About the Director

Testimony Before the
House Government Reform Committee

Project Bioshield

Dr. Mark B. McClellan, Commissioner, Food and Drug
Administration
and
Dr. Anthony S. Fauci, Director, National Institute of Allergy
and Infectious Diseases, National Institutes of Health

April 4, 2003

Although only the procurement and personnel provisions of this proposed legislation fall under the jurisdiction of the Government Reform Committee, Project BioShield is best understood when viewed in its entirety. It is important to appreciate how each of the three components contained in this proposal interact to quickly and safely develop and make available lifesaving bioterrorism countermeasures. As such, we would like to take this opportunity to describe the three main components of Project BioShield.

Pharmaceutical research and development historically has focused on development of products likely to attract significant commercial interest. Many countermeasures for potential agents of terrorism realistically have no market other than the government and thus have not generated a great deal of manufacturer interest. Because the market for developing medical countermeasures against terrorism is speculative private companies have not invested and engaged in developing the medical countermeasures that the current situation warrants. However, in the vaccine development area, representatives of the pharmaceutical industry have stressed that, to the extent that the federal government can define its vaccine requirements and assure up front that the requisite funds will be available to purchase the vaccines, the industry will meet the challenge.

In these post-9/11 times of increased potential for chemical, biological, radiological, and nuclear and other terrorist attacks, it is important now more than ever for the United States to take all necessary steps to protect its citizens from these agents. The current security environment dictates the need for rapid acquisition of countermeasures. Armed with technology that only recently was the stuff of science fiction, the U. S. armed forces are better equipped than ever to take military actions against threats to our national security and defend U.S. citizens against missiles, aircraft, guns and other traditional weaponry. But other not-so-traditional threats are lurking. Our enemies seek, and in some cases have already obtained, biological, chemical, radiological and nuclear weapons that could penetrate our military defenses and civilian surveillance systems, and cause significant harm. We need your help to confront these threats to our homeland.

The possibility of the intentional use of chemical, biological, radiological, and nuclear agents presents a true threat to our society. You have heard about many of these threats: anthrax, smallpox, tularemia, botulinum toxin, hemorrhagic fevers and plague. We will fight these new weapons, not with bombs and guns, but with countermeasures such as vaccines, therapeutics, and early diagnosis. We may be called upon to provide mass inoculation or drug treatment. The personnel who will lead the efforts to develop, acquire, regulate, and administer these medical tools will not necessarily wear military uniforms or be headquartered at the Pentagon. They are civilian administrators and scientists of the Department of Health and Human Services located in such places as the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA) and the National Institutes of Health (NIH), as well as State and local health officials.

We are making rapid progress in acquiring countermeasures for the agents of greatest concern such as smallpox, anthrax, and botulism toxin and have made advances in development of new products. We have sufficient Aventis smallpox vaccine to vaccinate the country in an emergency and the new ACAM2000 cell culture vaccine is coming into the stockpile at a rapid rate. We expect to have 155 million doses by this summer. NIH initiated the industrial development of a safer next generation smallpox vaccine by signing two contracts with manufacturers last month. On the NIH campus, a new, potentially safer smallpox vaccine entered the first stage of human testing. We currently have a stockpile of antibiotics to deal with an attack with anthrax, plague and tularemia. In addition, we have access to a stockpile of the current anthrax vaccine and are optimistic that an accelerated development program involving two manufacturers begun last October will result in production of a new recombinant anthrax vaccine sometime next year partially with BioShield funding. Tularemia and plague vaccines are in the research phase and expected to move into advanced development within 2 years. We also have acquired additional quantities of botulinum antoxins for the treatment of botulism.

Because of a relative lack of focused research on terrorist agents, the medical treatments available for some types of terrorist attacks have improved little in decades while there has been tremendous and rapid progress in the treatment of serious natural-occurring diseases. At a time when Americans must confront the realities of terrorism directed at the United States, it is imperative that the Federal government be prepared to protect our citizens from potential agents of bioterrorism.

