[Senate Hearing 111-970]
[From the U.S. Government Publishing Office]
S. Hrg. 111-970
DEFENDING AGAINST PUBLIC HEALTH THREATS
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HEARING
before a
SUBCOMMITTEE OF THE
COMMITTEE ON APPROPRIATIONS UNITED STATES SENATE
ONE HUNDRED ELEVENTH CONGRESS
SECOND SESSION
__________
SPECIAL HEARING
SEPTEMBER 29, 2010--WASHINGTON, DC
__________
Printed for the use of the Committee on Appropriations
Available via the World Wide Web: http://www.gpo.gov/fdsys
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COMMITTEE ON APPROPRIATIONS
DANIEL K. INOUYE, Hawaii, Chairman
PATRICK J. LEAHY, Vermont THAD COCHRAN, Mississippi
TOM HARKIN, Iowa CHRISTOPHER S. BOND, Missouri
BARBARA A. MIKULSKI, Maryland MITCH McCONNELL, Kentucky
HERB KOHL, Wisconsin RICHARD C. SHELBY, Alabama
PATTY MURRAY, Washington JUDD GREGG, New Hampshire
BYRON L. DORGAN, North Dakota ROBERT F. BENNETT, Utah
DIANNE FEINSTEIN, California KAY BAILEY HUTCHISON, Texas
RICHARD J. DURBIN, Illinois SAM BROWNBACK, Kansas
TIM JOHNSON, South Dakota LAMAR ALEXANDER, Tennessee
MARY L. LANDRIEU, Louisiana SUSAN COLLINS, Maine
JACK REED, Rhode Island GEORGE V. VOINOVICH, Ohio
FRANK R. LAUTENBERG, New Jersey LISA MURKOWSKI, Alaska
BEN NELSON, Nebraska
MARK PRYOR, Arkansas
JON TESTER, Montana
ARLEN SPECTER, Pennsylvania
SHERROD BROWN, Ohio
Charles J. Houy, Staff Director
Bruce Evans, Minority Staff Director
------
Subcommittee on Departments of Labor, Health and Human Services, and
Education, and Related Agencies
TOM HARKIN, Iowa, Chairman
DANIEL K. INOUYE, Hawaii THAD COCHRAN, Mississippi
HERB KOHL, Wisconsin JUDD GREGG, New Hampshire
PATTY MURRAY, Washington KAY BAILEY HUTCHISON, Texas
MARY L. LANDRIEU, Louisiana RICHARD C. SHELBY, Alabama
RICHARD J. DURBIN, Illinois LAMAR ALEXANDER, Tennessee
JACK REED, Rhode Island
MARK PRYOR, Arkansas
ARLEN SPECTER, Pennsylvania
Professional Staff
Erik Fatemi
Mark Laisch
Adrienne Hallett
Lisa Bernhardt
Michael Gentile
Alison Perkins-Cohen
Bettilou Taylor (Minority)
Sara Love Swaney (Minority)
Jennifer Castagna (Minority)
Administrative Support
Teri Curtin
C O N T E N T S
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Page
Opening Statement of Senator Tom Harkin.......................... 1
Statement of Kathleen Sebelius, Secretary, Department of Health
and Human Services............................................. 4
Prepared Statement of........................................ 7
2009 H1N1 Pandemic Influenza..................................... 7
Medical Countermeasures (MCMs)................................... 7
MCM Review....................................................... 8
Recommendations.................................................. 9
Implementation of the Recommendations............................ 11
Strategic Investor Fund and Development Authority................ 12
Pandemic Influenza Preparedness Activities....................... 13
MCM Spend Plan................................................... 15
H1N1 Vaccine..................................................... 16
Transferring Funds From HHS to DOD............................... 18
Statement of Colonel Randall J. Larsen, USAF (Ret.), Chief
Executive Officer, Weapons of Mass Destruction Center,
Washington, DC................................................. 19
Prepared Statement of........................................ 21
Statement of Eric A. Rose, M.D., Chief Executive Officer and
Chairman, Siga Technologies; Co-Chair, Alliance for
Biosecurity, Washington, DC.................................... 25
Prepared Statement of........................................ 27
Statement of Andrew T. Pavia, M.D., FAAP, FIDSA, Chief, Division
of Pediatric Infectious Diseases, University of Utah; Chair,
Infectious Diseases Society of America's Pandemic Influenza
Task Force, Salt Lake City,
Utah........................................................... 30
Prepared Statement of........................................ 32
DEFENDING AGAINST PUBLIC HEALTH THREATS
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WEDNESDAY, SEPTEMBER 29, 2010
U.S. Senate,
Subcommittee on Labor, Health and Human
Services, and Education, and Related Agencies,
Committee on Appropriations,
Washington, DC.
