[House Hearing, 108 Congress] [From the U.S. Government Publishing Office] PROJECT BIOSHIELD: CONTRACTING FOR THE HEALTH AND SECURITY OF THE AMERICAN PUBLIC ======================================================================= HEARING before the COMMITTEE ON GOVERNMENT REFORM HOUSE OF REPRESENTATIVES ONE HUNDRED EIGHTH CONGRESS FIRST SESSION __________ APRIL 4, 2003 __________ Serial No. 108-10 __________ Printed for the use of the Committee on Government Reform Available via the World Wide Web: http://www.gpo.gov/congress/house http://www.house.gov/reform ______ 87-141 U.S. GOVERNMENT PRINTING OFFICE WASHINGTON : 2003 ____________________________________________________________________________ For Sale by the Superintendent of Documents, U.S. Government Printing Office Internet: bookstore.gpr.gov Phone: toll free (866) 512-1800; (202) 512�091800 Fax: (202) 512�092250 Mail: Stop SSOP, Washington, DC 20402�090001 COMMITTEE ON GOVERNMENT REFORM TOM DAVIS, Virginia, Chairman DAN BURTON, Indiana HENRY A. WAXMAN, California CHRISTOPHER SHAYS, Connecticut TOM LANTOS, California ILEANA ROS-LEHTINEN, Florida MAJOR R. OWENS, New York JOHN M. McHUGH, New York EDOLPHUS TOWNS, New York JOHN L. MICA, Florida PAUL E. KANJORSKI, Pennsylvania MARK E. SOUDER, Indiana CAROLYN B. MALONEY, New York STEVEN C. LaTOURETTE, Ohio ELIJAH E. CUMMINGS, Maryland DOUG OSE, California DENNIS J. KUCINICH, Ohio RON LEWIS, Kentucky DANNY K. DAVIS, Illinois JO ANN DAVIS, Virginia JOHN F. TIERNEY, Massachusetts TODD RUSSELL PLATTS, Pennsylvania WM. LACY CLAY, Missouri CHRIS CANNON, Utah DIANE E. WATSON, California ADAM H. PUTNAM, Florida STEPHEN F. LYNCH, Massachusetts EDWARD L. SCHROCK, Virginia CHRIS VAN HOLLEN, Maryland JOHN J. DUNCAN, Jr., Tennessee LINDA T. SANCHEZ, California JOHN SULLIVAN, Oklahoma C.A. ``DUTCH'' RUPPERSBERGER, NATHAN DEAL, Georgia Maryland CANDICE S. MILLER, Michigan ELEANOR HOLMES NORTON, District of TIM MURPHY, Pennsylvania Columbia MICHAEL R. TURNER, Ohio JIM COOPER, Tennessee JOHN R. CARTER, Texas CHRIS BELL, Texas WILLIAM J. JANKLOW, South Dakota ------ MARSHA BLACKBURN, Tennessee BERNARD SANDERS, Vermont (Independent) Peter Sirh, Staff Director Melissa Wojciak, Deputy Staff Director Randy Kaplan, Senior Counsel/Parliamentarian Teresa Austin, Chief Clerk Philip M. Schiliro, Minority Staff Director C O N T E N T S ---------- Page Hearing held on April 4, 2003.................................... 1 Statement of: Fauci, Dr. Anthony S., Director, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services; Dr. Mark McClellan, Commissioner, Food and Drug Administration, Department of Health and Human Services; Michael Brown, Under Secretary for Emergency Preparedness and Response, Department of Homeland Security; and Dr. Dale Klein, Assistant to the Secretary of Defense for Nuclear, Chemical and Biological Defense Programs, Department of Defense..... 15 Rapoport, Frank, attorney at law, McKenna Long & Aldridge, on behalf of Aventis Pasteur; Michael Friedman, chief medical officer for biomedical preparedness, Pharmaceutical Research and Manufacturers of America; Una Ryan, president, Avant Immunotherapeutics, Inc., Needham, MA; Katherine Bowdish, Ph.D., president, Alexion Antibody Technologies, Cheshire, CT; and John Edwards, chief of infectious diseases, Harbor-UCLA Medical Center, on behalf of the Infectious Diseases Society of America..................... 65 Letters, statements, etc., submitted for the record by: Brown, Michael, Under Secretary for Emergency Preparedness and Response, Department of Homeland Security, prepared statement of............................................... 39 Davis, Chairman Tom, a Representative in Congress from the State of Virginia, prepared statement of................... 3 Edwards, John, chief of infectious diseases, Harbor-UCLA Medical Center, on behalf of the Infectious Diseases Society of America, prepared statement of.................. 105 Friedman, Michael, chief medical officer for biomedical preparedness, Pharmaceutical Research and Manufacturers of America, prepared statement of............................. 77 Klein, Dale, Assistant to the Secretary of Defense for Nuclear, Chemical and Biological Defense Programs, Department of Defense, prepared statement of............... 45 McClellan, Dr. Mark, Commissioner, Food and Drug Administration, Department of Health and Human Services, prepared statement of...................................... 20 Rapoport, Frank, attorney at law, McKenna Long & Aldridge, on behalf of Aventis Pasteur, prepared statement of........... 68 Ryan, Una, president, Avant Immunotherapeutics, Inc., Needham, MA, prepared statement of......................... 94 Shays, Hon. Christopher, a Representative in Congress from the State of Connecticut, prepared statement of............ 13 Waxman, Hon. Henry A., a Representative in Congress from the State of California, prepared statement of................. 7 PROJECT BIOSHIELD: CONTRACTING FOR THE HEALTH AND SECURITY OF THE AMERICAN PUBLIC ---------- FRIDAY, APRIL 4, 2003 House of Representatives, Committee on Government Reform, Washington, DC. The committee met, pursuant to notice, at 9:30 a.m., in room 2154, Rayburn House Office Building, Hon. Tom Davis (chairman of the committee) presiding. Present: Representatives Tom Davis, Shays, Waxman, Kucinich, Van Hollen and Norton. Staff present: Peter Sirh, staff director; Melissa Wojciak, deputy staff director; Keith Ausbrook, chief counsel; Randy Kaplan, senior counsel; John Hunter and David Young, counsels; David Marin, director of communications; Scott Kopple, deputy director of communications; Teresa Austin, chief clerk; Joshua E. Gillespie, deputy clerk; Susie Schulte, legislative assistant; Corinne Zaccagnini, chief information officer; Phil Barnett, minority chief counsel; Karen Lightfoot, minority communications director/senior policy advisor; Mark Stephenson, minority professional staff member; Earley Green, minority chief clerk; Jean Gosa, minority assistant clerk; and Cecelia Morton, minority office manager. Chairman Tom Davis. Good morning. A quorum being present, the Committee on Government Reform will come to order. We are here today to examine an administration proposal known as the Project BioShield Act, which is designed to protect the health and safety of the American people in the event of a bioterrorist attack. This proposal, first announced by the President in his 2003 State of the Union address, authorizes the government to conduct and support the development, acquisition and distribution of vaccines, treatments and other biomedical countermeasures to use during public health emergencies, including bioterrorist attacks. Over the past few decades, we have seen rapid progress in the development of treatments for many serious naturally occurring diseases. Pharmaceutical and biotechnology companies are highly capable of producing diagnostics and treatments to meet consumer demand. However, there has been little progress in treatments for deadly diseases like smallpox, anthrax, Ebola and plague, which currently affect few, if any, Americans. The reality is that for these diseases there is little manufacturer interest in developing necessary treatments, since there is no significant market other than the government. Should the United States be attacked with these deadly pathogens, however, the need for vaccines, tests and treatments would be great; and it would be immediate. The administration's Project BioShield initiative is designed to ensure that the United States is prepared. The bill would stimulate companies to develop modern and effective vaccines, drugs and devices to protect Americans in the event of a bioterrorist attack or other public health emergency. The bill has three main components: First, it sets up a process to expedite research and development of biomedical countermeasures. As part of this process, the Secretary of Health and Human Services would have flexible acquisition authorities to quickly and effectively buy cutting-edge products and services to support research, development, and production of vaccines and treatments. Additional acquisition flexibilities are put at the Secretary's disposal for the creation of a stockpile of these critical countermeasures. The Secretary would also have streamlined authority to hire technical experts and consultants. Second, the Secretaries of Homeland Security and Health and Human Services would be required to work together to identify and evaluate bioterrorist threats and determine which countermeasures are needed to combat these threats. The bill would also create a permanent funding authority designed to spur the development of medicines and vaccines by the private sector. Third, during national emergencies, the bill would permit the government to make available new and promising treatments prior to approval by the Food and Drug Administration. A version of the Project BioShield Act is introduced by Senator Judd Gregg in the Senate and was reported out of the committee last month. I intend to introduce a House version in the near future. We have assembled an impressive group of witnesses who will help us better understand this bill. I am particularly interested in learning how Project BioShield would assist in addressing the current public health emergency created by the epidemic known as Severe Acute Respiratory Syndrome [SARS]. More than 2,000 suspected cases of this mysterious disease have been reported in 17 nations, including the United States, with 78 fatalities. So far, there is no effective treatment or vaccine to combat this deadly syndrome. I thank all of our witnesses for appearing today. I look forward to their testimony. I would now yield to Mr. Waxman for his opening statement. [The prepared statement of Chairman Tom Davis follows:] [GRAPHIC] [TIFF OMITTED] T7141.001 [GRAPHIC] [TIFF OMITTED] T7141.002 Mr. Waxman. Thank you very much, Mr. Chairman. I want to welcome the distinguished members of the panel, this first panel, and the subsequent panel as well. We are holding a hearing on a proposal by the administration which I think all of us would support in its intent. We want to accomplish what the proposal would seek to have us accomplish, but our responsibility as Members of Congress is to scrutinize it carefully, to try to think about the unintended consequences, and to make sure that the job is done right. The development of effective countermeasures to bioterrorism is certainly vital to our natural security. The Project BioShield represents a proposal to encourage the development of these products. We all support trying to do that, but we have a responsibility to look closely at the provisions of the legislation, and some of those provisions give me some cause for concern. For example, the proposal removes important protections against waste and abuse that are standard for government contracts. I understand the concern that these protections, in an emergency situation, could impede the development of necessary products. However, any exceptions should be made only when necessary and should be subject to review. This proposal would make it nearly impossible for the courts, for Congress and even the executive branch to rein in abuses. The provision eliminating the government's access rights to contractors' books and records is particularly troubling. Another provision permits products to be distributed without FDA approval. Here again, I recognize there may be unusual circumstances that would require this step in case of a dire emergency. However, the proposal's language is overly broad and could be used to support products that are simply not safe enough for FDA approval. This provision could also permit widespread distribution of unapproved drugs without informed consent, recordkeeping or reporting of adverse events. The BioShield proposal also provides for unlimited guaranteed spending for procurement of vaccines and other countermeasures with little congressional guidance or limits on how much to spend. This is a blank check approach. It could be looked at as an abdication of congressional responsibility. We should work to improve this proposal in such a way as to preserve oversight and recognize that, in order for BioShield to work, we need to assure that commitments made will be honored. In this regard, it is ironic that the administration does not support a similar approach of assuring that commitments will be honored in the case of a smallpox vaccine compensation program. Here, the argument for mandatory spending is strong, because nurses, firefighters and other first responders deserve to know that they and their families will be supported in the case of severe injury or death. Yet in the case of smallpox vaccination compensation, the administration has proposed limiting compensation to the amount appropriated each year, explicitly refusing to guarantee its commitment to those Americans on the front lines of a bioterrorist attack. This inexplicable failure to assure funding is one of the reasons that the House voted down the administration's legislation on smallpox vaccines compensation last Monday. I raised this issue last week in the Commerce Committee to point out the inconsistencies. At the time I did that, many people raised the point, why should we allow automatic spending in this area? They argued we shouldn't allow automatic spending in any area. But Secretary Thompson made the case last week that we want to assure that funding will be there so that the companies that are taking the financial risk of developing these products know that they will be able to count on those funds. I thought that was a strong argument to make. But, equally strong is to make the assurances clear that if a first responder gets immunized for smallpox that they are going to be able to count on funding should there be, in rare circumstances, but nevertheless in some circumstances, an adverse event. Let me conclude by pointing out that the BioShield proposal includes provisions for public health emergencies, not just bioterrorism threats. The idea of including public health emergencies in a BioShield makes sense, because infectious diseases that occur in nature can claim many lives, can even become bioterrorist agents if intentionally spread. What justifies government intervention to support countermeasures is that the market fails to encourage their development on its own. This rationale also applies to the development of treatments for potential public health emergencies. In 2002, not a single new antimicrobial drug was approved by FDA; and apparently only a handful are in development by major pharmaceutical companies. One reason may be that the market for the few cases of multidrug-resistant bacteria is currently quite small. That leads to a market failure. And yet the need for such treatments is enormous. Just yesterday, the New England Journal of Medicine carried the first report of a common bacteria that is extremely resistant to an antibiotic that is usually the last line of defense. If properly designed, then, BioShield can serve valuable purposes, improving our preparedness against bioterrorist attacks and natural epidemics. I look forward to hearing from the witnesses today to help us understand this proposal and find ways to improve it. We need to work together collaboratively for what is certainly a shared goal that we all have. Thank you. Chairman Tom Davis. Thank you very much. [The prepared statement of Hon. Henry A. Waxman follows:] [GRAPHIC] [TIFF OMITTED] T7141.003 [GRAPHIC] [TIFF OMITTED] T7141.004 [GRAPHIC] [TIFF OMITTED] T7141.005 [GRAPHIC] [TIFF OMITTED] T7141.006 [GRAPHIC] [TIFF OMITTED] T7141.007 Chairman Tom Davis. The gentleman from Connecticut, the vice chairman of the committee, is recognized. Mr. Shays. Mr. Shays. Thank you, Mr. Chairman, for convening this very important hearing. I come to this discussion with significant skepticism, not about the urgency of the problem of countering biological threats but about the adequacy and efficacy of the proposed solution. Buying biologics is not like buying bullets. The cold war model of short-term research incentives and artificial markets to sustain defense contractors may not fit the intensely entrepreneurial pharmaceutical and biomedical industries. The Department of Defense [DOD], Joint Vaccine Acquisition Program and the Anthrax Vaccine Immunization Program should serve as cautionary tales. The latter rushed to procure last century technology to the detriment of research and development of a modern anthrax vaccine. The former spent 6 years and more than $300 million but has yet to finish a single vaccine. As the current outbreak of Severe Acute Respiratory Syndrome [SARS] attests, we remain hard-pressed to maintain our defenses against nature's evolving arsenal of biological threats. Hasty acquisition of medical countermeasures available within 5 years, as proposed in BioShield, applies only a short- term bandage to a long-term illness. Massive caches of stockpiled vaccines, antibiotics and drugs will protect no one if they cannot be administered quickly and safely. The missing element of the protective shield envisioned in this proposal is public health capacity. Surveillance systems, diagnostic tools and trained medical personnel are prerequisites to any effective defense against natural and man-made biological outbreaks. I look forward, Mr. Chairman, to discussing the BioShield proposal and biopreparedness priorities with our witnesses this morning. This is truly a very important hearing and one to which we should pay close attention. Chairman Tom Davis. Thank you very much. [The prepared statement of Hon. Christopher Shays follows:] [GRAPHIC] [TIFF OMITTED] T7141.008 [GRAPHIC] [TIFF OMITTED] T7141.009 Chairman Tom Davis. We now move to our first panel of witnesses. I want to thank our witnesses for appearing today. We have Dr. Anthony