[Federal Register Volume 72, Number 77 (Monday, April 23, 2007)]
[Notices]
[Pages 20117-20128]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 07-1983]


-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES


Office of the Assistant Secretary for Preparedness and Response; 
HHS Public Health Emergency Medical Countermeasures Enterprise 
Implementation Plan for Chemical, Biological, Radiological and Nuclear 
Threats

AGENCY: Office of the Assistant Secretary for Preparedness and 
Response, Department of Health and Human Services

ACTION: Notice.

-----------------------------------------------------------------------

SUMMARY: The United States faces serious public health threats from the 
deliberate use of weapons of mass destruction (WMD)--chemical, 
biological, radiological, or nuclear (CBRN)--by hostile States or 
terrorists, and from naturally emerging infectious diseases that have a 
potential to cause illness on a scale that could adversely impact 
national security. Effective strategies to prevent, mitigate, and treat 
the consequences of CBRN threats is an integral component of our 
national security strategy. To that end, the United States must be able 
to rapidly develop, stockpile, and deploy effective medical 
countermeasures to protect the American people. The HHS Public Health 
Emergency Medical Countermeasures Enterprise (PHEMCE) has taken a 
holistic, end-to-end approach that considers multiple aspects of the 
medical countermeasures mission including research, development, 
acquisition, storage, maintenance, deployment, and guidance for 
utilization. Phase one of this approach established the HHS PHEMCE 
Strategy for Chemical, Biological, Radiological, and Nuclear Threats 
(HHS PHEMCE Strategy). The HHS PHEMCE Strategy, published in the 
Federal Register on March 20, 2007, described a framework of strategic 
policy goals and objectives for identifying medical countermeasure 
requirements and establishing priorities for medical countermeasure 
evaluation, development and acquisition. These strategic policy goals 
and objectives were used to establish the Four Pillars upon which this 
HHS Public Health Emergency Medical Countermeasures Enterprise 
Implementation Plan (HHS PHEMCE Implementation Plan) is based. The HHS 
PHEMCE Implementation Plan considers the full spectrum of medical 
countermeasures-related activities, including research, development, 
acquisition, storage/maintenance, deployment, and utilization. The HHS 
PHEMCE Implementation Plan is consistent with the President's 
Biodefense for the 21st Century and is aligned with the National 
Strategy for Medical Countermeasures against Weapons of Mass 
Destruction.

DATES: This notice is effective as of April 16, 2007.

FOR FURTHER INFORMATION CONTACT: Dr. Susan Coller, Policy Analyst, 
Office of Public Health Emergency Medical Countermeasures, Office of 
the Assistant Secretary for Preparedness and Response at 330 
Independence Ave., SW., Room G640, Washington, DC 20201 or by phone 
202-260-1200.

HHS PHEMCE Approach to Medical Countermeasures

    The United States faces serious public health threats from the 
deliberate use of chemical, biological, radiological, or nuclear (CBRN) 
threat agents by hostile states or terrorists, and from naturally 
emerging infectious diseases that have the potential to cause illness 
on a scale that would impact national security. Within the Federal 
government, the mission of the Department of Health and Human Services 
(HHS) is to protect the civilian population by providing leadership in 
research, development, acquisition, deployment, and guidance for 
effective use of medical countermeasures for mitigation of CBRN events. 
This key role was identified in the National Strategy to Combat Weapons 
of Mass

[[Page 20118]]

Destruction,\1\ Biodefense for the 21st Century,\2\ and the National 
Strategy for Medical Countermeasures against Weapons of Mass 
Destruction,\3\ which together comprise the national blueprint for 
addressing CBRN defense.
---------------------------------------------------------------------------

    \1\ www.whitehouse.gov/news/releases/2002/12/WMDStrategy.pdf.
    \2\ www.whitehouse.gov/homeland/20040430.html.
    \3\ www.whitehouse.gov/news/releases/2007/02/20070207-2.html.
---------------------------------------------------------------------------

    The HHS Public Health Emergency Medical Countermeasures Enterprise 
(HHS PHEMCE) leads the mission to develop and acquire medical 
countermeasures that will improve public health emergency preparedness 
as well as prevent and mitigate the adverse health consequences 
associated with CBRN and naturally occurring threats. HHS PHEMCE is a 
coordinated, intra-agency effort led by the Office of the Assistant 
Secretary for Preparedness and Response (ASPR) and includes three HHS 
internal agencies: The Centers for Disease Control and Prevention 
(CDC), the Food and Drug Administration (FDA), and the National 
Institutes of Health (NIH). Additionally, HHS PHEMCE collaborates with 
its ex officio members: The Department of Defense (DOD), the Department 
of Homeland Security (DHS), the Department of Veterans Affairs (VA) and 
other interagency stakeholders as appropriate.
    The HHS PHEMCE Implementation Plan for CBRN Threats addresses 
twelve biological threat agents, a class of chemical threats (volatile 
nerve agents) and radiological and nuclear threats. The medical 
countermeasure programs described will involve the full range of 
activities from research through advanced development, acquisition, 
storage, maintenance, deployment and utilization and will include all 
of the PHEMCE. However, the detailed focus of this Plan will be on the 
acquisition phase using the remaining funds available under Project 
BioShield, recognizing that significant efforts both upstream and 
downstream of the acquisition will be required to ensure the successful 
development, maintenance and utilization of these critical response 
assets, that may be needed in the event of a public health emergency.
    The HHS PHEMCE Implementation Plan for CBRN Threats excludes 
pandemic influenza, which is addressed in the HHS Pandemic Influenza 
Plan. The HHS Pandemic Influenza Plan includes an overview of the 
threat of pandemic influenza, a description of the relationship of the 
HHS Pandemic Influenza Plan to other Federal plans, and an outline of 
key roles and responsibilities during a pandemic. It is aligned with 
the National Strategy for Pandemic Influenza, issued by President 
George W. Bush on November 1, 2005, and the Implementation Plan for the 
National Strategy for Pandemic Influenza, which guides the Nation's 
preparedness and response to an influenza pandemic. Significant 
progress has been made in the development and acquisition of medical 
countermeasures for pandemic influenza. Additional detailed information 
is available at http://www.pandemicflu.gov.

