Biodefense and Homeland Security

Technology Development:

Analysis of U.S. Policies and Process of Selection

David Clifford and Nicholas S. Vonortas Center for International Science and Technology Policy

The George Washington University

Report To

International Access Corporation (IAC) For

Ministry of Economy, Trade and Industry JAPAN

March 12, 2007

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Table of Contents

Chapter Page 1. Introduction 1 2. Program Overviews, Budget Plans 2 2.1. Federal Government Agencies 4 2.1.1. Department of Homeland Security 4 2.1.1.1. NBACC 5 2.1.2. Department of Defense 6 2.1.2.1. DTRA 7 2.1.2.2. USAMRIID 7 2.1.3. Department of Health and Human Services 9 2.1.3.1. NIAID 11 2.1.3.2. CDC 13 2.1.4. United States Department of Agriculture 14 2.1.4.1. APHIS 15 2.1.4.2. ARS 16 2.1.5. Food and Drug Administration 17 2.1.6. Department of Energy 18 2.1.7. National Science Foundation 19 2.2. New Programs & Advanced Research and Development 19 2.2.1. Homeland Security Advanced Research Projects Agency 19 2.2.2. Defense Advanced Research Projects Agency 20 2.2.3. National Institutes of Standards and Technologies: 22 Advanced Technology Program 2.3. Interagency Coordination 22 2.4. Cooperating with the Private Sector 24 3. Determining Priorities 26 3.1. Agents 26 3.2. Scenarios 28 3.3. Modeling 29 3.4. Monitoring 35 4. Business Development 36 4.1. Methods to Encourage Technology Development 36 4.1.1. Regional Incentives 38 4.2. Standards Development 40 4.2.1. Case Study: DoD Standards Development in Assays 40 4.2.2. Case Study: DHS Anthrax 41 4.3. Public-Private Partnerships 41 4.4. Trade Committees and Organizations 43

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Table of Contents

Chapter Page 5. Procurement 48 5.1. Homeland Security Contracting Methods 48 5.2. Program Management and Oversight 49 5.3. History of Funding Distribution Across Federal Agencies 51 5.4. State Funding 53 6. Future Plans, Trends, and Homeland Security Outlook 59 6.1. State Involvement: Illinois – A Case Study in State Response 59 6.2. New Government Agencies Involved in Homeland Security: 61 The Pandemic and All Hazards Preparedness Act 6.3. Other Planned Activities 63 6.4. Emerging Areas 64 7. Conclusion 65

Appendix 1 History of Federal Funding Distribution 68 On Biodefense Appendix 2 Glossary of Terms 71

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List of Figures

Figure Page 2.1. Changes in Federal Funding for Biodefense 2001-2007 3 2.2. FY2007 Funding for Biodefense by Federal Agency 3 2.3. FY2001-FY2007 Total Funding for Biodefense by Federal Agency 4 3.1. Los Alamos Model: Simulated Infection Rate Per 1000 People 30 3.2. UASI Risk/Effectiveness Model 32 3.3. Score Composition in UASI Model 2007 34 4.1. Regional Coverage by NIH Centers of Excellence 39 A1.1. FY2001 Funding for Biodefense by Federal Agency 68 A1.2. FY2002 Funding for Biodefense by Federal Agency 68 A1.3. FY2003 Funding for Biodefense by Federal Agency 69 A1.4. FY2004 Funding for Biodefense by Federal Agency 69 A1.5. FY2005 Funding for Biodefense by Federal Agency 70 A1.6. FY2006 Funding for Biodefense by Federal Agency 70

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List of Tables

Table Page 2.1. Unclassified Research Relating to Chemical-Biodefense 8 Funded by DTRA 2.2. DHHS Bioterrorism Funding 10 2.3. Areas of Major Progress by NIAID 12 2.4. Select List of Diseases Reportable to the World Organization 15 For Animal Health 2.5. Major DOE Labs Involved in Biodefense and Their Areas of Focus 18 3.1. Agents on CDC’s Threat List 27 3.2. Categories of Risk and Effectiveness Used by UASI 33 3.3. Five Largest Funding Increases as a Result of Model Implementation 33 3.4. Five Largest Funding Decreases as a Result of Model Implementation 33 3.5. CDC Disease Outbreak Data on Observed Infectious Diseases: 35 2001-2004 4.1. Three Biodefense Contracts 37 4.2. Major Non-Governmental Organizations Involved in Biodefense 43 And Biosecurity 5.1. Unobligated Funds Awarded Under the Public Health Preparedness 54 And Response for Bioterrorism Program (HHS-CDC) 5.2. States with the Highest Percentage of Unobligated Funds 55 5.3. Changes in Federal Funding for State and Local Bioterrorism 56 Preparedness FY 2005-2008

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1. INTRODUCTION In “Plagues and Peoples”, William McNeil very impressively demonstrated the astounding impact of viral diseases on human history and culture.1 This is a well known story on the American continent, of course, given the demise of Amerindians by unknown diseases carried over the Atlantic by the European new arrivals. The European invaders themselves at that point still had relatively fresh memories from their own major disruptions by widespread diseases in the Middle Ages, the better known one being the Black Plague. Epidemics in the Far East have been quite frequent during the past several centuries. Take the example of influenza. Influenza viruses have been a constant threat to the health of human (and animal) populations. Their diversity and propensity for mutation result periodically in pandemics due to newly emerging virus strains that has the ability to infect and be passed from individual to individual. As in the case of the hapless Amerindians before, since humans have little immunity to the new virus, a pandemic (worldwide epidemic) can ensue. Three human influenza pandemics have occurred in the 20th century, each infecting about one-third of the world population and terminal illness in 0.2 percent to 2 percent of those infected. Current models of disease transmission project that a modern pandemic could lead to the deaths of 200,000 to 2 million people in the United States alone.2 American vulnerability to biological attack became directly apparent beginning on October 15th, 2001, when a letter containing anthrax spores was discovered in a Senator’s office. In the weeks following, the government mail service was shut down, the United States Capital was closed for decontamination, and thousands of doses of ciprofloxacin (“Cipro”) were given to mail carriers and government employees. The attack resulted in 23 cases of anthrax infection and eleven deaths. There is little argument that the danger of pandemics is real. While the naturally occurring “Asian flu” has attracted a lot of attention, there is another very worrisome aspect of this: the deliberate engineering of viruses and release into the general populace with malicious intent. While an old technique to annihilate enemies, one is nowadays more familiar with the Tokyo subway attacks. Only that the attack experts have in mind is at a much, much larger scale. Countries are preparing to face either one of these two versions of a possible pandemic. This report concentrates on the current efforts of the United States of America. 1 William H. McNeill, Plagues and Peoples, 1998, New York: Anchor Books (Random House Inc.) 2 Homeland Security Council, National Strategy for Pandemic Influenza: Implementation Plan, May 2006.

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2. PROGRAM OVERVIEWS, BUDGET PLANS Within the US federal government, biodefense and biosecurity is a broad issue. Therefore, many government agencies have stakes in addressing various aspects of it, including:

DHS: Department of Homeland Security: national strategy for domestic defense.

DOD: Department of Defense

HHS: Department of Health and Human Services o CDC: Center for Disease Control and Prevention - monitor outbreaks and

conduct surveillance and testing on known and emerging pathogens o NIH: National Institutes of Health - coordinates research and development o NIAID: National Institute of Allergy and Infectious Disease o FDA: Food and Drug Administration - ensure that food remains free of

contaminants or intentionally introduced diseases.

USDA: Department of Agriculture: protect the food supply through agricultural biodefense research.

FDA: Food and Drug Administration

DOE: Department of Energy: DOE laboratories are used to conduct biodefense

research on behalf of DHS. Also, DOE has a role in the safety of nuclear material, therefore they are involved in non-proliferation aspects.

NSF: National Science Foundation

EPA: Environmental Protection Agency

State: Department of State

Other agencies: Department of Commerce, U.S. Post Office, and the Veterans

Administration There have been significant changes in both the volume and the structure of federal funding for biodefense during the current decade. These have accompanied equally significant changes in the organization of activities within the various agencies with the most important one being the creation of the Department of Homeland Security.

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Figure 2.1 shows the funding trends for biodefense in federal government. Figure 2.1. Changes in Federal Funding for Biodefense 2001-2007 ($ m.)

The most recent breakdown by Agency is shown in Figure 2.2 below. Figure 2.2. FY2007 Funding for Biodefense by Federal Agency ($ m.)

The average throughout the seven-year period by Agency is indicated in Figure 2.3. It must be emphasized that a core player, The Department of Homeland Security, appears on the scene only in 2003.

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Figure 2.3. FY2001-FY2007 Total Funding for Biodefense by Federal Agency ($m.)

2.1. FEDERAL GOVERNMENT AGENCIES

2.1.1. Department of Homeland Security The Department of Homeland Security (DHS) is the most recent addition to the Executive Branch of the federal government at the Secretary level. The main role of the Department is the prevention of any domestic security incidents and the preemption and deterrence of terrorist activities. Importantly, the Department of Homeland Security is responsible for ensuring that emergency situations are properly managed in the case of a catastrophe. In addition, DHS has assumed the interdiction role previously held by the Department of Commerce through the Customs Agency and the Coast Guard. Finally, DHS is responsible for securing travel and transportation conduits as well as immigration. The DHS Office of Health Affairs (OHA) has requested 118 million dollars as part of the President’s FY2008 budget. OHA serves as the principal advisor to the Federal Emergency Management Agency (FEMA) and leads the Department’s biodefense activities. Part of these activities are the National Biosurveillance Initiative and oversight of the BioWatch program. In addition, a new Office of Animal and Agro-Defense will develop the expertise to advise the Secretary on zoonotic and foodborne pathogens. The Chief Medical Officer of the Department of Homeland Security operates in the Office of Health Affairs and is responsible for coordinating the National Disaster Medical System, DHS activities on Project BioShield, and the construction of working groups and planning in response to the threat of pandemic influenza.

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In addition, the President’s budget for FY2008 allocates 228.9 million dollars to DHS’ Science and Technology Directorate for chemical and biological defense. These funds will be used to create effective measures for deterrence, detection, and mitigation. Included in this funding profile is the transfer of an additional 84.1 million to implement the BioWatch monitoring system in thirty cities (Box 1).

Box 1. BioWatch is an early warning system for metropolitan areas to alert the Department of Homeland Security of the release of aerosolized pathogens. DHS has a management and oversight role in a Memorandum of Agreement structure that exists between DHS, the Environmental Protection Agency (EPA) and the Centers for Disease Control (CDC). The program was first established in an 80 day period in 2003, and follow-up reviews were conducted in 2004 and 2005. Although initial after-action reviews in 2003 indicated successful outcomes, these later studies showed a slow deterioration in day-to-day affairs. 84 percent of laboratories improperly transferred filters from the field to the laboratory. 74 percent of all filters were transported in improperly cleaned chain-of-custody bags, exposing them to possible cross-contamination. Furthermore, DHS was lax in obtaining monthly and quarterly reports from its partners in the EPA and CDC, to whom it administers funds. DHS management responded to a January 2007 audit by claiming that year-to-year changes in grades were not indicative of performance. In addition, within 30 days of the issuance of the report on problems with the BioWatch program, DHS had issued corrective policy guidelines. As this program provides essential capabilities for early detection and response to the release of a threat agent, it is critical that problems of potential cross-contamination and improper attention to standards are appropriately rectified.

2.1.1.1. NBACC One critical element in the Department of Homeland Security’s attempts to provide for biosecurity and biodefense is the National Biodefense Analysis and Countermeasures Center (NBACC). Planning on this institution began in FY2003. The facility will be located on the National Interagency Biodefense Campus at Fort Detrick, Maryland, and although some scientists began research on the Fort Detrick grounds early on in 2007, the facility will not formally open until 2008. It will share grounds with offices of the National Institute for Allergy and Infectious Disease (NIAID), the Department of Agriculture’s Agricultural Research Service (ARS), and the U.S. Army Medical Research Institute of Infectious Disease (USAMRIID). These Agencies will share overlapping missions:

NBACC: Investigate a comprehensive understanding of biological agent characteristics

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NIAID: Elucidate the disease process

ARS/USAMRIID): Develop products to reduce risk to human health and agricultural productivity

NBACC’s core mission will be characterization and forensics. The Presidential Directive “Biodefense for the 21st Century” designates the National Bioforensic Analysis Center as the lead facility in technical forensic analysis in the aftermath of a biological attack. Complementary to this, the Biological Threat Characterization Center will conduct laboratory studies to improve risk analysis, identify gaps in current knowledge on potential threat agents, and provide information to determine priorities and set standards in the development of sensors and countermeasures. The construction and management of NBACC was awarded to the Battelle National Biodefense Institute (BNBI). The total contract award for facilities construction and management was awarded in December of 2006 and consists of 250 million dollars over five years with an option for five one-year extensions totaling another 250 million. It should be stressed that Battelle also manages or co-manages five Department of Energy laboratories and, thus, brings a history of expertise in chemical and biological countermeasures development. Although NBACC will conduct classified research, it will not be a weapons development facility, as critics of the program alleged early on. While NBACC experts will be encouraged to conduct “red team” exercises in order to generate possible scenarios used by enemies of the state, these tasks will only be used to identify weaknesses and prepare for threats. The DHS director of the NBACC program, Bernard Courtney, has stated that counter-force research will only be done in the case of a credible bio-threat, and that these exercises will comply with the Biological and Toxic Weapons Convention in scope and detail.

2.1.2. Department of Defense In 2001, the Department of Defense viewed chemical and biological defense as a problem it was uniquely situated to handle. Congressional testimony by the Deputy Director of Defense Research and Engineering identified modeling the dispersal of chemical and biological weapons as a “hard” problem that would require the leveraging of a significant amount of resources to create tractable action. The Deputy Director identified four major areas critical to warfare: detection of biological and chemical agents, diffusion and dispersal models for predicting hazards, improved understanding of agent toxicity, and increased comprehension of chemical and genetic composition. While tailored to the battleground, many of these issues have applications for the civilian population as well. Hence, even though homeland biosecurity is the specific charge of the Department of Homeland Security, the potential payoff of dual-use (civilian and

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military) technologies encourages incorporation of an overview of Department of Defense biodefense efforts into this review.

2.1.2.1. DTRA One agency of the Department of Defense that deals with threats to biodefense and biosecurity is the Defense Threat Reduction Agency (DTRA). DTRA was originally created to deal, mainly, with issues of counter-proliferation following the collapse of the Soviet Union. Much of its mission is the containment and monitoring of weapons of mass destruction. In addition, DTRA provides counter-weapons of mass destruction capabilities to the combatant on the tactical and operational level. DTRA models weapons effects for weapons of mass destruction and establishes protocol in the event of such an attack on American forces. Technologies developed by DTRA seek to safeguard the lives of American soldiers should they be exposed to a chemical, biological, nuclear, or radiological weapon. While DTRA’s mission largely focuses on the development of systems that are directly relevant to the combatant, as with other DOD programs, these technologies can be used in the case of a weapons of mass destruction attack on civilians. In FY 2007, DTRA’s budget contained several items dealing with chem.-bio defense (Table 2.1).

