The potential list of microbial pathogens that threaten civilian populations is larger than that of classical biological warfare threats. HHS's identification of the major bioterrorism threat agents a list developed in collaboration with experts in medicine and public health, law enforcement, and national security is included as an Appendix to this testimony. Moreover, the populations to be protected are different from those generally involved in combat situations because the civilian community includes people of all ages and health status.
As you know, local and state governments bear much of the initial burden and responsibility for providing an effective response by medical and public health professionals to a terrorist attack on the civilian population. If the disease outbreak reaches any significant magnitude, however, local resources will be overwhelmed, and the federal government will be required to provide protective and responsive measures for the affected populations. HHS is working on a number of fronts to assist our partners at the state and local level, including local hospitals and medical practitioners, to deal with the effects of biological, chemical, and other terrorist acts.
Metropolitan Medical Response System
Since Fiscal Year 1995, for example, HHS through its Office of Emergency Preparedness (OEP) has been developing local Metropolitan Medical Response Systems (MMRS). Through contractual relationships, the MMRS uses existing emergency response systems emergency management, medical and mental health providers, public health departments, law enforcement, fire departments, EMS and the National Guard to provide an integrated, unified response to a mass casualty event. As of September 30, 2001, OEP has contracted with 97 municipalities to develop MMRSs. During FY 2002, we intend to invest $20 million in 25 additional cities (for a total of 122) for bioterrorism-related planning through the MMRS and to help them improve their medical response capabilities. MMRS contracts require the development of local capability for:
- Early recognition - to be able to alert local, state, and federal public health officials of potential problems;
- Mass patient care -- including the establishment of auxiliary, temporary treatment facilities or procedures for the movement of overflow patients to other geographic areas for care;
- Local medical staff trained to recognize disease symptoms so that they can initiate proper treatment;
- In the case of a bioterrorist event, mass immunization or prophylactic drug treatment for groups known to be exposed, groups that may have been exposed, and populations not already exposed but at risk for exposure from secondary transmission and/or a contaminated environment;
- Acceptance and distribution of material from the National Pharmaceutical Stockpile;
- Mass fatality management to provide respectful and safe disposition of the deceased, including animals; and
- Infection control, including assessment of the extent of contamination to the environment and identification of risk management steps to assure safe re-entry of the potentially contaminated areas.
National Disaster Medical System (NDMS)
As HHS's action agent for responding to requests for assistance and resources, OEP also manages the National Disaster Medical System (NDMS), which was established in partnership with DOD, the Department of Veterans Affairs (VA), the Federal Emergency Management Agency (FEMA), and the Public Health Service Commissioned Corps Readiness Force. The NDMS can be called into action, depending upon the severity of the event, to assist in providing needed services to ensure the continued health and well being of disaster victims.
The National Disaster Medical System is a group of more than 7,000 volunteer health and support professionals who can be deployed anywhere in the country to assist communities in which local response systems are overwhelmed or incapacitated. Organized into 44 Disaster Medical Assistance Teams, these volunteers would provide on-site medical triage, patient care and transportation to medical facilities. Four National Medical Response Teams (NMRTs), which travel with their own caches of pharmaceuticals, have capabilities to detect illness-causing agents, decontaminate victims, provide medical care and remove victims from the scene. Three of the four NMRTs can be mobilized and deployed anywhere in the nation; the fourth is permanently stationed in the Washington, D.C. area. The NDMS also includes Disaster Mortuary Operations Response Teams that handle the disposition of the remains of victims of major disasters, as well as provide for victim identification and assistance to their families.
NDMS response teams can arrive in an area to supplement local responders within 12 hours of a request. The system capability includes providing in-hospital care for up to 100,000 victims. Other activities that OEP has undertaken to help states and local communities develop their preparedness for mass casualties include but are not limited to:
- Development of competency standards for physicians, nurses and paramedics that focus on the emergency care and definitive treatment of mass casualties from nuclear, biological or chemical incidents;
- Guidelines for hospital mass casualty procedures that focus on in-hospital decontamination and medical practices for mass contaminated patients who arrive in hospital emergency rooms; and
- Mass casualty treatment protocol reviews/updates that will provide clinical guidelines for the treatment of patients exposed to a biological or chemical weapon of mass destruction.