Current State of Medical Countermeasure Preparedness

    To date, HHS has significantly expanded national medical 
countermeasure preparedness utilizing significant investments from 
throughout the HHS PHEMCE, including NIH research and development; CDC 
Division of the Strategic National Stockpile (DSNS) acquisition, 
storage, and maintenance of medical countermeasures; and substantive 
technical and regulatory support provided by FDA to product developers. 
Funding support by the NIH for basic research, product development, and 
clinical research of CBRN medical countermeasures has increased 
dramatically between Fiscal Year 2001 (FY 2001) to FY 2006. Funding for 
the DSNS has increased more than ten-fold in that same period, 
providing for the acquisition and stockpiling of medical 
countermeasures and supplies to protect the American public. 
Furthermore, the Project BioShield Act of 2004 (Pub. L. 108-276) \4\ 
(Project BioShield) was enacted to accelerate the acquisition and 
availability of safe and effective medical countermeasures to protect 
the United States from CBRN threats. Project BioShield created a $5.6 
billion Special Reserve Fund (SRF) for use over 10 years (FY 2004-FY 
2013) to acquire appropriate medical countermeasures for DSNS.
---------------------------------------------------------------------------

    \4\ http://frwebgate.access.gpo.gov/cgi-bin/getdoc.cgi?dbname=108_cong_public_laws&docid=f:publ276.108.pdf.
---------------------------------------------------------------------------

    During its first two years of implementation, Project BioShield 
acquisitions were guided by requirements derived from interagency 
deliberations in 2003 that involved Cabinet-level Departments and the 
Executive Office of the President. Under this initial strategy, HHS 
pursued acquisitions for those highest priority threats for which there 
were candidate products at relatively advanced stages of development 
and for which there were opportunities to have a significant impact on 
improving preparedness. These products included medical countermeasures 
for anthrax, smallpox, botulinum toxins, and radiological/nuclear 
agents--the four threat agents initially determined by DHS to pose a 
material threat to national security.\5\ Acquisitions under Project 
BioShield to date include the currently licensed anthrax vaccine, 
anthrax therapeutics (monoclonal and human immune globulin), a 
pediatric formulation of potassium iodide to protect against absorption 
of radioactive iodine, calcium and zinc diethylenetriaminepentaacetate 
(DTPA), chelating agents to treat ingestion of certain radiological 
particles, and botulinum antitoxin.
---------------------------------------------------------------------------

    \5\ The Project BioShield Annual Report to Congress July 2004-
July 2006 is available at http://www.hhs.gov/aspr/ophemc/bioshield/bioshieldreport/index.html
---------------------------------------------------------------------------

    Additional acquisitions of medical countermeasures for the DSNS 
have also provided a substantial preparedness level for a number of 
material threats. Specifically, DSNS inventory includes smallpox 
vaccine to immunize every American and Vaccinia Immune Globulin to 
treat complications that may arise from smallpox vaccination; anthrax 
therapeutics and a substantial level of antibiotics to provide 
treatment (thousands of doses) or prophylaxis (millions of doses) for 
bacterial threat agents anthrax, plague and tularemia; thousands of 
treatment courses of the chelating agent Prussian Blue (which mitigates 
internal absorption of cesium-137, a component of dirty bombs); enough 
potassium iodide tablets (which protects against radioactive iodine) 
for over one million people; thousands of courses of growth factors 
that could be useful for addressing the hematopoietic effects of acute 
radiation syndrome (ARS); CHEMPACKs (pre-positioned antidotes for 
volatile nerve agent exposure) distributed throughout the country; and 
general supplies that will be required to treat the complex array of 
medical problems following a nuclear attack, including antibiotics, 
anti-nausea drugs, and large quantities of supplies to treat burn and 
blast injuries. Some of these stockpiled products are licensed, 
approved, or cleared by FDA for use as medical countermeasures. Others 
are investigational and would need to be used under an Investigational 
New Drug application or an Emergency Use Authorization \6\. In 2002, 
DSNS began participating in the Shelf Life Extension Program (SLEP) 
with FDA. SLEP allows

[[Page 20119]]

the extension of the expiration date of certain drugs in DSNS where 
adequate supporting data exist, so that critical medical 
countermeasures that are still safe and effective can continue to be 
used.
---------------------------------------------------------------------------

    \6\ See http://www.FDA.gov for further information regarding the 
Investigational New Drug application and the Emergency Use 
Authorization
---------------------------------------------------------------------------

    HHS has also acted to improve and strengthen the underlying 
national response capacity and distribution efficiency that is required 
to take full advantage of these stockpiled medical countermeasures. HHS 
has specifically worked to prepare public health systems for 
bioterrorism and other mass casualty incidents; expand America's public 
health laboratory capacity, a crucial element in detecting and 
understanding any disease outbreak; expand and improve communications 
capacity within the public health structure to make public 
communications clearer and faster in an emergency; enhance food defense 
and safety activities at the FDA; expand the biodefense research 
program at NIH; and address response capacity for at-risk populations 
including children, pregnant women, senior citizens and other 
individuals who have special needs in the event of a public health 
emergency, as determined by the Secretary.\7\
---------------------------------------------------------------------------

    \7\ As defined in the Pandemic and All-Hazards Preparedness Act 
(P.L.109-417), which is available at http://frwebgate.access.gpo.gov/cgi-bin/getdoc.cgi?dbname=109_cong_public_laws&docid=f:publ417.109.pdf.
---------------------------------------------------------------------------

Development of the HHS PHEMCE Implementation Plan For Chemical, 
Biological, Radiological and Nuclear Threats