2.1.2.2. USAMRIID The DOD also funds biological warfare countermeasures through the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID). Its main goal is providing protection to combatants against biological threats. USAMRIID vaccines have also been used in civilian emergencies, providing international allies with vaccines for outbreaks of equine encephalitis (Venezuela, 1971), Rift Valley fever (Egypt, 1977), tularemia (Italy, 1980s), as well as diagnostic support for foreign allies during the outbreak of Severe Acute Respiratory Syndrome (SARS). In addition, USAMRIID plays an important role in American civilian biodefense, providing information for clinicians on medical management in mass casualty events. USAMRIID funds extramural research through the US Army Medical Research and Material Command’s open competition as well as through technology transfer processes such as cooperative research and development agreements (CRADAs). The CRADA mechanism allows for commercial entities to be able to leverage off of military personnel and facilities that are properly cleared for the testing of biological warfare agents. In addition, USAMRIID patents can be licensed for commercial development.

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Table 2.1. Unclassified Research Relating to Chemical-Biodefense Funded by DTRA Program FY 2007

Amount* Description

Basic Research for WMD Knowledge Gaps

5,000,000 Broad scientific and technology basic research in critical assets for mitigating current, emerging, and future WMD threats. Incl. physics, materials science, structure, biology, chemistry, detection technology

Weapons Effects Technologies

76,462,000 Basic and applied research on weapons for purposes of defeat, deny, disrupt WMDs. Provides DOD-wide weapons effects models including hazardous release into atmosphere. Includes development and validation of chemical/biological weapon disruptiveness models

Small Business Innovative Research

2,411,000 Includes efforts on chemical/biological agent denial/defeat

Detection Technology 8,744,000 Develop technologies to monitor, detect, identify strategic conventional and unconventional weapons incl. biological/chemical sensor technology

Counterforce 76,849,000 Includes system capability to perform combat assessment relevant to deployment of chemical and biological weapons on existing combat assessment platforms (such as Unmanned Aerial Vehicles). Also includes tools to enable warfighters to engage in operations against chemical and biological weapons facilities. Includes tools to neutralize weapons in real-time

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Some patents developed by USAMRIID include3:

Ricin vaccine and methods of manufacture and use High throughput assays for neurotoxins A novel anthrax vaccine Antibodies against type A botulinium neurotoxin

Under Patent License Agreements (PLA), domestic industries and small businesses pay royalties to the institution, which passes some of the funding through to the inventor. This encourages USAMRIID employees to make steps not only for overall mission benefit to the agency, but for commercial benefit to themselves.

2.1.3. Department of Health and Human Services The Department of Health and Human Services administers many of the programs related to biosecurity. The National Institute of Allergy and Infectious Disease (NIAID) takes on much of the responsibility for ensuring progress on basic and applied research and development for pathogens of interest. The Centers for Disease Control (CDC) ensures that public health officials at the state and local level are informed and prepared to respond in the case of a biological threat incident. In addition, the CDC is the lead agency on implementation of a surveillance system to monitor and detect biological threat events. The President’s budget for FY2008 recommends a 4.3 billion dollar appropriation to the Department of Health and Human Services in order to address bioterrorism issues (Table 2.2). A portion of this will go to pandemic influenza vaccine development. Because H5N1 influenza is an avian strain there are difficulties in producing the vaccine through the regular methods of incubating the virus via chicken egg. As a result, HHS is pushing development of cell-based vaccine capabilities, and in May 2006 provided an initial 1 billion dollars in funding. This initial award was made to five firms, GlaxoSmithKline (274.5 million dollars), MedImmune (169.46 million dollars), Novartis Vaccines & Diagnostics (220.51 million dollars), DynPort Vaccine (40.97 million dollars), and Solvay Pharmaceuticals (298.59 million dollars).

3 USAMRIID. 2006. “Issued Patents Available for Licensing”. https://technologytransfer.amedd.army.mil/patents.asp?SearchText=RIID&SortBy=uspto

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Table 2.2. DHHS Bioterrorism Funding

Program/Agency FY2008 Request

Change: FY2007-2008

CDC Upgrading State and Local

Capacity 698 -125

Biosurveillance Initiative 88 +10 Upgrading CDC Capacity 137 ---

Anthrax Research --- -14 Strategic National Stockpile 581 +90

National Institutes of Health

Biodefense Research 1,628 +18

Food and Drug Administration

Food Defense 178 +23 Vaccines/Drugs/Diagnostics 57 +2

Physical Security 7 +.024

Office of the Secretary

Revitalization of the Commissioned Corps

38 +34

Assistant Secretary for

Preparedness and Response

Operations 13 +4 Preparedness and

Emergency Operations 48 +33

National Disaster Medicine System

53 +6

Hospital Preparedness Grants

414 -60

Training and Curriculum Development

--- -21

Advanced Research and Development

189 +135

BioShield Management 22 +22 International Early Warning

Surveillance 9 +.04

Media/Public Information 2 -.36

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2.1.3.1. NIAID

The National Institute of Allergy and Infectious Disease controls the majority of the research dollars allocated to the National Institutes of Health for biodefense research, and in 2006 were responsible for 1.7 billion dollars of a 1.79 billion dollar budget. The NIAID determines research priorities on Category A, B, and C threat agents (see Chapter 3) and oversees both intra-mural and investigator initiated research that is responsive to their overall priorities. Priorities are determined on a pathogen by pathogen basis. High priorities include:

High titer/concentrated Vaccinia Immune Globulin (VIG) or replacement product based on monoclonal antibodies (Mabs)

Botulinum antitoxin including: safe and effective alternatives to toxoid vaccine, monoclonal antibodies, and polyclonal antibodies

Development of an alternative vaccine against smallpox that could be delivered to those at high risk of serious complications to the current vaccinia vaccine (e.g., MVA)

Second generation anthrax vaccines (e.g., rPA) Ebola and Marburg hemorrhagic fever vaccines Tularemia vaccines Plague vaccines Rift Valley Fever vaccines Cell culture (e.g. Vero cells) based vaccines for influenza Antivirals for smallpox and viral hemorrhagic fevers Arenavirus and specific viral encephalitis vaccines (e.g., Tickborne

encephalitis viruses, West Nile virus, Eastern equine encephalitis virus, Western equine encephalitis virus)

In 2006, the NIAID completed a review of research and development addressing Category A bioagents.4 Overall they were able to report progress in addressing the threats posed by some of these threat pathogens, and demonstrate success in many areas since the previous report was issued in 2003. The report highlights seven areas where NIAID had made major progress (Table 2.3).

4 NIAID. 2006. NIAID Biodefense Research Agenda for CDC Category A Agents.

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Table 2.3. Areas of Major Progress by NIAID Area Progress Next Generation Vaccines for Anthrax and Smallpox Recombinant protective antigen vaccine for

anthrax tested rabbits and primates and clinical human cohort

Post-exposure prophylaxis scenario developed for administration of anthrax vaccine

Modified vaccinia Ankara vaccine to counter smallpox developed, manufactured, and moved to Phase II clinical trials

Novel smallpox vaccine developed based on sub-units of the virus and tested in mice and non-human primates

Animal models developed for smallpox infection and inoculation

Multiplex Diagnostics: Rapid Detection of Emerging Pathogens

Methods developed capable of rapidly screening for the presence of several pathogens

Platform capability exceeds 20 biothreat agents Dengue Vaccine Development Methods determined to weaken live, attenuated

virus for use in vaccine Tetravalent dengue vaccine slated for clinical

trial in near future Botulism Multi-monoclonal antibody approach

determined for manufacture and use in animal models

Decoding Anthrax Demonstration of previously unknown similarities between various strains of anthrax

Strain differentiation and diagnosis demonstrated through genomic sequencing

Innovative Therapeutics Against Smallpox Two poxvirus therapeutics developed and could potentially be used in concert with one another

Lipid enhanced cidofivr can be orally administered and does not accumulate in the kidneys

ST-246 therapeutic against separate viral target; safe preclinical toxicity profile

Fast-Acting Ebola Vaccine Vaccines offer capability to treat currently untreatable disease

Prime-boost method successfully tested on primates exposed to infection

Many of these activities were conducted under the auspices of Project BioShield. While the majority of funding for Project BioShield is for procurement of vaccine stockpiles, NIAID manages the portion of funding allocated for research and development tasks. NIAID is able to use expedited authorities granted by the Project BioShield legislation to fund problems which respond to urgent needs. The 2006 annual report on Project BioShield highlights the decision to expedite research, stating:

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“NIAID first considered using the normal NIH review and award process; however, because this process averages 18 months from the conception of an initiative to award, the NIAID rejected this option. Instead, because the Project BioShield mechanism shortens the award process timeframe to approximately nine months, NIAID elected to utilize Project BioShield authorities to expedite these high-priority programs.”

2.1.3.2. CDC The Centers for Disease Control support biodefense by providing information on incidents and outbreaks of threat pathogens of interest and coordinating public health readiness and preparedness efforts. In addition, the CDC confirms the presence of pathogens in a given biological sample should an outbreak occur. The CDC also educates the public on public health awareness issues. Further, as previously discussed, it is the CDC that takes the lead in determining the levels of threat posed by various pathogens. The CDC manages federal funding for state and local readiness programs through a cooperative agreement process. Under this cooperative agreement, the CDC supports efforts to implement the CDC Preparedness Goals and the National Preparedness Goal. The National Preparedness Goal is a cross-agency standard framework for actors at multiple levels of the public health system. The CDC Preparedness Goals include:

Prevent: Increase the use of interventions known to prevent human illness from chemical, biological, radiological agents, and naturally occurring health threats

Detect and Report: Decrease the time necessary to classify events as

terrorist or naturally occurring; Decrease the time needed to detect and report chemical, biological, or radiological agents in tissue, food, or environmental samples; Improve the timelines and accuracy of communications regarding the public’s health

Investigate: Decrease the time to identify causes, risk factors, and

appropriate interventions for those affected by threats to the public’s health

Control: Decrease the time needed to provide countermeasures and

guidance to those affected by threats to the public’s health

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Recover: Decrease the time needed to restore health services and environmental safety to pre-event levels; increase the long-term follow-up to those affected by threats to the public’s health

Improve: Decrease the time needed to implement recommendations from

after-action reports following threats to the public’s health

There is little room for discretionary funding in the cooperative agreement process. All states will receive a minimum amount of funding of 3.91 million dollars (last available year), and additional amounts based on proportional share of the national population. The District of Columbia, Chicago, Los Angeles, and New York City receive an additional 5 million dollars. However, expenditure of funds is restricted by CDC guidance, and the CDC retains the right to terminate funding. In addition, funding provided through the cooperative agreement process cannot be used to support research. The CDC also funds the Early Warning Infectious Disease Surveillance (EWIDS) program through the cooperative agreement program (Box 2).

Box 2. EWIDS is an initiative that attempts to improve epidemiological capabilities for cross-border states in order to prevent the incursion of foreign-borne or emerging pathogens. States along the U.S.-Mexico border have begun to implement an additional system that will allow coordination between public health data collection agencies in the United States and those in Mexico. Award size is determined by the number of border crossings.

In addition, the CDC maintains information for interested parties on various characteristics of biological threat agents. Through the Clinician Outreach and Communication Activity (COCA) and the Clinician Registry for Terrorism and Emergency Response Updates and Training Opportunities, the CDC attempts to ensure a baseline level of awareness for interested medical practitioners. Finally, the CDC conducts verification tests on biological samples for state and local public health officials. By publishing guidelines and providing a final verification measure on the severity of a potential threat, the CDC can act as a single standard for the presence or absence of a threat agent.

2.1.4. United States Department of Agriculture The Department of Agriculture plays several roles in ensuring biodefense and biosecurity. The USDA is responsible for monitoring the spread and outbreak of zoonotic diseases, several of which can pose severe threats to biosecurity (avian influenza, bovine spongiform encephalopathy). Further, the USDA ensures the safety of agricultural products for consumption and attempts to place safeguards to prevent tampering at the pre-market stages.

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Roles are divided into several sub-services. The Animal and Plant Health Inspection Service (APHIS) is responsible for monitoring animal and plant populations. The Agricultural Research Service (ARS) leads the development of technical solutions and research programs targeted at major areas of concern.

2.1.4.1. APHIS The data collected by the Animal and Plant Health Inspection Service on animal-animal transmissions of a virus assists the Centers for Disease Control in their ability to track and react to the spread of disease. It was in this capacity that APHIS played a part in observing the outbreak of the West Nile encephalitis, a mosquito-borne disease that is fatal in humans, from 1999 to 2001, with their data on horse populations informing researchers into areas of likely outbreak. As this disease was novel in the United States, APHIS played a critical role in informing epidemiological modelers, who then were able to better educate the public as well as contain the disease by introducing measures to limit mosquito populations. APHIS also has a role in interdiction. On average, 38,000 animals enter the United States per day. These animals may be carrying one of 150 zoonotic diseases foreign to populations in the United States, some of which have potential for serious disruption if introduced into existing flocks. The World Organization for Animal Health (OIE), an international animal health monitoring organization, maintains a list of reportable diseases for its members. A number of the diseases of concern to the OIE also appear on the CDC list of biological threat agents. Table 2.4. Select List of Diseases Reportable to the World Organization for Animal

Health Disease Animal CDC Classification Anthrax Multiple Species A Tularemia Multiple Species A Brucellosis Multiple Species B Glanders Equine B Q Fever Multiple Species B Viral encephalitis Multiple Species B Nipah virus Swine C Bioterrorism in animal and plant populations may not be conducted solely for the purposes of damages to human populations. Plant or animal pathogens may be introduced into populations in order to cause economic disruption. The structure (concentration) of modern agro-business in the United States enables such outbreaks to be potentially devastating.

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While the United States has a diverse agricultural production base, often production of a given crop is geographically homogenous. Over 90 percent of all grape production is located in California. Around 75 percent of citrus is produced in Florida. By introducing a plant-specific agent into these concentrated agricultural zones, a group could feasibly eliminate the ability to produce a certain crop. Naturally occurring wheat seed blights in the 1990s caused nearly $3 billion in damages and led to agricultural sanctions against the United States from 50 nations. A directed attack could lead to magnitudes greater damage. In animal populations the modern farm is especially vulnerable. Poultry farms can contain hundreds of thousands of birds, all of whom may need to be culled if exposed to pathogen. Feedlots for cattle can hold up to 300,000 head. Introduction of zoonotic diseases into such facilities could cause global fluctuations in the price of beef. Clearly, monitoring and surveilling animal populations for the introduction of foreign disease or intentional infection becomes a priority in an environment where biological terrorism and bio-security are major concerns.

2.1.4.2. ARS The Agricultural Research Service enhances the abilities of APHIS to monitor animal populations by continuing to research and refine new methods and models for disease detection. While they traditionally focus on therapeutics development, vaccines, and diagnostics for naturally occurring outbreaks, biodefense has moved up on their priority list in recent years. Under National Program 103 (NP 103) the ARS has structured a plan for future engagement in animal health research. In the area of biodefense, foreign animal diseases were identified as the lead concern by the beef and poultry industry at a 2005 stakeholder meeting conducted by the USDA. The leading strategy of control, disease eradication by elimination of the animal, would both lead to immediate economic losses and potential future repercussions in the form of closure of foreign and domestic markets. This was deemed as unacceptable by the stakeholders, who also found current methods to monitor and prevent disease transmission as inadequate. In addition, the potential damage caused by an emergent disease was also seen as a high risk. The ARS determined the following outputs would be necessary goals for future research and program management:

Better anticipation of introduction of foreign animal diseases Researcher advisory roles in the regulatory process Increased capability to produce effective control and elimination products Real-time detection of agents across differing types of farms Searchable genomic and proteomic databases for major known foreign

animal disease agents Discovery of effective biotherapeutics and candidate vaccines that would

allow differentiation of infected and vaccinated animals

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Predictors of emerging livestock diseases Identification of pathogens associated with emerging disease Methods to detect and characterize the etiology of new disease Development of predictors of outbreak Establishment of early warning systems Tools and expertise to implement countermeasures to disease outbreaks

By monitoring the outbreak and spread of disease and interdicting potentially devastating foreign animal diseases, the USDA attempts to ensure biosecurity in the production capability of the food supply. Through working together with stakeholders on identifying areas of major concern to producers, the USDA attempts to guide research funding to enable the greatest impact. In doing so, the USDA bolsters economic security against potential threat and strengthens the safety and well-being of the American population from food-borne and zoonotic pathogens.