The Department of Veterans Affairs is one of the largest purchasers of pharmaceuticals and medical supplies in the world. Capitalizing on this buying power, HHS and VA have entered into an agreement under which the VA manages and stores specialized pharmaceutical caches for OEP's National Medical Response Teams. The VA has purchased many of the items in the pharmaceutical stockpile. The VA is also responsible for maintaining the inventory, ensuring its security, and rotating the stock to ensure that the caches are ready for deployment with the specialized National Medical Response Teams.
HHS has also developed the National Pharmaceutical Stockpile Program (NPS) into a major national security asset. The purpose of the NPS is to be able to rapidly respond to a domestic biological or chemical terrorist event with antibiotics, antidotes, vaccines and medical materiel to help save lives and prevent further spread of disease resulting from the terrorist threat agent. Operated by HHS's Centers for Disease Control and Prevention (CDC), the NPS Program would provide an initial, broad-based response within 12 hours of the federal authorization to deploy, followed by a prompt and more targeted response as dictated by the specific nature of the biological or chemical agent that is used.
One of the NPS "12-hour Push Packages" was brought to operational status on September 11th. CDC delivered a 12-hour Push Package of pharmaceuticals and medical supplies by ground, vendor managed inventory by air, and a technical advisory team in New York City, all within 7 hours of my order to deploy. Three out of the four non-military aircraft in United States airspace on the night of September 11th were carrying National Pharmaceutical Stockpile assets and personnel to New York City.
The Stockpile Program was developed as a supplementary response asset mainly to address biological and chemical terrorism. But following the events of September 11th, the program is now being expanded for response to an all-hazards event. The Stockpile presently is able to provide a full course of anthrax post-exposure prophylaxis to more than 2 million persons. I have directed that the Stockpile development should be accelerated to provide anthrax prophylaxis to 12 million persons, and CDC will reach that level of response within the next 12 months. We will also add four more push packs to the eight already located across the country, making more emergency supplies available and augmenting our existing supplies of 400 tons by another 200 tons.
But we must accelerate the production of vaccines and antibiotics and invest in essential programs to ensure the speedy and orderly distribution of antibiotics and other supplies in the event of a biological event. That is why the President has called for an additional $1.5 billion in federal funding for those areas most critical to our ability to respond to bioterrorist threats. His proposal includes include $643 million to expand the National Pharmaceutical Stockpile and $509 million to speed the development and purchase of smallpox vaccine.
HHS ROLE IN VACCINE RESEARCH AND DEVELOPMENT
With the support of Congress, the President has implemented a government-wide emergency response package to help deal with the tragic events of September 11th. This complements efforts already underway to prepare our nation against such heinous attacks, including threats of bioterrorism. For example, CDC, the Food and Drug Administration (FDA), and the National Institutes of Health (NIH), all within HHS, are collaborating with the DOD and other agencies to support and encourage research to address scientific issues related to bioterrorism. The capability to detect and counter bioterrorism depends to a substantial degree on the state of relevant medical science. In some cases, new vaccines, antitoxins, or innovative drug treatments need to be developed, manufactured (or produced), and/or stocked. Moreover, we need to learn more about the pathogenesis and epidemiology of the infectious diseases that do not affect the U.S. population currently. We have only limited knowledge about how artificial methods of dispersion may affect the infection rate, virulence, or impact of these biological agents. HHS's continuing, collaborative, research agenda at CDC, FDA, NIH, and with DOD, is critical to overall preparedness.
Let me briefly outline the vital role that HHS agencies, particularly the FDA and NIH, play in our Nation's research and development agenda for vaccines.
Food and Drug Administration
Even before the events of September 11, HHS's Food and Drug Administration actively cooperated with DOD in the operation of DOD's vaccine development program and the maintenance of their stockpile program. Any vaccine development, whether by DOD or private industry, must be in accordance with FDA requirements that ensure the safety, effectiveness and manufacturing quality of the finished product. FDA provides assistance to DOD and others regarding the studies required to develop new vaccines, as well as assistance during all phases of development. FDA also works with DOD's office that screens new and unusual ideas for development of products to treat diseases and develop diagnostic tools.
Within FDA, the Center for Biologics Evaluation and Research (CBER) reviews biological products, including vaccines, products derived from human blood, and many products produced by recent advances in biotechnology. The scope of CBER's regulatory responsibility extends to both approved (licensed) products and investigational products (unlicensed products). CBER is responsible for evaluating the safety, purity, and potency of these biological products. Bio-warfare defense vaccines undergo the same CBER review process as for all other vaccines and biologic products.