    HHS approached the development of the HHS PHEMCE Implementation 
Plan recognizing that the past investments outlined above have resulted 
in an armamentarium of medical countermeasures in DSNS that provides a 
substantial preparedness level for a number of CBRN threats. HHS 
recognizes that while it was important to achieve the current level of 
preparedness, it is equally as important to maintain and improve this 
capability.
    HHS PHEMCE has taken a holistic, end-to-end approach that considers 
multiple aspects of the medical countermeasures mission including 
research, development, acquisition, storage, maintenance, deployment, 
and guidance for utilization. Phase One of this approach established 
the HHS Public Health Emergency Medical Countermeasures Enterprise 
Strategy for Chemical Biological, Radiological and Nuclear Threats (HHS 
PHEMCE Strategy).\8\ The September 2006 BioShield Stakeholders Workshop 
brought together stakeholders from all aspects of the mission to 
discuss the framework and approach for the HHS PHEMCE Strategy. The 
valuable input solicited from stakeholders at the Workshop, combined 
with the responses received to the medical countermeasures Request for 
Information issued in October 2006 \9\ and through the Federal 
Register, was incorporated into the HHS PHEMCE Strategy.
---------------------------------------------------------------------------

    \8\ Available at http://frwebgate.access.gpo.gov/cgi-bin/getdoc.cgi?dbname=2007_register&docid=%5bDOCID:fr20mr07-65.
    \9\ http://www.fbo.gov/servlet/Docments/R/589030.
---------------------------------------------------------------------------

    The HHS PHEMCE Strategy, published in the Federal Register on March 
20, 2007, described a framework of strategic policy goals and 
objectives for identifying medical countermeasure requirements and 
establishing priorities for medical countermeasure evaluation, 
development and acquisition. These strategic policy goals and 
objectives were used to establish the Four Pillars upon which this HHS 
PHEMCE Implementation Plan is based.

Pillar One: Identify and Assess CBRN Threats

    DHS leads the Federal response to National Response Plan incidents, 
conducts integrated assessments of the risks posed by CBRN agents, and 
issues Material Threat Determinations (MTDs) as to which CBRN pose a 
material threat sufficient to affect U.S. national security.\10\ The 
Secretary of Homeland Security has issued MTDs for threat agents (Table 
1) and has conducted Population Threat Assessments (PTA) to estimate 
the number of individuals who might be exposed to each of these threats 
in plausible, high-consequence scenarios. A Population Threat 
Assessment has been conducted for volatile nerve agents.
---------------------------------------------------------------------------

    \10\ Material Threat Determinations are authorized under section 
319 F-2(c)(2) of the Public Health Service Act, as added by section 
3 of the Project BioShield Act and are a legally required precursor 
to procurements under that authority.
---------------------------------------------------------------------------

    In the future, additional MTDs may be issued if technology advances 
or if our understanding of the potential threats changes. The PHEMCE 
strategy is to have specific medical countermeasures that address each 
of the threats for which an MTD has been issued while also providing 
broad spectrum medical countermeasures to address as many as is 
practicable of those threats that did not rise to the level of an MTD.
[GRAPHIC] [TIFF OMITTED] TN23AP07.000

Pillar Two: Assess Medical/Public Health Consequences

    The information supporting the MTDs and PTAs regarding population 
exposures from high consequence scenarios provided by DHS is used by 
HHS to inform subsequent medical and public health consequence 
assessments using multiple sources of information, including modeling. 
HHS uses modeling to help to explore potential outcomes when medical 
countermeasures are employed in operationally realistic timelines. The 
HHS assessments provide public health impact estimates for a given 
threat scenario and use of medical countermeasures for each threat 
agent.

[[Page 20120]]

Pillar Three: Establish Medical Countermeasure Requirements That 
Incorporate Assessments of Current Levels of Preparedness, Concepts of 
Utilization, and Product Specifications

    Our current state of preparedness and medical countermeasure 
requirements have been assessed for these fourteen CBRN threats. To 
establish medical countermeasure requirements for the top priority 
threat agents, HHS combines the threat prioritization and medical and 
public health consequence assessments, along with subject matter expert 
evaluations, domestic and international intelligence information, and 
information on current State, local and tribal response capabilities.

Pillar Four: Identify and Prioritize Near-, Mid-, and Long-Term 
Development and Acquisition Programs, Informed by Assessment of the 
Maturity of the Product Development Pipeline and Estimated Costs

    The mission to develop and acquire agent-specific medical 
countermeasures for the entire U.S. population for all fourteen threats 
and broad spectrum medical countermeasures against the remaining 
current and future threats encompasses a vast range of activities and 
dictates priority-setting. The process for setting the priorities for 
the portfolio of investments ultimately outlined in this plan required 
careful consideration and deliberation. Specifically, HHS PHEMCE 
evaluated three possible approaches during the priority setting 
process. The first option was to focus only on a single, highest 
priority threat. In line with this, all available acquisition dollars 
would be spent trying to fully address the requirements for this one 
agent with the aim of eliminating it as a material threat to national 
security. The second option was to divide the available resources 
equally among the known fourteen threats. The third option, and the 
approach that the PHEMCE ultimately pursued, was to prioritize 
strategic policy decisions, framed by the HHS PHEMCE Strategy, which 
will most effectively improve overall public health preparedness. This 
decision-making process to set priorities included extensive discussion 
with Federal government subject matter experts \11\ and was guided by 
the principles of the National Strategy for Medical Countermeasures 
against Weapons of Mass Destruction. As a result, HHS has prioritized 
the medical countermeasures programs--including, research, development, 
and acquisition in the near-term, mid-term and long-term--that were 
determined to provide the greatest opportunities to improve public 
health emergency preparedness across the threat spectrum.
---------------------------------------------------------------------------

    \11\ Including subject matter experts from HHS (CDC, FDA, and 
NIH), DOD, DHS, VA, and the respective HHS PHEMCE Chemical, 
Biologics, Radiological and Nuclear Working Groups.
---------------------------------------------------------------------------