2.1.5. Food and Drug Administration The Food and Drug Administration (FDA) is responsible for ensuring the safety of the food supply as well as for regulatory oversight of biotherapeutics and vaccines. Therefore, the FDA plays a number of roles in biodefense by both ensuring that food supplies are not tampered with through the introduction of a pathogen and by ensuring that necessary countermeasures to a potential biological attack are available. In its role in ensuring the safety of biological products, the FDA requires commercial products to undergo lengthy and rigorous clinical trials to demonstrate safety and efficacy for their intended use. In the case of agents that have applications in countering potential bioterrorist agents, the FDA has considered using expedited review processes to ensure adequate stockpiles are available to the public. The difficulty in properly testing such agents is compounded by the difficulty in conducting validation studies, as human studies are not typically feasible, and it is not clear how useful animal data is without clear human correlates. The FDA operates under the recognition that something is better than nothing, and that the American public expects some type of response to be available. The FDA has an office of Counter-Terrorism Policy and Planning that works in partnership with the Departments of Health and Human Services (incl. NIH and CDC), Defense, and Homeland Security to identify gap areas where there is a critical need for countermeasures. Some leading areas of concern are in the development of vaccines for anthrax and smallpox, Botulinum anti-toxin, and vaccinia and anthrax immune globulins. In addition, the FDA attempts to ensure the development of assays capable of resolving and validating the efficacy of these agents. Commercial sector entities are encouraged to contact the FDA early and often to ensure that their product receives proper treatment, and more attention is spent on agents that are responsive to the higher priority concerns. This process was used in 2005, when the FDA expedited the review of two products which lessened the impact of complications caused by smallpox vaccines.

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2.1.6. Department of Energy

Historically, one of the charges of the Department of Energy has been Nuclear Security, with a number of programs in this policy area administered by the National Nuclear Security Administration (NNSA). Over time, the reach of the NNSA grew to incorporate countermeasures against other weapons of mass destruction. In 1997, the Defense Against Weapons of Mass Destruction Act authorized the creation of the Chemical and Biological National Security Program under the auspices of the NNSA’s Office of Non-proliferation Research and Engineering. This program operates between researchers at various Department of Energy laboratories with a focus on countering domestic threats against civilians. The DOE laboratories are Federally Funded Research and Development Centers (FFRDCs), each laboratory is managed either by a university or by an industrial firm. FFRDCs are not subject to the same labor regulations that apply to the rest of the civil service. This flexibility allows an FFRDC to more directly focus on sets of core competencies, and various FFRDCs have become known for their areas of specialization. Table 2.5. Major DOE Labs Involved in Biodefense and Their Areas of Focus Laboratory Managed By Focus Idaho National Laboratory Bechtel BWXT Idaho, LLC Biological threat detection,

agricultural threat agent countermeasures

Sandia National Laboratories

Lockheed Martin Corp. Biological countermeasures, sensors, decontamination, modeling and simulation, non-proliferation

Argonne National Laboratory

University of Chicago Molecular and cell biology for therapeutics

Lawrence Livermore National Laboratory

University of California Pathogen detection and identification, bio-forensics

Los Alamos National Laboratory

University of California Modeling and simulation, vaccine development, pathogen detection and analysis, bio-forensics

Oak Ridge National Laboratory

UT-Battelle, LLC Biological sensors, chem.-bio countermeasures,

Pacific Northwest National Laboratory

Battelle Memorial Institute Biological sensors, systems biology modeling, early warning systems for pathogen detection

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2.1.7. National Science Foundation

The National Science Foundation also has an interest in homeland security and biodefense. Specifically, the NSF attempts to leverage against its access to core communities in information technology and computing sciences in order to bolster robust responses to biodefense. In 2002, the NSF expressed an interest in a National Biodefense Information Service. Early detection in the case of a biodefense attack is dependent on correct identification. In 2002, the system architecture was such that relevant data was not captured by the system. In order to identify an attack, clinicians would have to observe relevant symptoms in their local practices and identify these symptoms as anomalous. Then, these clinicians would contact local public health agencies, who would filter data upwards to state agencies, and finally to the CDC. Identification in an early stage would require patients presenting to clinicians at early time points following an attack, and many potential agents could be transmissible prior to the appearance of symptoms. A large portion of the data relevant to a biological attack would simply fall through the cracks of the system Given these limitations, the NSF proposed an alternative system with many more points of data capture. The “National Biodefense Information System” would track data such as absenteeism from work, pharmacy purchases, laboratory and clinical information, calls to emergency services, and potential other relevant pieces of information. This system would serve as a constant anomaly detector. Such a detector would require high specificity and sensitivity to maintain accuracy while preventing false alarm.

2.2. NEW PROGRAMS & ADVANCED RESEARCH AND DEVELOPMENT New agencies and new programs in biodefence and homeland security are the subject of Sections 6.2-6.4 in this document. We refer the reader to those Sections. The remainder of this Section is devoted to advanced research and development.

2.2.1. Homeland Security Advanced Research Projects Agency The Homeland Security Advanced Research Projects Agency (HSARPA) was formed as part of the Department of Homeland Security’s research and development portfolio. HSARPA was modeled after the Defense Advanced Projects Agency (DARPA). However, while DARPA is charged exclusively with producing and sponsoring cutting-edge research, HSARPA includes acquisition of near-market products essential to Homeland Security in its portfolio.

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HSARPA has used the Broad Agency Announcement (BAA) system for most of its work in chemical and biological defense solicitations. Published solicitations have, for example, included the following subjects:

Detection Systems for Biological and Chemical Countermeasures (HSARPA RA-01): Develop, field-test, and transition next-generation biological and chemical detectors for counter-WMD

Bioinformatics and Assays Development Program (HSARPA BAA04-03):

Extend existing detection and forensics assays; develop next-generation assays and tools for assay development

Instantaneous Bio-Aerosol Detector Systems (HSARPA BAA04-18):

Develop, test, transition next-generation rapid bio-aerosol sensors for use in “Detect-to-Protect” architectures

Food Biological Agent Detection Sensor (HSARPA BAA05-06): High-

confidence microbial detection systems capable of rapid throughput and implementation at food manufacturing facilities

Low-Cost Bio-Aerosol Detector Systems (HSARPA BAA05-08):

Specifically aimed at enhancing Detect-to-Protect architecture by implementation of < $1000 sensors

RA-01 serves as the backbone for the BioWatch system, developing the sensors integral to the “Detect-to-Protect” architecture. As this program began in 2003 and the first sensors were implemented later in the same year, BioWatch clearly has a very aggressive research and development pathway. The majority of other efforts by HSARPA are also in the field of sensor and detection technologies. HSARPA also coordinates with the Technical Support Working Group (TSWG) on a variety of projects. The Technical Support Working Group is a counter-terrorism working group that assists the federal agencies in coordinating interagency efforts. TSWG has coordinated with HSARPA and DHS on implementing, developing, and testing some of the sensors and methods resulting from HSARPA’s biodefense programs.

2.2.2. Defense Advanced Research Projects Agency Founded in 1958 in response to the Soviet launch of Sputnik, the Defense Advanced Research Projects Agency (DARPA) has been tasked with ensuring that America avoids strategic surprise on the battlefield and that the technological capabilities of the fighting force are unparalleled. Through sponsored research, DARPA has made notable achievements that have seen use in both the civilian and military sectors including the development of the Global Positioning System, the Unmanned Aerial Vehicle, the Titan

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missile, stealth technology, titanium steel, and, most famously, the Internet. DARPA programs challenge existing paradigms and attempt to push the boundaries of innovation. Organizationally, DARPA is split up into six program offices, each with a distinct portfolio. The Defense Sciences Office (DSO) establishes and manages programs in the realm of biodefense and biosecurity as part of its Biological Sciences mission. Currently, the agency has an interest in the following areas:

Accelerated Manufacture of Pharmaceuticals (AMP) – Provide essential therapeutics on demand in response to a pathogen outbreak

Intestinal Fortitude – Utilizing beneficial bacteria in the intestinal tract to

prevent the acquisition of enteric disease from foodborne pathogens

Rapid Vaccine Assessment (RVA) – Assess the viability of vaccines at early stages of development through the use of simulated environments

Self Decontaminating Surfaces - Create biocidal coatings that are self-

cleaning and renewable based on their surface morphology In addition, the DSO is investigating areas such as pre-symptomatic disease detection and rapid vaccine production. These programs are all funded through the Broad Agency Announcement (BAA) process and have specific milestones and metrics provided in the solicitations. Performers can also apply to the open BAA which highlights areas of general interest to the office. Proposals funded under the open BAA generally must provide fundamental shifts in understanding of their respective topic; the office rarely considers technology or research that would provide an incremental advance, or technology that is near-market in terms of viability. Such tasks are outside of what DSO sees as its essential mission profile, that of being the office in the agency that explores the far side of scientific investigation. Other program offices in DARPA that deal with biodefense do so inside their specific mission profile. The Strategic Technology Office, charged with innovation in generating technologies that have theatre-wide impact, sponsors the Threat Agent Cloud Tactical Intercept and Countermeasure (TACTIC) program, which seeks to notify commanders in the field of a chemical or biological warfare agent attack and provide capability to neutralize the attack. Additionally, DARPA uses DOD’s Small Business Innovation Research program (SBIR) and the Small Business Technology Transfer program (STTR) to make further awards in biodefense and biosecurity. Many DARPA programs have eventual dual-use applications in the civilian sector, and technology developed by DARPA for the military can be applied by other agencies for homeland defense. While methods for countering pathogens are designed to ensure the viability of our fighting force, these technologies could be put to clear use in maintaining strategic stockpiles of counter-agent.

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2.2.3. National Institutes of Standards and Technology: Advanced Technology

Program The National Institute of Standards and Technology (NIST) is also interested in the high-technology research and development. Through their Advanced Technology Program (ATP), NIST engages in cost-sharing agreements on programs that are high-risk and high-reward that have potential payoffs for the overall public good. During 2001-2004, NIST had expended 164 million dollars on biotechnology applications. ATP programs are generally concerned with two major areas, scientific and technological merit and potential for broad-based economic benefits. Each area is equally weighted in the decision process and consists of three major criteria. Scientific and technological merit is judged on the basis of technical innovation, technical risk with evidence of scientific feasibility, and technical plan. Potential for broad-based economic benefits is measured by national economic benefits, need for ATP funding, and how difficult the pathway is to realizing those economic benefits. Each proposal goes through four gates:

Gate 1: Detailed information addressing scientific and technical merit selection criteria and preliminary information address the potential for broad-based economic benefit

Gate 2: Detailed information addressing the potential for broad-based

economic benefit and submission of a budget narrative

Gate 3: Oral review and submission of additional information per request of ATP

Gate 4: Final selection

ATP does not fund basic research or very applied research such as Phase II through Phase IV clinical trials. While funding is available for general biotechnology research, there are no programs specifically related to biodefense or biosecurity. However, this does not prevent ATP from funding efforts in that program area, should the proposer meet the various other criteria generated by ATP.

2.3. INTERAGENCY COORDINATION A good deal of interagency coordination is conducted at the strategic planning level by the office of the President. One example of this approach to coordinated response can be seen in the National Strategy for Pandemic Influenza. The National Strategy for Pandemic Influenza

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document outlines specific metrics and milestones for each of the federal agencies involved with coordinating and mobilizing a response to pandemic flu. The Implementation Plan for the National Strategy was first published in May of 2006, and requires follow-up every six months. Many of the efforts covered under the National Strategy for Pandemic Influenza also build biosecurity and biodefense infrastructure in the case of an outbreak of a man-made agent. Six months later (December 2006) progress was observed on numerous inter-agency milestones, including:

Travel notifications on avian and pandemic influenza outbreaks coordinated by the Department of State and the Department of Health and Human Services

Transportation and border-related pandemic planning was conducted

through the Departments of Transportation, Homeland Security, Health and Human Services, and Agriculture through a review of grants and federal funding programs

Workforce educational materials for airline crews and passengers as well

as Travel Industry employees were generated by the Departments of Labor, Transportation, Health and Human Services, and Homeland Security

Screening of cargo and travelers from affected was improved through

coordination between the Department of Homeland Security, the Department of Health and Human Services, the Department of State, and the Treasury

The Department of Homeland Security, the Department of Health and

Human Services, the Department of Justice, the Department of Transportation, and the Department of Defense fulfilled 70 percent of all submitted training requests for incident response to pandemic influenza

In addition, a working group on bioterrorism has been mandated by Sec. 108 of P.L. 107-188, the Public Health Security and Bioterrorism Preparedness and Response Act of 2002. This working group consists of the DHHS and DOD Secretaries, as well as other agency leaders. Interagency guidance is provided by the Homeland Security Council. Furthermore, Memorandums of Agreement such as the one covering BioWatch are also used to implement policy in areas of overlap between agencies. However, evidence from the BioWatch program shows that such programs are often difficult to properly implement. Although the Department of Homeland Security was in control of the funding for the Environmental Protection Agency and the Department of Health and Human Services on that program, they were unable to properly ensure that those agencies carried out their tasks in the appropriate fashion.

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Distinct from the operational level of strategic planning is the level of coordination on mandate tasks at the operational level. For example, while the Department of Homeland Security is directed to take the lead in the Medical Countermeasure Development, they are expected to take advantage of overlap with other departments and agencies that have similar goals. Frequently, these opportunities arise not from formal direction on the part of management in the federal agencies, but from discussion between program managers at government agencies assigned with responsibility in a specific program area.

2.4. COOPERATING WITH THE PRIVATE SECTOR Coordination for research and development in the public interest is done in a variety of ways. Apart from direct dialogue between funding agencies and potential performers, some organizations have been established in order to better facilitate cooperation. Entities like research parks receive subsidies in order to provide low- or no-cost facilities to entrepreneurial researchers, often from local universities. Scientific incubators provide a clearinghouse for research and development firms with common interests and goals, offering contacts with venture capitalists or well-developed contacts with federal funding agencies. One of the most interesting examples of business incubators with an edge on national security (including biodefense) is the Chesapeake Innovation Center (CIC), located in Maryland’s Anne Arundel County.5 Characterized as a “business accelerator”, the CIC was established by the Economic Development Corporation of the County to focus entrepreneurial talent on security-related opportunities. The CIC maintains partnerships with both public and private sector entities. It sources and screens early stage technology companies and connects them to networks of large industrial companies. In addition to playing the role of active network gateway, the CIC operates incubation facilities where selected early stage technology companies are mentored and provided with a menu of services typical to incubators of small high-tech companies including customer contracts, funding, staffing, subject matter experts, clearances, government contracting issues, and office facilities. In 2005 the CIC joined forces with six other partners, each from a different state, to form the Technology Acceleration for National Security (TANS) network of high-tech business incubators (Box 3).