The subcommittee met at 2:35 p.m., in room SD-124, Dirksen
Senate Office Building, Hon. Tom Harkin (chairman) presiding.
Present: Senators Harkin, Pryor, Specter, and Cochran.
opening statement of senator tom harkin
Senator Harkin. The Appropriations Subcommittee on Labor,
Health, Human Services, and Education, and Related Agencies,
will come to order.
It's sometimes said that, while the Defense Appropriations
Subcommittee defends America, this subcommittee actually
defines America. For the most part, that's true. This
subcommittee also defends America in one very important area,
and that's public health. Funding provided by this subcommittee
is what pays for the Nation's medical countermeasures (MCM),
including the drugs, medicines, and devices that protect
Americans against bioterrorism, pandemic influenza, and other
emerging infections. This subcommittee has taken that
responsibility very seriously, and we can point to important
advances. But, America still remains vulnerable to an epidemic
or a bioterrorism attack.
A good example is pandemic flu. Since fiscal year 2006,
this subcommittee has provided $15 billion--$15 billion--to
improve pandemic preparedness in the United States. Many of
these investments paid off during last year's H1N1 outbreak.
For example, an improved surveillance system allowed us to
detect the new strain very quickly. Second, State and local
public health agencies had more capacity than ever to
administer vaccines. Third, we stockpiled antivirals, such as
Tamiflu, which allowed us to treat patients who'd already
gotten sick with the flu.
But, despite all those improvements, a continuing
vulnerability is our dependence on egg-based technology to
produce influenza vaccines. This contributed to serious delays
in the development and manufacture of the H1N1 vaccine. Indeed,
the vaccine didn't become widely available until after the flu
season had already peaked. Fortunately for us, H1N1 was milder
than expected. But, we may not be so lucky the next time.
Another example is anthrax. It's been almost 10 years since
letters laced with anthrax were sent through the U.S. mail.
Future attacks remain a very real threat. Yet, we are still
using the same anthrax vaccine that was developed 40 years ago.
One reason that we've been slow to prepare for such threats
is that we need a stronger partnership with biotech companies
that could produce countermeasures such as the next-generation
anthrax vaccine. There's a problem, and that is this: The
Federal Government is the only buyer for these countermeasures.
So, we have to work closely with small biotech companies to
make sure they have the capacity to do what we're asking of
them. Right now, this partnership doesn't seem to be working as
well as it should.
This summer, Secretary Sebelius released a plan--a very
comprehensive plan--to address these various challenges and to
take a comprehensive approach to improving our Nation's
countermeasures. For that, Madam Secretary, we are all very
grateful for your leadership in this area.
Some of what the Secretary has proposed will require this
subcommittee's approval, since it requires transferring or
redirecting unobligated balances for pandemic flu and Project
BioShield. This hearing, therefore, is an opportunity both to
take stock of how prepared we are as a Nation to meet the
threats that confront us in this area, and to evaluate the
administration's plan for addressing these issues. We will hear
from Secretary Sebelius, as well as a panel of experts from
outside the Government.
And before we begin, I'll turn to Senator Cochran for an
opening statement.
Senator Cochran. Mr. Chairman, thank you for convening this
hearing to consider our Nation's important obligation of
defending against threats to public health.
The Department of Health and Human Services (HHS) monitors
and recommends how we go about discharging this important
responsibility to defend our country against bioterrorism and
other public health threats. We're pleased to welcome the
Secretary of HHS, Kathleen Sebelius, to the subcommittee
hearing, and we look forward to working with her to help
develop and implement plans to enhance this Nation's investment
in MCM and public health preparedness.