    The key elements that established the foundation for the priority-
setting decisions were as follows:
Prevention Versus Mitigation and Treatment
    HHS has generally adopted a strategy of developing and acquiring 
medical countermeasures for post-event response to CBRN threats. 
Preventive measures are appropriate only for threats of such potential 
catastrophic consequence that a pre-event strategy will be examined in 
order to reduce vulnerability and mitigate post-event consequences. 
Therapeutics and diagnostics or the use of post-event prophylaxis will 
be the preferred strategy for all other threats. Priority will be 
placed on medical countermeasures that focus on post-event prophylaxis 
or post-exposure treatment.
Concept of Operations
    In alignment with the National Strategy for Medical Countermeasures 
against Weapons of Mass Destruction, HHS will prioritize the 
development and acquisition of medical countermeasures that are 
associated with an effective concept of operations (CONOPs). These 
CONOPs include a deployment strategy and utilization policy that is 
supportable by the present and future programmed distribution 
capabilities of Federal, State, local, and tribal public health 
emergency responders to rapidly ship and distribute critical items 
following a CBRN event. Within HHS, ASPR coordinates with the CDC 
Coordinating Office for Terrorism Preparedness and Emergency Response 
(COPTER) in determining processes, procedures, tactics, and techniques 
for how DSNS deploys countermeasures \12\ and the utilization 
strategies for those materials and medical countermeasures. ASPR's 
Office of Preparedness and Emergency Operations (OPEO) works with its 
response partners, using event and response modeling, to outline how 
the current DSNS inventory will be used. These approaches are exercised 
with interagency partners to ensure that the plans are based on 
realistic and achievable timelines.
---------------------------------------------------------------------------

    \12\ The authority of the Secretary of HHS to deploy the SNS is 
codified at 42 U.S.C. Sec.  247d-6b.

---------------------------------------------------------------------------

[[Page 20121]]

    The CONOPs for a particular threat scenario and medical 
countermeasure are a crucial component in setting specific product 
requirements and contribute directly to the acquisition strategy. While 
there is much in common in medical countermeasure development for 
civilian and military medical countermeasures, CONOPs for HHS and DOD, 
respectively, have differences which must be considered in the 
requirements and acquisitions processes. HHS is committed to continuing 
to work with all its emergency responder partners to improve public 
health response capabilities.

Broad Spectrum Medical Countermeasures and Platform Technologies

    A fixed defense \13\ or ``one-bug, one-drug'' approach for medical 
countermeasure development is determined to be effective and viable for 
some of the highest priority threats such as smallpox and anthrax. As 
the list of material threats increases, and technology advances, HHS 
will be focusing its medical countermeasure research, development and 
acquisition efforts on broad spectrum and platform approaches.
---------------------------------------------------------------------------

    \13\ Relman DA. Bioterrorism--Preparing to Fight the Next War, 
NEJM, 2006, 354(2):113-115. In the context of defense against 
biological threats, a fixed defense is a medical countermeasure 
intended for use against a specific organism and not useful in 
scenarios that employ a different organism.
---------------------------------------------------------------------------

Preparing for New Threats

    In order to address emerging, enhanced, and advanced threats,\14\ 
HHS will be investing in research and development on innovative 
approaches and platform technologies.\15\ These technologies will 
facilitate rapid identification and characterization of novel threat 
agents, thereby creating the capability to rapidly produce relevant 
medical countermeasures. This policy is aligned with the National 
Strategy for Medical Countermeasures against Weapons of Mass 
Destruction which targets the use of existing, proven approaches for 
developing medical countermeasures to address challenges posed by 
traditional CBRN agents while calling for a flexible capability to 
develop new medical countermeasures. These latter activities emphasize 
the need to capitalize upon the development of innovative and future 
technologies that will enhance our ability to respond swiftly and 
effectively to potential, emerging, and future unknown CBRN threats. 
This will require targeted, balanced, and sustained investments to 
support fundamental basic research to discover new technologies and 
update platforms as well as applied research for technology development 
to deliver new medical capabilities and countermeasures.
---------------------------------------------------------------------------

    \14\ As defined in the National Strategy for Medical 
Countermeasures against Weapons of Mass Destruction: Enhanced Agents 
are traditional agents that have been modified or selected to 
enhance their ability to harm human populations or circumvent 
current countermeasures, such as a bacterium that has been modified 
to resist antibiotic treatment; Emerging Agents are previously 
unrecognized pathogens that might be naturally occurring and present 
a serious risk to human populations, such as the virus responsible 
for Severe Acute Respiratory Syndrome (SARS); and Advanced Agents 
are novel pathogens or other materials of biological nature that 
have been artificially engineered in the laboratory to bypass 
traditional countermeasures or produce a more severe or otherwise 
enhanced spectrum of disease.
    \15\ Examples of platform technologies include strategies that 
permit rapid commercial scale production of threat-specific 
countermeasures or expression systems that permit rapid production 
of new vaccines.
---------------------------------------------------------------------------

Top Priority Medical Countermeasure Research, Development, and 
Acquisition Programs to Increase Public Health Emergency Preparedness

    Following the principles and processes described above, HHS has 
assessed the top priority CBRN threats from a medical countermeasure 
perspective and has developed medical countermeasure acquisition 
priorities for the near-term (FY 2007-FY 2008), the mid-term (FY 2009-
FY 2013), and, in less detail, the long-term (beyond FY 2013).\16\ This 
prioritization spans the CBRN threat spectrum and best utilizes 
available resources in addressing the highest priority threats to 
maximize risk mitigation. Table 2 arrays the top priority medical 
countermeasure programs against the specific threat agents addressed by 
the program. The broad spectrum antibiotic, broad spectrum antiviral, 
and diagnostics programs address multiple threat agents, while other 
programs are, of necessity, agent-specific.
---------------------------------------------------------------------------

    \16\ SRF that supports Project BioShield released $3.4 billion 
for use between FY 2004-2008 and the remaining $2.2 billion will be 
available for use between FY 2009-2013.
---------------------------------------------------------------------------

    Medical countermeasure requirements are based primarily on the 
number of persons exposed to clinically significant levels of a threat 
agent in a single-event, plausible, high-consequence scenario. In 
setting appropriate targets for an acquisition program, a number of 
factors in addition to the single event, exposure-based medical 
countermeasure requirement could be considered, including:
    <bullet> Multiple events
    <bullet> Citizens concerned about exposure \17\
---------------------------------------------------------------------------

    \17\ Non-exposed population seeking medical care for non-
specific symptoms or concerns about exposure.
---------------------------------------------------------------------------

    <bullet> The lack of availability of rapid, point-of-care 
diagnostics
    <bullet> Potential nationwide demand after a single large-scale 
event
    <bullet> Pre-positioning of individual medical countermeasures to 
meet specific response time requirements
    <bullet> Economies of scale for production \18\
---------------------------------------------------------------------------