Fauci from the National Institute of Allergy and Infectious Diseases; Dr. Mark McClellan, the Commissioner of the Food and Drug Administration; from the Department of Homeland Security, we have Michael Brown, who is the Under Secretary for Emergency Preparedness and Response; and rounding out the first panel is Dr. Dale Klein, who is the Assistant to the Secretary of Defense for Nuclear, Chemical and Biological Defense Programs. It is the policy of this committee that witnesses be sworn. So if you would stand with me and raise your right hands. [Witnesses sworn.] Chairman Tom Davis. Dr. Fauci, we will start with you and move right down the line. Thank you for being with us. STATEMENTS OF DR. ANTHONY S. FAUCI, DIRECTOR, NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NATIONAL INSTITUTES OF HEALTH, DEPARTMENT OF HEALTH AND HUMAN SERVICES; DR. MARK McCLELLAN, COMMISSIONER, FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES; MICHAEL BROWN, UNDER SECRETARY FOR EMERGENCY PREPAREDNESS AND RESPONSE, DEPARTMENT OF HOMELAND SECURITY; AND DR. DALE KLEIN, ASSISTANT TO THE SECRETARY OF DEFENSE FOR NUCLEAR, CHEMICAL AND BIOLOGICAL DEFENSE PROGRAMS, DEPARTMENT OF DEFENSE Dr. Fauci. I appreciate the opportunity to discuss Project BioShield with you today. As you know from the legislative language, the purpose of Project BioShield is to accelerate the research, development and purchase and availability of effective medical countermeasures against chemical, biological, radiological and nuclear terrorism and public health emergencies. Project BioShield, as you, Mr. Chairman, summarized so well, is a three-pronged program. It increases the authorities of and flexibilities of the NIH to expedite research, it establishes a secure funding source to purchase countermeasures, and it establishes an FDA emergency use authorization. I am going to very briefly discuss the first two components in the context of how they relate to the work at the NIH; and my HHS colleague, Dr. Mark McClellan, the FDA Commissioner, will discuss both the procurement issues and how they relate in the context of the FDA's responsibilities. The NIH research system has served the country and the world extraordinarily well for many decades. The NIH employs traditional funding mechanisms that include grants, contracts, cooperative agreements and other partnerships as well as time- tested personnel functions, a system that has resulted in numerous major advances that have improved the health of the Nation, including the development of interventions for a number of emerging and reemerging infectious diseases. However, the events of September 11, 2001, and the subsequent anthrax attacks have changed, probably forever, how the biomedical community is going to respond to emerging threats. We are now in a wartime mode and are compelled to modify the way that we do business without compromising the elements that have made us so successful. With regard to the first component of Project BioShield, the legislation provides for a number of special authorities at NIH that will have the aggregate effect of expediting the research process. This is what we call the push toward the countermeasure development. Among those, BioShield provides for expedited peer review of grants and contracts, and I emphasize without compromising the scientific, technical and programmatic standards. It also streamlines procurement authority, bolsters authorities for acquisition and renovation of facilities, expedites personal services contracts and provides flexibility with regard to personnel authority. We feel that these expanded authorities will considerably hasten the pathway from basic research concept up to and including effective countermeasure development. Let me switch gears quickly and speak briefly about the mandated appropriations authority for the procurement of countermeasures. We at NIH and our colleagues at DHHS have had numerous occasions to discuss the development of countermeasures with companies ranging from small biotech firms to big PLRMA. These are our industrial partners that are essential to bringing countermeasure development to fruition. Many of those firms are willing to help in the development of biodefense countermeasures, but the fact remains that they are business and are not nonprofit organizations, and they need a tangible incentive to get involved. Now when it is evident that a given product has a potential to make a profit, few incentives are needed to engage industry. However, when you are dealing with a product for which there is no guarantee of a return or for which the market is tenuous, these companies clearly need some assurances that there will ultimately be a return for their investment. Without such assurances, they will simply pursue the development of other products. When we meet with companies, we hear one of two things. First, they may already be involved in the early stages of development of biodefense countermeasures on their own initiative. They are willing to take on a fair amount of risk, but they want some assurances if they are actually successful that there will be a market for their product. Many state, quite frankly, that they do not want to be vulnerable to the vicissitudes of the cyclical appropriation process, as sound as that is in so many arenas. The other scenario in which we are trying to engage reluctant companies to get involved, namely people who have many other things to do with their efforts and with their expertise, in this instance, we do as we are doing now. We push with discretionary research dollars. However, in our experience, that does not seem to be enough. With Project BioShield, we will further be able to tell these companies that they can partner with us such that if at their end they meet milestones and come up with a licensable countermeasure they have our assurances that there will be money available to them for advanced procurement and, ultimately, purchase. These are examples of what we call the pull of the process. In summary, the accelerated development of effective countermeasures against terrorism requires a new research paradigm and new ways to engage our industrial partners. Project BioShield will help us meet the challenges of bioterrorism effectively and expeditiously. Thank you again, Mr. Chairman and members of the committee, for the opportunity to testify today about this important initiative to improve our homeland security; and I would be happy to take questions after the others. Chairman Tom Davis. Thank you, Dr. Fauci. Dr. McClellan. Dr. McClellan. Mr. Chairman, Congressman Waxman, distinguished members and staff of the committee, thank you for inviting me here today to discuss the Project BioShield Act of 2003. As you know, FDA has been engaged with other government agencies and the private sector in an accelerated major new focus on helping to develop and make available better countermeasures for biological, chemical, radiological attacks and other types of attacks. This bill will significantly enhance those efforts and improve our ability to protect our citizens from these threats. In light of the heightened security risk facing our Nation and our troops, we appreciate your timely consideration of finding better ways to acquire the countermeasures that we need. I am pleased to tell you that in the last 2 months alone we have approved safe and effective treatments for certain nerve gases and radiological agents. We have enhanced our stockpiles of vaccines and treatments for smallpox and other possible agents of biowarfare. Working with the Department of Health and Human Services, particularly NIH, as well as DOD and the Department of Homeland Security and private companies, we are taking further steps to determine as quickly as possible whether other available agents may be of benefit. Such products include drugs that may be active against smallpox and viral hemorrhagic fever, new treatments for exposure to radiologic agents, as well as novel treatments for smallpox and anthrax vaccines and immunoglobulins to treat botulism or complications of smallpox vaccinations. We are also working on some new diagnostic and treatment methods for the Severe Acute Respiratory Syndrome. FDA recognizes that early and ongoing consultation with product developers is essential to get rapid approval of safe and executive products. We focused intense efforts on the rapid turnaround of requests for information, review of study plans and data, development of plans for appropriate product production and use where needed under streamlined investigational new drug procedures for agents of terror, for treating agents of terrorism. Our experience with the approval of a new treatment for the effects of a certain nerve gas, pyridostigmine, was approved under a new animal rule as a result of legislation last year. In this case, FDA worked closely with the sponsors of the application to define not only the criteria that would help in evaluating the drug's safety and effectiveness for this use, we also worked closely to develop appropriate animal models that ultimately helped us verify safety and efficacy. At the same time, we realize that we can't easily solve the problem of getting safe and effective countermeasures to the public with the existing financial incentives for developing them. Our close work with the developers of these new products, which now includes around 200 professional staff in our biologic program alone, has reminded us that proof of concept is still a very long way from large-scale production of effective countermeasures that pose acceptable safety risks. In some cases, we have done the work to demonstrate safety and effectiveness of certain products for counterterrorism use, but we don't yet have companies willing to produce these products. To bring badly needed, safer and more effective countermeasures to our Nation's defense, we are going to need to do more to encourage all parties, basic science researchers and government labs as well as the major medical companies, to take up the cause of developing countermeasures. Consequently, while the countermeasures we have made available already have given us a deeper and more effective stockpile of treatments, in many cases they are based on old technologies. For example, monoclonal antibodies have changed the way that we treat everything from heart disease to cancer. It is considered a master technology in many biomedical circles. Many researchers believe that this technology can be effectively applied to developing countermeasures from anthrax and botulinum toxins to even the Ebola virus. Yet there is only limited research at the developmental stage into the application of these bioterrorism countermeasures. Instead, there is currently available an antitoxin to botulism, which is based on a technology that was available when the FDA came into existence in 1906. This is a useful and very-much-needed treatment, but there is strong reason to believe that new technology can produce antidotes and vaccines that are even safer and more effective and so much more valuable, and that is what has been available to us now. So I agree with Congressman Shays about the need to get to a next generation of countermeasures through this approach. Research and development into next generations countermeasures has been much slower for naturally occurring diseases, largely because there is no clear financial reward for success. Many companies that I have talked to, just like Tony has, know that the development of medical products is a very uncertain process. They are used to taking risks and knowing that they might fail, but what they want to know is that if they succeed there is a certainty of a reasonable financial reward. Today, when it comes to countermeasures, there are plenty of risks but few clear defined rewards; and that is why Project BioShield is critically important. It includes new procurement authorities to provide certainty of payment in advance for the delivery of effective new products. By creating conditions for a market that is reasonable, predictable and consistent over time, government will set the stage for the private sector to make the investments and problem-solving efforts required to develop more effective next-generation countermeasures. Furthermore, in the event that a national emergency has been declared, the bill allows for a limited and highly targeted use of countermeasures for treating a select agent without the completion of the full FDA process. To be clear, this would only occur if a product in the approval pipeline is urgently needed because there are no effective approved treatments available and if we conclude that in the emergency the product's potential benefits outweigh its potential risks for those persons who don't have a better alternative. We expect more antidotes and vaccines to flow out of BioShield, and at FDA we are ready to help facilitate their development and to make sure the best available treatment can be used effectively in an emergency. We live in a new biomedical era today. It is an era of great promise but also of very serious risks in the years ahead from those who would deliberately use biological, chemical, radiologic and other agents as weapons of mass destruction. In addition to the great need for translating biomedical research breakthroughs into effective new treatments for naturally occurring diseases like cancer and Alzheimers and antibiotic resistant bacterial infections, we also need to create much-needed new incentives and authorities to respond to these unnatural threats. We are proud to be able to participate in this process to help the Nation, and we appreciate the strong bipartisan effort in both the House and the Senate to respond to this urgent critical challenge. Thank you, and after the panel's introductory statements, I will be glad to take questions as well. Chairman Tom Davis. Thank you very much. [The prepared statement of Mr. McClellan follows:] [GRAPHIC] [TIFF OMITTED] T7141.010 [GRAPHIC] [TIFF OMITTED] T7141.011 [GRAPHIC] [TIFF OMITTED] T7141.012 [GRAPHIC] [TIFF OMITTED] T7141.013 [GRAPHIC] [TIFF OMITTED] T7141.014 [GRAPHIC] [TIFF OMITTED] T7141.015 [GRAPHIC] [TIFF OMITTED] T7141.016 [GRAPHIC] [TIFF OMITTED] T7141.017 [GRAPHIC] [TIFF OMITTED] T7141.018 [GRAPHIC] [TIFF OMITTED] T7141.019 [GRAPHIC] [TIFF OMITTED] T7141.020 [GRAPHIC] [TIFF OMITTED] T7141.021 [GRAPHIC] [TIFF OMITTED] T7141.022 [GRAPHIC] [TIFF OMITTED] T7141.023 [GRAPHIC] [TIFF OMITTED] T7141.024 [GRAPHIC] [TIFF OMITTED] T7141.025 Chairman Tom Davis. Mr. Brown. Mr. Brown. Thank you, Mr. Chairman, Mr. Shays and Mr. Waxman. My name is Michael Brown. I am the Under Secretary for Emergency Preparedness and Response Directorate of the Department of Homeland Security. I am honored to appear before you today on behalf of Secretary Ridge to discuss our role in bioterrorism preparedness in general, and in BioShield specifically. Preparing our citizens for the event of a bioterrorism event is one of several significant challenges that the new Department faces. But before I discuss the Emergency Preparedness and Response's role in BioShield, I want to give you a broader perspective about our mission. Members of Congress have been very good to us in our years as an independent agency, the Federal Emergency Management Agency. But we are pleased to join the Department of Homeland Security and bring a wealth of knowledge from our experiences in preparing for, mitigating against, responding to, and recovering from disasters of all kinds. I want to assure the members of this committee that EP&R will not lose sight of its responsibility of helping people and communities affected by disaster. The mission statement of the Directorate--to lead the Nation to prepare for, mitigate the effects of, respond to and recover from major domestic disasters, both natural and man-made, including acts of terrorism--contains the same core responsibilities that guided the Federal Emergency Management Agency. During fiscal year 2002, FEMA expended nearly $3.9 billion in disaster funds to aid people and communities who were overwhelmed by disasters, which included earthquakes, floods and ice and winter storms, fires, hurricanes, tornados and tropical storms. FEMA has responded to 42 major disasters, including 37 States and 4 of the U.S. territories. I assure you that role will not change, it will only expand, and the Department is committed to helping our country and citizens in time of disaster. The risk associated with acts of terrorism poses a significant challenge for the Emergency Preparedness and Response Directorate. FEMA's rapid and decisive response to the events of September 11th demonstrated our role in consequence management. As a result, the Nation is looking to the emergency management community to face this new challenge. Project BioShield was announced by the President in his January 28th State of the Union Address. The doctors on the panel discussed many of the program's specific details, so I want to limit my comments to a few brief statements. Our Director has the direct responsibility to do a couple of things: One, allow the Federal Government to purchase critically needed vaccines or medication for biodefense. There is $900 million in permanent indefinite authority in the President's 2004 budget. Two, ensure the adequacy of the Nation's stockpiles of pharmaceutical, vaccines and other medical supplies that can be delivered to emergency sites in 12 hours or less. $400 million are proposed in the President's 2004 budget for this. And, third, to remove the barriers to the development and production processes, the Department of Homeland Security's role is to do three things: One, serve as the national incident manager coordinating the preparedness and response to any incident that overwhelms or has the potential to overwhelm the resources of State and local government