5 See http://www.cic-tech.org/index.html.

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Box 3. The Technology Acceleration for National Security (TANS) is an example of a technology business incubator focusing on security issues, including biodefense. Launched in 2005, TANS is headed up by the Chesapeake Innovation Center (CIC) and incorporates partner business incubators from Alabama, Colorado, Georgia, Maryland, New York, and Texas. At the time of launch, the network encompassed over 100 small businesses and planned to grow into several more states. One of the partners is the Georgia component of TANS is the Advanced Technology Development Center (ATDC). ATDC is affiliated with the Georgia Institute of Technology and is located proximal to Atlanta, Georgia. Its membership includes firms with expertise in wound healing, pharmaceutical quality control, and treatment of central nervous system diseases and disorders. ATDC also maintains close relationships with Georgia Tech Entrepreneur Services, a company affiliated with the State of Georgia in creating partnerships for technology development that assists small companies through the SBIR process. Another partner is the Texas Research & Technology Foundation (TRTF), itself a partnership of organizations whose work involves various stages of complex drug development process. Yet a third partner is the Watervliet Innovation Center (WIC), a modern business incubation program focused on accelerating the growth of emerging homeland defense and security technology companies. The interesting aspect of TRANS is the envisioned large network of high-tech business incubation facilities and programs, some of them more explicitly focused on security issues than others, which may create the critical mass to harness entrepreneurial ingenuity to resolve some of the pressing problems in homeland security.

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3. DETERMINING PRIORITIES

3.1. AGENTS One common standard for the classification of biological warfare threats comes from the Centers for Disease Control. The CDC maintains a list of potential threat agents based on several criteria, including:

• ease of dissemination • mortality rates • potential for social disruption • capability for public health actors to readily respond

The CDC standards are used throughout the government as a common point of reference. For instance, the National Institute for Allergy and Infectious Diseases uses it to allocate funding for pathogen research and countermeasures by severity of threat agent, with proposals dealing with Category A agents receiving priority for funding. The list is maintained by the CDC’s Preparedness and Response Office. The origins of CDC’s list of potential threat agents can be traced back to a meeting in June of 1999 which established basic criteria for inclusion and categorization. The panel was composed of cross-section of civilian, military, and intelligence experts. The threat agents considered for assessment were drawn from a variety of unclassified sources, including the Select Agent Rule list, the Australian Group List for Biological Agents for Export Control, the unclassified military list of biological warfare agents, the Biological Weapons Convention List, and the World Health Organization Biological Weapons List. Those individuals with security clearances reviewed classified intelligence information relevant to the threat agents of interest. However, no information was provided on the likelihood of use of one agent over another. The Inclusion criteria included:

Public health impact based on illness and death

Potential delivery methods based on agent stability, ability to mass produce, and potential person-to-person transmission

Public perception related to fear and potential disruption

Special preparedness requirements based on diagnostic needs, stockpile

requirements, or enhanced surveillance

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The list contains three categories of diseases/threat agents: category A, category B and category C. Category A Diseases/Agents:

Transmission: Can be easily transmitted from person to person Mortality: Have a high mortality rate potential for “major” public impact Social effects: May cause public panic/social disruption Infrastructure: Require special attention to public health preparedness

Category B Diseases/Agents:

Transmission: Are moderately easy to disseminate Mortality: Result in low mortality but high morbidity Infrastructure: Require CDC’s diagnostic capability and disease

surveillance Category C Diseases/Agents

Emerging threats and pathogens that may be easy to disseminate, readily available, and have the potential for high mortality/morbidity

Table 3.1. Agents on CDC’s Threat List Category Disease

Anthrax Botulism Plague Smallpox Tularemia

Category A

Viral hemorrhagic fevers (incl. filoviruses such as Ebola, Marburg and arenaviruses such as Lassa and Machupol) Brucellosis Epsilon toxin of Clostridium perfringens Food safety threats (Salmonella, E. Coli) Glanders Meliodosis Psittacosis Q Fever Ricin toxin from Ricinus communis (castor beans) Typhus fever Viral encephalitis

Category B

Water safety threats (Vibro cholorae, Cryptosporidium parvum) Nipah Virus Category C: Emerging Infectious Diseases Hantavirus

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3.2. SCENARIOS One type of analysis utilized by policy makers interested in bio-defense is scenario based forecasting. In these exercises, actors from a variety of relevant backgrounds in public sector management, health care, and clinical and scientific expertise gather and discuss potential outcomes from given events. Through role-playing, these groups are able to determine gaps in capability that they may have otherwise overlooked. In 1999, the CDC, along with Johns Hopkins University, examined two possible scenarios of a Category A agent attack on a fictional United States city. The two scenarios, using anthrax and smallpox, highlighted shortcomings in disaster preparedness pre-September 11th. Both scenarios demonstrated potential catastrophe (Box 4).

Box 4. The anthrax scenario investigated the acute and chronic response to deployment via aerosol spray onto a major sports stadium during a game, targeted from a nearby highway. Symptoms would begin to emerge two days later, appearing as flu-like symptoms. At the point at which the appropriate cause, anthrax, would be diagnosed, hospitals across the city would be beyond capacity. Treatment for anthrax must be administered pre-symptomatically in the event that care is unavailable in the early stages of the disease, and without the ability to trace the attack back to a common event, the football game, there would almost certainly be improper distribution of an already limited supply of countermeasure. By the seventh day following attack, 2,400 onlookers, of 16,000 exposed in the initial attack, will have died, city morgues will have filled up far beyond capacity, and most city employees responsible for maintaining infrastructure and civic order will not be attending work. 1,600 more will die in the chronic phase of illness, and 250,000 will receive antibiotics. The area around the stadium will have to be decontaminated at the cost of millions to the city, and property values will plummet. Economic damages will range in the billions, both from treatment cost and lost man hours6.

Since the 1999 exercise, additional information can be gathered from the anthrax attack that did occur. In October 2001 a still unidentified individual mailed anthrax specimens to the U.S. House of Representatives and U.S. Senate. In the months that followed the Illinois Department of Public Health received 1,500 samples for testing, at a location remote from the initial attacks. Potential overflow of the alertness system with false alarms such as these could present a complication in the case of an actual attack7.

6. Inglesby, T. V. July 1999. “Anthrax: A Possible Case-History”, Emerging Infectious Diseases, 5(4): 556-560. 7. Dworkin, M., Ma X., and R. G. Golash. April 2003. “Fear of Bioterrorism and Implications for Public Health Preparedness,” ”, Emerging Infectious Diseases, 9(4): 503-505.

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The economic damage and loss of life posed by an anthrax attack are limited in comparison with the potential damage of smallpox (box 5). Unlike anthrax, which requires inhalation of the spores, smallpox transmits from individual to individual as an aerosol.

Box 5. The 1999 smallpox scenario explored the chain of events following initial exposure on a crowd of people gathered to support a political candidate, the vice president, on a campaign stop. One thousand people are gathered to watch the vice president speak. Eleven days after initial exposure, patient zero, a 20 year old male, presents to the emergency room with fever, paleness, and a rash. An initial diagnosis of Dengue is made. The appropriate diagnosis is made fourteen days after initial exposure, and the hospital where the first appropriate diagnosis is made is quarantined. Over the following two days thirty-five more individuals test positive for smallpox at eight emergency rooms in the area, and ten more individuals test positive in an adjoining state. One week later, the disease has spread to another major urban center one week over. Three days following that, over 700 cases have been reported worldwide. All patients have been quarantined as soon as the virus has been identified. Two months after initial exposure the virus has spread out across the country. Smallpox, a disease once thought eradicated, has returned. Civic life has ground to a halt in many parts of the country, and foreign travel is limited. By the end of the year, endemic smallpox is present in fourteen countries8.

Exercises such as this allow policy makers to highlight weak points in preparedness for biological attack using discrete and relevant outcomes in constrained systems. While they are imperfect, in that conclusions are generated based on suppositions and estimates, they still provide a feasible range of events. Measurable terms such as virulence, length of incubation, and initial number of individual exposed provide a statistical backbone.

3.3. MODELING In addition to determining the level of threat through scenario type exercises, some agencies will attempt to create discrete models of potential damage caused by a biological agent. Los Alamos National Labs created one such model in an attempt to measure the potential damage caused by pandemic influenza (H5N1). In their model they assumed that a small group of individuals would arrive in the Los Angeles Airport carrying the virus. Following initial exposure, individuals would follow travel advisories and limit long-range travel. By mathematically representing such factors as rate of travel, incubation time, and viral spread, the researchers were able to model how a biological agent could be transmitted if prophylaxis and vaccine measures were not readily taken9.

8 O’Toole, T. July 1999. “Smallpox: An Attack Scenario,” Emerging Infectious Diseases, 5(4): 540-546. 9 Germann, T, Kadau, K, Macken, C, and I Longini Jr. 2005. Pandemic Flu. http://www.lanl.gov/news/images/avianflu.shtml

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Figure 3.1. Los Alamos Model: Simulated Infection Rate per 1000 People.

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Blue: < 1 person infected per 1,000 people Green: 50-100 infections per 1,000 people Red: > 100 infections per 1,000 people Rates of infection peak at the 90 day mark Models such as this can be created for a variety of other biological agents, and provide clear demonstration of risks involved to populations. Census and labor statistics are used, in this example, in order to determine population flows. The introduction of other variables such as quarantine measures, school closures, or outright travel bans can be measured vis a vis successful containment. While epidemiological models of potential virulence, such as that composed by Los Alamos, serve as indicators of severity of illness, policy makers also use risk analysis in order to determine where best to allocate resources. The Urban Areas Security Initiative (UASI) is a Department of Homeland Security program that allocates funding to states and municipalities based through the Homeland Security Grant Program. After early criticism that some of its funding was allocated along political lines rather than need, the DHS implemented risk analysis models in order to determine where funding was most appropriately directed. In Fiscal Year 2006 this model was constructed in a three part process. Initially, risk analysis models were used to compute an overall risk score. Following this, peer review determined the relative effectiveness of proposed solutions. A combination of the risk and effectiveness scores was used to create a risk/effectiveness matrix.

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Figure 3.2. UASI Risk/Effectiveness Model

The risk model was constructed by measures of threat, vulnerability, and consequence. In addition, geographic and asset-based risk scores for a given urban area were calculated independently. Geographic risk was computed based on counts of suspicious incidents, numbers of visitors from countries of interest, and overall population. Asset-based risk was generated using a variety of “attack scenarios” on targets of value such as chemical plants, dams, or commercial airports. In computing the final score, geographic risk was weighted twice as heavily as asset-based risk. This score determined the minimum risk that an urban area required before it could apply for funding. The effectiveness analysis was a new requirement for the FY 2006 funding period. Proposers were required to identify sets of solutions to homeland security needs that were defined during the strategic planning process. The Department of Homeland Security then assembled seventeen panels composed of cross-sections of stakeholders that attempted to be representative of required expertise as well as levels of government. Proposals were scored based on relevance to National Preparedness Goals, potential impact, state, local and regional needs, implementation of investment, and sustainability of proposed investment. These scores then were used to prioritize funding amounts by separating proposals into four categories, with all forty-six urban areas deemed relevant by the initial risk analysis receiving some amount of funding (Table 3.2).

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Table 3.2. Categories of Risk and Effectiveness Used by UASI Category Description Category I High risk, high effectiveness Category II High risk, low effectiveness Category III Low risk, high effectiveness Category IV Low risk, low effectiveness Approximately seventy percent of all funding was granted to Category I and II Urban areas. Risk was preferable to effectiveness, as the risk score comprised two-thirds of the determinant for funding. Use of this process resulted in, in several cases, drastic changes to funding profiles for some metropolitan areas (Tables 3.3, 3.4). Table 3.3. Five Largest Funding Increases as a Result of Model Implementation Metropolitan area Fiscal Year 2005

Allocation Fiscal Year 2006 Allocation

Percentage change

NJ – Jersey City/Newark

19,172,120 34,330,000 +79%

NC – Charlotte 5,479,243 8,970,000 +64% GA – Atlanta 13,117,499 18,660,000 +42% WI – Milwaukee 6,325,872 8,570,000 +35% FL – Jacksonville 6,882,493 9,270,000 +35% Table 3.4. Five Largest Funding Decreases as a Result of Model Implementation Metropolitan area Fiscal Year 2005

Allocation Fiscal Year 2006 Allocation

Percentage change

CO – Denver 8,718,395 4,380,000 -50% LA – New Orleans 9,305,180 4,690,000 -50% PA – Pittsburgh 9,635,991 4,870,000 -49% TX – Dallas/Fort Worth

24,335,870 13,830,000 -43%

OH – Columbus 7,573,005 4,320,000 -43% For the UASI process in Fiscal Year 2007, the Department of Homeland Security proposed further changes in the model. In order to make the process more easily understood to stakeholders, DHS simplified the risk model into a single hundred point score mechanism. Additionally, the model focused on consequences of a serious attack

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and eliminated differential vulnerability assessments, choosing to view all areas as equally vulnerable. Further, decision-makers at DHS were able to draw from historical threat information compiled by the intelligence services. For purposes of the 2007 model, threat was assigned a 20 point value, and consequences of an attack were assigned 80 points. A breakdown of the composition of the score is shown in Figure 3.3 below. Figure 3.3. Score Composition in UASI Model 2007

(DIB: Defense Industrial Base) Infrastructure assets were grouped into two tiers. Tier I infrastructure assets were those which, if attacked, would result in losses similar to scale as those generated by the attacks of September 11th and the natural devastation of Hurricane Katrina. Tier II assets were defined as assets which, if attacked, would have national and regional impact. In the analysis, Tier I assets were scored with three times the weight of Tier II assets. In the 2007 process, the effectiveness analysis remained the same. However, an addition was added for computation of final score. A five to eight percent multiplier was granted to those plans that included investments that would assist more than one region. The 2007 process also implemented a mid-year review which would allow interested areas to submit proposals for review and comment before submission of a final proposal. A GAO audit of this process completed in February of 2007 provided several areas which DHS can continue to improve:

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• The risk modeling that DHS currently uses in the process could be bolstered by the inclusion of standards on uncertainty modeling developed by the Office of Management and Budget. OMB guidelines, specifically, attempt to capture outcome sensitivity to various sources of uncertainty.

• DHS does not seem to fully understand the effect of modifications to its modeling

processes on policy outcomes. While changes in funding levels have resulted from changes to modeling, it is unclear as to which factors, specifically, resulted in these outcomes.

• The modeling process relies on expert judgment for computing several factors,

which, while preferred to an uninformed model, is still somewhat arbitrary.

3.4. MONITORING Another tool used by policy-makers to determine priorities when dealing with potential biological threat agents is monitoring existing information on disease outbreak. The CDC, through the National Notifiable Diseases Surveillance System conducts weekly updates on identified cases of some threat agents of interest. This information is voluntarily provided to the CDC by actors at the state level, and is not comprehensive for all potential agents of interest. However, such information can be used to inform policy-makers as to “normal” levels of these agents in the wild, with large deviations from the baseline serving as markers of abnormal occurrence. Through observing this data it becomes clear, for example, that the Anthrax outbreak resulting from the introduction of the disease into the US Senate offices in 2001 was a clear deviation from the norm. Table 3.5. CDC Disease Outbreak Data on Observed Infectious Diseases: 2001-2004

Anthrax Botulism, Foodborne

Botulism, Other

Brucellosis Cholera Encephalitis, western equine

Plague Tularemia

2001 23 39 116 136 3 66 2 129 2002 2 28 90 125 2 2840 2 90 2003 0 20 109 104 2 2866 1 129 2004 0 14 124 114 5 1142 3 134 Total 25 101 439 479 12 6914 8 482

Monitoring and surveillance of disease can be improved past current capabilities. Voluntary reporting by state agencies may not be the preferable solution in order to gather information in a timely manner. Emerging infectious diseases such as Marburg or Nipah, or eradicated diseases such as smallpox, may be incorrectly identified initially at the local level whereas an aggregate view of disparate data from numerous states may indicate that an outbreak is taking place. Nevertheless, monitoring and surveillance provides a continuous background against which new information can be validated for deviance from a trend.