    \18\ A production process in which an increase in the number of 
units produced causes a decrease in the average cost of each unit.
---------------------------------------------------------------------------

    <bullet> Providing a target acquisition size sufficient to drive 
industrial development of the medical countermeasure.
    HHS will continue to coordinate medical countermeasure development 
and acquisition efforts with DOD; however, separate development and 
acquisition programs may be necessary in situations where military 
requirements differ from civilian requirements, including with regard 
to concepts of use of particular countermeasures. Consistent with the 
National Strategy for Medical Countermeasures against Weapons of Mass 
Destruction, the Secretary of Health and Human Services is tasked with 
civilian medical countermeasure preparedness, and it is National policy 
that ``the Secretary of Defense shall retain the exclusive 
responsibility for research, development and acquisition of medical 
countermeasures to prevent or mitigate the health effects of WMD 
threats * * * to the Armed Forces.'' \19\
---------------------------------------------------------------------------

    \19\ www.whitehouse.gov/ news/releases/2007/ 02/20070207-2.html.
---------------------------------------------------------------------------

BILLING CODE 4150-37-P

[[Page 20122]]

[GRAPHIC] [TIFF OMITTED] TN23AP07.001

Strategies for Addressing High Priority Medical Countermeasures

Research and Development

    NIH is the lead agency within the Federal Government for conducting 
and supporting biomedical research relating to causes, diagnosis, 
treatment, control, and prevention of diseases. NIH will align research 
and development efforts with the PHEMCE priority medical countermeasure 
programs. In addition, NIH will support Research and Development for 
next-generation products to replace currently-held medical 
countermeasures in DSNS, as needed. These next generation products 
include medical countermeasures with broad spectrum activity against a 
wide variety of threat agents; broad spectrum technologies that enhance 
effectiveness of multiple classes of medical countermeasures; and broad 
spectrum platforms that permit more rapid generation of required 
medical countermeasures. Continued research and development efforts 
will ensure a sustainable, continuous stream of promising medical 
countermeasures in the pipeline that are aligned with top priority HHS 
PHEMCE requirements for future acquisitions and/or replacement of DSNS 
inventory. NIH's long-term focus is on platform technologies and broad 
spectrum medical countermeasures that will allow for the rapid 
introduction of additional response capabilities for emerging 
infectious agents.

[[Page 20123]]

Advanced Development \20\
---------------------------------------------------------------------------

    \20\ The Pandemic and All-Hazards Preparedness Act (Pub. L. 109-
417) definition of advanced research and development: ``with respect 
to a product that is or may become a qualified countermeasure or a 
qualified pandemic or epidemic product, activities that 
predominantly are conducted after basic research and preclinical 
development of the product; and are related to manufacturing the 
product on a commercial scale and in a form that satisfies the 
regulatory requirements under the Federal Food, Drug, and Cosmetic 
Act or under section 351 of this Act.''
---------------------------------------------------------------------------

    The use of advanced development efforts that support multiple 
candidates for each medical countermeasure need is a key element to 
mitigating risk in the Project BioShield acquisition phase of the 
product development pathway. The Pandemic and All-Hazards Preparedness 
Act (Pub. L. 109-417) established the Biomedical Advanced Research and 
Development Authority (BARDA). Utilizing those tools, HHS plans to 
promote innovation, reduce risk to both medical countermeasure 
developers and the Government, and invest in medical countermeasure 
advanced development that will carry products through the crucial 
middle phase \21\ of drug development between basic research and 
acquisition of final products. HHS anticipates that available funding 
through these authorities, in FY 2007 and beyond, will be aligned with 
the highest priority medical countermeasure development programs. 
Finally, Advanced Development activities will depend on congressional 
approval of the President's FY 2008 budget request of $189 million. The 
future funding levels for BARDA remain to be determined.
---------------------------------------------------------------------------

    \21\ Often referred to as the ``Valley of Death.''
---------------------------------------------------------------------------

Projected Acquisitions

    The HHS PHEMCE will consider opportunities for acquiring medical 
countermeasures using both DSNS appropriations as well as SRF monies 
under Project BioShield. Acquisitions under DSNS will be limited to 
commercially available products. Current funding levels were considered 
in projecting acquisition forecasts. While BARDA funding has been 
established to support the advanced development of medical 
countermeasures, Project BioShield acquisition contracts may still 
include late-stage development costs for scale-up manufacturing, 
clinical trials, and pivotal animal efficacy studies, in addition to 
final production and delivery.
    The near-term is defined as FY 2007-FY 2008, which is the time 
frame of allocation of approximately half of the Project BioShield SRF. 
The mid-term is defined as FY 2009-FY 2013, which is the remainder of 
the ten year duration of the Special Reserve Fund. Medical 
countermeasures will be procured in the near-term and mid-term using 
both the SRF as well as from the DSNS appropriations. During the near-
term, HHS also will pursue acquiring a number of medical 
countermeasures for which utilization of the Project BioShield Special 
Reserve Fund has been approved, but for which funds have not yet been 
fully obligated.
    Table 3 summarizes the proposed near-term and mid-term acquisitions 
for the priority medical countermeasures. In some cases, the estimated 
funding ranges indicated are based on identified potential medical 
countermeasure candidates currently under development; whereas in other 
cases the estimated ranges are based on industry standard information 
for vaccine and drug development costs. Descriptions of the 
acquisitions for priority medical countermeasures follow Table 3.