as declared by the President. We will also work with the Department of Health and Human Services to jointly determine that adequate countermeasures do not exist for a particular threat without the use of BioShield authorities. Third, along with the FDA, the Department of Homeland Security must declare that chemical, biological, radiological or a nuclear threat is real and requires the use of the BioShield provisions. For this intelligent assessment, we will be looking to the Information Analysis and Information Protectorate Directorate within the Department of Homeland Security. In short, Homeland Security will coordinate with Health and Human Services to trigger the use of BioShield. We will fund the program's activities and will make a product available through the Strategic National Stockpile. I am committed to working closely with the various components of the Department of Health and Human Services as they identify the contracting and procurement mechanisms within the pharmaceutical industry, as they work to certify the safety and efficacy of developing new medicines, and as they make recommendations for programmatic progress in areas of needed improvement. As the custodian of these significant Federal dollars, the Department of Homeland Security is committed to working closely with Health and Human Services to make sure that BioShield authorities are triggered after its use is determined in the Nation's best interest. Emergency Preparedness and Response is assuming the responsibility for several biopreparedness activities, including developing a bioterrorism response plan called Bio- Watch, participating in the Metropolitan Washington Council of Government's Bioterrorism Task Force, and participating in major bioterrorism response exercises such as TOPOFF 2 and Exercise Silent Night. First, Emergency Preparedness and Response has assumed the responsibility of maintaining and deploying the Strategic National Stockpile together with the Center for Disease Control and Prevention. The Strategic National Stockpile is made up of pharmaceuticals, vaccines and medical supplies housed in various areas around the country in cases of emergency. By dispersing these assets, the goal is to deliver the necessary supplies to disaster sites in 12 hours or less. Bio-Watch, which we have talked about, is also included in the responsibilities of Homeland Security and is our effort to make sure that we are ahead of the game in case of emergencies. The Metropolitan Washington Council on Government's Bioterrorism Task Force is another area that we are working in, including the exercise that we have done in TOPOFF and Silent Night. The National Disaster Medical System I have already mentioned is also a responsibility assumed by the Department of Homeland Security under the act. This system assists State and local governments by providing primary care to disaster victims in the field, patient evacuation disaster areas, and definitive care when needed. Our Federal partners include the Departments of Health and Human Services, Defense and Veterans Affairs. While I have not limited my remarks to BioShield, I think it gives you a good overview of our responsibility in the Department of Homeland Security. We are happy to work in this area and are pleased to answer any questions the committee may have at the close of these opening remarks. Chairman Tom Davis. Well, thank you very much. [The prepared statement of Mr. Brown follows:] [GRAPHIC] [TIFF OMITTED] T7141.026 [GRAPHIC] [TIFF OMITTED] T7141.027 [GRAPHIC] [TIFF OMITTED] T7141.028 [GRAPHIC] [TIFF OMITTED] T7141.029 [GRAPHIC] [TIFF OMITTED] T7141.030 Chairman Tom Davis. Dr. Klein. Dr. Klein. Chairman Davis, distinguished members of the committee, I am pleased to be provided the opportunity to appear before you today. As indicated, my name is Dale Klein; and I currently serve as Assistant Secretary of Defense for Nuclear, Chemical and Biological Defense Programs. Within the Department of Defense, I have the responsibility for all matters concerning the formulation of policy and plans for nuclear, chemical and biological defense programs. In this role, I am responsible for the Department of Defense programs to develop and field biological countermeasures our warfighting forces need. Due to the support of Congress and with the help of the resources you have made available to the Department, our fighters that are now in the vicinity of Baghdad are much more prepared than they were in 1991 under Operation Desert Storm. The Department of Defense is very interested in the prompt approval of the administration's Project BioShield initiative. New authorities are needed with appropriate safeguards to assure rapid and effective medical treatments can be introduced quickly to counter weapons of mass destruction. The President's Project BioShield initiative would enhance the Food and Drug administration's ability to make needed medical products available in response to declaration of an emergency. DOD stands ready to assist civilian agencies in their efforts to provide modern, effective drugs and vaccines to protect against attack by biological, chemical, nuclear or radiological weapons. The Department looks forward to working closely with Congress, the Department of Health and Human Services and the Department of Homeland Security to collaborate as the lessons of the 2001 anthrax attacks are fresh in our minds. Currently, we are working with the Department of Health and Human Services and other Federal agencies to develop the next generation anthrax vaccines for future use and several other programs. Mr. Chairman, in summary, I request that my full statement be placed in the record; and I want to reemphasize that the Department of Defense supports the President's Project BioShield initiative. I will be happy to answer questions you may have later. Thank you. Chairman Tom Davis. Well, thank you very much. [The prepared statement of Dr. Klein follows:] [GRAPHIC] [TIFF OMITTED] T7141.031 [GRAPHIC] [TIFF OMITTED] T7141.032 [GRAPHIC] [TIFF OMITTED] T7141.033 Chairman Tom Davis. I want to thank all of the panelists. We are going to start the questions. I just have a quick question before I yield to Mr. Waxman, and then we will get another round. Dr. Fauci, next week this committee is going to be holding a hearing on the Severe Acute Respiratory Syndrome [SARS] epidemic. Can you give us an update on what we now know about SARS, including how it is transmitted, how far it has spread and what we can do to protect ourselves? Dr. Fauci. Certainly, Mr. Chairman. SARS, standing for Severe Acute Respiratory Syndrome, has now spread through several countries, at least 17 countries. There are over 2,200 cases, and about 80 deaths. There has now been 100 cases in the United States in 27 States. This is a new disease. It is what we refer to as an emerging microbe, an emerging infectious disease. The data from the CDC and from other laboratories indicate that the corona virus, which is an interesting group--it is a very common virus. It is what causes about 10 to 20 percent of the common colds. There are two groups of corona viruses. This is likely a member of a new third group. It has not been definitively demonstrated that this is the, or the only, cause of SARS, but the evidence is mounting every day from a variety of approaches that we are taking. It has the capability of being a very severe syndrome. The death rate in this is 3.5 percent, which may sound small, but when you think about the possibility of infecting hundreds of millions of people, this can turn out to be a major public health threat. In fact, in parts of the world it already is, leading to such draconian measures as quarantines and isolation in several countries. The CDC has done a magnificent job thus far, and we know that they will continue to, in not only identifying and tracking but essentially now moving ahead in collaboration with the NIH and a variety of other agencies, the FDA, in developing diagnostic therapeutics and on our way to a vaccine. So, in summary, Mr. Chairman, it is a serious threat. We must take it very seriously. We don't feel there is a need to panic at this point, but we must continue to do the very stringent public health measures that we are approaching, as well as the research that is going into it. Chairman Tom Davis. Thank you. That is just a synopsis. We will have a fuller hearing next week with more questions. But thank you for that. Let me yield to our ranking member, Mr. Waxman. Mr. Waxman. Thank you very much, Mr. Chairman. That was very interesting, what you had to say about this SARS. Our committee is going to hold a hearing on it next week. I think it is important for us to understand this very looming threat to the public and how best to deal with it. On this BioShield proposal, the administration is suggesting that NIH conduct a research and development program for biological countermeasures. It then authorizes the procurement of countermeasures but only after determinations by the Secretary of HHS and Homeland Security and Presidential approval. But, Dr. Fauci, who makes the decisions about the research and development phase? Dr. Fauci. We do, sir; and that is the point that I alluded to briefly in my opening remarks. There is the push and the pull. The NIH and other research agencies make a scientific decision about the kinds of research that we need to do. We rely heavily, as others do, on intelligence reports, particularly from the new Department of Homeland Security about the threat assessment. But the fundamental basic research, that is our decision; and the way we execute this research is a scientific decision. Mr. Waxman. You will be making decisions about research into countermeasures at the same time you oversee research against present threats to health. Dr. Fauci. Yes, sir. Mr. Waxman. Should Congress be worried that traditional medical research will slow down as NIH focuses on biodefense? Dr. Fauci. I don't believe so, Mr. Waxman. There is always a concern when you have to rev up and ratchet up your activities that there will be resources taken away from other areas, but if you look now thus far at the track record of the providing of resources for biodefense at the NIH, it has been quite extraordinary. We appreciate not only the administration but the Congress and their bipartisan support of that. But if you look at the other areas of the naturally emerging and reemerging diseases, that has not suffered and in fact has grown at a rate commensurate with the rather substantial growth of the rest of the NIH. So, in fact, we have not seen that. Mr. Waxman. Is there a potential for dual use where the research of biodefense may well lead us to research breakthroughs for other diseases? Dr. Fauci. I think it is not only a potential, Mr. Waxman, I think it is inevitable that there will be an important contribution to the research that we put into emerging and reemerging diseases to inform us about biodefense research, and it is without a doubt that the research that goes into biodefense will help us with naturally occurring. Because as a matter of fact, as we have discussed before, as you know we feel that deliberately released microbes is just another form of emerging and reemerging disease. Instead of occurring naturally, it is done with malice and deliberately, but the end result can be the same. In some respects, nature itself can be our worst bioterrorist. So the resources and the manpower and the expertise that goes into one will naturally flow seamlessly back and forth into the other. Mr. Waxman. Let me ask you about antibiotic resistance. This certainly poses a threat to public health now and a potential bioterrorist threat for the future. Yet drug companies have few antibiotics in development, and some people believe there is a market failure for drugs to treat resistant bacteria. How urgent is the crisis in antibiotic resistance and does it make sense for BioShield to cover research into new antibiotics to treat resistant bacteria? Dr. Fauci. The answer to your question is it is a serious threat, and it has been a threat for some time. I think you alluded to, in your opening statement, the fact that, you know, as months go by, we are pushing the envelope further and further about the emergence of resistance to microbes for which we have maybe one last firewall of an antibiotic against that. We are recognizing this at the research level, and we are putting more resources into it. But I believe, and we all believe, that the basic research that we will be doing on microbes for biodefense will directly and indirectly address the concerns that you have and the concerns that we have. For example, as part of our biodefense research endeavor, we are involved in a major program for the sequencing of pathogenic microbes, not only those on the category A or B list, but microbes for which one can, by a simple mutation, lead to a microbe that would be a bioterror weapon. So that kind of research that we have been doing before in emerging and reemerging disease research and that we have accelerated greatly with biodefense will address the question you are concerned about. Mr. Waxman. As you know, our vaccine infrastructure is very fragile, and we always have to be concerned about the vaccines for childhood diseases. Do you see any potential where the efforts to develop and produce bioterror vaccines could negatively impact childhood vaccine capabilities? Dr. Fauci. I don't think it would negatively do that at all. In fact, if we can, which I hope that we do, that the long-range effect would be to add a degree of robustness and vigor to the whole field of vaccinology, that there will be positive spin-offs. You are quite correct. We are walking a very thin line, notwithstanding biodefense in the whole field of vaccinology, because of so few companies that are involved for a variety of reasons. We feel that if we get both the basic research and the actual production flow of vaccines in general that this will have positive spin-offs on vaccines for childhood diseases as well as adult nonbiodefense vaccines. Mr. Waxman. Thank you very much. Dr. McClellan, the BioShield proposal would allow the Secretary of Health and Human Services to waive virtually all of the consumer protections in the Federal Food and Drug Cosmetic Act in case of an emergency. Moreover, the proposal would then severely curtail judicial review of the Secretary's decision. What is the rationale for allowing informed consent, recordkeeping, adverse event reporting, and other key requirements to be waived; and what is the rationale for severely limiting oversight of these extraordinary powers? Dr. McClellan. The rationale for the emergency use authorization is to provide the most potentially effective treatments to Americans in emergency situations. This is a limited authority program that only applies when the Secretary and others have determined there is a national emergency because of a bioterrorism threat or another type of public health emergency, and it only involves agents where there are not effective approved treatments already available but where there may be treatments in the pipeline where the potential benefits outweigh the potential risks. We have a few now that are marching as quickly as possible toward approval and toward a full demonstration of safety and effectiveness. That remains our goal. I would highlight that we are going to have even better incentives for that under the BioShield program. You don't get full payment for development of a countermeasure under BioShield unless it is approved and licensed, fully licensed, fully shown to be safe and effective by the FDA. That is a strong incentive for getting to the finish line that doesn't exist today and would move us out of the world we are in now, where there are a lot of products that may be of use, but no companies, as I talked about before, are willing to make the investments and come up with the good ideas needed to translate proof of concept into a truly effective treatment. Mr. Waxman. I understand that. That is an important part of why this bill is necessary. But in creating this balance we let the Secretary waive all of these consumer protections, and it looks to me like this authority is quite broad to waive FDA approval standards. Will that give incentives that are needed to conduct the kinds of safety and efficacy trials that are needed, or are some of these companies going to figure they can get around that? Dr. McClellan. I agree we need more incentives to conduct the needed safety and effectiveness trials. That is the main reason for the procurement authority for BioShield that only makes payment on delivery of--a full payment for an approved product. The emergency use authorization does include a number of protections to make sure that in the limited circumstances of the emergency we do as much as possible to limit distrubution, limit who can administer, require studies, require recordkeeping and access to records. All of those are elements of the BioShield proposal, and the Secretary would specifically design its use with our recommendations and those of others to do as much of all of those activities as possible. Mr. Waxman. You are giving me assurances that we are not going to pay these companies unless they do what they are required to do, but I am concerned about the broad authority to waive some of the consumer protections like informed consent or making sure we know about the adverse events and other aspects, where right now the law is set up to not just make sure the company does what it needs to do to get paid but the consumers and adverse consequences--the consumers are monitored with and dealt with adequately. Dr. McClellan. Right. We want to get to approved treatments as quickly as possible. But with these products in development there may be a number that have been