We have other witnesses, as well, who are coming before the
subcommittee today, and we look forward to hearing the
testimony of all of our witnesses.
Thank you.
Senator Harkin. Thank you, Senator Cochran.
Senator Specter wanted to----
Senator Specter. Well, thank you, Mr. Chairman. I had asked
for an opportunity to say a few words, because, regrettably I
cannot stay for the hearing.
But, this is a very important project that will be
discussed today, and something that you and I and many have
worked on. But, flexible manufacturing has been high on my
agenda for a long time, when I used to chair the subcommittee.
And a portion of my concern is State-oriented, because UPMC is
a major player, and seeks to engage in the competitive bidding.
And we're just at the--really, at the second inning of a very
long process here. But, I wanted to express a couple of
concerns.
One concern is over the $1.2 billion ceiling for funding
over the next 25 years, because the analysis which I have seen
indicates that will be insufficient. That goes to about $48
million a year. And some people are talking about $300 million.
I think that's probably too high, perhaps way too high. There
have been some discussions about $100 million. But, I wanted to
raise that issue, and would hope that would be addressed by the
Secretary during the hearing today.
The other subject of concern is the thrust of having the
recipient of the contract to build a facility cooperate with
other research entities to produce more vaccines with greater
flexibility as these threats arise, and there's a concern that
these entities will be in competition with one another and will
not be interested in the high level of cooperation which would
best suit the Government, best suit the public interest.
So, I raise these two considerations at the outset.
I thank the Secretary for the attention she has given to
this matter. I have talked to her about it on several
occasions. I even talked to two people who are higher up on the
chain of command than is the Secretary about the matter. They
call them the Vice President and the President. And I've talked
to many people who are lower on the chain of the command. And
I--the principle of equality is important, and very often
somebody far down on the chain of command can be as influential
as somebody at the top of the chain of command. Some say that
the staffs run the Senate. I don't think they run all the
Senators, but they are very, very influential.
But, I wanted to call those couple of matters to the
attention of the Secretary and the subcommittee. And, while
I'll be working with Secretary Sebelius much more, because we
have a very lengthy lame duck session--I heard it was going to
last until December 15--but, I just want to thank her for what
she's done, especially coming to Philadelphia on the first
Sunday in August of the year 2009, when the first of the
raucous town meetings occurred. And she and I were there that
day, speaking to a group of lawyers. The organizer was a
Philadelphia lawyer who asked me to speak. They finally got a
better speaker, but I was second because the president of the
association's from Kansas, and knew the Secretary, and was able
to get a high-quality speaker without an honorarium. And since
she was coming to town--when I say a ``high-quality speaker,''
Madam Secretary, that's because Senators don't charge
honoraria; we're not permitted to. But, since she was coming to
town, she decided to hold a town meeting. And since I was in
town with her at the same lunch, I was asked to join her. And
it was historic, and you were terrific.
Thank you, Mr. Chairman.
Senator Harkin. I have to get a video of that one, then.
Thank you very much, Senator Specter.
Secretary Kathleen Sebelius became the 21st Secretary of
HHS on April 29, 2009. In 2003, she was elected as Governor of
Kansas and served in that capacity until her appointment as
Secretary. Prior to her election as Governor she served as the
Kansas State insurance commissioner. She is a graduate of
Trinity Washington University, just up the street from here,
and the University of Kansas.
Madam Secretary, welcome. And your statement will be made a
part of the record in its entirety. Please proceed as you so
desire.
STATEMENT OF KATHLEEN SEBELIUS, SECRETARY, DEPARTMENT
OF HEALTH AND HUMAN SERVICES
Secretary Sebelius. Well, thank you so much, Chairman
Harkin and Senator Cochran and Senator Pryor. I'm sorry that
Senator Specter had to leave. He doesn't advertise it much, but
he is also a Kansan. He was born and raised in Russell, Kansas,
and was the debate champion of his high school. So, it was
great to be with him at the town hall in Philadelphia. And I
appreciate the opportunity to be here and talk a bit about our
recent review of the MCM Enterprise and some recommendations we
have about how we can move forward.