[[Page 20124]]

[GRAPHIC] [TIFF OMITTED] TN23AP07.002


[[Page 20125]]



PROJECTED NEAR-TERM (FY 2007-FY 2008)

Medical Countermeasure Development and Acquisition Programs To Enhance 
Preparedness

Programs for Biological Threats

Broad Spectrum Antibiotic(s)
    MTD: Bacillus anthracis and multi-drug resistant bacillus 
anthracis, burkholderia mallei, burkholderia pseudomallei, franciscella 
tularensis, rickettsia prowazekii, yersinia pestis.
    Many of MTDs address bacterial species that can be treated using 
antibiotics. Broad spectrum antibiotics, therefore, will continue to be 
a critical component of strategy HHS will take to maintain and improve 
public health preparedness. For each biological threat agent or class 
of agents, however, there is a limited array of antibiotics with 
demonstrated efficacy. In the near-term, HHS will continually evaluate 
the antibiotics in the DSNS and, as needed, will acquire commercially 
available antibiotics using DSNS appropriations.
Anthrax Vaccine(s)
    MTD: Bacillus anthracis, multi-drug resistant bacillus anthracis.
    Antibiotics represent the first line of defense to protect the 
nation following an anthrax attack. However, anthrax vaccines are also 
an essential element of our national preparedness. Vaccines may be 
given as post-exposure prophylaxis in combination with antibiotics to 
potentially provide longer-term protection; this combination may also 
allow for a reduction in the duration of the antibiotic regimen. 
Vaccines can also provide pre-event protection to the relatively small 
population that is at high risk of frequent occupational exposure to 
Bacillus anthracis.
    In December 2006, a contract for the development and acquisition of 
a recombinant Protective Antigen (rPA) anthrax vaccine was terminated 
by HHS; however, the Department remains committed to acquiring next-
generation anthrax vaccines that will be part of a balanced and 
diversified portfolio of medical countermeasures. HHS has developed a 
comprehensive strategy for advanced development and acquisition of 
current and next generation anthrax vaccines and anticipates that these 
activities will be pursued in the near-term.
Smallpox Vaccine(s)
    MTD: Variola virus.
    HHS has made significant progress in providing smallpox vaccine to 
the DSNS. In addition, a requirement has been established for a 
smallpox vaccine to protect immunocompromised persons for whom use of 
the existing smallpox vaccines is medically contraindicated in the 
absence of smallpox exposure.
    One candidate next-generation smallpox vaccine, modified vaccinia 
Ankara (MVA), is based on a strain of the vaccinia virus that, in 
contrast to current smallpox vaccines such as Dryvax, does not 
replicate effectively in human cells and, therefore, may cause fewer 
side effects. The MVA development programs were supported by the 
National Institute of Allergy and Infectious Diseases (NIAID) with 
milestone-driven contract awards in 2003 and 2004. HHS is well-advanced 
in the pre-award stage of an MVA vaccine acquisition program.

Programs for Radiological and Nuclear Threats

ARS/Hematopoietic Syndrome Medical Countermeasure(s)
    MTD: Radiological/nuclear agents.
    HHS regards radiological and nuclear agents as a significant threat 
to national security and is committed to purchasing safe and 
efficacious medical countermeasures to treat Acute Radiation Syndrome 
(ARS). In March 2007, HHS withdrew the ARS RFP because it was 
determined, after extensive scientific and technical expert evaluation, 
that no competing offeror had a product that met USG requirements for a 
Project BioShield acquisition. HHS will continue to pursue an initial 
acquisition of a safe and effective medical countermeasure to treat 
ARS. In moving forward to meet this goal, HHS will make use of 
scientific developments that have occurred since the previous RFP 
closed, as well as new authorities provided by the Pandemic and All-
Hazards Preparedness Act that could accelerate the advanced development 
of promising countermeasures.
    HHS supports further development of the radiological and nuclear 
medical countermeasure pipeline. The NIAID's Radiation Countermeasures 
Research Program has funded numerous projects, including: ARS medical 
countermeasure screening programs in cell-based and rodent models at 
multiple institutions around the country; development of three Good 
Laboratory Practices (GLP) animal testing facilities to evaluate the 
efficacy of medical countermeasures against ARS; eight Centers for 
Medical Countermeasures against Radiation at academic institutions 
around the country; and intramural research programs at the DOD Armed 
Forces Radiobiology Research Institute (AFRRI) and the National Cancer 
Institute.

PROJECTED MID-TERM (FY 2009-FY 2013)

Medical Countermeasure Development and Acquisition Programs To Enhance 
Preparedness

    HHS will pursue the following medical countermeasure acquisitions 
in the mid-term using the remaining SRF and pending availability of 
other funding for those acquisitions that do not use the SRF. These 
anticipated acquisitions are also predicated on the availability of 
products at the appropriate developmental stage that meet U.S. 
Government civilian requirements.

Programs for Biological Threats

    The ideal medical countermeasures for biological agents will be 
highly effective for post-exposure prophylaxis as well as early 
symptomatic treatment, will display an excellent safety profile and 
could be easily self-administered.
Broad Spectrum Antibiotic(s)
    MTD: Bacillus anthracis, multi-drug resistant bacillus anthracis. 
burkholderia mallei, burkholderia pseudomallei, francisella tularensis, 
rickettsia prowazekii, yersinia pestis.
    In addition to the near-term strategy for acquisition of 
commercially available antibiotics, HHS anticipates maintaining a 
robust basic research and development program along with advanced 
development for broad spectrum antimicrobials that will specifically 
provide support for regulatory approval for clinical indications that 
address bacterial agent MTDs. In order to better balance antimicrobial 
DSNS holdings in light of newer MTDs, HHS will pursue a potential 
acquisition of additional broad spectrum antimicrobials in the mid-
term.
Diagnostics (Point-of-Care)
    MTD: All biological threat agents.
    Following a terrorist event, clinical diagnostic assays (in vitro 
diagnostics, IVDs) are critical tools for distinguishing infected 
(symptomatic) individuals needing treatment from potentially exposed 
but asymptomatic individuals needing post-exposure prophylaxis. 
Overall, the requirements for diagnostic assays to facilitate a 
response to a bioterrorism event will focus on rapid, point-of-care 
assays. Rapid triaging of the symptomatic patients will be required to 
provide, as necessary, treatment, isolation and implementation of 
universal precautions for infectious diseases and may also be useful in 
the