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4. BUSINESS DEVELOPMENT

4.1. METHODS TO ENCOURAGE TECHNOLOGY DEVELOPMENT The Federal government uses a variety of methods to encourage technology development. Each federal agency involved in research and development approaches the topic slightly differently, but most agencies use either grants or contracts. At some Agencies, such as the NIH, a large portion of the research is investigator-initiated based on broad solicitations on a given topic. Other Agencies, such as the DOD or the DHS, tend to use contractual agreements that originate from solicitations that include specific milestones and deliverables. One common method for funding research and development is the NIH R01 Grant. These are investigator-initiated grants along a given topic line. The National Institute for Allergy and Infectious Disease uses the NIH parent R01 (PA-07-070), generic to all of the National Institutes, and does not use a specific solicitation to handle R01 Grants on biodefense topics, although they do have a separate R01 for non-biodefense related emerging infectious diseases (PA-07-246). However, there is a specific P01 grant, or “program project” grant, for multi-investigator research in the area of biodefense. All grants over $500,000 per year must be approved by the NIH prior to submission. Review of NIH grants is conducted via peer review. A council of experts on a given subject is convened by the NIH several times throughout the year to discuss proposal submissions in a “study section”. At study section, three reviewers, a primary, secondary, and tertiary reviewer each provide an overview of the merits and drawbacks of a program vis a vis current progress in the field. The panel then assigns a score to the proposal, and proposals are funded based on these scores. Typically, an investigator can expect to wait up to eighteen months following submission of their application prior to hearing back from reviewers. Responses are generally detailed, and provide areas for improvement should the investigator be interested in resubmitting. Information on membership of various study sections is available to the public, and study sections can either be standing or convened due to special emphasis in a given area. Separate from grants, the NIH also funded three contracts in FY2006 in the area of biodefense for a total of 129.72 million dollars. These contracts were for the specific development of therapeutic strategies for Category A, B, or C biological threat agents (Table 4.1).

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Table 4.1. Three Biodefense Contracts Proposer Topic Amount (Millions) SRI International Services for Pre-Clinical

Development of Therapeutic Agents

56.89

Alnylam Pharmaceuticals Development of Therapeutic Agents for Select Viral Diseases

23.02

NexBio, Inc. Development of Therapeutic Agents for Select Viral Diseases

49.81

The DOD and DHS, on the other hand, prefer contractual mechanisms to grants as their research and technology development portfolio tends to be objectives and mission-driven. A variety of DOD and DHS agencies contract out for research and technology development in biodefense, and most contracts are awarded through the Broad Agency Announcement (BAA) process. In FY2006, several BAA calls relevant to biodefense were open for submission. These included:

The second phase of a DHS program to develop assays and informatics systems capable of detecting biological threat agents (HSARPA BAA 06-01)

A biological weapons countermeasures program for accelerated

development of medical therapeutics (DTRA BAA 06-01)

Methods to diagnose an individual infected with a pathogen prior to emergence of symptoms (DARPA BAA 06-19 Addendum 4)

The Medical Chemical and Biological Defense Research Program (Joint

Science and Technology Office for Chemical and Biological Defense USAMRMC BAA 06-01 Supplemental)

These contracts are often performed phase by phase, with individual phases rarely exceeding two years. However, few BAA solicitations provide guidelines for total budget amounts, and it is up to the sponsoring agency to determine whether or not the applicant has appropriately rationalized their proposed budget. Unlike NIH grants, which go through a process of peer review, BAA proposals are reviewed by government-employed experts from a variety of fields and agencies.

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In addition to grants and contracts, the federal government also uses Small Business Innovation research (SBIR) and Small Business Technology Transfer (STTR) awards in order to administer R&D funds to encourage small-business growth as well as cooperation between academia and the private sector. By statute, two-and-a-half percent of all federal funding for extramural research is earmarked for SBIR programs. An additional three-tenths of a percent set aside for STTR programs which involve cooperative agreements between academia and industry. The SBIR program is authorized until September, 2008, by the Small Business Reauthorization Act of 2000 (P.L. 106-554), and P.L. 107-50, the Small Business Technology Transfer Program Reauthorization Act of 2001, authorizes the STTR program until 2009. These programs are often high-risk high-reward programs that larger companies may not be agile enough to engage in. Awards are set at $100,000 for the first six to twelve months of performance, with a potential second phase of up to $750,000 over two years. Proposers can also apply for a third, unfunded, phase specific for application/commercialization. Examples of SBIR and STTR development projects related to Biodefense include:

An in-situ gelling nasal vaccine delivery platform (NIAID, awarded to Delsite Biotechnologies, Inc.);

Microfluidic Controlled Gel-Drop Microarrays for Biothreat Diagnostic

Devices (NIAID, awarded to Akonni Biosystems, Inc.);

Chem/Bio Sensor Network Design Tool (SNDT) (DHS, awarded to Applied Nanotech, Inc.);

A Computational Framework for Interpreting Metabolomics Data (DOE,

awarded to Genomatica, Inc.);

TIGER Biosensor for Broad Viral Detection and Genetically Engineered Microbes (DOD, Isis Pharmaceuticals)

4.1.1. Regional Incentives The most prominent regional development is done through the CDC's EWIDS program (see Section 2.1.3). This program funds biosurveillance capabilities for states at the U.S. Canada and U.S.-Mexico border. Further funding is available through the CDC's cooperative agreement program for U.S.-Mexico border states. In addition, the NIH funds ten Regional Centers of Excellence for Biodefense and Emerging Infectious Diseases Research. An initial eight institutions shared 350 million dollars in funding over eight years beginning in 2003. They included: Duke University, Harvard Medical School, New York State Department of Health, University of Chicago,

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University of Maryland, University of Texas Medical Branch (Galveston), University of Washington and Washington University in St. Louis. In 2005 the University of California, Irvine, and Colorado State University, Fort Collins, were added and received 80 million dollars in four-year grants. Regional coverage can be seen on Figure 4.1. Figure 4.1. Regional Coverage by NIH Centers of Excellence

The mission of the Regional Centers of Excellence is to provide research on Category A-C pathogens (see Section 3.1) and specifically to:

• Support investigator-directed research • Train researchers and other personnel for biodefense research activities

• Create and maintain supporting resources, including scientific equipment

and trained support personnel, for use by the RCEs and other researchers in the region

• Emphasize research focused on development and testing of vaccine,

therapeutic and diagnostic concepts

• Make available core facilities to approved investigators from academia, government, biotech companies and the pharmaceutical industry

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• Provide facilities and scientific support to first responders in the event of a national biodefense emergency

4.2. STANDARDS DEVELOPMENT In biodefense, a number of agencies have developed standards in terminology, to ensure that discussion is conducted with a similar set of principles, standards in quality of biological agent, to ensure that countermeasures are efficacious against a given pathogen threat, standards in bioassays, to ensure that detection and verification methods for threats are similar, and standards in product development, to ensure that treatments are both functional and safe. Standards in categorization of bio-agent according to threat are composed by the CDC and are discussed in Section 3.1. Standards in quality of pathogen countermeasure and bioassays used for threat detection are discussed below in Section 4.2.1 on DOD assay development. Standards in product development are controlled by the FDA, discussed in Section 2.1.5. Finally, the importance of standards was underlined in a recent report by GAO (Section 4.2.2).

4.2.1. Case Study: DOD Standards Development in Assays One set of standards applicable to commercial research and development is used by the Department of Defense in regular operation of biodefense laboratories. These standards are developed not for agent identification and classification, but rather for construction and development of assays used in detection of bio-agents. The majority of the biological detection assays are manufactured by a disparate group of DOD labs underneath a joint directorate, the Chemical Reagents Program. CRP kits were used to identify the Anthrax used in the attacks on the US Senate in Oct of 2001 as well as the ricin toxin deployed against the Senate in 2004. Prior to September 11th there was a low need for these assays DOD-wide. They were, in essence produced in low quantities on a relatively as-needed basis. As the threat of bioterrorism went from an on-the-horizon threat to a current and continuing threat, several laboratories began producing assays for stockpile. However, different labs produced different types of assays, without a uniform-standard developed. Each armed service operated independently of the others to set criteria. Each lab collected data and established benchmark metrics on their own per the demands of their “customer”, the service which they were attached to. In response, the DOD conducted a total overhaul of the system of development and acquisitions. Rather than focus on development on a service by service basis, the DOD organized production of assays into six core areas. Data relevant to the development of these assays was standardized across the services under a 12.4M fund managed by the Defense Threat Reduction Agency (DTRA). Development of standard criteria would also inform the transition of some bioassay development into the commercial realm through the Joint Biological Agent Identification and Diagnostic System, which would

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manage deployment of FDA approved devices for DOD use. By unifying data across laboratories it will be easier for DOD labs to identify gaps that can be covered through commercial development, or for which off-the-shelf technology options do not exist. Moreover, DOD labs now work from a shared set of cell cultures. All laboratories receive portions of batches of biological agents in order to control the number of unknown factors. Information on each cell line is used to supplement repositories of information on characteristics of threat agents such as the Genomics Repository in Washington, DC (DNA/RNA information) and the Antigen Repository in Utah (inactive agent repository). These repositories provide information that allows researchers in academia and private firms to conduct research on biothreats without a need for direct access to the bioagent. Lessons learned from this process were presented to other government agencies, including the US Department of Agriculture, the Department of Homeland Security, and the National Institutes of Health. The Department of Homeland Security and the National Institutes of Health also use CRP-generated reference materials. Some of the lessons included the need to standardize language and create memorandums of agreement between researchers which allowed them to maintain control over the IP. An additional area of concern was the ability to replicate results generated by the CRP, as difficulties arose in verification of characteristics or detection of bioagents when the threat agent was compromised by various additives.

4.2.2. Case Study: DHS Anthrax In May of 2006, the GAO published a comprehensive report analyzing the ability of the Department of Homeland Security to respond to the threat of Anthrax. An 877.5M contract was put out in 2004 by DHS in order to acquire 75 million doses of vaccine. As of 2006, the vaccine produced was inadequately tested and studied. The GAO pointed out that to that point there were no standards regarding optimum number of doses, no studies of long-term effects, and minimal data on short term reactions. Further, there was no single standard model for determining the presence of anthrax contamination. Overall, the GAO recommended that the Department of Homeland Security establish a clean roadmap that delineated specific interagency responsibilities and the contribution that individual agencies would provide to anthrax detection and vaccine validation.

4.3. PUBLIC-PRIVATE PARTNERSHIPS In 2004, the U.S. Congress legislated the creation of Project BioShield in order to acquire and develop vaccine stockpiles in response to potential biological threats. This program authorized 5.593 billion dollars of funding for the acquisition of vaccines for a range of biological threats. Out of this total authorization, 3.418 billion was obligated for

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FY2004-FY2008. A portion of this funding was used in development of the Anthrax vaccine that the GAO found to be inadequate (previous section). When interviewed, one problem cited by researchers was that Project BioShield did not appropriately account for the risk that pharmaceutical companies are exposed to during the development process. The government essentially provided funding for the acquisition of vaccine through Project BioShield, and for development of vaccines at early stages through other funding opportunities administered by agencies such as NIAID, DTRA, or DARPA. The government rarely provided funding during clinical trials, a period at which pharmaceutical companies can pay over $26,000 per patient enrolled. This provides a disincentive for companies to provide new and more efficacious vaccines, and can result in stagnation in vaccine development for emerging pathogens. In 2005, Dr. Philip Russell, former Army Medical Corps Officer and senior advisor to the Department of Health and Human Services from 2001 to 2004 on acquisition of medical countermeasures testified as to the shortfalls of the BioShield legislation in countermeasure capacity building. While he recognized the important initial accomplishments of the NIAID in basic research on countermeasures, he stated:

“Whether the potential products are eventually developed depends on whether funding is available for industrial product development to the point where they are considered viable candidates for a BioShield acquisition.”

Continuing, he highlighted that most of the products in the acquisition process under Project BioShield had received government funding through mid-level development and observed that:

“When adequate government support of early and mid level development is lacking, products will not progress to the point where they can be purchased under BioShield. The present process does not fully meet the needs of the government as evidenced by the slow development of anthrax treatment products to the point where they are eligible for BioShield procurement. Most small biotech companies with promising products need government support in the preclinical and early clinical phases of the R&D. Many large companies need government funding to share the risk of initial development for products where the government is the only market. This transition between laboratory research and early industrial development is one of the more serious and controversial problem areas in the current federal program for developing and acquiring medical countermeasures.”

Recognizing the shortfall between intent and action, in December 2006, Congress made changes to the acquisition process for vaccines and created the Biomedical Advanced Research and Development Authority (BARDA). BARDA would be able to serve as a

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venture capitalist, of sorts, and could fund the development of vaccines between initial research and procurement, which occurs at the end of clinical trials. By doing this, the federal government would be able to limit the potential risks in development for commercial firms. While providing the funds up front increases risk to the federal government, there would also be stringent reporting and oversight requirements.

4.4. TRADE COMMITTEES AND ORGANIZATIONS Several standing bodies advise the U.S. government on trade issues. One of these is the Industry Trade Advisory Center (ITAC) comprised of several Advisory Committees each dealing with a section of industry (sixteen plus one committee of the sixteen committee chairs). The system of ITACs are jointly administered by the Department of Commerce and the United States Trade Representative (USTR). The ITACs provide a public-private forum to ensure industry has a voice in formulating the trade policy of the United States. They act as a mechanism to allow stakeholders in a given industry direct input on legislation and trade agreements that may positively or adversely affect them. The industry advisors serving on the ITACs provide valuable input as the Administration advances its trade agenda to improve economic opportunities for America’s businesses, workers, and consumers. ITAC 3 represents the Chemicals, Pharmaceuticals, and Health/Science Products and Services. Moreover, a number of experts on chemical and biological defense work outside the government in non-profit organizations. Some of these organizations advise on matters of policy, others represent professional or academic interests. Table 4.2 lists of some of the major organizations with involvement in biodefense and biosecurity, along with brief descriptions of their major policy focus. Table 4.2. Major Non-Governmental Organizations Involved in Biodefense and

Biosecurity Organization Type Activity American Society of Microbiology

Academic association Professional education, workshop and conference organization, standards governance and journal publication

The National Academies Academic Organization Brings together committees of experts. Engaged in broad array of counter WMD studies in the area of biodefense

Arms Control Association

American NGO Promotes public education and research on arms control policies

Center for Arms Control and Non-Proliferation

American NGO Program on Biological and Chemical Weapons Control and Scientists Working Group reinforce

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norm against development of chem/bio-weapons and enhance prevention and defense through working papers, policy recommendations, and briefings to Congress

Center for Strategic and International Studies

American NGO Biotechnology and Public Policy Initiative: seeks to clarify intersections of science and policy to increase benefits and avoid dangers. Homeland Security Program: Advance policies, practices, partnerships to keep America safe and secure at home and abroad

Chemical and Biological Weapons Control Institute

American NGO Research organization with focus on chem/bio-defense.