As you all know well, we don't really know where the next
public health crisis is going to come from. It could be a dirty
bomb in a subway car, it could be a naturally occurring
superbug that's resistant to all treatments, it could be a
biological weapon that we've never seen before, assembled from
the building blocks of life by a terrorist in a lab. And, as
we've seen, it could be a naturally occurring novel strain of
the influenza virus.
So, I had my introduction to MCM less than an hour after I
was sworn in on April 29, when I went and was briefed, by John
Brennan in the situation room, on the rapidly expanding H1N1
virus, which was beginning to appear, not only in the United
States, but in other nations. And we had a rapid and
coordinated response across government, made possible in large
part by the efforts of this subcommittee, Mr. Chairman, who had
been directing resources and planning and preparedness dollars
over a series of years so that we would be ready to respond.
So, with the first pandemic in 40 years, the good news is,
we were able to develop and distribute a safe vaccine. The bad
news is that our production peaked 3 weeks after the peak of
the flu season, so we were still not able to respond in a
timely fashion.
So, we knew we needed to do better, and the President
encouraged our Department to look at not only what occurred
during the H1N1, but to use it as an opportunity to review the
entire MCM Enterprise. And so, we launched that study in
December 2009.
As you know, countermeasures are vaccines, antivirals,
antibiotics, pharmaceuticals, diagnostics, and the medical
equipment that are the most direct and effective defense in any
public health crisis. So, I asked Dr. Nicky Lurie, who's our
ASPR--to lead the review. And we engaged not only all of our
departments and entities in HHS, but also reached out to our
local and State health departments, who had been great partners
in the flu response, to industry groups, to venture capital
experts, academics, scientists, and our partners in the
Department of Defense (DOD), as well as biotech developers
around the country, to help us analyze sort of where we are and
where the glitches are in the system.
And we found that the pipeline that we rely on to provide
critical countermeasures is, unfortunately, full of leaks and
chokepoints and dead-ends. And, in an age of new threats, where
delays cost lives, we aren't developing and manufacturing new
countermeasures fast enough. And, Mr. Chairman, you referred to
both the flu and the anthrax situation as two examples of that.
So, at a moment when the most dangerous threat may be something
we've never seen before, we don't have the flexibility to
adapt. And our challenge is to get from where we are today to
the goal that the review laid out, a Nation with, and I quote,
``The nimble, flexible capacity to produce MCM rapidly, in the
face of any attack or threat, known or unknown, including a
novel, previously unrecognized, naturally occurring, emerging
infectious disease.'' That's where we need to be as a Nation.
And our plan, which we have submitted to this subcommittee and
to Congress, is a step to getting us there.
We think it's important to focus on five major areas where
we begin to act now to make big improvements in public health
defenses:
First, upgrade regulatory science at the Food and Drug
Administration (FDA), to modernize product development and
evaluation. By identifying and solving scientific problems
earlier, we can take products across the finish line faster,
confident in their safety and effectiveness. And I would say,
Mr. Chairman, that we used some of these new techniques in the
production of the H1N1 vaccine, brought the companies to the
table at a much earlier stage, and I think it's one of the
reasons we were able, in record time, to get that vaccine into
the production lines.
Second, want to work with highly experienced developers--
and this is what Senator Specter referenced--to establish
facilities capable of providing core, advanced development and
manufacturing services here in the United States. So, on
September 15, we released a draft solicitation for new centers
of innovation for advanced development and manufacturing
facilities. These will be new plants, here in the United
States, to develop flexible manufacturing platforms, giving us
a dependable source of surge capacity for flu vaccine, as well
as the ability to manufacture other MCM, so we don't have to
rely on foreign producers, as we did during the H1N1 crisis.
We released the draft for comment, and anticipate producing
the final solicitation before the end of the year. And, in
fact, next week we have interested parties coming in for 3 days
of discussion so we can home in on what are the real strategies
for the best possible request for proposal.
The centers also can serve as a resource for small biotech
companies with big ideas that can help them get the
manufacturing and regulatory support they need to get the
products to market. Just this week, we've awarded eight
contracts to businesses, with the goal of developing innovative
tools and techniques that improve numerous aspects of the MCM
pipeline, from increasing the shelf life of the flu vaccine to
advanced disease surveillance.