FDA will work with potential sponsors of experimental therapies, such as vaccines, at all stages of the product development process in order to stimulate scientific interchange and clarify FDA regulatory requirements. From a regulatory perspective, there are four stages in vaccine development:
- The pre-Investigational New Drug (IND) stage (before the product is used in people);
- The IND stage (where human use occurs under well-defined study conditions);
- The license application stage for vaccines (where FDA reviews the results of the clinical studies and the manufacturing process, facilities and equipment); and,
- The post-licensure stage (surveillance following approval of the product for marketing).
Under statutory authority, a sponsor of a new vaccine must submit an IND prior to initiating clinical trials. FDA determines within 30 calendar days from receipt of an IND whether it is appropriate for the IND to proceed or, if necessary, to place an IND on clinical hold, in order to protect the safety of human subjects. This is a difficult task for novel therapies with relatively unknown risks. IN emergency situations, FDA provides a more rapid review. FDA may approve immediate emergency use of an investigational product, in advance of an IND submission, in cases where FDA has ordinarily previously reviewed the product information.
In the IND, the sponsor describes the composition, source, and method of manufacture of the product and the methods used in testing its safety, purity, and potency; provides a summary of all laboratory and pre-clinical animal testing performed; and provides a description of the proposed clinical study and the names and qualifications of each clinical investigator.
The IND process generally is described as having three phases prior to product approval. However, the distinctions between these phases are not absolute. Phase 1 trials are focused on basic safety. For vaccines, Phase 1 trials also usually evaluate the immune response elicited by the vaccine. These trials are usually small - generally between 20 and 100 subjects - and they frequently are done in healthy "normal volunteers" and may last just several months. Phase 2 trials often include several hundred subjects, are often randomized, and last anywhere from several months to several years. These trials usually include individuals who are at high risk for the infectious disease of interest. Unless severe reactions or a lack of effectiveness surface during the first two phases, the sponsor may decide to perform one or more Phase 3 studies that can include from several thousand to tens of thousands people. These Phase 3 trials are intended to provide a definitive measure of effectiveness, as well as continue the evaluation of the product's safety. The size of the efficacy trial will depend upon the expected incidence of disease that the vaccine is intended to prevent. If, at the end of Phase 3 trials, the manufacturer believes there are adequate data to show that the vaccine is safe and effective for its intended use, the manufacturer submits a license application to the Agency.
A sponsor of a vaccine under review must also provide adequate product labeling to allow health care providers to understand the vaccine's proper use, including its potential benefits and risks, to communicate with patients, and to safely deliver the vaccine to the public.
When all of the clinical, chemistry, pre-approval inspection, manufacturing, labeling and other issues have been adequately resolved, FDA will approve the application. Licensing a new vaccine is only one stage of FDA's oversight of vaccine safety. Following issuance of the license, there is continued post-marketing surveillance of the product by monitoring adverse events through the Vaccine Adverse Event Reporting System. Subsequent to the issuance to the license, FDA also monitors the manufacturer's production activities through FDA inspections to determine the manufacturer's compliance with good manufacturing practices (GMP) regulations. Because of the complex manufacturing processes for most biological products, manufacturers generally must submit samples of each licensed vaccine lot, along with manufacturing testing results, to FDA for review and permission to release the lot for distribution.
National Institutes of Health
The NIH bioterrorism research program, spearheaded by the National Institute of Allergy and Infectious Diseases, includes both short- and long-term research targeted at the design, development, evaluation and approval of diagnostics, therapies and vaccines needed to control infections caused by microbes with potential for use as biological weapons. Specifically, this research includes the development of:
- Rapid, accurate diagnostics for natural and bioengineered microbes;
- Effective antimicrobial medicines to treat those infected;
- Protective vaccines for those at risk of exposure;
- Basic research to provide the essential underpinnings for other research areas; and
- Genome sequence research on potential bioterrorism agents. (The results of this, coupled with other biochemical and microbiological information, are expected to facilitate the development of diagnostics, therapies and vaccines.)
The National Institute of Allergy and Infectious Diseases efforts have primarily focused on the bioterrorist threats posed by anthrax and smallpox, and many of these efforts are carried out in collaboration with other Federal agencies.