Council for Responsible Genetics

American NGO Public education about social, environmental, educational aspects of genetics. Biowarfare program works to end development and use of bioweapons as well as research for defense purposes that could have offensive applications

Federation of American Scientists

American NGO Organization of American scientists chiefly concerned with security and non-proliferation issues. The Biological and Chemical Weapons Security Project seeks to raise awareness among scientists of their ethical responsibilities and potential misuse of their research

Henry L. Stimson Center

American NGO Analysts with national security focus. Chemical and Biological Weapons Nonproliferation and Response Project is concerned with WMD capabilities, counter-WMD capabilities, proliferation controls, and likelihood of deployment

Mitretek Systems American NGO National center of expertise on chemical/biological defense systems. Supports US Armed Services in disposal of stockpile

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National Memorial Institute for the Prevention of Terrorism

American NGO Founded in wake of Oklahoma City bombing. Funded by Congressional appropriation. Conducts research on social and political causes of terrorism and the development of counter-WMD technologies

Potomac Institute for Policy Studies

American NGO Promotes discussion and debate on key issues. In the area of bio-defense, the Institute holds numerous workshops and publishes their findings

RAND Corporation American NGO Research and advisory role on scientific and technological issues. Specific expertise in security policy

Trust for America’s Health

American NGO Public health advocacy organization. Specific policy recommendations relevant to bio-defense

American Association for the Advancement of Science

International NGO Advocacy on behalf of science in the public interests

British-American Security Information Council

International NGO Independent analysis and advocacy on global security issues; strategic goal of bioweapons program is to “increase public awareness in the United States and Europe of the problems and dangers of bioweapons proliferation and the opportunities for developing national, regional, and global responses”

Carnegie Endowment for International Peace

International NGO Non-proliferation project that provides authoritative information on WMD proliferation

International Coalition of the Red Cross

International NGO ICRC initiative on Biotechnology, Weapons, and Humanity seeks to reduce risk of biotechnology being used against humanity. Seeks to educate public as to risks, rules, and responsibilities related to scientific advancement

Nuclear Threat Initiative International NGO Global Health and Security Initiative primarily focused on areas of disease surveillance, early detection, and rapid response as well as promoting science security

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Pugwash Conferences International NGO Promotes meetings between military and scientific communities. Specific aim is to prevent catastrophic threat from WMDs

The Sunshine Project International NGO Non-proliferation through public education. Seeks to strengthen international agreements and bolster norms against deployment and development of bioweapons

Alfred P. Sloan Philanthropic organization

Program area in bioterrorism

John D. and Catherine T. MacArthur Foundation

Philanthropic Organization

Funds a Science, Technology, and Security Initiative in counter-proliferation and mitigation of WMD threat

Ploughshares Fund Philanthropic Organization

Supports efforts in non-proliferation as well as improving security of existing dangerous chemicals and pathogens, standards creation for responsible research, international conventions against chemical and biological weapons, destruction of existing stockpiles, and reduction of risk created by research for bio-defense

American Biological Safety Organization

Professional association

Advocacy and education for biosafety professionals

Association of Public Health Laboratories

Professional association

Advocacy and collaboration between public health laboratories; focus on preparedness

Infections Diseases Society of America

Professional Organization

Represents scientists, clinicians, physicians involved in the study or treatment of infections disease. Lobbying organization capable of mobilizing 7,500 members

International Council for the Life Sciences

Professional Organization

Represents scientists with interests in the life sciences. Seeks to promote global health and security. Identification of risk and standards setting.

Representation is not limited to professional organizations, academic organizations, or public advocacy groups. In addition, commercial firms can hire professional lobbyists in order to influence decision-making in the area of biodefense. Of these lobbying firms, the most notable is McKenna, Long and Aldridge (MLA). McKenna, Long, and

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Aldridge offer comprehensive services for clients interested in government access, with capabilities ranging from scientific advisory to legislative action and cost proposal analysis. McKenna, Long, and Aldridge have been involved in numerous procurement and grant-making processes. For instance, MLA has negotiated 98 million dollars in funding to develop cell-based vaccine for pandemic flu, and expanded their business for that client to 200 million in further treatment for SARS and general pandemic preparedness. They have negotiated 3.4 million dollars from the NIH for construction of a new biodefense laboratory. McKenna, Long, and Aldridge has been actively involved in crafting the next stage of legislation on the BioShield effort. MLA associates frequently testify before congress on biosecurity and biodefense issues. In addition, they leverage their network to bring venture capitalists into the development process, providing transition partners for government-sponsored research. Further, MLA serves as an international liaison for various governments and overseas businesses. MLA has extensive offices in Canada and represents several EU-biodefense firms interested in blood product substitutes and vaccine development. They also liaise to the media, and MLA associates are experts for major television news networks and newspaper and print media. Organizations such as MLA wield tremendous influence across sectors of American business and public life. They can craft the public debate through media access as well as negotiate specific contracts. They testify before Congress as experts, and at the same time, lobby for the interests of specific clients in authorization bills. The role of lobbyists in the American political process is pervasive, and McKenna, Long, and Aldridge illuminates the extent of this practice in the biodefense and biosecurity policy area.

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5. PROCUREMENT

5.1. HOMELAND SECURITY CONTRACTING METHODS The Department of Homeland Security was only created in 2003 as an amalgam of Agencies which previously existed under other branches of the executive government. Because each of the constituent parts imported their own culture and way of doing business when they joined DHS, the Department has yet to create a distinct culture. The Department of Homeland Security was seen as a showcase for more efficient government practices. The Department sought expediency and flexibility through bringing modern business practices to federal bureaucracy. It has had, however, to confront the different cultures of its constituent parts. In response to the Global War on Terrorism, Agencies involved in Homeland Security have been given additional acquisition authorities outside of the standard competitive acquisitions process. Both the Homeland Security Act (P.L. 107-296) and the Defense Department Authorization Act of 2004 (P.L. 108-136) increase the maximum award allowable under a non-competitive contract and increase the micro-purchase maximum for essential capabilities building activities. By simplifying the process, bureaucratic oversight is reduced. One addition to the Department of Homeland Security’s capabilities is the Indefinite-Delivery Indefinite-Quantity (IDIQ) contract. These contract vehicles allow for an open line between the Department of Homeland Security and a proven performer outside of the regular procurement process. If DHS has an IDIQ with a given performer and would like to expand their statement of work to allow for additional material, more labor hours, or increased services, it can add additional funding onto the contract and modify the statement of work accordingly. There have yet to be any IDIQ awards by DHS specifically for work relating to biodefense. The biggest change in contracting methods used for biodefense was the establishment of Project BioShield. Prior to 2001, there were few commercial opportunities for market-ready vaccines for CDC Category A threat agents (Chapter 3), as the majority of them were relatively unseen in the United States. Smallpox, for example, had been eradicated from the United States for several decades. Federal Acquisition Procedures for procurement required that biological countermeasure purchases be limited to $100,000 increments and undergo full and open competition. Commercial companies were discouraged from making major research investments without a clear pathway to market.

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Project BioShield relaxed many elements of the acquisition process and implemented mechanisms to assist companies developing necessary countermeasures:

Increases of contract award under simplified acquisition procedures from a 100,000 dollar to a 25 million dollar ceiling

Expedited peer review in awards of 1.5 million or less by approval of the

Secretary of Health and Human Services

Guaranteed path to market and acquisition to the Strategic National Stockpile eight years prior to commercial readiness in cases where the Secretary of Health and Human Services and the Secretary of Homeland Security find a concurrent need for a product

In addition, rather than year-to-year appropriations by Congress, appropriations under Project BioShield are guaranteed until Congress decides to rescind funding. Although it has encouraged some development activities, Project BioShield has come under criticism since the legislation was enacted for not going far enough to encourage research and development. Critics have alleged that it does not adequately shield companies from litigation, should a therapy be approved for emergency use or be acquired before fully tested through emergency measures and deployed in response to a threat pathogen. In addition, Project BioShield does not fund basic research, nor does it fund high-risk, high-reward research of the type engaged in by entities such as DARPA. Recently, the Pandemic and All-Hazards Preparedness Act (S. 3678) was signed into law. This bill establishes several new mechanisms for the acquisition of biological threat agent countermeasures. For more information on estimated outcomes of the Pandemic and All-Hazards Preparedness Act, please see discussion in Chapter 6.

5.2. PROGRAM MANAGEMENT AND OVERSIGHT Program management and oversight differs from agency to agency and varies according to the type of program and the mechanism of funding. Contracts are generally reviewed regularly, with performers required to submit monthly or quarterly reports. Grants are generally reviewed on the completion of the award period if the performer is seeking additional funding. Cooperative agreements are continually monitored to assess whether or not partners with the federal government, such as the states and municipalities in the case of CDC’s programs, are meeting their obligations. In research and development contracts and SBIR awards, performers must typically demonstrate the ability to meet benchmark milestones in order to receive continued funding. In a high-risk research and development agency such as DARPA, programs which do not meet early milestones are terminated in their first phase with no opportunity for additional funding. At other agencies, such as Homeland Security, the need for

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capability building may allow for performers to slip on milestones as long as they deliver a completed product. However, the DHS has come under repeated scrutiny for allowing abuse and waste through a lax oversight process that relies heavily on mechanisms outside of the normal full competition process. In 2003, when DHS was created, 655 million of 3.5 billion dollars in total contracts were awarded outside of the full competition process. By 2005, this amount had increased to 5.5 billion out of a total pool of 10 billion dollars in funding. In addition, DHS was accused to have major problems in its contracting organization, frequently losing files and, in some cases, approving contracts with unjustified cost proposals. While some of these problems stem from the fact that the DHS is an amalgamation of new programs and previously existing agencies, major reform is often argued to be necessary, and DHS officials have recognized the need to implement change in their oversight processes. Project BioShield is operated through fixed-price contracts, so there are no opportunities for overruns that typify some other major acquisitions. In addition, there is a standard oversight process across all Federal Agencies. Internally, Federal Agencies have an Office of Inspector General, responsible for auditing programs and attempting to reduce waste. Externally, agencies are responsive to the Office of Management and Budget (OMB) and the Government Accountability Office (GAO). Additionally, there is Congressional oversight through the budget process and subpoena before committee or subcommittee. The Office of Management and Budget operates a standards and metrics program known as Program Assessment Rating Tool (PART) that measures how various government programs are performing. Programs are rated as:

• Effective (well-managed, will approve efficiency) • Moderately effective (ambitious goals, well-managed, need to improve

problems with efficiency or design) • Adequate (need to develop more ambitious goals, improve accountability,

or strengthen management) • Ineffective (unable to achieve results due to lack of clarity regarding

program purpose/goals, poorly managed, or some other significant weakness)

• Results not demonstrated (unable to develop acceptable goals or collect performance data).

Assessed programs must then create action plans on how to improve performance regardless of what performance category they were placed in. In 2006, the OMB evaluated the Department of Homeland Security’s Preparedness and Medical Coordination program using PART and found that results could not be determined for a variety of reasons. While the Program received a high score on purpose and design (meeting eighty percent and eighty-three percent of benchmarks), the program received poor scores on strategic planning and program results and accountability (scoring thirty-eight percent and twenty percent respectively). The Program was determined to be well designed and free of flaws, but it was unclear whether activities

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under Project BioShield were directed at problems of greatest threat, risk, or vulnerability. In addition, the Program was said to lack ambitious targets and specific annual performance measures and did not establish baselines for performance. Individual evaluations were not occurring in sufficient scope or quality and budget requests were independent of program goals. The Program was determined to not demonstrate adequate progress in achieving these goals both annually and in the long-term, and was not demonstrating efficiency or cost effectiveness. The GAO conducts similar audits of program effectiveness, although where the OMB has a tendency to be focused on efficiency vis a vis the bottom line, the GAO evaluates programs for responsiveness to the public good. The GAO Strategic Plan outlines its aims and strategic goals. In the area of biodefense, these include:

Assessment of federal homeland security management, responsibility, effectiveness, and achievement of mission goals;

Identification of means to strengthen strategies related to homeland

security and implementation;

Evaluation of homeland security resource priorities, costs, and approaches to stimulate investments;

Assessment of effectiveness of U.S. and international efforts on non-

proliferation of WMD technology Through repeated assessment of federal capabilities against these strategic goals, the GAO assists law-makers in identifying gaps in current implementation of programs by the executive agencies.

5.3. HISTORY OF FUNDING DISTRIBUTION ACROSS FEDERAL AGENCIES

Funding for biodefense and biosecurity has steadily increased since FY2001 as the nation attempts to build capability to countermeasure potential biological threats. Funding grew rapidly as programs initially were implemented, increasing over three-fold between 2001 and 2002. Research and development budgets for biodefense doubled between 2001 and 2002, and again between 2002 and 2003. Some agencies received single large influxes of funds in order to deal with a specific threat, and the Department of Homeland Security established itself as a cabinet level agency. For the discussion in this section we draw on Chapter 2 and, in particular, Figures 2.1-2.3 and Appendix Figures A1.1-A1.6. In FY2001, the majority (64%) of the 1.624 billion dollars for biodefense was allocated to the Department of Defense. Procurement made up 470 million dollars of DOD’s

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activities, and Research and Development comprised 522 million dollars of the remainder. The DOE allocation of 46 million dollars was expended by the National Nuclear Security Agency programs. The 175 million dollars allocated to the United States Postal Service was entirely spent on response to the Anthrax attacks of the fall of 2001. Of the State Department’s 39 million, 35 was spent on counter-proliferation efforts. DHHS expended 80 million on public health response and preparedness, 53 million on NIH research, 182 million by the CDC to build the Strategic National Stockpile, upgrade state, local, and CDC capacity, and basic and applied research. In FY2002, the budget for biodefense had increased to 5.3 billion dollars and HHS replaced DOD as the major recipient of federal expenditures. Approximately 1 billion dollars of the total 2.98 billion was allocated to the CDC to improve stockpile capabilities for Anthrax and smallpox. In addition, the CDC expended 940 million through the cooperative agreement program to improve state and local preparedness. The research budget of NIH quadrupled, from 53 to 198 million. Expenditures at the FDA for food safety and defense increased from 1 million to 98 million. Also notable in 2002 is the 587 million received by the United States Postal Service in order to improve protection and screening capabilities. Last, the USDA expended 143 million to develop a biohazards laboratory at Ames, Iowa. In FY2003, the Department of Homeland Security received its first allocations for biodefense. While exact budget numbers are unclear, it is estimated that the DHS expended approximately 114 million dollars on biological countermeasures. The budget for biodefense at HHS increased by another billion dollars, while the NIH was the recipient of 1.5 billion dollars for biodefense research, a five-fold increase from the previous year. NIH spent 373 million dollars on the construction of extramural facilities and another 370 million on improving internal security. The CDC’s expenditures on the Strategic National Stockpile and development of smallpox countermeasures were cut in half, and this was the last year that smallpox received a supplemental appropriation. Year 2003 marks the beginning of budget transparency for the cooperative threat reduction program by the Department of Defense and the program received a three-fold increase in biodefense non-proliferation funding. In 2004, the Department of Homeland Security received slightly more funding for biodefense than the Department of Defense. The Department of Homeland Security received a 480 million dollar appropriation for the Federal Emergency Management Agency (FEMA). Project BioShield began in 2004 allocating an additional 885 million to the Department of Homeland Security for acquisition of vaccines. In addition, 88 million dollars was allocated for the development of NBACC, and 455 million was allocated for biodefense research and development. The Department of Health and Human Services had their first budget decrease for bioweapons funding since 2001, with specific cuts to the Metropolitan Medical Response System, and a zeroing out of funding for extramural laboratory development. In Fiscal Year 2005, the overall budgets of the Federal Agencies and the programs which funding was allocated to remained relatively static. The decrease in the DHS budget for

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2005 was largely due to a decrease in acquisition activities through Project BioShield. The United States Postal Service received another allocation for screening and prevention. The CDC re-established control of the Strategic National Stockpile in 2005, after an experiment with Department of Homeland Security oversight the previous year. In addition, the budget for biodefense at FEMA decreased to 63 million after initial capacity building. The Department of Health and Human Services resumed funding for extra-mural laboratory construction with approximately 150 million dollars in funding. Installation force protection, hardening military bases to a bio-weapons attack, received an initial 105 million in DOD funding. In Fiscal Year 2006, the Department of Homeland Security expended 870 million dollars through Project BioShield. Funding for biosurveillance initiatives at the CDC increased from 79 million in FY2005 to 133 million in FY2006. DOD funding for installation force protection nearly doubled, receiving 202 million dollars. In addition, DOD basic research in biodefense increased from 52 million in 2005 to 94 million in 2006. While no formal budget was passed in 2006, continuing resolutions for 2007 placed most federal agencies at approximately the same levels of programmatic funding for FY2007 as they were for FY2006. The most major changes to 2007 estimated budgets were in installation protection by the DOD, where funding was cut in half, and a 176 million dollar increase in Project BioShield funding.