The third area where we think we need to turn our focus is
doing more to nurture the discoveries at their earliest stages
by taking full advantage of the world-class resources and years
of experience at the National Institutes of Health (NIH). We'll
aggressively seek out those ideas and discoveries that have the
best potential to fuel the product pipeline. And to assure that
no breakthroughs sunset with the publication of a paper in a
scientific journal, we want to be more proactive in harnessing
the ideas and incubating new products.
Fourth, reducing the time it takes to get flu vaccines to
people by producing vaccine seed strains that grow better and
by modernizing potency and sterility testing methods.
These are some of the steps recommended in the President's
Council of Advisors on Science and Technology report, and
they'll ensure we're better prepared for flu seasons to come.
The Centers for Disease Control and Prevention (CDC), FDA,
Biomedical Advanced Research and Development Authority (BARDA),
and NIH are already engaged in a planning framework to address
each of these needs.
And, again, Mr. Chairman, I want to recognize your
leadership and support in this area. You have been a champion
of this for years, and it's something we take very seriously.
And finally, we're exploring the possibility of launching a
nonprofit venture capital firm that can support critical
financial and business planning to small companies with big
ideas that have the potential to improve our public health
preparedness. In the coming years, HHS will direct nearly $2
billion in preparedness funds to these five areas, helping us
build a MCM enterprise with a solid base of discovery, clear
regulatory pathway, and the agile manufacturing that's
necessary if we're going to be able to respond to any threat at
any time.
We've also submitted an amendment to the fiscal year 2011
President's budget to provide the new authorities where they're
needed.
So, coming off this review, we hit the ground running. We
just awarded a contract to a California company to create next-
generation ventilators for use during a potential health
emergency or pandemic. And today we're announcing further
investment in our ongoing international cooperative agreement
with the World Health Organization to support global pandemic
influenza vaccine preparedness, a partnership that improves
health safety, both here and abroad.
In the end, if a product fails to make it into our national
stockpiles, it should only be based on its failure to meet our
stringent standards for safety, efficacy, or quality, and not
because we failed to provide the needed business, regulatory,
and technical support for success.
Mr. Chairman, there's an old saying in sports, that most
victories are actually won on the practice field, when no one
is watching. And we feel in the same way how successfully we
respond to tomorrow's public health crisis when the spotlight's
on actually determined by how hard we work behind the scenes to
build a 21st century countermeasures enterprise that can
respond quickly and effectively to any threat.
prepared statement
So, we'll continue to look for ways to build, not just a
stronger countermeasures enterprise, but a stronger end-to-end
public health response, all the way from disease surveillance
to administering MCM to people in our cities and towns.
I look forward to working with you, Mr. Chairman, and your
subcommittee, and again want to applaud this subcommittee for
your focus and attention on this over the last number of years.
[The statement follows:]
Prepared Statement of Kathleen Sebelius
Chairman Harkin, Senator Cochran, and members of the subcommittee,
thank you for the opportunity to discuss the Department of Health and
Human Services (HHS) recent review and recommended initiatives to
improve our medical countermeasures enterprise.\1\
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\1\ The Public Health Emergency Medical Countermeasure Enterprise
Review is available
online at: http://www.phe.gov/Preparedness/mcm/enterprisereview/Pages/
default.aspx.
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Our greatest responsibility in Government is keeping the American
people safe. We have always maintained a powerful military that can
guard against conventional threats. But in today's world, the range of
threats is ever-widening to include biological, chemical, nuclear, and
radiological hazards in addition to the conventional threats. The next
public health emergency could be a dirty bomb set off in a subway
system. It could be a biological weapon we've never seen before,
assembled by a terrorist in a lab. And, as we have seen, it could be
naturally occurring novel strain of influenza virus.
2009 h1n1 pandemic influenza
Right after I was sworn in as Secretary of HHS, I was briefed by
John Brennan, the President's Advisor for Homeland Security and
Counterterrorism, on 2009 H1N1 influenza, and immediately found myself
immersed in the national need to respond to this new threat.
