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24 April 2007
[Federal Register: April 23, 2007 (Volume 72, Number 77)]
[Notices]
[Page 20117-20128]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr23ap07-48]
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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.
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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.
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\1\ http://www.whitehouse.gov/news/releases/2002/12/WMDStrategy.pdf.
\2\ http://www.whitehouse.gov/homeland/20040430.html.
\3\ http://www.whitehouse.gov/news/releases/2007/02/20070207-2.html.
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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.
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\4\ http://frwebgate.access.gpo.gov/cgi-bin/getdoc.cgi?dbname=108_cong_public_laws&docid=f:publ276.108.pdf
.
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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.
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\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.
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\6\ See http://www.FDA.gov for further information regarding the
Investigational New Drug application and the Emergency Use
Authorization
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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\
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\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
.
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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.
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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.
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\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.
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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.
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\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.
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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.
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\12\ The authority of the Secretary of HHS to deploy the SNS is
codified at 42 U.S.C. Sec. 247d-6b.
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[[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.
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\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.
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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.
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\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.
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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.
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\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.
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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:
Multiple events
Citizens concerned about exposure \17\
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\17\ Non-exposed population seeking medical care for non-
specific symptoms or concerns about exposure.
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The lack of availability of rapid, point-of-care
diagnostics
Potential nationwide demand after a single large-scale
event
Pre-positioning of individual medical countermeasures to
meet specific response time requirements
Economies of scale for production \18\
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\18\ A production process in which an increase in the number of
units produced causes a decrease in the average cost of each unit.
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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\
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\19\ http://www.whitehouse.gov/ news/releases/2007/ 02/20070207-2.html.
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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\
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\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
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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