5.4. STATE FUNDING In FY2002, the CDC budget for state and local programs to ensure preparedness in case of a bioterrorism attack increased from 49.9 million dollars to 918 million dollars, a nearly twenty-fold increase. These funds were allocated to states for research and development, build-up of necessary infrastructure and emergency response capability, and training of medical personnel. The program was administered by the Centers for Disease Control, which provided funding to the states and major municipalities and served as a coordination center and clearinghouse for knowledge. While this program, overall, was considered successful, large amounts of funding provided to the states under the program were never expended or obligated. Out of nearly one billion dollars in FY05 funds, 157 million remained unspent at the end of the period (Tables 5.1, 5.2). A large portion of these funds were reclaimed by the CDC and distributed to labs and other programs. One possible explanation for the success of Kansas in obligating all of its allocated funds can be derived from their metrics-driven approach to program administration. Kansas, unlike many other states, utilized a CDC developed survey in order to measure changes in preparedness from 2002-2003 and index capacity at the local and state levels. The Kansas Health Institute worked closely with the Kansas Association of Local Health Departments in developing priorities and appropriate levels of response to shortfalls.

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Table 5.1. Unobligated Funds Awarded Under the Public Health Preparedness and Response for Bioterrorism Program (HHS-CDC)10

State FY05 Award11 Unobligated Funds Percent Unobligated Washington D.C. $20,032,292 $12,227,280 61.0% Nebraska 7,513,167 3,057,592 40.3 Los Angeles 28,414,156 10,198,192 35.9 Oregon 16,048,213 5,239,116 32.6 Nevada 13,077,219 3,943,518 30.2 Chicago 14,615,376 4,299,727 29.4 New Hampshire 8,725,305 2,534,624 29.0 South Dakota 7,794,491 2,222,848 28.5 North Carolina 21,288,709 6,068,396 28.5 Indiana 17,998,528 5,097,866 28.3 Delaware 9,673,981 2,593,009 26.8 Vermont 7,209,406 1,918,590 26.6 South Carolina 16,091,145 4,100,247 25.5 Arizona 20,020,724 5,012,352 25.0 Louisiana 20,235,952 4,375,905 21.6 Texas 67,170,118 13,825,974 20.6 Maryland 14,806,853 3,014,538 20.4 Wisconsin 17,361,517 3,490,789 20.1 North Dakota 5,631,748 991,825 17.6 Illinois 25,569,678 4,304,396 16.8 Wyoming 7,719,940 1,187,200 15.4 Massachusetts 28,553,869 4,059,361 14.2 Alabama 17,079,781 2,389,461 14.0 New Mexico 11,826,157 1,647,489 13.9 New Jersey 30,516,430 4,026,766 12.2 New York 34,254,995 4,353,356 12.7 Pennsylvania 50,776,737 6,448,560 12.7 Mississippi 14,303,036 1,806,822 12.6 Idaho 8,485,043 1,021,810 12.0 Kentucky 15,632,906 1,839,894 11.8 Ohio 39,091,923 4,588,466 11.7 New York City 25,875,515 3,000,218 11.6 Rhode Island 6,561,276 755,783 11.5 Alaska 5,412,040 575,633 10.6 Tennessee 15,929,481 1,676,313 10.5 Minnesota 15,129,116 1,516,784 10 Colorado 16,084,461 1,546,554 9.6 West Virginia 9,529,605 835,198 8.8 Florida 43,704,396 3,471,791 7.9 Virginia 21,790,488 1,727,866 7.9 Michigan 30,704,353 2,294,482 7.5 Connecticut 15,839,873 1,147,914 7.5 Maine 6,892,377 485,954 7.1 Arkansas 12,123,140 848,721 7.0 Montana 7,635,483 527,821 6.9 Missouri 17,324,425 1,039,976 6.0 Oklahoma 14,394,566 843,468 5.9 Hawaii 6,752,866 346,003 5.1 Utah 8,964,779 316,908 3.5 California 68,819,980 1,882,804 2.7

10 Audit of unobligated balances of funds awarded under the Public Health Preparedness and Response for Bioterrorism Program. HHS Office of the Inspector General. December 2006. 11 Includes carryover from previous awards

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Washington 19,684,947 429,550 2.2 Kansas 9,504,019 0 0 Georgia *** *** *** Iowa *** *** *** Total $995,726,586 $157,125,715 15.8% Table 5.2. States with the Highest Percentage of Unobligated Funds State FY05 Award12 Unobligated Funds Percent Unobligated Washington D.C. $20,032,292 $12,227,280 61.0% Nebraska 7,513,167 3,057,592 40.3 Los Angeles 28,414,156 10,198,192 35.9 Oregon 16,048,213 5,239,116 32.6 Nevada 13,077,219 3,943,518 30.2 The CDC commended the approach that Kansas took in administering these funds, commenting on a report in Morbidity and Mortality Weekly Report, one of the CDC’s in-house journals by saying:13

“While determining the optimal level of preparedness capacity for LHDs [local health departments] in Kansas was not an objective of this study, the findings suggest that when attention and funds are allocated, preparedness capacity improves in specific and measurable ways. Investments in such a critical field as public health preparedness should be accompanied by consistent evaluation methods. For this purpose, CDC is shifting attention from assessment of public health capacity to evaluation of actual public health performance that can be expected as a result of the increased capacity. These findings also demonstrate that when the same measurable indicators are used repeatedly, important information can be obtained regarding successes and areas in need of further improvement.”

However, an HHS audit of the overall CDC program discussed shortfalls on accounting practices on the state and federal level which led to many of the failures in ensuring that funds were properly expended:14

“Although CDC had methods in place to monitor the obligation and expenditure of funds, many awardees did not fully execute their expenditure plans or submit timely financial status reports. Thus, CDC did

12 Includes carryover from previous awards 13 CDC. 2005. “Improvement in Local Public Health Preparedness and Response Capacity --- Kansas, 2002-2003,” MMWR WeeklyReport 54 (18): 461-462. 14 Levinson, Daniel R. 2006. “Audit of Unobligated Balances of Funds Awarded Under the Public Health Preparedness and Response for Bioterrorism Program.” HHS Office of the Inspector General. December 5, 2006.

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not always receive the information needed to encourage the expenditure of funds and to minimize unobligated balances. In addition, CDC officials did not offset (reduce) new- year awards by the amount of unobligated funds carried over from the prior budget year, even though the Department's "Awarding Agency Grants Administration Manual" (the Manual) authorizes offsets. Although CDC is not required to implement the Manual, the use of such offsets could have minimized unobligated balances and made additional new-year funding available for awardees with greater needs.”

The audit acknowledged that the CDC had since resolved many of the issues with their own accounting practices, by standardizing guidance and oversight controls as well as by allowing states to carry awards forward in order to offset new funding. While the CDC has begun recommending reform since December of 2004, they agreed to implement the major suggestions of the report in December of 2006. Federal funding administered to states for public health preparedness related to bioterrorism has continually decreased since the FY2005 budget (Table 5.3). Table 5.3. Changes in Federal Funding for State and Local Bioterrorism Preparedness

FY 2005-2008 ($m) FY2005

Actual funding FY2006 Enacted

appropriation

FY2007 Continuing resolution

FY2008 Proposed budget

Bioterrorism Cooperative agreement

857,337 760,470 761,008 698,267

Centers for public health preparedness

29,425 30,699 30,690 0

Advanced practice centers

5,424 5,342 5,346 0

All other state and local capacity

26,692 26,618 26,630 0

Total 919,148 823,099 823,674 698,267 These cuts alarmed public health advocacy groups, who were particularly troubled that budgets for entire programs had been zeroed out. Richard Hamburg of the Trust for America’s Health stated that:

"The reduction of the bioterrorism and public health preparedness programs is particularly troubling. We are cutting core boots-on-the-ground support for emergency disaster response, leaving the country at unnecessary levels of risk."

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While the GAO had found improvements to state and local public health preparedness in a 2004 study of programs conducted over 2002-2003, they had also asserted that more work was yet to be done, as states were continuing to fall short of CDC program goals.15 Out of fourteen critical benchmarks, most states met four, the majority of states demonstrated capacity to meet eight, but only a few states were responsive to the remaining two. Four critical benchmarks were met by most states:

Designation of an executive director of bioterrorism preparedness and response program

Establishment of a bioterrorism advisory committee

Assessment of epidemiologic capacity and achievement of goal of one

epidemiologist for each major metropolitan area

Coverage of ninety percent of the population by the Health Alert Network Eight critical benchmarks were met by a majority of states:

Assessment of emergency preparedness and response capabilities

Assessment of statutes, regulations, and ordinances that provide for credentialing, licensure, and delegation of authority for executing emergency measures

Development of interim plan to receive and manage items from the

Strategic National Stockpile

Development of a system to receive and evaluate urgent disease reports at all times

Development of a plan to improve working relationships between clinical

and public health laboratories

Development of a communications system the provides for flow of critical health information at all times

Development of an interim plan for risk communication

Preparation of a timeline to assess training needs

15 GAO 04-360R. 2004. “HHS Bioterrorism Preparedness Programs.” February 10, 2004.

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Finally, two benchmarks were met by few states:

Development of a statewide incident response plan for incidents of bioterrorism and emergencies and provisions for exercising the plan

Development of regional response plan across state borders for incidents

of bioterrorism In discussing the efforts with state officials, the CDC was able to determine that key areas of concern were:

Redirection of resources allocated to bioterrorism to the National Smallpox Vaccination Program

Difficulties in increasing personnel as a result of state and local budget

deficits

Delays caused by state and local management practices The GAO report concluded by stating that:

“Although states’ progress fell short of 2002 program goals, CDC’s and HRSA’s cooperative agreement programs have enabled states to make much needed improvements in the public health and health care capacities critical for preparedness. States are more prepared now than they were prior to these programs, but much remains to be accomplished.”

State and local programs have not undergone another formal evaluation by the GAO since 2004. However, the budgeting issues in FY2004 and FY2005 allocations indicate that there are still bureaucratic snags in the process. With a decrease to funding for bioterrorism preparedness and response at the state and local level, it remains to be seen whether states can meet the fourteen critical benchmarks.

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6. FUTURE PLANS, TRENDS, AND HOMELAND SECURITY OUTLOOK

6.1. STATE INVOLVEMENT: ILLINOIS – A CASE STUDY IN STATE RESPONSE

The State of Illinois can be used as a model for a general state response to public health. Illinois, demographically, is roughly representative of the nation in total. The state has municipal and rural areas with distinct priorities, and the state government is not dominated by a single party. Illinois has a public health agency that closely collaborates with its emergency management agency, and a homeland security coordinator operates to ensure optimal inter-agency coordination. In addition, the state public health agency has been continually led by physicians with experience in the public health sector for the past two decades, and the state public health agency is professionally operated as a result. Furthermore, at the local level, ninety four independent health officials contribute their expertise in jurisdictions that cover ninety nine percent of the state’s population. The primary vehicle for state funding for public health and biodefense in Illinois is Local Health Preparedness grants. These grants support preparedness at the community level, and are based on population and need. In addition, Illinois receives funding from the CDC for state and local public health preparedness. Prior to 2001, Illinois received approximately one million dollars per year from the CDC, half of which was allocated to the Health Alert Network, an information system, and a quarter of which supported the development of public health laboratories. Beginning in 2002, the CDC assigned Illinois thirty one million dollars for response to bioterrorism, twenty seven million of which was allocated for public health preparedness and response and 4 million allocated directly to hospitals. Chicago received an additional thirteen million. Funding continued at these levels through 2006. These funds were guided towards the critical benchmark areas discussed in Chapter 5. Specifically, Illinois has used the funds to boost the following areas:

Preparedness Planning: Bioterrorism planning is conducted by the Illinois Emergency Management Agency. Twelve Public Health Regional Response Planning Areas of 250,000 people are overseen by emergency response coordinators who are in charge of taking the lead on implementing community and agency-wide response plans.

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Surveillance and Epidemiologic Capacity: In 2003, Illinois developed I-NEDSS as a branch of the National Electronic Disease Surveillance System. In addition, the state began to hire professional epidemiologists to fill ten positions in large local health jurisdictions and twelve positions in the state agency.

Laboratory Capacity: While the state has attempted to push for greater

development in identification of pathogens at the state public health laboratory level, it is as of yet unable to fill all vacancies due to a lack of qualified personnel due to a hiring freeze in the state budget. This is a problem common to many states seeking to improve capacity, as state budget priorities and federal benchmarks conflict.

Health Alert Network Development: Illinois attained complete coverage of

all public health jurisdictions by 2002.

Hospital Readiness: Hospital Readiness was a major focus of Illinois officials. By 2002 they had implemented the Illinois Mobile Emergency Response Team (IMERT), which began as an association of toxicologists and emergency physicians in 1998. Currently, IMERT is made up of trained teams from state police, the Department of Nuclear Safety, the Illinois Environmental Protection Agency, the state health agency, and the state emergency management agency. IMERT provides Illinois the capability for indigenous mass decontamination following a chemical or biological attack. In addition, this network is supported by the Mutual Aid Box Alarm System (MABAS), which is a consortium of nine tenths of Illinois fire departments linked to the state emergency plan through a memorandum of understanding.

In addition, in 2004 Illinois developed the Illinois Public Health Mutual Aid System (IPHMAS). This system enhances a network by which resources can be shared among local public health departments in the case of a bioterrorist incident or other disaster. IPHMAS was patterned after MABAS, and was the first agreement of the kind in the country, although it had been under discussion for five years. While only thirty three of the ninety five health departments had signed on in 2004, all public health departments in the state had become members by late 2005. In 2003, Illinois created a Department of Homeland Security to coordinate state strategic planning in counter-terrorism and communicate information to the public. While Illinois Homeland Security does administer grants, these grants are largely for law enforcement and emergency personnel. The Illinois Department of Public Health does fund research grants, but not in the area of bioterrorism, and preparedness funds are available only for the addition of defibrillators to public schools, parks, universities, and colleges. This is typical of state response, with a greater burden of interest placed on ensuring responsiveness rather than conducting investigative research.