Fortunately, HHS was already in the process of rapidly responding to
2009 H1N1, working in close partnership with virtually every part of
the Federal Government under a national preparedness and response
framework. We characterized the new virus, disseminated the information
to researchers and public health officials, and developed and began
shipping to States a new test to diagnose cases of the infection. We
distributed antiviral drugs to the States from the Strategic National
Stockpile. We also completed key steps in the vaccine development
process--preparing a virus strain for vaccine production, contracting
with manufacturers for vaccine, performing necessary clinical trials,
and licensing multiple 2009 H1N1 influenza vaccines. After close
collaboration with State and local authorities and healthcare
providers, we began the voluntary national vaccination program in
October. HHS was in constant communication with State health officers
and hospital administrators to monitor stress on the healthcare system
and to be prepared in case Federal medical assets were necessary to
augment State and local surge capabilities.
We responded as quickly as possible to the H1N1 emergency, and the
speed of these efforts was due in large part to the prior investments
in pandemic preparedness. I would like to thank this subcommittee for
its support in this area over the past 4 years. We did, however,
experience challenges with the vaccine manufacturing and availability.
No matter how quickly we responded, we were still dependent on vaccine
technology from the 1950s, relying on the virus to grow in eggs. We
also had to depend, in part, on foreign vaccine manufacturers, which
meant there were two instances in which our vaccine deliveries were
delayed in order to meet another country's vaccine needs first. HHS had
already taken steps to expand domestic vaccine manufacturing with the
opening of a new cell-based influenza vaccine manufacturing facility in
North Carolina in November 2009. But, further action was needed to
provide a more robust and nimble domestic manufacturing surge capacity.
We continue the process of that investment today.
medical countermeasures (mcms)
The success of a response to a public health crisis depends on many
factors, including the expertise of our healthcare workforce, the
capacity of our Nation's hospitals, the ability of Federal, State,
local, tribal, and community partners to coordinate, and the engagement
of the public. The success of a response also greatly depends on
medical countermeasures. These are the medical treatments, vaccines,
diagnostics, personal protective equipment, and nonpharmaceutical aids
like ventilators that help reduce the spread of infections, reduce
health consequences, and ultimately save lives. In a public health
crisis, medical countermeasures are typically our most direct and often
our most effective response.
Medical countermeasures take years to develop, are very expensive,
and must follow the rigorous development and regulatory pathway to
demonstrate safety and efficacy. Unlike the drugs destined for everyday
or frequent use, the countermeasures needed for biodefense threats in
many cases may have greater development risks, due largely to the
absence of significant commercial markets and the difficulty in
demonstrating efficacy in the absence of human clinical trials.
The Federal Government has invested considerable resources over the
past 10 years in expediting the development of these products. However,
it was apparent from both the 2009 H1N1 experience and the paucity of
medical countermeasure candidates moving from early to advanced
development that we needed a better understanding of how the Federal
Government and industry are generating new products. We realized that
the greatest danger we may face is a microbe that we have never seen
before and for which we do not yet have a medical countermeasure. We
clearly need the capacity to develop a medical countermeasure quickly.
mcm review
Recognizing this need, with the encouragement and strong support of
President Obama, I called for a comprehensive review of our entire
medical countermeasure enterprise in order to transform these efforts
into the highly responsive and flexible system we know we need. In
order to get the 21st century products essential for our national
security, we understood that we must invest in 21st century technical
approaches as well as 21st century financial, legal, and regulatory
frameworks that nurture a viable commercial sector and create
incentives for companies to build these advanced countermeasures. In
his 2009 State of the Union address, the President called for a renewal
of our national capability to respond to bioterrorism and infectious
disease.
The review was led by HHS's Assistant Secretary for Preparedness
and Response (ASPR), Dr. Nicole Lurie. She was joined by
representatives from across HHS (the Office of the ASPR, the Centers
for Disease Control and Prevention (CDC), the National Institutes of
Health (NIH), the Food and Drug Administration (FDA), the Office of the
Assistant Secretary for Financial Resources, the Office of the
Assistant Secretary for Planning and Evaluation, the Office of the
Assistant Secretary for Legislation, and the National Vaccine Program
Office; Federal interagency partners (the Department of Agriculture,
the Department of Defense (DOD), the Department of Homeland Security,
and the Department of Veterans Affairs); and the Executive Office of
the President to dissect the issues, identify critical gaps, and
respond to the challenges that would be uncovered as the review
proceeded.