shown to have potential benefits for conditions where there are no effective treatments approved. Under those circumstances, we think it is appropriate, with all of these restrictions in place, to do as much recordkeeping as possible, as much monitoring and standards for production as possible, as much mandatory reporting of adverse events, and informing the consumer, informing the public as possible about appropriate use as can be done under the circumstances. I would be happy to continue to work with your staff to make sure that we tailor that language appropriately. We think the bill does a pretty good job now of getting as much done as possible on informing consumers, on collecting adverse event data and the like. We think that is very important in the emergency use process. But it is an emergency, and it is a very special limited use condition that requires some special considerations. Mr. Waxman. Your answer is very useful. I have other questions, but we will pursue them in a subsequent round. I appreciate your offer to work with us to improve the bill. Mr. Shays [presiding]. As the ranking member points out, we will have a second round. What we are doing is we are doing 5-minute doubles, so we are doing a 10-minute questioning period. I will recognize myself. I would like to ask each of you, what is your assessment of the seriousness of the threat we face with bioterrorism? Just start with you, Dr. Fauci. Dr. Fauci. I think the threat is serious. The risk of it happening is something that we can't quantify. But if one looks at the history of what has gone on in the production of weapons of bioterrorism decades ago, that we have no real assurance of their full accountability, for example, by the Soviet Union, the recognition of weapons of bioterror that were clearly recovered in the first Gulf war, and right now obviously we need to see what happens in the current engagements. The fact that we have already been hit in the fall of 2001 and the potential for this has us feel strongly that we need to err very strongly on the side of preparedness. So it is difficult to quantify a risk, but we are concerned. Mr. Shays. Dr. McClellan. Dr. McClellan. I agree with that assessment. There is a real reason for concern. In addition to the specific risk that Dr. Fauci has outlined, I would like to highlight that, as part of our preparedness efforts, we have already undertaken a number of threat assessments and at FDA we have got responsibility for the security of most of the food supply. As Secretary Thompson has said, he is very concerned about the real risk of bioterrorists or other type of terrorist events involving foods. I would like to highlight that it is not only bioterrorism that we are concerned about here. Recently discovered terrorist cells in Europe that were attempting to manufacture Ricin and previous episodes of cyanide poisoning highlight that various chemical agents also pose a real risk to the health of the public. Mr. Shays. Mr. Brown. Mr. Brown. I want to emphasize what Dr. McClellan just said, the threat is real. But I want to add a different dimension to it. Even if terrorists are not successful in launching a wide-scale biological attack or a chemical attack, they will launch a small-scale attack, just for the effect, for the terror effect alone. So that even if they don't infect a wide, broad spectrum of society, if they can put the fear in the American public that they have this capability, by launching a small attack somewhere, they will do that. Mr. Chairman, it is real. Mr. Shays. Dr. Klein. Dr. Klein. Mr. Chairman, I would also like to acknowledge that the threat is real and serious. I think the events of September 11th demonstrated that. The anthrax attacks also demonstrated that. The Department of Defense has a fairly significant monitoring program; and I think, on the biological threat side, one of the reasons that is a concern is the capital investment to produce those materials are less than it would cost to develop, for example, a nuclear weapon. Mr. Shays. I am going to work backward, Dr. Klein. We will go the other way. What do you think the future of bioweapons will be? Should we focus mostly on natural pathogens or enhanced pathogens? And what enhancements to these pathogens should concern us most? Dr. Klein. Well, Mr. Chairman, I think when we look at what specific threats we look at, we have a process, both at the Department of Defense and with our interagency colleagues, to define what those threats are. So we have a process to evaluate those specific threats. What we look at at the Department of Defense, for our men and women in uniform, we look at not only what is it that might be available but what can be weaponized. I think my colleagues at the Department of Homeland Security and the Department of Health and Human Services have other areas where the terror threats would be different. So I think what we need to do collectively, and I think BioShield addresses this, is that we need to work collectively as an interagency to define those threats. Mr. Shays. Just quickly. The other part of the question, though, is it the natural pathogen or the enhanced pathogens, in other words, the altered biological agent? Dr. Klein. In my opinion, in the near term, it will be the natural ones that have been modified for a weapon. Then we will look at the modified ones. Mr. Shays. Mr. Brown. Mr. Brown. Based on the intelligence I have been receiving and looking at, I think it is the natural pathogens, those that they can use quickly and easily. Mr. Shays. Dr. McClellan. Dr. McClellan. We rely on the Department of Homeland Security and others for help with these threat assessments, so I defer to them. I do think we need to be prepared for both types of agents, both naturally occurring and modified ones. Some of the technologies that we have outlined that we think would result from a BioShield initiative such as monoclonal antibody techniques and better techniques for producing vaccines quickly will support our ability to deal with modified pathogens as well as the naturally occurring ones. So the approach that we are outlining here would provide a useful strategy for addressing both. I would like to emphasize again, though, that the only threats out there are not bioweapon agents. Also, chemical agents and radiologic and nuclear agents are real threats, too. Mr. Shays. Thank you. Dr. Fauci. Dr. Fauci. I agree with my copanelists' statements. We also rely heavily on the Department of Homeland Security for threat assessment. But the strategic plan and research agenda for the NIH is weighted to both naturally occurring as well as genetically modified microbes. Mr. Shays. Dr. McClellan, I will start with you and work to Mr. Brown. How many medical countermeasures, diagnostic drugs and vaccines do you estimate we will need in the end to protect ourselves? Dr. McClellan. I can't give you a specific number. One of the things that comes out of the threat assessments and that will come out of our work under BioShield is a much clearer assessment of what is possible. Mr. Shays. When will that be? Dr. McClellan. By passing this legislation we will generate a higher level of interest among the private sector researchers and others in identifying countermeasures. We have identified a number that we think can be developed right away, including better treatments for smallpox, better treatments for botulism, better treatments for anthrax. But we think there are a lot of other opportunities out there, so I can't give you an exact number. But I do think that, because this is an unexplored and really underutilized area---- Mr. Shays. You have explained. I want to move on. Mr. Brown. Mr. Brown. Homeland security has to rely on their expertise for those kinds of matters. Mr. Shays. OK. You have no sense. Dr. Klein. Dr. Klein. It is difficult to say exactly which numbers. I agree with my colleague, Dr. McClellan, it is difficult to come up with an exact number. But we will--if we have a system in place that can be versatile, I think that is what would protect the American public. Mr. Shays. OK. The Defense Science Board listed 19 priority bioterror agents. First, Dr. Fauci, would you just respond to the question, and then I want--the question I started with Dr. McClellan. The question is, how many medical countermeasures, diagnostic drugs and vaccines do you estimate? Dr. Fauci. Difficult to assess. But we are at least aiming at the six high-priority category A and several on the category B list. So I would say the number we cannot tell you for sure, but we want to be flexible enough to move as new threats arise. Mr. Shays. OK. I will ask whoever can answer this. The Defense Science Board listed 19 priority bioterror agents, and found that today we have none of the diagnostics we need, none of the vaccines we need, and only one of the therapeutics we need to deal with them. Is this list of 19 pathogens the definitive list, or do we need to prepare for these and many other pathogens, some of which don't even exist yet? Dr. Klein. As you might expect on that list, we do have some vaccines available. For example, anthrax is on the list, smallpox is on the list. So we do have vaccines and treatments available. We need to continue those. That list is relatively accurate but, again, as others have indicated, there will be future threats that are not on that list. Mr. Shays. CDC list, 36 selected agents. Do we need countermeasures for all of them? Dr. Fauci. Dr. Fauci. Potentially we do. We are using that list which includes the top priority category A list of six that we are putting our major effort on, but there are several on the secondary or B or C lists that we are also developing countermeasures, or at least studying the basic biology of the microbes to prepare us better in case genetically modified microbes appear. Mr. Shays. Let me just ask about the issue of surveillance diagnostic tools and training medical personnel. Isn't that more important than any of the stuff that we are talking about right now, to be able to have a surveillance system and diagnostic tools and training medical personnel? Do these come first? Dr. McClellan. It is all part of a comprehensive strategy with dealing with the new threats of terrorism to this country. We need effective surveillance and supporting research on better diagnostic techniques as well as building up our laboratory and monitoring capabilities is an important part of the response, but so is research on developing effective countermeasures and strategies for containing an event if it actually occurs. Mr. Shays. Anybody disagree with that? Dr. Fauci. Agree. Mr. Shays. Let me just ask this one last question then. We are in a dangerous position with regard to antibiotics and have few antivirals. Do we need some major research breakthroughs to develop products that we need to protect ourselves against a bioterror attack and antibiotic-resistant organisms? Dr. Fauci. The answer is yes. That is a problem, as I mentioned in response to Mr. Waxman's question, and it is an important part of our biodefense program in general as well as our nonbiodefense emerging and re-emerging disease, which I believe shows you the seamlessness between the two programs. Mr. Shays. In my second round I want to ask about the DOD joint vaccine acquisition, and I will be asking you, Dr. Fauci, some questions and Dr. Klein about that. And, Mr. Van Hollen, you have the floor for 10 minutes. Mr. Van Hollen. Welcome to all of you, and I am very proud to have both the NIH and the FDA in the Eighth Congressional District, so it is great to see both of you and have a chance to visit with you. I appreciate your willingness to work with our office on not just national issues, but some of the local issues as well. Much ground has been covered, but I want to followup on a couple of things just so I am clear in my mind. The determination as to what the priorities are going to be in terms of what--whether it is biological weapons, chemical weapons, which ones we focus on as a priority, is that decision--I understand it is part of a collaborative process, but is it part of the Department of Homeland Security to say that these are the ones we want to focus on? Who is responsible for making that decision as to what the priorities are for investing resources? Dr. Klein. Congressman, I think what happens in that regard is that we--both the Department of Defense and Department of Homeland Security will both work together to determine those. Sometimes they are slightly different. What the Department of Defense considers is not only the threat, but has it been weaponized to negatively impact the men and women in uniform accomplishing their mission. What we do, we will come up with that threat list. We will evaluate it through our intelligence system. Certainly as we develop those lists, we will work with the Department of Homeland Security. But which list is more important than others, it depends on exactly what your mission is, for example, whether it is a warfighting mission or protecting civilians. Mr. Van Hollen. I assume we are going to be putting together a plan. What is your time line in terms of deciding-- there are a lot of chemical agents out there. There are lots of potential biological agents, a lot of different mutations, I understand. What are we---- Dr. Klein. We already have that list, and it is prioritized. We have them ranked. We typically don't publicize that list at the Department of Defense. Mr. Van Hollen. You have that list, and NIH is doing research based on that list? Dr. Klein. The Department of Homeland Security and Department of Health and Human Services also have a list, and their list, Department of HHS, their list A and B, and it is publicized. Mr. Van Hollen. Does that also deal with the production of countermeasures as opposed to research? Who makes the decision as to what point we need to move into the actual production of the countermeasures? Dr. McClellan. The production is a decision that is made with input from the Department of Health and Human Services based on the threat assessment. Where we ought to focus our resources and BioShield more generally is based on the combination of where the greatest threats are and where the greatest opportunities are, and where you get that match, the potential for bringing new countermeasures forward that will address a significant terrorist threat, that is the priority in BioShield. Dr. Fauci. I see where your question is going, because there really needs to be distinguished both the basic fundamental research that informs any list. The decisions about that and how you track that is an NIH decision when it comes to research and FDA or CDC decision in the Department of Heath and Human Services. As we mentioned earlier, we rely heavily on our colleagues in DHS and even in DOD in helping us to get a better feel for the actual threat assessment. However, there is a formal process in BioShield that Dr. McClellan just referred to that when you trigger the procurement component of it, it is the Department of Homeland Security and Secretary Ridge determines that this is a serious threat that we need to have the countermeasure for, and then the Department of Health and Human Services executes the research and public health measures to go into getting that particular countermeasure. Mr. Van Hollen. Have there been any decisions to date with respect to the need to move forward on the production of any countermeasures? Dr. Klein. In terms of looking at production, we need the R&D to develop a product, and then as soon as that is evaluated, all of our agencies look with the limited resources how can we best meet the threats as we see them. We at the Department of Defense have an anthrax producing program. We work closely with Department of Health and Human Services with the smallpox, for example. Mr. Van Hollen. I remember at the time there was a lot of questions about whether we had adequate anthrax supplies or not. Other than anthrax and smallpox, have there been any decisions with respect to moving ahead on countermeasures on other agents whether chemical or biological? Dr. McClellan. We have worked with the Department of Homeland Security and others to identify some of the immediate opportunities that we think BioShield would help us fulfill even more quickly. So, for example, a better vaccine for anthrax, a better, safer vaccine for smallpox, and better antitoxins for botulinum toxin are all areas where the technology exists, and what's needed is the funding to get companies to follow through to produce the actual products. Mr. Van Hollen. Thank you, Mr. Chairman. Next round of questions I do have a concern that Mr. Waxman raised with respect to resources--we have limited. Chairman Tom Davis [presiding]. Keep going. You have 5 more minutes. Mr. Van Hollen. One question. Obviously there are all these possible threats out there, biological, chemical, nuclear. As a Nation we obviously have to evaluate the threat--the level of the threat posed and the likelihood--what kind of damage it will cause, and the likelihood of that threat versus what we know are very known threats that we are facing every day, heart disease and a whole range of medical problems that NIH is engaged in research with right today. And I am concerned that this will--you know, it is one thing to add additional resources to this effort at a time since September 11th, an emergency and a focus on this, but I would hate to see it come at the expense of what we know are diseases that are harming and killing Americans every day. And so my question is of the amount of resources that is being invested in this effort and research, how much of that is coming out of what otherwise would be invested in nonbiological and chemical research? Dr. Fauci. If you look at the resource curve of the last 2 years, which have been heavily