[[Page 20126]]

allocation of limited critical therapeutic materials to only those 
patients in need. Multiplexed, adaptive platforms that confer 
flexibility, offer alternative commercial opportunities, and allow for 
the rapid introduction of additional tests for emerging infectious 
agents are highly desired.
    These IVDs used for clinical purposes are distinguished from 
detection assays used for environmental samples (air, water, food, 
surface swabs) in that they are required to be approved or cleared by 
the FDA. To date, limited incentives have been available to sustain 
commercial market production of IVDs; however, once specific 
requirements in this area are developed and prioritized, HHS will 
pursue a potential mid-term acquisition of biological agent diagnostics 
to enhance public health preparedness capability.
Anthrax Antitoxin
    MTD: Bacillus anthracis, multi-drug resistant bacillus anthracis.
    The primary mortality and morbidity of anthrax disease is mediated 
through toxins produced by the bacteria, B. anthracis. Antibiotics 
(currently within DSNS) target the B. anthracis bacteria itself; while 
vaccines (discussed under Near-Term Acquisitions) provide long-term 
protection from disease. Antitoxins are required to neutralize the 
effects of the toxins and may contribute to a more successful 
therapeutic outcome. Given the current status of anthrax antitoxins and 
animal model development, HHS will continue its phased acquisition 
program and will pursue a mid-term acquisition of additional anthrax 
antitoxin to allow HHS to more fully meet medical countermeasure 
requirements, including to address the threat from MDR anthrax.
Filovirus Medical Countermeasure(s)
    MTD: Ebola virus, marburg virus.
    Infection with filoviruses produces an aggressive disease that is 
highly lethal. Currently, no FDA-approved filovirus-specific medical 
countermeasures exist. An antiviral is preferred to treat infected 
patients and to provide pre-exposure prophylaxis to health care workers 
and personal contacts. A vaccine will be useful for civilian 
populations if it provides rapid onset of protective immunity. HHS will 
continue to invest in research and development and will pursue an 
acquisition for filovirus medical countermeasures in the mid-term.
Smallpox Antiviral
    MTD: Variola virus.
    Currently there is no treatment available for smallpox disease once 
the symptoms manifest. An effective antiviral treatment could mitigate 
the effects of smallpox disease. It is likely that such an antiviral 
may also be effective against other pox viruses. Given the current 
status of the most advanced products as well as the status of animal 
model development, HHS will pursue a mid-term acquisition of a smallpox 
antiviral for the treatment of smallpox. The ideal antiviral will be 
highly effective post-exposure as well as an effective treatment early 
in the symptomatic phase of the disease.

Programs for Radiological and Nuclear Threats

ARS/DEARE Medical Countermeasure(s)
    MTD: Radiological/nuclear agents.
    Acute Radiation Syndrome (ARS) often called radiation sickness, 
results when humans are exposed to a large dose of ionizing radiation. 
ARS develops in the timeframe of hours to weeks, and the Delayed 
Effects of Acute Radiation Exposure (DEARE) injury in weeks to months 
following radiation exposure. HHS will pursue one or more ARS/DEARE 
medical countermeasure acquisition(s) in the mid-term to continue the 
phased acquisition strategy launched in the near-term.
Biodosimetry and Bioassay
    MTD: Radiological/nuclear agents.
    Biodosimetry and radionuclide bioassay capabilities are essential 
for medical management of ARS/DEARE following acute radiation exposure 
and are integral to triage and management processes. HHS anticipates 
that rapid biodosimetry assays for on-scene triage should be available 
for acquisition in the mid-term. A system of biodosimetry and 
radionuclide bioassay laboratories is also proposed to increase overall 
national capacity. While the diagnostics portion of this requirement 
may be funded through the Project BioShield SRF, appropriate funding to 
establish this laboratory network is yet to be determined.
Radionuclide-Specific Medical Countermeasure(s)
    MTD: Radiological/nuclear agents.
    Radionuclide-specific medical countermeasures are a key component 
to managing the medical consequences of radiation dispersal device 
(RDD) events, both explosive and non-explosive, as well as nuclear 
power plant events. In the near term, HHS will continue to fund the 
development of improved formulations of diethylenetriaminepentaacetate 
(DTPA) and other novel decorporating agents that remove radioactive 
particles from the body. If continued progress is made on the 
radionuclide-specific countermeasures currently under development, it 
is conceivable that oral formulations of DTPA (which would considerably 
ease the logistical requirements for rapid delivery of this medical 
countermeasure) and/or other novel decorporating agents could be 
available for acquisition in the mid-term.

Programs for Chemical Threats

Enterprise CHEMPACKs
    PTA: Volatile nerve agents.
    The CHEMPACK program is an ongoing initiative of the DSNS, begun in 
2003, that provides antidotes (three countermeasures used 
concomitantly) to volatile nerve agents for pre-positioning by State, 
local, and/or tribal officials throughout the U.S. In its current form, 
the program will receive continued funding in the near-term for 
procurement and fielding of additional CHEMPACKs, replacement of 
expired product, and administrative support. The proposed Enterprise 
CHEMPACK program would build upon the existing system, improving it by 
adding an education, training and exercise component and by optimizing 
the pre-positioning of antidotes. In the near-term, HHS will begin 
performing the operations analysis that is prerequisite to such 
improvements. It is anticipated that acquisition of some next-
generation replacement products and the implementation of changes to 
improve the program could occur in the mid-term, pending availability 
of DSNS funds.

PROJECTED LONG-TERM (BEYOND FY 2013)

Medical Countermeasure Development and Acquisition Programs To Enhance 
Preparedness

Program for Biological Threats

Broad Spectrum Antiviral(s)
    MTD: Ebola Virus, Junin Virus, Marburg Virus, Variola Virus.
    Three families of viruses are represented among the existing MTDs: 
Poxviridae (variola virus), Filoviridae (Ebola and Marburg viruses), 
and Arenaviridae (Junin virus). These different viral families have 
diverse biological and pathological characteristics and cause unique 
diseases in humans. All of these viruses can be disseminated via 
aerosolization, a feature which enhances their potential use as 
bioterrorism agents. There are no approved antiviral drugs available 
for either post-exposure prophylaxis or for

[[Page 20127]]

therapeutic use for any of these viral diseases. Overall, the 
development of broad spectrum medical countermeasures that can address 
several threat agents would maximize the efficiency and flexibility of 
the DSNS, thereby reducing storage and maintenance costs. HHS will 
prioritize research and development funding in this area in the near- 
and mid-terms. Due to its relative immaturity in the development 
pipeline, it is unlikely that a broad spectrum antiviral will be 
acquisition-ready until after FY 2013.