Many of the available countermeasures have been made using traditional, older technologies, and some have significant side effects (e.g., the traditional "Dryvax" smallpox vaccine). Newer products produced using advanced technologies such as the production of recombinant anthrax or botulinum toxin proteins or more attenuated viral strains to protect against smallpox hold out hope of reducing adverse reactions while maintaining effective protection. Extensive studies must be performed to assure that these products are both safe and effective. Showing effectiveness when diseases do not occur naturally can be challenging and requires the use of appropriate animal models and careful studies of the critical immune responses to a vaccine. These studies are best planned with close interaction between government scientists and the countermeasure sponsors. Such early product development planning has been going on in partnership with FDA, NIH, CDC, and others (e.g. the development and evaluation of new smallpox and anthrax vaccines). Other examples where older vaccines or other technologies have been employed (often effectively) include vaccines for plague and anthrax and immunoglobulins for treating smallpox vaccine complications and botulism. Also, the promise of rapid productions of large amounts of monoclonal antibodies that could be used to protect against a variety of bioterrorist pathogens or vaccine adverse events is becoming a reality.

This must be a public and private partnership. The pathway from idea to final product is complex. The optimal scientific approach to identifying the best drug and vaccine candidates must be based on laboratory studies. Testing must be performed in appropriate animal models to document safety and appropriate protective or treatment response, and to help determine dosing. Human studies must be carefully initiated to assure the basic safety of the product, and then appropriate dosing and response must be determined based on measurements of levels of drug or antibody predicted to have a protective effect. Steps must be taken to assure that the materials used to make the countermeasures ---and the final product itself--- can be manufactured safely, free of contaminants, and with reproducible and predictable purity, potency, and composition. Careful trials in humans, or where not possible, animal models, must be performed to show that the product is safe and effective for the types of populations which might receive it and against the methods of infection or exposure that could be encountered. All of these steps require careful planning, experience, and ongoing management and scientific evaluation. Costs to develop and manufacture high quality biological products and perform and evaluate the needed animal and human studies are high. Grants and contract mechanisms may not always be sufficient or attract the most experienced manufacturers. Manufacturing capacity for biological products, particularly for vaccines, is not substantial. For all these reasons, the best possible support and public-private partnerships and teamwork are essential.

The President announced BioShield in his 2003 State of the Union Address. This is a key legislative priority for this Administration. The BioShield bill is designed to speed the development and availability of medical countermeasures in response to the current threats our Nation faces. The goals of Project BioShield are: 1) to accelerate and streamline government research on countermeasures; 2) to create incentives for private companies to develop countermeasures for inclusion in the stockpile; and, 3) to give the government the ability to make these products widely available quickly in a public health emergency in order to protect our citizens from an attack using a select agent. This legislation is a critical component of our Nation's homeland security strategy.

The three major provisions of the Bill are described below.

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Expediting Research and Development at NIH

First, the Department, working primarily through the National Institute of Allergy and Infectious Diseases at NIH, would be given new authorities to speed research and development in promising areas of medical countermeasures against potential bioterrorism agents. The increased authority will provide additional flexibility in awarding contracts, cooperative agreements, and grants for research and development of medical countermeasures including vaccines, drugs, biologics, and diagnostics, and streamlined authority to hire necessary technical experts. Funding awards would remain subject to rigorous scientific peer review, but expedited peer review procedures could be used when appropriate.

NIH is leading the Federal government's campaign to improve the Nation's public health through biomedical research. The major reason that NIH has been entrusted with this vital leadership role is its proven record in combating naturally occurring emerging and re-emerging diseases, which is fortified by its rigorous system for ensuring that only the best science is supported by Federal dollars. Underpinning NIH's research is a rigorous peer review system, which brings together top experts from the public and private sectors of scientific research, as well as patient representatives and other members of the public, to evaluate research grant applications. NIH applies stringent management controls over contracts, personnel, leasing, and construction to ensure careful and responsible use of taxpayer dollars. These safeguards have served the country well. Currently, NIH is leading us through the greatest era of discovery in the history of medical research.

The President's Project BioShield initiative is intended to speed up NIH research and advanced development in targeted areas by providing more flexible authorities for NIH including procurement and personnel recruitment for critical biodefense work. Our BioShield proposal would authorize the Secretary of Health and Human Services, acting through NIH, to simplify and expedite acquisition requirements for material and services through such mechanisms as raising the dollar threshold for simplified acquisitions and using noncompetitive procedures when necessary. The Act would allow the Secretary to expedite scientific peer review requirements in urgent circumstances, but still require a process of quality review.