The review was conducted in multiple stages. First, we analyzed a
large body of work on medical countermeasure development, financial and
market incentives, and procurement of science. We looked at how the
needs of the medical providers are considered in the design of MCM
products, and which mechanisms are employed to get products to those
providers. Second, the successes and failures of the MCM enterprise
were examined in order to identify the critical components for success
and impediments to realizing our goals. In addition, we interviewed
numerous opinion leaders, representatives from the pharmaceutical and
biotechnology industry, members of the investment community, and
leaders in State and local public health for their views on the role of
HHS in MCM development. A series of meetings and workshops were
conducted, including: a 2-day workshop hosted by the Institute of
Medicine's Forums on Public Health Preparedness and Drug Development, a
town hall meeting at the National Association of County and City Health
Officials Preparedness Summit, and a meeting with leaders of the
President's Council of Advisors on Science and Technology. Finally, the
ASPR, on my behalf, asked the National Biodefense Science Board, an HHS
Federal Advisory Committee, to convene a workshop to review the overall
strategic management, leadership, and accountability structure of the
MCM enterprise.
I released the review, The Public Health Emergency Medical
Countermeasures Enterprise Review: Transforming the Enterprise to Meet
Long-Range National Needs, last month. This review highlights the need
for the MCM enterprise to adopt a new strategy that incorporates our
ability to rapidly and flexibly respond to a new or unknown threat
balanced against our longstanding requirements for producing MCMs to
counter identified threats. This new strategy is articulated through
the following vision statement: Our Nation must have the nimble,
flexible capacity to produce MCMs rapidly in the face of any attack or
threat, known or unknown, including a novel, previously unrecognized,
naturally occurring emerging infectious disease.
The principle at the heart of this strategy is that our public
health response is only as strong as its weakest link. So, using it as
a guide, we have worked to upgrade our entire end-to-end response, from
how we assess and identify threats to how we distribute and administer
products to counter those threats in cities and towns across the
country. That is why we will continue to look for ways to build--not
just a stronger countermeasures enterprise with a solid base of
discovery, a clear regulatory pathway, and agile manufacturing--but
also a stronger public health response all the way from disease
surveillance to administering countermeasures to people in our cities
and towns.
recommendations
The MCM review recommends five new infrastructure initiatives as
well as other enhancements to the MCM enterprise. The review found that
the unique products required by the public health emergency medical
countermeasure enterprise are not of general commercial interest to the
major pharmaceutical companies, due to the risks and opportunity costs
to produce and receive approval for products with very limited
commercial market value. The Federal Government often partners with
smaller pharmaceutical or biotechnology companies, many of whom would
benefit from additional resource or management investments to become
successful and reliable entities. We came to realize that we need to
provide a variety of supports to ensure the viability of these
partners. In the end, if a product fails to make it into our national
response capability, it should only be based on its failure to meet our
stringent standards for safety, efficacy or quality, and not because we
failed to provide the needed business, regulatory, and technical
support for success. We also realized that the approach to the threats
of the future requires building a ``capability-based'' system that can
quickly adapt to a rapidly emerging or sudden, novel threat.
21st Century Regulatory Science
The first infrastructure investment, which enjoyed nearly universal
support, is the strengthening of regulatory science at the FDA.
We heard from stakeholders that one of the greatest risks to
successfully developing a product was the uncertainty associated with
the complex regulatory process that governs the approval of these
particular drugs, vaccines, and diagnostics.
FDA has been testing and producing cutting-edge products using
science that's decades-old and it is prudent to invest in providing the
FDA with the tools, models, methods, and knowledge necessary to 21st
century technologies and assist industry in reviewing and regulating
these new products.