weighted in the arena of biodefense, the other areas, in fact, have not suffered. Now, obviously the NIH has gone through a doubling, which it has completed successfully. The next few years, obviously if one looks at what is coming forth as the budget from the administration as was expected, it is not going to continue at that level, it is reaching a point of plateauing. But within the framework of that, again, we have tried as best as possible to not damage the effort and the momentum in other areas. So what has happened thus far with the doubling of the budget has not taken away from other areas. It has been a substantial and very generous increase in NIH's budget. Dr. McClellan. I would like to respond to that from the standpoint of product development. After you have done the basic research, approve the concept, is this going to take away from the development of much-needed new products for cancer, heart disease and other priority areas? We have seen over the past decade a huge expansion of the biotech sector, pharmaceutical research and development and so forth. While NIH's budget has been doubling, the research investments in development and applied stages on the private side have also been doubling as well. And what is responsible for that is the potential for some real breakthroughs especially in naturally occurring diseases that the private sector is trying to step up to address. By adding on these additional financial incentives for BioShield, we provide more incentives to get more investment activity, research and development in these other priority areas as well. As long as the financial incentives are there, the incentives to develop products will be there. We aren't taking away incentives in cancer, heart diseases and naturally occurring diseases. We are correcting a deficiency that exists in these unnatural diseases. Mr. Van Hollen. Thank you, Mr. Chairman. Chairman Tom Davis. Thank you very much. I have a question for the panel. Do you consider the acquisition flexibilities that are contained in the Senate bill, do you think they provide adequate incentives to spur the development and supply of critical countermeasures? Dr. McClellan. We do think that they would provide some much-needed incentives. Obviously there have been some different views expressed about what's needed to actually bring these next-generation products to the public, and we are absolutely willing to work with this committee and other experts on making sure we have the right framework in place to do that. I do think the most critical element's there, making sure that there's a certainty of payment, sometimes years in advance, if an effective, highly valuable product is actually developed, approved and delivered for use by the public in the event of a terrorist or other emergency health threat. Chairman Tom Davis. There is a consensus here that we just don't have the in House capability to take this in government and do it by ourselves. Everyone agree with that? There is no way we could build that up in a short period of time. So we are by necessity forced to go to the private sector to incentivize them to do things they otherwise wouldn't do. Dr. Fauci. Of which they do very, very well. They do it very, very well. Dr. McClellan. It's not easy to develop a product that is safe and effective and reliably produced even after you have gotten through the basic research and have a proof of concept. There is a lot of testing that needs to be done of potential toxicities that need to be determined in each individual case. There is effectiveness testing, which is particularly challenging in this area because you can't do normal testing on humans. And there are all kinds of challenges to getting ramped efficient production, labeling and delivery of the product. These are things that the private sector does extremely well in many other areas of medical technology, and we have seen the benefits of that for the public. We haven't seen the same kinds of benefit here, and we need them. Chairman Tom Davis. I guess one of the differences we have is--in the next panel, we are going to hear concerns that the BioShield does not really afford manufacturers of the biomedical countermeasures enough protection against product liability lawsuits. Obviously they are going to be engaging in research and development and manufacture of things they wouldn't do otherwise. We are trying to get them to do it. If they are exposed to massive lawsuits, it could bring the company down, expose the rest of their business. I don't know what the right balance is. That is something we need to try to find. And the companies, I think, are trying to get as much protection as they can. Anybody have a feel for the right balance here? Dr. McClellan. As a general matter, the administration has expressed some concerns about problems of liability exposures for manufacturers creating roadblocks to developing needed new treatments, and in this case it is something that we all need to think carefully about. We believe that there's a lot that can be done under authority, Section 85-804 authorities, that we have and under the Safety Act to provide protection for manufacturers for products that are being purchased by the government and used in these emergency situations. But obviously this is an issue that needs careful attention and should be addressed effectively. Chairman Tom Davis. It has been a tough issue in the Congress. The House and Senate are a little divided on it as well. Finally, the administration's proposal gives the President permanent funding authority for research, development and production of biochemical countermeasures. What do you think this could end up costing at the end of the day? Dr. Fauci. The initial projection that was made based--and again, this is something we try to scope out because you are dealing with scientific opportunities that can change due to breakthroughs as well as change in the risk assessment, but in the President's proposal, the 10-year proposal for the Project BioShield procurement was about $5.6 billion over 10 years. Chairman Tom Davis. Our problem, of course, is we don't know what diseases could come forward. Dr. Fauci. It could be more, it could be less. Dr. McClellan. I would like to emphasize, though, that none of this money gets spent unless, No. 1, we make a determination that the countermeasure is needed and is truly valuable. We set the term for the contract. If we don't think a countermeasure is worth the cost, it is not going to get a contract, and we don't actually pay--we don't pay any significant amount unless that countermeasure actually gets delivered and does work. Chairman Tom Davis. What's clear is that the current law does not afford us the flexibility that we need to encourage industry. Dr. Fauci. We can't give assurances to them, as I said in my opening statement. We can't tell them and say we want to get involved in this. We are willing to take risks even. We have people who come to us and say, we've reached a certain point, and now we need to go to the next step of building a new plant or investing another $100 million or so, but we are willing to take that risk, but we're not willing to take a risk of being successful in what we do and then finding out that no one wants to buy the product. So can you give us an assurance under current law given the vicissitudes of the appropriation process? We really can't give them firm assurances that if they deliver, as Dr. McClellan said, a licensable or licensed biomedical countermeasure, we can't give them the kind of assurances under the current situation that we would be able to do under Project BioShield. Chairman Tom Davis. Any other questions over this side? Mr. Waxman. Thank you, Mr. Chairman. Let me ask about the streamline procurement acquisition procedures. There is a simplified acquisition authority here, and these authorities in the law were established for commercially available items such as office furniture and automobiles. And the idea is there is a developed market for these products, and the government can rely on market forces to keep the prices low. When the government is bidding for a special government service, however, there is no market that's available to keep costs low, and two basic safeguards have been developed; one, requirements for bidding and full and open competition and, when the contract is cost-based, the ability to inspect the contractors' books. As I understand it, the procurement provisions waive or relax both of these standards. I am in favor of speeding up the procurement where there is a need, but at the same time how do we protect the taxpayers? If the contract is cost-based, how does the government know it is not being overcharged if it can't audit the contractors' books? Anyone want to respond? Dr. Fauci. I'll take just a brief shot at it. We appreciate that concern, and there's obviously a lot of scrutiny in what we'll be doing, because we're acting in only special circumstances. But your point is very well taken, and we're very sensitive to it. The main concern that we have is that we do not slow down the procurement process to the point where it interferes with the responsibility for what we have. We are not dead set against relooking at that with you, and we, in fact, would be willing to work with you and the committee on that concern which you've expressed. But the critical, really bottom-line issue is that we really cannot slow down the process, and if we can figure out a way to get it to do that, we would be---- Mr. Waxman. I understand that, but we are changing the procurement law, and if the government doesn't have a market to drive the prices lower, and it is a cost-based reimbursement, and we don't have the ability to look at their books and know whether they're getting ripped off, that puts us in a position of being deep pockets. And I think we've got to evaluate that balance here to make sure we're protecting the taxpayers and not just the American public. Dr. McClellan. And if I could add, the whole goal here is to create something like a market. You're right, there is no market that exists now, but the contracting authorities that BioShield would create would permit more than one firm to compete to get this countermeasure produced first. And again, we're paying for results primarily, not for just costs along the way. The simplified acquisition authorities have been shown to work pretty well in combination with antikickback laws and fraud laws and the like to prevent those kinds of concerns in many cases. Mr. Waxman. It will be a while before there would be a market. If you're helping a company develop a product for which there's no availability at the present time, do we help them with money, and then we streamline the process for them, and they develop it, and we give them the patent, and they'll have exclusivity over that, and then we're buying it from them, and we want to be sure since there's no real competition we're protecting our taxpayers' money? Dr. McClellan. I do think we can create some competition there by contracting with more than one company and giving a larger payment to the one that gets there first. Chairman Tom Davis. Would the gentleman yield? Mr. Waxman. On the antikickback, that's a protection, but as I understand it, the antikickback law is exempted under the proposal, so we wouldn't have that available to us if that's something that won't come into play. Chairman Tom Davis. I think the gentleman raises an interesting point. On the other hand, for the most part we're going to give this on a results-oriented basis. If companies go out and do research, and they come up with basically a dry hole, they probably get nothing; is that correct? Dr. McClellan. That's right. Chairman Tom Davis. Unlike a lot of IT contracts where we end up buying information technologies and spend billions and sometimes get systems that don't work. At least it is results- oriented, which cuts down the fraud, waste and abuse that could come otherwise. But there is a question of balance, and it's how sophisticated are we on our side, and look forward to working with Mr. Waxman and others trying to find the right balance. Mr. Waxman. Let me ask a question on this liability issue. I understand why we want to give liability protection to the manufacturers of these products, and it is very much on their minds if you want to give them all the incentives. But on the other hand, if we're going to indemnify the companies that manufacture countermeasures by providing the liability protection, some of these products still may harm consumers. If the administration can guarantee liability protection to manufacturers, should it also compensate those who are injured by the products? Dr. McClellan. There is a lot of discussion ongoing now about compensation in the case of smallpox, which is a countermeasure that does have some significant adverse effects in certain cases. The idea for the kinds of technologies that we hope to develop here is to have some that are significantly safer and more effective that would reduce the need for those kinds of compensation activities. And also the use here will be under conditions that are very much defined by the government in emergency situations and the like and that we at FDA approve and determine that treatments are appropriate for use under these circumstances. So it is a more limited case and problem. I know smallpox is on your mind, but it is a much more limited situation than that. Mr. Waxman. Mr. Chairman, I want to take advantage of the fact that Dr. McClellan is here to ask him about a different issue unrelated to the BioShield. At a hearing---- Chairman Tom Davis. I am sure that wouldn't happen, but that's fine. Mr. Waxman. If he doesn't feel ready to answer the question, I would certainly accept that response. But we had a hearing on Internet pharmacies, and a representative from the Federal Trade Commission testified that any claim that a dietary supplement containing ephedra is safe would be false and misleading under his view at the Federal Trade Commission. I want to know if you agreed with their view on the safety claims on ephedra products, and to ask you whether you are aware of any studies that prove that ephedra containing dietary supplements are safe for the general public. Dr. McClellan. We just completed a review by the RAND Corp., that I know that you are familiar with because we talked with your staff about it, on the safety and effectiveness of ephedra. And as you know, under the dietary supplement law we don't get the evidence up front on dietary supplements if they are safe and effective before they go on the market. We have to prove a safety problem or an effectiveness problem before we can take any regulatory action, and that was the point of the RAND study. Subsequent to the RAND study, we have reopened the record on FDA's old 1997 regulation to restrict use of ephedra based on safety and effectiveness concerns, and we have asked for comments from the public, and I noted today we just got one in from the American Heart Association, and I hope that there's going to be more coming before this comment period closes. That is going to help us address this issue of ephedra safety. What the RAND report said, as you know, was that while there have been some serious adverse events associated with ephedra, they could not prove a causal link between ephedra use and those events. Mr. Waxman. Let's flip it the other way. If you can't show that it's harmful, do you know of any studies that prove that ephedra-containing dietary supplements are safe? Dr. McClellan. It hasn't been proven to be safe, but the statutory standard is not---- Mr. Waxman. I am not asking about the statutory standard. I understand that is important. But what do you think about the comment by the representative of the Federal Trade Commission if there was a claim that the supplements that contained ephedra was safe, that this would be a false and misleading statement? Dr. McClellan. It could well be a problem with truthful and not misleading standards, which do govern both FTC's advertising regulations and our labeling regulations. So that is a potential concern. My hope is we can do more to address the concerns that exist today about the way that ephedra is marketed, and that's the reason that we reopened this comment period and have laid out our preliminary view that the law doesn't require us to prove that ephedra is unsafe; rather we need to demonstrate that it presents an unreasonable risk to the public as it's currently marketed, and we hope that we'll get comments from you about how we can best address that as well. Mr. Waxman. Thank you very much. Chairman Tom Davis. Mr. Shays, any more questions? Mr. Shays. Yes, I do. Dr. Fauci, what is the relationship between NIH and DOD joint vaccine acquisition of the JVAP program? Dr. Fauci. Thank you for the question, Mr. Shays. The NIH has worked in the past with DOD and in some respects with the JVAP program, and we are now increasing our collaborations particularly with USAMRIID. The Joint Vaccine Acquisition Program, which was operational in 1998, was focusing more on the long-term development of products against biological warfare, and we at the NIH feel that it doesn't directly address the urgent and civilian needs and demands that we have. And that's one of the reasons why we've looked for alternative ways to hasten the development and interest in industry in vaccine development. Although we've interacted with them on JVAP, but even more intensively, broadly with USAMRIID, this is not an important part of our program. Mr. Shays. So your basic position is it's not going to fit into the Project BioShield program. Dr. Fauci. No, it's not in our minds, sir. Mr. Shays. Has the JVAP been the subject of third-party evaluations? Dr. Fauci. Yes, it has. In December 2000, there was