Project BioShield is intended to strike a balance, during times of crisis, between the Federal government's need to guarantee that the best research is conducted effectively and efficiently, and the national need to have a quick turnaround in responding to biological, chemical, and nuclear weapons of terror. With the authorities contained in the Act, we can improve our ability to respond to chemical, biological, radiological or nuclear attacks against American citizens and soldiers.

It often takes many months to issue research grants, engage pharmaceutical companies to manufacture vaccines and other drug therapies, hire personnel and consultants, or acquire material and services. In times of emergency, we cannot afford the time that it currently takes to accomplish these goals and events. We need vaccines and drugs to fight bioweapons right now. We need expertise right now. We need to build biocontainment facilities to conduct research right now. Project BioShield gives us the tools to cut through red tape and accomplish our mission.

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Procurement of Countermeasures

Second, and perhaps most important to this Committee, as it falls under your jurisdiction, the Administration's bill creates a new permanent, indefinite funding authority within the Department of Homeland Security (DHS) to procure medical countermeasures for inclusion in the DHS Strategic National Stockpile. This Department will play a major role along with DHS in identifying and evaluating critical biomedical countermeasures. Certain countermeasures, including antibiotics, are procured and distributed by the Department of Veterans Affairs' National Acquisition System. A great deal of work has been done to identify vaccines and antitoxins that would be needed to protect the U.S. population from dangerous pathogens, e.g. anthrax, smallpox, botulinum toxin, tularemia, Ebola, and plague. In the interest of national security and public health, it is essential that the Administration engage in the process as early as possible with sponsors and organizations that are developing the therapeutics, vaccines, and other countermeasures. This Department will maintain a proactive role to help ensure that the products are developed as efficiently as possible.

The Administration already has identified several products as promising countermeasures and is meeting with sponsors to help foster the successful development of these products. Such products include new generation smallpox and anthrax vaccines and therapies to treat botulism, plague, and Ebola and other hemorrhagic diseases.

The bill requires the HHS and DHS Secretaries to identify specific countermeasures that would be appropriate for procurement and, in coordination with the OMB Director, make recommendations to the President. The following determinations must be made in order for the DHS and HHS Secretaries to make a procurement recommendation: 1. determination of material threats, including risk of use and the public health impact; 2. an assessment of the availability and appropriateness of certain countermeasures to address the specific threats identified in the first determination; and 3. determination of countermeasures that are appropriate for procurement under BioShield. This third determination includes: (a) determination that the product is a qualified countermeasure (the bill defines a qualified countermeasure as a drug or biologic product that is approved or licensed by FDA or one that is likely to be FDA approved or licensed within five years); (b). determination of quantities needed and feasibility of production and distribution; and (c). determination of no significant commercial market for the product other than as a homeland security threat countermeasure. This authority will enable the government to purchase vaccines and therapies for which no other significant commercial market exists, as soon as experts believe that the countermeasures can be made safe and effective.

The Administration has carefully constructed this system of technical determinations and processes leading to a recommendation to the President because of the extraordinary nature of the proposal for permanent, indefinite funding authority. The Administration is committed to ensuring that recommendations to use this new authority are carefully considered with input from all experts within the Executive Branch, and that the final determination to exercise this spending authority is made by the President. Any countermeasures that do not meet the criteria laid out in our bill, or that are otherwise determined not to be appropriate for procurement through this authority, may still be purchased through the existing DHS discretionary stockpile authority.

The Administration recognizes that no other significant commercial market exists for many of these products that will be needed to protect our military and civilian population. This authority will enable the government to purchase vaccines, therapies and other interventions provided experts believe that the countermeasures can be made safe and effective. The Secretary of HHS and the Secretary of DHS will collaborate in identifying these critical medical countermeasures, by evaluating likely threats, new opportunities in biomedical research and development, and other public health considerations.