Program for Chemical Threats

Volatile Nerve Agent Single Antidote
    PTA: Volatile Nerve Agents.
    The optimal medical defense against volatile nerve agents would be 
a single, rapidly effective countermeasure that could be used, for 
example, via intranasal or inhaled routes and by untrained persons at 
risk or by first responders dealing with large numbers of exposed 
individuals. HHS will continue research and development funding in this 
area in the near- and mid-terms. Given the current immature status of 
the development pipeline, a single antidote for volatile nerve agents 
would likely not be available for acquisition until the long-term 
timeframe.

Conclusion

    This HHS PHEMCE Implementation Plan identifies top priorities for 
medical countermeasure research, development and acquisition programs 
that HHS has determined, in collaboration with interagency partners, to 
have the greatest potential to improve public health emergency 
preparedness. It is anticipated that this plan will be reviewed at 
least biennially to encompass potential changes in assessments of the 
threat, consequences (particularly with regard to the evolution of 
CONOPs), and maturity of the medical countermeasure development 
pipeline.
    The prioritization of medical countermeasure programs described in 
this HHS PHEMCE Implementation Plan represents the current thinking of 
HHS informed by material threat determinations, population threat 
assessments, or the assessments of medical and public health 
consequences. DHS is conducting an integrated CBRN threat assessment, 
to be completed in June 2008 that will further inform the next version 
of the HHS PHEMCE Implementation Plan. Additionally, future versions 
are anticipated to incorporate more detailed assessments of potential 
multipliers of medical countermeasure requirements, based on the 
potential for enhanced, emerging, or advanced biological agents, 
multiple and simultaneous CBRN events and other factors informed by 
scientific and threat analysis. As State, local, and tribal medical 
countermeasure delivery capabilities and event response planning 
evolve, they will also open new flexibilities with respect to the types 
of medical countermeasures that can be incorporated into Federal 
planning efforts, and will influence HHS assessments of potential 
medical and public health consequences following CBRN events.
    The development and acquisition strategies to most effectively 
improve preparedness resulted from critical evaluation of the status of 
medical countermeasure development pipelines. HHS recognizes that 
developing, acquiring, and utilizing medical countermeasures to prepare 
for and respond to CBRN events requires significant resources and 
unprecedented cooperation among many stakeholders, including Federal 
counterparts outside HHS; private industry (domestic and 
international); State, local and tribal governments; first responders 
and healthcare workers; academia; and the public. HHS will build upon 
its 2006 RFI for medical countermeasures against CBRN threats, 
including the technology readiness levels (TRLs) defined in that RFI, 
to continue to explore new, more efficient ways to reach out to the 
academic and medical countermeasure development communities to ensure 
that future versions of the HHS PHEMCE Implementation Plan are informed 
by the latest breakthroughs in the field.
    In addition, while this HHS PHEMCE Implementation Plan focuses on 
the further enhancement of public health emergency preparedness, HHS is 
simultaneously evaluating the costs and benefits associated with the 
mid- and long-term maintenance of existing and projected stockpiles of 
medical countermeasures. HHS anticipates that such an evaluation will 
be detailed in a future version of the HHS PHEMCE Implementation Plan.
    Finally, Advanced Development activities will depend upon 
congressional approval of the President's FY 2008 budget request and 
will increase the chance of programmatic success. Through the Pandemic 
and All-Hazards Preparedness Act, HHS now has the authority to promote 
innovation, increase the potential for success for both medical 
countermeasure developers and the Government, and invest in medical 
countermeasure advanced development that will carry products across the 
so-called ``Valley of Death'' to meet medical countermeasure 
requirements. It is anticipated that future versions of the HHS PHEMCE 
Implementation Plan will more fully incorporate implementation of these 
authorities and funding levels that may be appropriated in support of 
the robust advanced development programs that are critical to mission 
success.
    The prioritization of medical countermeasures to improve public 
health preparedness reflected in this HHS PHEMCE Implementation Plan 
was an interagency process led by HHS and involving significant 
collaboration with DHS, DOD, VA, and others. The HHS PHEMCE 
Implementation Plan has also benefited tremendously from the 
information provided by Stakeholders, particularly at the BioShield 
Stakeholders Workshop held in September 2006, and from the many formal 
comments received in response to the Federal Register notice of the 
draft HHS PHEMCE Strategy. Notice of the issuance of this HHS PHEMCE 
Implementation Plan will be posted in the Federal Register and HHS 
welcomes comments from stakeholders.
    The HHS PHEMCE Implementation Plan will be a feature of the 
upcoming HHS Public Health Emergency Medical Countermeasures Enterprise 
Stakeholders Workshop to be held in Washington, DC, July 31--August 2, 
2007. HHS is committed to improving transparency and continuing to find 
the most appropriate venues to work with stakeholders who are likewise 
committed to meeting the goals of this critical mission of preparing 
the nation for the adverse health consequences of public health 
emergencies.
    Improving preparedness will be an ongoing process as science 
advances, innovations mature, and the threat scope changes. HHS 
resources beyond the SRF, when it ends in FY 2013, will continue to be 
strategically invested in programs throughout the medical 
countermeasure development and acquisition pipeline to achieve this 
goal. It is anticipated that targets for the timeframe beyond FY 2013 
will be articulated with increasing clarity and granularity with each 
successive revision of the HHS PHEMCE Implementation Plan.
    Finally, to successfully execute the program objectives outlined in 
the HHS PHEMCE Implementation Plan for Chemical, Biological, 
Radiological and Nuclear Threats, ASPR will strengthen and build upon 
its achievements to develop, recruit, and support a world-class 
workforce. To realize this goal, ASPR will intensify its efforts to 
attract

[[Page 20128]]

and expedite hiring of qualified candidates; focus and align training, 
education, and career development; recognize staff accomplishments; and 
foster learning and growth with improved knowledge management.

    Dated: April 17, 2007.
Gerald Parker,
Principal Deputy Assistant Secretary, Office of the Assistant Secretary 
for Preparedness and Response, Department of Health and Human Services.
[FR Doc. 07-1983 Filed 4-18-07; 12:17 pm]
BILLING CODE 4150-37-C