a report called the Top Report, a report to the Deputy Secretary of Defense by an independent panel of experts, and they came up with some areas that were problematic with regard to JVAP and talking about ways that need to be improving it. And I think instability of funding was cited as a major deficiency as well as some lack of scientific oversight. So it has been somewhat of a problem. I haven't---- Mr. Shays. Are you being a little gentle in describing the evaluations? There is $300 million that's been spent? I mean, weren't the reviews pretty strongly critical? Dr. Fauci. They were quite critical of the program, yes. Mr. Shays. Dr. Klein, how would you kind of respond--first off, Dr. Fauci, is there anything you want to say about this program? You are basically telling me you're not going to--you don't see being involved in the BioShield program. Are there lessons we have learned from this in terms of what we do with BioShield? Dr. Fauci. I think so. We learned a lot of lessons along the way. One of the things I think we've learned that we have to have is we have built into BioShield a significant amount of scientific oversight and stability of funding and some strategic planning of where you are going to go and to try to bring in the very best of industry and not give them the full component, as Dr. McClellan has mentioned, until we have a deliverable product. One of the difficulties with putting a lot of money up front and up forward without getting a guarantee of a product is that there is always the risk of failure, and that's what we're trying to avoid by making the stipulation of BioShield that you have to have a licensable product that's delivered before you get your full payment. Mr. Shays. Dr. Klein, is there anything you want us to know about JVAP? Dr. Klein. Congressman Shays, I think the comments made earlier are quite accurate. As you know, this program was started in about 1997. It's a 10-year program. So it was a start. But I think our experience with JVAP demonstrates BioShield's value; for example, incentives for companies to go toward making products. And then the other one I think is more important, certainly after September 11th, is that the interagency cooperation between DOD, DHHS and Homeland Security. So I think we really need to look at this in a more comprehensive manner. As you know, JVAP was intended to meet the needs of the men and women in uniform. That was its initial intent. After September 11th I think we realized they are not the only ones that need these vaccines. Mr. Shays. So far the program has spent a lot of money, and it has been found wanting, correct? Dr. Klein. The original JVAP, the intent was good, but it has not been as successful as we wanted. Mr. Shays. Let me just ask, Dr. Fauci, if we manage to engage the industry, what is the most useful role for NIH and its grantees? How does it focus on research that is not competitive and duplicative with that of the industry? Dr. Fauci. Traditionally, and we hope it continues and amplifies, that the NIH research has really been the fuel that fires the engine toward the ultimate translation into products, which the industry does so well. That is not to say that the industry does not do some very important research themselves, but it has really been essentially a continuum where NIH grantees provide the basic research, the proof of concept, and even the development up to, but not including, advanced development. We generally push the envelope into phase 1/phase 2 trials and the early part of development. That would be a natural marriage that we would see work well with BioShield to then call upon industry to make the investment, and what they do so well is delivering a product. So it's quite complementary, sir. Mr. Shays. Mr. Chairman, may I ask one more question? Mr. Brown, what are the problems the government faces in trying to engage biotech and pharmaceutical companies in launching research and development projects to develop medical countermeasures? Mr. Brown. I think it's the lack of a secure source of funding. They need to know that if we make the determination that there is an imminent danger and real threat out there, and they can produce what is results-oriented, they can show us a product, they're going to get paid for it. It is the lack of incentive. Mr. Shays. Thank you. Thank you, Mr. Chairman. Chairman Tom Davis. Thank you all very much. We appreciate it very much and thank you for being here. It has been very, very helpful, and we are ready to move to our next panel of witnesses. Our second panel includes industry and academic experts who will give us their views on this proposal. We have Frank Rapoport an attorney representing Aventis Pasteur. Next we will hear from Dr. Michael Friedman on behalf of the Pharmaceutical Research and Manufacturers Association of America. We also have Dr. Una Ryan, president of the AVANT Immuno-therapeutics located in Needham, MA. And Dr. Katherine Bowdish. She is president of the Alexion Antibody Technologies located in Cheshire, CT. And rounding out the panel is Dr. John Edwards, chief of infectious diseases at UCLA. Give everyone a minute to make sure we have your name tags appropriately, and thank you for bearing with us through the questioning of the first panel. We have a light in front, and it will be green for 4 minutes, and then it turns orange for the last minute. When it turns red, we want you to sum up. Your entire testimony is in the record, and we and our staff have read it all and have questions prepared on that, but you can use your 5 minutes to highlight. I'm going to ask you to stand with me to be sworn in. [Witnesses sworn.] Chairman Tom Davis. We will start with Mr. Rapoport and move straight down the line. STATEMENTS OF FRANK RAPOPORT, ATTORNEY AT LAW, MCKENNA LONG & ALDRIDGE, ON BEHALF OF AVENTIS PASTEUR; MICHAEL FRIEDMAN, CHIEF MEDICAL OFFICER FOR BIOMEDICAL PREPAREDNESS, PHARMACEUTICAL RESEARCH AND MANUFACTURERS OF AMERICA; UNA RYAN, PRESIDENT, AVANT IMMUNOTHERAPEUTICS, INC., NEEDHAM, MA; KATHERINE BOWDISH, Ph.D., PRESIDENT, ALEXION ANTIBODY TECHNOLOGIES, CHESHIRE, CT; AND JOHN EDWARDS, CHIEF OF INFECTIOUS DISEASES, HARBOR-UCLA MEDICAL CENTER, ON BEHALF OF THE INFECTIOUS DISEASES SOCIETY OF AMERICA Mr. Rapoport. Good morning, Mr. Chairman and members of the committee. I am Frank Rapoport, a partner in the Philadelphia office of McKenna Long & Aldridge, where I practice government contract and public health law. I had the privilege of working both in the Reagan and Carter Justice Departments in the Government Contracts Section and more recently was involved in both smallpox procurements, the first one pre-September 11th, and the anthrax procurement more recently at NIH on behalf of Aventis Pasteur, the largest vaccine manufacturer in the world devoted entirely to vaccine research, development and manufacturing, manufacturing a billion and half doses annually, based in its headquarters in northeast Pennsylvania. My purpose today is limited to offer some technical amendments to this bill which may make the difference between success and failure in either attracting the best and the brightest or simply those who have nothing to lose but accepting government money. I offer five points to achieve broader and bolder procurement authority, all giving discretion to the various Secretaries to use as arrows in their quiver. There is no doubt that the existing government regulations, known affectionately as the FARS, give contracting officials ample authority to make contractors perform. Our five points today will protect the contractor against all but its own failure. Point one, the bill, quite frankly, is a little stiff. It does not amply provide for a single procurement that combines both research and development and a guarantee of production. There must, in our view, be a linkage to get the attention of companies like Aventis, who are going to be passing up lost opportunities and feeling the uncertainty without commitment for production. Point two is related to this. These contracts should also recognize the costs of capital and return on capital. It should assure payments sufficient to amortize investment, which would include return of capital and return on capital. The point is if we're not going to be accepting government money under R&D within this contract, we need to make sure that our investors feel comfortable that there is a product at the end of the pipeline and in the event, most importantly, of an early termination for convenience because, for instance, Dr. Fauci has found yet a better drug. The company must know that it's going to get reimbursed for the work that it spent under its own nickel under that government contract. The existing termination for convenience regulations do not allow for recovery of what we would call loss of interest or investor cost. So when I suggest the bill is a little stiff, we feel it's a very good bill, but you need to be heard loud and clear that we want to give much broader authority to the Secretary to encourage companies to perform. How can this be accomplished in one contract vehicle? It would be one contract where research and development is included. We're not suggesting who's going to pay for that. That's up to the government to negotiate with the company. At the same time, there's a guarantee of production, but the cost of the units will not be determined until the research and development is over. This is always done in a privatized procurement. We call it price determination. That can be done to include the estimated costs of production as well as a capital charge. Point three, we strongly encourage to move beyond plain vanilla government contracts, something you're well aware of which this committee called ``other transactions'' and is used routinely by DARPA and NASA and actually generated the Predator, the unmanned vehicle that is being used in Afghanistan. These are commercial-like arrangements that entice and allow government contractors like Aventis to feel free that they will get to protect their rights. Point four as proposed in the bill, a 5-year contract without subsequent guaranteed appropriations appears to run afoul of 31 U.S.C. 1341. You certainly can take a minor correction to make sure that this act is taken care of. Finally, the issue that you've heard already today, indemnity. We truly understand the urgency of this bill, but we feel obligated to note the issue of liability protection remains a concern for us. Both HHS and DHS have authority under Public Law 85-804. It has been used rarely. Most recently President Bush signed an Executive order which even cuts back on the authority of Public Law 85-804. Currently, while HHS has used this act, we understand it is not until after a contract is awarded. Imagine a bidder looking at dealing with inhalation airborne anthrax, doing clinical studies. A bidder company such as Aventis would like to know for its shareholders that it can bank on likelihood of indemnity postaward. In summary, Mr. Chairman, thank you for the opportunity to testify on this important issue. As you know, we were the donor of 85 million doses of smallpox vaccine. We will be committed to supporting the efforts of the Secretaries to contributing to our common defense. Thank you again. Chairman Tom Davis. Thank you very much. [The prepared statement of Mr. Rapoport follows:] [GRAPHIC] [TIFF OMITTED] T7141.034 [GRAPHIC] [TIFF OMITTED] T7141.035 [GRAPHIC] [TIFF OMITTED] T7141.036 [GRAPHIC] [TIFF OMITTED] T7141.037 [GRAPHIC] [TIFF OMITTED] T7141.038 [GRAPHIC] [TIFF OMITTED] T7141.039 [GRAPHIC] [TIFF OMITTED] T7141.040 Chairman Tom Davis. Dr. Friedman. Dr. Friedman. Thank you, Mr. Chairman and distinguished Members. On behalf of the Pharmaceutical Research and Manufacturers of America, I am pleased to be here today to share with you the views of the research-based pharmaceutical industry and the President's Project BioShield Initiative. Biological weapons represent an increasingly serious danger to people around the world. The dynamic complexity of the problem is demonstrated by science's difficulties in dealing with naturally occurring infectious disease as well as intentional bioterrorist threats. While PhRMA companies are developing more than 200 new medicines to treat or prevent various infectious diseases, reports by the National Academy of Sciences, the NIH Blue Ribbon Panel for Biodefense Research, and the U.S. Defense Science Board make it clear that an even larger number of more diverse types of countermeasures must be developed, and they must be developed promptly. Although the basic science research required for countermeasure development is being supported by Federal agencies, it is widely recognized that more sponsored research is needed. There also needs to be more flexible authority and more resources for regulatory agencies; in short, those things which will advance the development and production of the countermeasures. PhRMA member companies have been active in moving forward on countermeasure research and development. As indicated in my written testimony, for example, PhRMA is working with CDC, DOD, NIH, FDA and academia to support invitro studies of five important pathogens as model systems for antibiotic testing. Several companies are working with the National Institutes of Allergy and Infectious Diseases to help test existing antibiotics against plague. Other examples of ongoing collaboration are outlined in my testimony. A cooperative and collaborative research and development effort which engages industry, government and academia will, however, be essential to this effort. PhRMA believes that Project BioShield is an important step toward this, and we support the three main components of the President's proposal. The President's proposal speaks primarily to the early and to the later stages and the lengthy high risk and costly process of bringing new medicines to the market. It does not, however, speak to the time-consuming and resource-intensive middle portion of that process, which is largely our responsibility. Further, research into biothreat countermeasures presents challenges beyond those ordinarily encountered in nonbiodefense R&D. These include scientific challenges, economic challenges and legal challenges, and I will enumerate a couple, if I may. For example, some products will be distributed without the typical battery of clinical trials that are required for FDA approval. All medicines present inherent and unavoidable risk of adverse events. As a result manufacturers may be exposed to devastating product liability suits. Private insurance can be unavailable or prohibitively expensive. Second, the need for rapid development of countermeasures may require the sharing of scientific information and cooperation among companies; for example, the sharing of data by researchers working in different laboratories. Collaboration and cooperation in this research might create exposure under current antitrust laws. Third, diverting resources from research and development of other medicines will affect the future availability of treatments and cures for patients with other serious health conditions, especially since only a tiny percent of all drugs that enter testing ever demonstrate sufficient human safety and acceptable efficacy. The allocation of resources can be particularly difficult with few products in the pipeline. In order to best meet the public health needs of our citizens, PhRMA looks forward to working with in, a transparent manner, Congress and the administration to enact measures that will provide appropriate product liability protection for products that are procured under BioShield and for products that are distributed under the emergency authorization procedures of BioShield. Although existing indemnification authorities are a helpful step in the right direction for some government contractors, they are not an appropriate model for legislation implementing Project BioShield. Instead, we would urge Congress and the administration to expand and, as appropriate, modify the liability protection model that this Congress has already put in place for smallpox. PhRMA also looks forward to working closely with Congress and the administration to enact narrowly tailored measures to address existing antitrust constraints as appropriate in order to allow needed collaboration and consortium among scientists and industries. My written testimony includes the memorandum from outside counsel explaining both the need and the precedent for a narrowly tailored antitrust provision that would apply in this very special context. Cooperation and strong commitment from all parties will be necessary in the months and years to come as our Nation seeks to protect itself against the terrible threats of biowarfare and bioterrorism. America's pharmaceutical companies look forward to doing our part. I thank you for this opportunity to address you and look forward to answering your questions. Thank you. Chairman Tom Davis. Thank you very much. [The prepared statement of Dr. Friedman follows:] [GRAPHIC] [TIFF OMITTED] T7141.041 [GRAPHIC] [TIFF OMITTED] T7141.042 [GRAPHIC] [TIFF OMITTED] T7141.043 [GRAPHIC] [TIFF OMITTED] T7141.044 [GRAPHIC] [TIFF OMITTED] T7141.045 [GRAPHIC] [TIFF OMITTED] T7141.046 [GRAPHIC] [TIFF OMITTED] T7141.047 [GRAPHIC] [TIFF OMITTED] T7141.048 [GRAPHIC] [TIFF OMITTED] T7141.049 [GRAPHIC] [TIFF OMITTED] T7141.050 [GRAPHIC] [TIFF OMITTED] T7141.051 [GRAPHIC] [TIFF OMITTED] T7141.052 [GRAPHIC] [TIFF OMITTED] T7141.053 [GRAPHIC] [TIFF OMITTED] T7141.054 Chairman Tom Davis. Dr. Ryan. Ms. Ryan. Mr. Chairman and members of the committee, thank you very much for inviting me to testify before you on Project BioShield. I am the president and CEO of AVANT Immunotherapeutics, a small 60-person biotech company in Massachusetts. I am also on the board of the Biotechnology Industry Organization, and