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Emergency Use Authorization

The FDA approval process for drugs, devices, and biological products is the gold standard for the world. Sixty percent of the world's drugs are introduced first in the United States. Research and development pipelines hold the promise of dramatically advanced treatments, thanks to breakthroughs in genomics, proteomics, nanotechnologies, and other biomedical sciences. In the years ahead, we can look forward to more sophisticated, individualized, and effective treatments. Our policies and regulations help ensure that products that get to market are safe and effective. In addition to animal studies, sponsors of new drugs and vaccines typically conduct three phases of clinical trials in humans to demonstrate the safety and efficacy of a product. This process can take years, and is procedurally cumbersome.

In preparing for the challenges we face today, we may not always have a desirable amount of time to address the threat presented by agents of bioterrorism. The current FDA approval process is too long to be used during emergency situations. We have some mechanisms in place to get products to market faster, e.g. the accelerated approval mechanism, and expedited review. The animal efficacy rule provides a new avenue for approval for products whose efficacy cannot be tested in human clinical trials. The single patient IND process and the treatment IND process permit access to unapproved products. However, these mechanisms alone are not sufficient in an emergency.

This Bill will permit the Government to make new and promising treatments still under development available quickly, if needed, for use in emergency situations where no effective approved or licensed products are available, potentially saving many lives. This authorization will only be used when a national emergency has been declared. In the absence of FDA approval of a product for a specific countermeasure use, the BioShield Bill permits the HHS Secretary to issue an emergency authorization that would provide Americans with access to certain unlicensed countermeasures. The Secretary has discretion to facilitate the availability of these important products. Before issuing an emergency authorization, the HHS Secretary must make the following conclusions:

• the agent specified in the determination can cause serious or life-threatening disease;
• the product may reasonably be believed to be effective in detecting, diagnosing, treating, or preventing the disease;
• the benefits of the product may reasonably be believed to outweigh its risks;
• there is no adequate alternative to the product that is approved and available; and
• any other criteria prescribed in regulation are met.

This bill would allow use of the best technology available at the time of a declared emergency. The emergency use authorization would remain in effect no more than one year, unless the specific terrorist threat justifies extension of the authorization.

FDA regulations are stringent when it comes to informed consent for investigational products. Because urgent situations may require mass inoculations and/or drug treatments, such informed consent requirements may prove impossible to implement within the necessary time frame when trying to achieve the public health goal of protecting Americans from the imminent danger. The legislation would provide for the Secretary to impose conditions on the authorization, either by regulation or on a case-by-case basis, where appropriate to protect public health. Specifically, the bill provides that such conditions shall include labeling and other requirements to ensure that health care professionals are informed of the special emergency nature of the authorization; of the benefits and risks (and the extent to which such benefits and risks are unknown); and of the alternatives to the product, and their benefits and risks. In addition, the conditions of authorization may include the following:

• labeling and other requirements to ensure that patients are informed of the special emergency nature of the authorization; of the benefits and risks (and the extent to which such benefits and risks are unknown); of any option to refuse the product; and of the alternatives to the product, and their benefits and risks;
• limitations on who may distribute the product and how distribution should be performed;
• limitations on who may administer the product, to whom it may be administered, and when it may be administered;
• requirements to perform further studies or clinical trials;
• record keeping and reporting requirements;
• requirements, or waiver of otherwise-applicable requirements, regarding good manufacturing practice; and
• requirements for monitoring and reporting adverse events.

The language of this bill is narrowly tailored to address the essential components for use of an emergency authorization. It provides specific conditions and criteria for issuance of such an authorization. It requires a declaration of emergency and provides for a limited duration of use. It gives the Secretary authority to require record keeping and access to records. Finally, it provides civil monetary penalties for violations.

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Conclusion

The Department of Health and Human Services is committed to ensuring the health and medical care of our citizens. Project BioShield is another step towards enhancing our Nation's ability to respond to biological or chemical threats.

• Ensure that sufficient resources are available to procure the next generation of countermeasures;
• Accelerate NIH research and development by providing more flexibility in the contracting process, procurement authorities, and grant making for critical biodefense work; and,
• Make promising treatments available more quickly for use in emergencies by establishing new emergency use authorization procedures at the FDA.

Mr. Chairman and members of the Committee, we seek your bipartisan support to move this issue forward and support this bill. We look forward to working closely with this and other Committees to pass this important legislation and improve our nation's preparedness for and response capability to the threat of bioterrorism.

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