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6.2. NEW GOVERNMENT AGENCIES INVOLVED IN HOMELAND

SECURITY: THE PANDEMIC AND ALL-HAZARDS PREPAREDNESS ACT As the Department of Homeland Security continues to assert its role in public policy formation in the United States, new agencies and organizations are created to address gaps in capability. In order to fill some of these gaps, the Pandemic and All-Hazards Preparedness Act (S. 3678) was signed into law. The bill created an Assistant Secretary position in the Department of Health and Human Services to specifically serve the area of preparedness response. The bill also created the Biomedical Advanced Research and Development Authority (BARDA) and its complement the Biodefense Medical Countermeasure Development Fund, and the National Biodefense Science Board. BARDA was created to address the shortfall in funding between vaccine discovery and product development. The Biodefense Medical Countermeasure Development Fund would serve as a funding source for BARDA’s activity. The National Biodefense Science Board will serve in an advisory capacity to the Department of Health and Human Services on specific biodefense issues. The Pandemic and All-Hazards Preparedness Act reorganizes national public health planning by authorizing the Assistant Secretary for Preparedness and Response to:

Serve as principal advisor to the Secretary on federal public health and medical preparedness and response for public health emergencies

Be responsible for logistics, personnel, and supplies in the case of public

health emergency

Oversee development and procurement of countermeasures and management of the Strategic National Stockpile

Coordinate public health and medical capabilities with state and federal

agencies

Provide leadership in international programs, initiatives and policies that deal with medical preparedness and response and public health

The Act requires the Secretary of HHS to submit a National Health Security Strategy and include an assessment of federal, state, and local public health preparedness. The act also requires the Secretary to build capabilities at the state and local level for real-time situational awareness in the event of a catastrophic disease outbreak and provides for a pilot program to provide loan repayment for individuals who serve in a shortage area or high risk area. In addition, S. 3678 established BARDA as the single agency in the federal government for research and development on civilian countermeasures to bioweapons. Specifically, BARDA was charged to:

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Coordinate activity to develop advanced research and development on

qualified countermeasures for pandemic and epidemic

Ensure collaboration between components of HHS, other federal agencies, industry and academia

Promote advanced research and development of countermeasures or

biodefense related technologies

Facilitate interaction between the Food and Drug Administration and interested commercial entities

Promote innovation which shortens development time for advanced

countermeasures These activities will be supported by the Biodefense Medical Countermeasure Development Fund, a 1.07 billion dollar fund that will carry funding from FY2006-2008. The Biotechnology Industry Organization (BIO), a professional organization representing biotechnology industry interests, recognized S. 3678 as an essential piece of legislation for ensuring preparedness and addressing the concerns of industry, stating:

“This bill includes critical BARDA provisions and provisions to reauthorize bioterrorism grants and is a necessary step toward improving America’s defense against bioterrorism and pandemic diseases… This legislation recognizes that the ‘Valley of Death’ remains a barrier to effective countermeasure product development… Through BARDA, contracts and grants for advanced research and development will be made to companies working on products to protect the American people. The bill also contains important contract reforms that improve upon the advances made under Project BioShield, by allowing, for example, milestone payments and surge capacity provisions to improve the viability and sustainability of biodefense product development and manufacture.”

In addition to providing reform to components of Project BioShield, S. 3678 created the National Biodefense Science Board to serve in an advisory role to the Department of Health and Human Services. During his period as Secretary of Homeland Security, Tommy Thompson established the National Science Advisory Board for Biosecurity. At this point it is unclear whether this existing board, which has a mandate to guide biosecurity development, will be replaced by the new National Biodefense Science Board, or whether it will simply be renamed. Whereas the National Biodefense Science Board serves in a specific advisory capacity, the National Science Advisory Board for Biosecurity more generally provides standards to prevent misuse of scientific knowledge and fosters collaboration for potential dual-use research.

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6.3. OTHER PLANNED ACTIVITIES

With major reform to the Project BioShield program, the 110th Congress is likely to evaluate several issues of public health preparedness over the next two years:

Federal coordination: In the aftermath of Hurricane Katrina, it was unclear how DHS and HHS managed their overlapping mandates to ensure public health security. The 110th Congress will observe reforms to this process established in S. 3678 to view whether additional legislation is needed.

HHS Response Capability: With HHS’ scope of responsibility for

disaster management broadened, policy-makers will attempt to determine whether more effective means can be established to fund disaster relief or whether current methods are adequate. Currently, the emergency fund of the HHS Secretary is empty. In addition, mental health counseling response to disaster may also be investigated.

State Grants: HHS has yet to publish performance evaluations for

recipients of state preparedness grants. As these programs have been broadened through S. 3678, Congress may become more inquisitive as to management of these funds.

Biodefense Research and Development: With reform to Project

BioShield complete, Congress may become more interested in research conducted at NBACC and through the NIH.

Isolation, Quarantine, and Mandatory Vaccination: Increasing threats

of serious pandemic may lead to Congress becoming seriously interested in various aspects of managing pandemic threats. This could lead to establishment of federal authority on emergency management in an area where state and local government have taken the lead.

Rationing of Scarce Resources: In the case of an outbreak of an emerging

pathogen, the mobilization of existing resources may not be sufficient to deal with a serious biological threat. Congress may need to consider directing planning for prioritizing of insufficient quantities of countermeasures.

Expiring Authorities: Program authority for the HHS Select Agent

Program, which deals with potential bioterrorism agents, expires in FY2007. General program authority for the Strategic National Stockpile was not extended in FY2006. HHS professions programs expired in FY2002, and reauthorization may include language to support emergency preparedness and response.

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6.4. EMERGING AREAS As new pathogens emerge, governments must be prepared to detect and intercept these threats. Avian influenza of the H5N1 strain could be an emerging threat in human populations if the disease mutates to the point where it can pass between human hosts. Currently, mortality rates for H5N1 when human hosts acquire it are on the order of mortality rates from the Spanish influenza of 1918, which killed between fifty and a hundred million people over an 18-month span. In addition, the NIAID is interested in emerging and re-emerging pathogens, and have recognized several pathogens discovered or rediscovered in the last two decades as pathogens of interest for continued study. These include diseases such as Enterovirus 71, first recognized in 1969 in Brazil. Enterovirus 71 has re-emerged in the last decade in Asia, with cases found in Singapore, Vietnam, Malaysia, and Taiwan. Traditionally, the disease travels through a fecal-oral route, but evidence seems to suggest that the latest strain of the virus may transmit along respiratory pathways. Foreign incursion of serious disease such as this could lead to rapid spread among a less resistant population. Further, drug-resistant and treatment resistant bacteria continue to emerge. As bacteria continue to struggle for survival, the ability to treat them with common antibiotics has decreased. In a study which isolated Pseudomona aeruginosa between 2000 and 2004, 10.1 percent of all the bacteria isolated were resistant to a single therapeutic agent, while 4.3 percent were resistant to multiple treatment agents.16 If the mechanisms by which bacteria evolve multiple drug resistance are better elaborated, persons interested in producing biological agents may be able to leverage off of this. On the other hand, that same knowledge could lead to capabilities to target pathways along which resistance is developed when developing countermeasures. Finally, better understanding of emerging diseases can lead to improved biosecurity and biodefense. As many of the diseases that could potentially be used as threat agents are rare in United States populations, detection methods for novel and emerging diseases will also capture the anomalies presented by biological threats. In addition, capabilities of mobilization of material and preparedness are essentially the same when dealing with an unknown and emergent epidemic or an intentional bioterrorism agent.

16 Moniri, R., Mosayebi, Z., Movahedian, AH, and GhA Mossavi. 2006. “Increasing Trend of Antimicrobial Drug-Resistance in Pseudomona aerudinosa Causing Septicemia,” Iranian Journal of Public Health 35 (1): 58-62.

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7. CONCLUSION The United States has invested heavily in improving capability to respond to biological threats. However, almost six years after the anthrax incident in Congress, the United States government has a patchwork approach to biodefense and biosecurity research and development. While the federal government is making steps to unify disparate programs, there is still a lack of total preparedness at the state and local levels. There is not a standardized process for addressing biosecurity issues due to the following factors:

• There is a large set of government agencies at both the Federal and the State levels that are tasked with parts of the job making coordination within the public sector difficult.

• The new Federal Agency mandated with a coordinating role (DHS) has

had ‘teething’ problems in the past few years. These problems are slowly receding.

• The public sector cannot handle the broad solution space on its own;

private sector ingenuity and technology is needed.

• The private sector can engage in research and development of new products (such as sensor systems or treatments for diseases) but they need government funding.

• Academia needs to be involved in both basic and applied research; as well

as support through training of personnel.

• Other non-governmental organizations play a role in facilitating interactions and coordination between these sectors: public, private, and academic.

In order to ensure that all business and research is carried out towards common goals, the government attempts to create universal standards. For instance:

• Common strains of identified threat agents are available to researchers with proper security clearances.

• Therapeutics must conform to minimum standards of efficacy and safety.

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• Assays and sensors for detection of pathogen should be calibrated to detect specific levels of threat agent.

However, these standards have yet to be adopted by all researchers funded by the various agencies. It is as of yet unclear what the future benefits of the large US investments may be. At least, stockpiles for emergency treatment in case of outbreak exist now that did not exist in 2001. Currently, programs in the Federal government seek means to rapidly develop and screen vaccines for safety and efficacy, to monitor millions of livestock for zoonotic illness, to place sensor grids across metropolitan areas capable of providing early warning of chemical and biological attack, and to detect disease in an individual before the development of symptoms. Interagency cooperation and coordination across levels of government still have room to improve, but policy-makers remain aware of potential problems and seek rational means for their solution. Industry and academia are involved at multiple levels, and the government seeks to actively partner with the private sector to ensure successful outcomes. With a greater understanding of the risks involved and the mechanisms that will need to be implemented in case of a response, the federal government has attempted to improve the quality of preparedness through guided funding. Equally important is ensuring that response is prepared to the right types of biological threats. There are limited resources available and the government is attempting to apply those resources in a more efficacious and directed fashion. In addition, advanced research and development can assist in attaining strategic advantage against those who would deploy a biological threat agent. Procurement and oversight continues to be an area of concern for biodefense, and as investments and acquisition move forward, the government will seek to balance disparate needs. The government desires the ability to acquire developed and safe drugs without having to pay for development costs. However, due to the low market need for some of these drugs, they simply are not available at late-stage development. Government programs in biodefense have traditionally been unsuccessful at creating and achieving set milestones and metrics. In order to continue receiving high levels of funding and ensure that the American people are receiving the appropriate level of security for the funds expended, programs may need to implement more measurable milestones and goals. A case in point is the CDC program which directs funding to states under agreements where the state merely needs to indicate progress towards goals. Such objectives may need to be reformed. Finally, as new threats to biosecurity emerge, the government should be prepared to detect and respond to them. Unifying leadership on pandemic preparedness and funding the Biomedical Advanced Research and Development Authority is an important first step, and continued improvement in the response capacity at the state level is essential should an outbreak occur. As multi-drug resistant diseases and new pandemic illnesses emerge, lessons learned from treatment of these new threats may be applied to biodefense.

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APPENDIX 1

History of Federal Funding Distribution on Biodefense Funding for biodefense and biosecurity has steadily increased since FY2001. Figures A1.1-A1.6 show the estimated distributions among agencies. Figure A1.1. FY2001 Funding for Biodefense by Federal Agency ($m)

Figure A1.2. FY2002 Funding for Biodefense by Federal Agency ($m)

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Figure A1.3. FY2003 Funding for Biodefense by Federal Agency ($m)

Figure A1.4. FY2004 Funding for Biodefense by Federal Agency ($m)

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Figure A1.5. FY2005 Funding for Biodefense by Federal Agency ($m)

Figure A1.6. FY2006 Funding for Biodefense by Federal Agency ($m)

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APPENDIX 2

Glossary of Terms

AMC: Army Medical Corp AMP: Accelerated Manufacture of Pharmaceuticals APHIS: Animal and Plant Health Inspection Service ARS: Agricultural Research Service ATDC: Advanced Technology Development Center ATP: Advanced Technology Programs BAA: Broad Agency Announcement system BARDA: Biomedical Advanced Research and Development Authority BIO: The Biotechnology Industry Organization BNBI: Battelle National Biodefense Institute CDC: Centers for Disease Control and Prevention CIC: Chesapeake Innovation Center COCA: Clinical Outreach and Communication Activity CRADAs: Cooperative Research and Development Agreements CRP: Chemical Reagents Program DARPA: Defense Advanced Research Projects Agency DHHS: Department of Health & Human Services DHS: Department of Homeland Security DIB: Defense Industrial Base DOC: Department of Commerce DOD: Department of Defense DOE: Department of Energy DOJ: Department of Justice DOT: Department of Transportation DSO: Defense Sciences Office DTRA: Defense Threat Reduction Agency EPA: Environmental Protection Agency EWIDS: Early Warning Infectious Disease Surveillance FDA: Food and Drug Administration FEMA: Federal Emergency Management Agency FFRDCs: Federally Funded Research and Development Centers GAO: Government Accountability Office GPS: Global Positioning System

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HHS: Department of Health and Human Services HSARPA: Homeland Security Advanced Research Projects Agency IDIQ: Indefinite-Delivery Indefinite-Quantity IMERT: Illinois Mobile Emergency Response Team I-NEDSS: Illinois Electronic Disease Surveillance System IPHMAS: Illinois Public Health Mutual Aid System ITAC: Industry Trade Advisory Center LHD: Local Health Department MABAS: Mutual Aid Box Alarm System MLA: McKenna, Long and Aldridge NBACC: National Biodefense Analysis and Countermeasures Center NBSB: National Biodefense Science Board NEDSS: National Electronic Disease Surveillance System NIAID: National Institute of Allergy and Infectious Diseases NIH: National Institutes of Health NIST: National Institute of Standards and Technology NNSA: National Nuclear Security Administration NSABB: National Science Advisory Board for Biosecurity NSF: National Science Foundation OHA: Office of Health Affairs OIE: World Organization for Animal Health OMB: Office of Management and Budget PART: Program Assessment Rating Tool PLA: Patent License Agreements RCE: Regional Centers of Excellence RVA: Rapid Vaccine Assessment SARS: Severe Acute Respiratory Syndrome SBIR: Small Business Innovation Research Program SNDT: Chem/Bio Sensor Network Design Tool State: Department of State STO: Strategic Technology Office STTR: Small Business Technology Transfer Program TACTIC: Threat Agent Cloud Tactical Intercept and Countermeasure TANS: Technology Acceleration for National Security TRTF: Texas Research and Technology Foundation TSWG: Technical Support Working Group

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UASI: Urban Areas Security Initiative UAV: Unmanned Aerial Vehicles USAMRIID: U.S. Army Medical Research Institute of Infectious Disease USDA: Department of Agriculture USPS: U.S. Post Office USTR: United States Trade Representative VA: Veterans Administration VIG: Vaccinia Immune Globulin WHO: World Health Organization WIC: Watervliet Innovation Center WMD: Weapons of Mass Destruction