I am chairman-elect of the Massachusetts Biotechnology Council. As the Federal Government embarks on BioShield, a new and challenging program to fight bioterrorism and biological warfare, let me assure you that the biotechnology industry stands ready to contribute and work toward its success. Our eagerness to participate, however, cannot be unqualified. As the leader of a small company, I cannot embark on the development and supply of biodefense vaccines if doing so doesn't make business sense. Let me, if I may, give you my view of BioShield from the perspective of a small company. AVANT is a small company, and it's a vaccines company. Prior to September 11th we made vaccines for protecting travellers against cholera, typhoid fever and dysentery. We make antiviral vaccines for diarrhea in babies, for food safety, and we even have a vaccine that raises your HDL, your good cholesterol. After September 11th, we moved to apply our advanced vaccine technologies to biodefense, as they have much to offer. For example, the current inventory anthrax vaccine provided to U.S. troops is administered through multiple injections, about 6 over about 18 months, which are often painful with side effects. And once the injections have begun, the protection develops gradually over several months. We think we can do better, and to my great pride we signed a contract in January that allows us to supply most advanced vaccine know-how to the biodefense effort. Under our contract with DVC, DynPort Vaccine Co., the prime contractor to the Defense Department's JVAP, Joint Vaccine Acquisition Program, we have begun development of a single-dose oral vaccine that will protect our troops against both anthrax and plague at the same time. This vaccine will have the same features as our cholera vaccine developed for the travellers' market, administered in a single oral dose, safe and well tolerated by the recipient, with immunity developing very rapidly in days, not weeks or months. Manufacture of this vaccine is easy and inexpensive to current--by comparison with current generation vaccines. And in addition, we can provide this in a form that does not require refrigeration. Under the current plan we expect to complete preclinical development of this vaccine by the end of calendar year 2004. To my knowledge, it is the most advanced vaccine technology currently under development anywhere in the government's biodefense program, civilian or military. So how does this experience shape my view of BioShield? Here are the central characteristics that I'll be looking for in BioShield. First, BioShield must create a market of sufficient size to convince the industry that we have a partner who understands the costs and complexity and risk of developing therapeutics and bringing them to market. Now, the research in any clinical stages may take tens of millions. But as you move through the final stages of clinical development over the finish line, it takes hundreds of millions, and biotech companies will want to see a Federal program of sufficient size to convince them that our effort can be funded throughout the life cycle of the program. Second, there must be a long-term commitment of funding. The development of biomedical countermeasures takes time; 5 to 10 years is very aggressive, and more than 10 years is not uncommon, and although we are making quick progress on things such as anthrax and plague, there are other less well known agents that may become terrorist threats. And we have heard a lot of talk about SARS, and we have barely begun to work on that yet, though some of the technologies will apply. To meet the nuclear missile threat, the government has spent a minimum of $3 million annually for I think now 20 years. That kind of long-range commitment will convince companies that the government is serious about defeating biological threats. Third, there must be careful coordination, and we touched on this earlier, among the agencies, including a program management function that can bridge the divide between the NIH and the early discovery and research phases and the procurement at the Department of Homeland Security. And one of the most experienced acquirers of complex products is the Department of Defense, and in the Department of Defense, in JVAP, they have a program management function that I think could well be applied through the life cycle of products as they progress through BioShield and bridge the gap between the NIH and the Department of Homeland Security. Fourth, two of my colleagues have mentioned it, there must be adequate liability protection. I am not going to go into it further, but simply say that from the point of view of a small company, it isn't even a meritorious legal case that is a threat; even just the threat itself of liability is enough to prevent investment and put small companies out of business. So this is a risk that small companies simply can't take. The bill introduced by Senators Lieberman and Hatch also provides for liability protection. Their legislation offers us protection in the context of comprehensive incentives for biotechs, and perhaps an approach like that can be incorporated into the BioShield concept of government-created markets that pull firms into this worthy effort. So although I am very optimistic about the opportunity for success, I want to close with a personal experience that actually leaves my hope tinged with concern and, frankly, keeps me awake at night. We at AVANT have put huge amounts of resources into our program for a single-dose oral anthrax/ plague vaccine, and we have a partner who is willing, the Joint Vaccine Acquisition Program, but we found that the 2004 budget has been slashed from the level it received in fiscal 2003. So even if we are successful and deliver absolutely on the contract that we have now for the preclinical 2-year program, I am very concerned about the future of what is a really outstanding vaccine approach, because, as you heard, there may be rather little incorporation of the Department of Defense programs into BioShield. So I want to be sure that this doesn't become an example of how, despite the best of intentions, failure of the many agencies involved to keep their coordinated eye on the biodefense ball could undermine effective programs and partnerships. So I remain hopeful that working together the government and industry can make BioShield work for the national interest. I applaud your leadership in holding this hearing and meeting the challenge, and I assure you that our industry will be a willing partner. Thank you very much, and I will be happy to answer questions. Chairman Tom Davis. Thank you very much. [The prepared statement of Ms. Ryan follows:] [GRAPHIC] [TIFF OMITTED] T7141.055 [GRAPHIC] [TIFF OMITTED] T7141.056 [GRAPHIC] [TIFF OMITTED] T7141.057 [GRAPHIC] [TIFF OMITTED] T7141.058 [GRAPHIC] [TIFF OMITTED] T7141.059 [GRAPHIC] [TIFF OMITTED] T7141.060 [GRAPHIC] [TIFF OMITTED] T7141.061 [GRAPHIC] [TIFF OMITTED] T7141.062 Chairman Tom Davis. Dr. Bowdish, thanks for being with us. Ms. Bowdish. Chairman Davis and distinguished members of the committee, I am honored to present this testimony on the application of monoclonal antibodies, the very latest biotech solution for defense against the very real threat of bioterrorism facing our Nation today. It's my understanding that the BioShield Initiative is designed to give key Federal agencies what amounts to fast-track authority for the review and approval of private sector solutions to fight the agents of bioterrorism. I wholeheartedly support the concept behind this and other legislative approaches such as the Lieberman-Hatch bill in the Senate. There is no better way to generate new therapies than to let the top people in their respective fields bring the best ideas to the table. I know these legislative efforts importantly address long- term problems, but I also hope that NIH and other Federal agencies will take immediate steps that address the very real threats that we all face right now. As we saw in the attacks against our Nation in 2001, inhalation anthrax is a highly fatal disease if not identified early enough for antibiotics to be of use. Death usually occurs within a few days of the onset of acute symptoms, primarily from the toxins produced by the anthrax bacteria, not the bacteria itself. In addition to antibiotics directed against the bacteria, successful anthrax defense will require agents against the toxins otherwise known as antitoxins. Monoclonal antibodies are among the most logical and natural antitoxins that could be developed for the treatment of anthrax. Human monoclonal antibodies have been proven safe and effective for many therapeutic purposes, and I am confident that they will have similar success as bioterror antitoxins. Alexion has successfully isolated human monoclonal antibodies with therapeutic potential for biodefense. For over a year we have had antibodies that could provide the most complete protection from anthrax toxin available. These antibodies, either alone or in combination, may be useful as a prophylactic at the onset or during or at the course of an active infection. As detailed in the written testimony, this work has been discussed with and presented to a large number of scientific experts on anthrax and biodefense in industry, academia and government. All of these individuals agree that the approach we are taking is a necessary and achievable component to U.S. biodefense initiatives. Alexion's biodefense program against anthrax has been entirely self-supported to date. We saw a need, and we recognize that we had the ability to offer our technology and our expertise. And most importantly, we have demonstrated that our approach works. It is our hope that Congress can help us ensure that the appropriate decisionmakers in our Federal Government are aware of our critical and highly relevant work for consideration for civilian and military defense. It is our desire to coordinate with government officials to see that our antibodies and our expertise are utilized for emergency stockpile generation to protect both the civilian and military populations. Building the necessary emergency stockpiles is certainly something that no one company can or should accomplish solely with private funding. Therefore, we are looking for assistance from the Federal Government through NIH for the final phase of development of this critical therapy. Further, we are currently applying the same technology to additional agents of bioterror in our research laboratories. Preliminary results suggest we will have similar successes with smallpox, botulinum, plague and others. At the minimum, we hope emergency stockpiles of monoclonal antitoxins would deter would-be terrorists and alleviate public anxiety. Above all it is my hope we never have to look back from another bioterror attack and wonder what more could we have done and why did we wait. I thank the committee for this opportunity to present this testimony, and I welcome any questions. Chairman Tom Davis. Thank you very much. Dr. Edwards. Dr. Edwards. Chairman Davis and members of the committee, thank you for inviting the Infectious Diseases Society of America [IDSA], to present our views on the administration's Project BioShield. I am Dr. John Edwards, a professor of medicine at the School of Medicine at UCLA, and chief of the division of infectious disease at the Los Angeles County/ Harbor-UCLA Medical Center. Before I begin, I want to thank Dr. Fauci for his work on Project BioShield and his work at infectious diseases in general. He is a member of our society. I am testifying today on behalf of the IDSA to convey our strong support for Project BioShield and the novel incentives it creates. However, the United States' most pressing infectious disease problems are not limited to infections that terrorists may propagate. An immediate crisis exists currently in U.S. hospitals and in our communities as naturally occurring infections become increasingly resistant to approved antimicrobial products. Additionally, naturally occurring infectious diseases exemplified by meningitis pneumonia, tuberculosis and AIDS are still the leading cause of death worldwide and the third leading cause of death in the United States. Furthermore, emerging infections such as Severe Acute Respiratory Syndrome [SARS], and West Nile virus are continuing threats. Antimicrobial resistance whereby microbes mutate and become less susceptible to drugs has created special concerns. You probably know of the cases of vancomycin-resistant Staphylococcus aureus [VRSA], that occurred in Michigan and Pennsylvania last year. This occurrence is highly significant since vancomycin is typically a last resort agent. Similarly methicillin-resistant Staphy aureus, which previously affected mainly hospitalized patients, now is infecting healthy and strong individuals and communities across our country. Upon this background, the IDSA has learned that a, ``perfect storm,'' if you will, is brewing as many pharmaceutical companies are considering or already have withdrawn from anti- infective drug development. Many companies have greatly curtailed, wholly eliminated or spun off their anti-infective research components especially over the last 5 years. A list of these major pharmaceutical companies is provided in our written statement. Antimicrobials work often quickly and with successful results. Understandably, pharmaceutical and biotechnology companies are inclined to develop products that treat long-term chronic illnesses because such products provide greater returns on investment. As U.S. demographics shift toward a more elderly population, we predict that companies will focus even more on chronic diseases in the future. Within the context of these realities, it is highly unlikely we can reverse the antimicrobial market failure without some form of specific well-designed intervention. Therefore, a national solution is needed to solve this national crisis. Project BioShield's long-term legacy will be enhanced significantly if it is amended to address the precipitous decline in the development of antimicrobial products to treat naturally occurring and resistant infections. Such amendments are supported by recommendations made by the Institute of Medicine in the Microbial threats report issued on March 18th. Thousands more Americans will succumb to naturally occurring infections in the next 10 to 15 years than to agents of bioterrorism, even if a bioterrorism attack occurs, and yet no plan is currently on the table to address this immediate public health crisis. We strongly support the concept Project BioShield, but we unequivocally urge that it be amended to include a framework for action to protect Americans against naturally occurring and drug-resistant and emerging infections that are increasingly present in our hospitals and communities. Chairman Davis, in your opening statement, you asked how can BioShield assist to address the SARS outbreak. In its current form, its assistance would be tangential. However, with amendments it could do much. In closing, we sincerely thank the chairman and all members of the committee for the opportunity to discuss the urgent need for new technologies and tools to protect U.S. citizens and global populations from both the threat of bioterrorism and the highly prevalent naturally occurring infections. The IDSA is available to assist in any way that it can. Thank you for sharing these concerns with us. Chairman Tom Davis. Thank you very much, Dr. Edwards. [The prepared statement of Dr. Edwards follows:] [GRAPHIC] [TIFF OMITTED] T7141.063 [GRAPHIC] [TIFF OMITTED] T7141.064 [GRAPHIC] [TIFF OMITTED] T7141.066 [GRAPHIC] [TIFF OMITTED] T7141.067 Chairman Tom Davis. The point you make, that with some amendments we may be able to shape this legislation up where it can help us with the SARS or the next Ebola or whatever, is very, very important. Sometimes we get an opportunity like this legislatively when we want to make it as inclusive as we can. So I think your point is well taken. We don't know what will happen from a bioterrorism point of view over the next decade. Hopefully nothing. But there are going to continue to be SARS and mutations and things that the private marketplace is going to be reluctant to get into without strong Federal help. And having a system up that could include these areas, I think would be very, very helpful. So we will take all of your comments into account as we try to write this legislation and move it through. I am concerned, and I am--I guess I will ask everybody. Putting--if we get this fund up, we put limited liability and the other things that are asked for in the legislation, a concern of an unintended consequence downstream being that all of a sudden putting so much into biomedical countermeasures, could it affect other biomedical research into more conventional areas? Can you find pharmacy companies all of a sudden putting their research into these areas where you have a guaranteed fund at the end that will pay for these, instead of taking the chance in the marketplace, and how will this affect more conventional research and development? Dr. Friedman. Thank you. I will begin. I am sure others will join in as well. The problem is, in a sense, caused by the fact that there are so many opportunities that are available. These are opportunities that have been made available because of the scientific investments that have been made in this country over the last 40 or 50 years. I think it is true to say that whether you are talking about an academic medical center, a pharmaceutical company, a large pharmaceutical company or a small company, there are vastly more promising ideas for helping people today than we have the time, the energy, the resources, the expertise or the dollars. And that is a continuing challenge for us all. As was pointed out, one