NIAID formed a Working Group on Anthrax Vaccines (WGAV) in 1998 to develop and test a new vaccine that could be used in response to a bioterrorist event. Such a vaccine must be capable of generating protective immunity against inhalation spores within a relatively short period of time after 1-2 immunizing doses. Through an Inter-Agency Agreement, NIAID is collaborating with the Department of Defense's U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) on a research plan to develop a new vaccine based on the use of recombinant protective antigen vaccine (rPA) to protect all ages of the American public, including military personnel. In preparation for Phase 1 clinical trials of rPA vaccines, NIH is working with CDC, FDA and DoD to refine standard serological tests to assess the effectiveness of anthrax vaccines. These tests would enable comparison of new rPA vaccines to the currently licensed anthrax (or AVA) vaccine. If the new vaccine is capable of generating a rapid immune response, it may provide a quick transition to protective immunity to those individuals undergoing treatment with antibiotics due to an anthrax exposure.
The NIAID also has expanded the national research capacity substantially over the past few years on those bioterrorist threat agents of greatest concern. First, NIAID has solicited from the scientific community research proposals on anthrax and other bacterial pathogens, in an effort to further encourage research that may lead to better means of diagnosis, prevention, and treatment.
Second, NIAID recently awarded administrative supplements to several active research grants to further studies on how anthrax causes disease, which could expedite the development and implementation of novel, more effective therapeutic intervention strategies. NIAID also anticipates funding several new research proposals on the molecular mechanisms involved in the germination of anthrax spores in vivo; such work may provide the basis for a novel and very promising post-attack strategy, one that would be more acceptable than the widespread use of antimicrobial drugs which are not specific for anthrax and, when given to large groups of exposed individuals, may promote the development of antibiotic resistant strains of other bacteria.
Through an Inter-Agency Agreement with the Office of Naval Research, NIAID has provided funding to help complete work on sequencing the DNA of the chromosome of anthrax; additional funds were also provided by the Department of Energy for this purpose. The information derived from this genome-sequencing project should be of great value in developing rapid diagnostic tests, as well as new vaccines and antibiotics therapies against mutant strains of anthrax.
NIAID research on smallpox focuses on extending existing vaccine stocks to increase the number of available doses, developing new vaccines and treatments, as well as diagnostic tools to detect the disease quickly. Although a worldwide immunization program eradicated smallpox disease decades ago, small quantities of smallpox virus still exists under guarded conditions at CDC and in Russia, but several rogue nations may have samples. NIAID, in collaboration with DOD, CDC, and the Department of Energy, funds increased research to:
- Develop and evaluate at least three antiviral drugs with preclinical activity against smallpox and vaccinia viruses and acceptable clinical safety;
- Extend the usefulness of the currently available, older vaccine by doing human studies to see if we can "stretch" available stocks by diluting it;
- Help develop a safe, sterile smallpox vaccine grown in cell cultures using modern technology;
- Explore development of a vaccine that can be used in all segments of the civilian population (i.e., the immune-suppressed, pregnant mothers, etc.); and
- Increase our knowledge of the genome of smallpox and related viruses.
Currently, NIAID is preparing to launch a Phase 2 clinical trial to further evaluate the effectiveness of different strengths of vaccine in order to possibly expand the use of the limited smallpox vaccine supply; CDC and FDA have cooperated to ensure that the NIH study is carried out as expeditiously as possible.
In addition, NIAID and DOD's Defense Advanced Research Projects Agency (DARPA) have funded a collaborative effort involving those two agencies along with four academic centers, the CDC, USAMRIID, and the American Type Culture Collection that will focus on designing and implementing an "Orthopoxvirus Genomics and Bioinformatics Resource Center." This Center will conduct sequence and functional comparisons of genes to provide insights for the selection of targets for the design of antiviral and vaccine strategies. The Center will design and maintain relational databases to store, display, annotate and query genome sequences, structural information, phenotypic data and bibliographic information. Part of the effort will include development of and maintenance of a "Poxvirus Bioinformatics Resource Center" website to facilitate the availability of this data for other researchers.
Mr. Chairman, let me again emphasize that the Administration is taking aggressive steps to make sure that our country is well protected from bioterrorism. Moreover, the government at all levels is responding to bioterrorist threats, and responding well. We should be vigilant and cautious, but should not let terrorists frighten us unduly. Do not let them scare you into not living your life. That would help our enemies achieve what they are trying to do terrorize American citizens.
Contemplating bioterrorism is unpleasant, but it is imperative. Under the leadership of President Bush, we are taking all the steps necessary to keep America safe in an era when biological and chemical attacks are as possible as they are unthinkable.
Thank you, Mr. Chairman, for letting me speak about this matter of critical importance. I will be happy to answer any questions which you or members of the Subcommittee may have.