of the reasons why pharmaceutical manufacturers have been putting less emphasis on infectious disease over the last decade is that there have been more urgent public health opportunities, cancer, Alzheimer's, other very serious diseases, where companies thought that important investments made there would help more patients. As we have come to recognize that the threats to our health change, we must rebalance the equation. There are no simple answers. There aren't enough resources or people or time to address all of the scientific and medical questions that legitimately exist. It is a real challenge for all of us to try and define what that right balance is. We must make those assessments and then we must constantly reevaluate and question those and decide how we can make the greatest contribution to the public health, with which source of investments of our energy and time and people. Chairman Tom Davis. I mean, in all fairness, you want to make contributions to public health, but you have a bottom line to your shareholders too. And if the money is available out there in these--in some of these other areas, it may be a more sure investment than some of the other areas. Dr. Friedman. It is theoretically possible. I think by far the more driving consideration will be how likely it is to be successful. So if we have a wonderful insight into multiple sclerosis or diabetes, the opportunity to contribute there--as you are well aware, because you understand this, there is a huge number of things that are screened and begin testing, and a tiny, tiny percentage that end up--not because people are sloppy or because they don't care, because we don't have the biological insights. As sophisticated as we are, we are not sophisticated enough. Chairman Tom Davis. This is tough stuff. Dr. Ryan. Dr. Ryan. I think the unintended consequences will be all benefits. If you look at the countermeasures and the technologies we can offer now, they were all built on peacetime research and activities. And much of what I think we would benefit from in developing needle-free, nonrequiring-refrigeration vaccines, would be equally useful for travelers' vaccines, food safety vaccines, vaccines for global health. So it is the same intellectual property and technology that we would be leveraging into another area. So I would see all of the boats rising, and I wouldn't see competition being a problem at all. Chairman Tom Davis. All right. Thanks. For a countermeasure to be appropriate for procurement under the Project BioShield as envisioned by the administration, the Secretary of Health and Human Services has to make a determination that the product is either approved by the FDA or is likely to be approved within 5 years. Is that a reasonable approach? And what type of products would be covered by this timeframe? And what type do you think would be excluded by this timeframe? Any thoughts on that? Ms. Bowdish. I believe that monocromial antibodies will be able to be approved in this timeframe. I think that in our case, speaking from a small-company perspective, we already have antitoxin therapy available for anthrax. I think it will take us the next 6 months to get it through the next series of studies that we need to do, and then likely into phase 1 safety studies. I think that our approach will be successful against the other agents that we are working on now and will be working on in the future. I think that we can very quickly have a rapid success with antitoxin therapies and antiviral therapies in the case of monocromial antibodies. Chairman Tom Davis. Thank you. One of the areas you are going to see debated on both sides of this is, are we giving away too much to the companies? Are we in fact not being tough enough, that they are going to walk off with big profits? Are we giving them too many protections and the like? But the bottom line for us is to be able to get incentives so the companies will step forward, take the risk, do the research. It is clear from the last panel that government doesn't have this in-house capability. We have got to go out to private sector. We can write a law here that may have all kinds of safeguards and protections so that the government isn't getting taken. But if companies don't step up to the plate, the losers at the end of the day are going to be the consumers and people are who are suffering from this. What we wrestle here with is striking the right balance. As we look at the administration's proposal, does it have enough incentives for private companies to begin research and development? Do you think it has enough? Do you think it needs more? Do you think it goes too far? We ought to bring other safeguards in? I think all of you have different perspectives on that. But does anybody want to take that? Dr. Friedman. Very briefly, sir. I think there are some incentives that are being discussed. I think equally important is addressing the disincentives that exist to try and optimize the system. I think that at the totality of what we are trying to create for the American public balances careful discussions. These are complicated issues. And, as others have said, we look forward to working with you and others to try and craft this. Specifically, where there are special descriptions in the legislation, we think those should be transparent, they should be clear, and they should be well focused. Chairman Tom Davis. OK. Thank you. Anyone else on that? Dr. Ryan. What I like about the 5-year idea is that there is a clear philosophy to support product opportunities, not just support research. What I don't like about the 5 years is I think it is a bit tight. I mean, if somebody is progressing extremely well, I think it would not be useful to the country to cut it off if it went another couple of years. Chairman Tom Davis. So, some waiver extension? Dr. Ryan. A question of progress. Again, as I keep stressing, program management through the life cycle from research to having a product that could actually be used. Chairman Tom Davis. I mean, your company spends a lot of money that sometimes ends up going nowhere, right, with the research? Dr. Ryan. Oh, yeah. Chairman Tom Davis. What percent? As you go off on a trail, how much times does it lead nowhere? Dr. Ryan. Most of the time, is the depressing thought. But in fact the research is still useful. Others studies have been done, not just by my company, but when you get to the end of the road, it is 1 in 100 is what makes it through to success. Dr. Friedman. I think it depends where you start. It could be as small as 1 in 10,000 or 100,000 if you look at the very earliest steps, when something begins clinical testing. You are happy if it is 1 in 100. Again, this is not just for anti- infectives, but for a variety of different medications. Mr. Rapoport. Mr. Chairman, I think the incentives are there, but they need to be firmed up. And let me give you a specific example. In the last anthrax procurement, which was won by a company whose name I can't recall, but the basic provision, the RFP, was for research and development only. So you stand back, and you are chairman of a multinational drug company. And you look at, am I going to do research and development? I would love to help. I want to be there. In fact, it looks like the government is paying my way. What happens at the end of the contract? Nothing. You get no widget. You get no promise. In fact, the procurement said there will be another RFP at the end of the research and development. And you wonder, as outside counsel, how do you advise your company on, well, do you get the rights to the work that has been developed by the other companies that have won the R&D? So it is very simple in the sense that if you want to attract companies like Aventis, I think they are willing to share the risk, but they need to know that if they show you their stuff and they are successful, there is a guarantee that there is going to be a market there. It is as if to say we fight a war in Iraq, and Boeing is not there, Lockheed is not there, Northrup is not there. We have got some very sophisticated companies, but we need some of the big players with unlimited resources to participate in this as well. Chairman Tom Davis. Thank you. I mean, that is the American system. There is a huge up-side when you get success. If you don't get success, you end up eating the cost. But there is a huge up-side. And what you are saying here is there is no assurance of that in some of these cases. Thank you very much. Mr. Waxman. Mr. Waxman. Thank you, Mr. Chairman. I want to thank all of the witnesses for their testimony. I had a conflict in my time schedule so I wasn't here to hear you, but I have had a chance to review the testimony and will certainly take into consideration all of the things that you have given us because I think it is very helpful. Mr. Rapoport, you testified you assumed checks and balances are in place to ensure appropriate stewardship to protect the taxpayers' money. It seems to me that the bill eliminates many guarantees to protect the taxpayers' interest: eliminating government access; rights to the books of contractors, for instance, seems questionable. What kind of checks do you think are in place? Mr. Rapoport. I noticed from your earlier question that you were concerned about that. Remember, the simplified acquisition is only up to $25 million. After that, the full panoply of Federal Acquisition Regulations, with the masses of government auditors that are already over the pharmaceutical industry, they will be there. In my days at the Justice Department, we had the FBI, we had the IG. There is everybody there from those enforcers to the contracting officials who ask for one thing: Get the stuff out the back door. As long as you can keep producing, there will be no audits. So the $25 million, quite frankly, is a very low number to receive a relaxation of government acquisition enforcement. Most of this will be far in excess of $25 million. Mr. Waxman. Well, the production side, however, it is not limited to that $25 million. Mr. Rapoport. It is our view that the production side doesn't even have this simplified acquisition in it. There is no relaxation. There is total--in fact, it is a very aggressive position which says that if you don't produce, Mr. Pharmaceutical Co., within 3 years, we are going to terminate you for default. That didn't have to be in there. There is already that ample authority under the FAR. Mr. Waxman. You have testified that companies need the certainty that research and development contracts will lead to a manufacturing agreement. This is an important part as far you can see to tie the two together? Mr. Rapoport. Yes. We are not assuming that the price has to be decided until later in the contract. But the government does this type of price determination midway through a procurement all of the time. Mr. Waxman. Do companies make money on research and development contracts? And, if so, why would you need a guarantee of a manufacturing agreement up front? Mr. Rapoport. There is probably a difference between a company like Aventis and a biotech. We are not anxious to accept government money, as you suggest. We are not government contractors. The pharmacy industry, I guess the Wall Street Journal calls them the new biodefense contractors. But a large pharmaceutical company wouldn't have the institutional competency to deal with what Boeing and Lockheed has. So they are not anxious to take government R&D money simply to earn a 7 or 8 percent profit on top of the R&D. It is the manufacturing capability that they want, and that they are best at, that they deliver. That is really why they are where they are. So at the beginning when I said our tinkering with the bill--and it is a good bill--is simply not only to encourage biotechs who absolutely have to be there, but also the companies that have the ability to produce masses of quantities of vaccines. And they don't need the government's R&D money as long as they know that there is some kind of back-end commitment. Mr. Waxman. Dr. Friedman, good to see you again. You have indicated the importance of the liability protection. Why wouldn't the government contractor defense shield you from liability? Dr. Friedman. I am sorry, sir? Mr. Waxman. You indicated that--the concern about the potential liability companies manufacturing these countermeasure could face, and their inability to retain private insurance. I am trying to understand why wouldn't the government contractor defense shield be adequate for protection? Dr. Friedman. This is an area that skirts my expertise in terms of legal understanding. But as it has been explained to me, and I believe it is accurate, the indemnification activities that exist for many kinds of contractural procedures are really not anywhere near as flexible or appropriate or useful as some of the liability kinds of protections that exist. I believe the recent example of how smallpox has been dealt with is a very reasonable model for us to take forward. And if I may just expand on my answer for a moment, to answer a question not--that you didn't address to me, but you did address earlier, because I really feel it is worth some further discussion. Our feeling is that the liability protection should be afforded not just to the manufacturer. We think there is a very strong case for that. I am happy to further define that. But we also believe that there should be some equitable, appropriate consideration of the people who are receiving the product, and, I would even add, the people who are delivering the product; that is, the health care providers, physicians and so forth. The reason is I think that we are operating--anytime you have a product considered, even approved by the Food and Drug Administration, there is a balance of what we know and what we don't know. At a certain point the FDA and its scientists say, we know enough to say that this is relatively safe and relatively effective, because there is nothing that is absolutely safe and absolutely effective. And we have confidence when there is a lot of information there. Our concern is that for some of these products, because of the difficulty of testing them, because of the fact that they may be in the midst of development, that balance will be shifted and we won't know quite as much as we would like to. And there will be more unknowns about risks and benefits. Mr. Waxman. So you think that the manufacturers should be protected from liability to give the incentive to development of these products, but the public that is exposed to them, that may have some adverse effects, should also be compensated? Dr. Friedman. Yes, sir. Mr. Waxman. Dr. Edwards, I want to welcome you because you are from UCLA, among other reasons. There was a report in yesterday's New England Journal of Medicine that a common bacteria is now highly resistant to Vancomycin, one of the most powerful antibiotics in modern medicine. Do you believe that more research needs to be done to find alternative treatment for Vancomycin-resistant bacteria? Dr. Edwards. Absolutely. This is just a major problem that we are facing every day in our hospitals. And in fact, I would like to give a very brief example that sort of summarizes a conundrum. In our institution we recently had a patient who was a 60-year-old, brought in by her family, her daughter and her grandchildren, and had severe asthma and also had evidence of an infection that seemed to be mild. A deliberate decision was made not to put the patient on Vancomycin, because that drug has become so valuable, and there is so little in the background available to counteract the Vancomycin-resistant organism. So the patient was relatively stable at the time she came into the hospital. But she rapidly decompensated and died, unfortunately. And at the time of her autopsy, an organism that was multiplying resistantly to antimicrobials was recovered, but it was sensitive to Vancomycin. And this example illustrates how we are faced with the situation now of trying to conserve the use of specifically that agent, but also others, because there is so very little in the background for support for resistant organisms. And the situation is very complex and intricate. And I think this example displays some of those intricacies of the kinds of decisions that are being made in hospitals all over the country now based on this resistance problem. Mr. Waxman. Do you think there are natural security implications? Dr. Edwards. Absolutely. The resistance issue is tied to some of the basic science of bioterrorism agents as well. Mr. Waxman. Thank you. That is very helpful to have on the record. Thank you very much, Mr. Chairman. And I want to thank the panel. Chairman Tom Davis. I want to thank the panel as well. It has been very helpful to us as we try to formulate some meaningful legislation over the next few months. Anyone want to add anything before we go? If not, let me just again thank you. I want to thank the staff for working on this hearing. We will be following up on a SARS issue at a hearing scheduled for next Wednesday, April 9th, at 10 a.m. We will keep the record open for 2 weeks if you want to supplement your comments. If you think of anything you didn't say or respond to, please feel free to do that. And the hearing is adjourned. Thank you. [Whereupon, at 11:50 a.m., the committee was adjourned.] [Additional information submitted for the hearing record follows:] [GRAPHIC] [TIFF OMITTED] T7141.068 [GRAPHIC] [TIFF OMITTED] T7141.069 [GRAPHIC] [TIFF OMITTED] T7141.070 [GRAPHIC] [TIFF OMITTED] T7141.071 [GRAPHIC] [TIFF OMITTED] T7141.072 [GRAPHIC] [TIFF OMITTED] T7141.073 [GRAPHIC] [TIFF OMITTED] T7141.074 [GRAPHIC] [TIFF OMITTED] T7141.075 [GRAPHIC] [TIFF OMITTED] T7141.076 [GRAPHIC] [TIFF OMITTED] T7141.077 [GRAPHIC] [TIFF OMITTED] T7141.078 [GRAPHIC] [TIFF OMITTED] T7141.079 [GRAPHIC] [TIFF OMITTED] T7141.080