As part of this initiative, FDA is launching a new program
entitled, Advancing Regulatory Science for Public Health, designed to
augment the tools used to assess the safety, efficacy, and quality of
medical products, with a particular focus on MCMs. The FDA will create
new Action Teams to work with those manufacturers who are developing
the high-priority products and platforms. This strategy is based on an
approach that worked well several years ago when the United States
licensed its vaccine for smallpox, ACAM 2000. The Action Teams,
composed of experts from across the FDA, will work with sponsors to
identify and help resolve scientific issues as early and efficiently as
possible, and to facilitate more rapid evaluation of these high-
priority candidate products. Finally, the FDA will launch a
collaborative project with other HHS and interdepartmental members of
the MCM enterprise to resolve several of the real challenges that have
been identified for these types of products. For example, one of these
challenges is the difficulty in using the Animal Efficacy Rule. This
rule allows appropriate studies in animals in certain cases to provide
substantial evidence of effectiveness in humans of new MCMs against
biological threats.
These initiatives will both give our world-class FDA scientists the
cutting-edge resources they need to analyze promising new discoveries
faster as well as help industry navigate the complex regulatory
processes to ensure that safe, effective, and high-quality products are
ready for our use. The FDA has already begun to identify areas of
needed scientific investment via internal discussions with science
leaders from among its various centers, as well as the processes and
metrics they will use to track return on this investment.
Flexible Manufacturing and Advanced Development Core Services
Partnerships
The second initiative we are investing in is the development of
flexible manufacturing capable of producing the next generation of
medical countermeasures.
As noted previously, the Federal Government often partners with
smaller pharmaceutical or biotechnology companies in the development of
medical countermeasures. Many of these companies would benefit from
technical expertise and guidance in scaling up from small to large
production and in the approval of an MCM product. Further, many of
these innovators do not have the capital or experience to construct and
operate commercial-scale manufacturing facilities.
To fill this need, HHS will establish Centers for Innovation in
Advanced Development and Manufacturing. These centers will provide a
variety of core services to less-experienced innovator companies with
federally supported medical countermeasure candidates through public-
private partnerships with fully integrated pharmaceutical partners. HHS
will coordinate these core services with regulatory science assistance
and other services already provided by the Federal Government, such as
clinical studies and animal-challenge model development. In addition,
these centers will be expected to fill the remaining gap in domestic
pandemic influenza vaccine manufacturing and surge capacity, utilizing
new recombinant and molecular platform technologies. Last, the
manufacturing output from these centers will be coordinated by HHS with
a domestic network of fill-finish manufacturers to ensure that the
first and last doses of vaccine or other medical countermeasure become
available as soon as possible. These centers are expected ultimately to
aid in controlling the costs of developing and procuring medical
countermeasures in emergencies and of stockpiling. The centers will
provide development and pilot-manufacturing activities for vaccine
candidates, allowing their associated costs to be absorbed into the
center's operating budget and thereby reducing the total amount of the
R&D contract. Similarly, the costs for commercial-scale manufacturing
of MCMs destined for stockpiling in the Strategic National Stockpile
will be lower than the costs under the current fixed-price contracts.
The centers will be managed by the Biomedical Advanced Research and
Development Authority (BARDA) within ASPR in coordination with other
HHS agencies and the DOD. BARDA issued a draft solicitation earlier
this month to seek public comment and engagement in this envisioned
public-private partnership capability. We expect that the final
solicitation will be available by the end of the year, and that
competitive contracts will be awarded in 2011.
Accelerating Discovery and Translation of Product Concepts
The third initiative we will invest in is nurturing discoveries in
their earliest stages.
The Federal Government has invested heavily in a strong, vibrant
basic research and discovery program with the ultimate goal of
translating important scientific discoveries into licensed medical
countermeasures. However, most individual scientific discoveries do not
lead directly to an identifiable product. Scientists may make a
discovery without realizing that it could be turned into a useful
countermeasure, or, if they do see its potential, they may have trouble
attracting private investment with an uncertain commercial development
path to market. The Conception Acceleration Program at NIH's National
Institute of Allergy and Infectious Disease (NIAID) aims to change that
dynamic.
A key component of this initiative will be Early Development Teams,
that will work closely with partner agencies and programs (NIH, CDC,
DOD, ASPR/BARDA, and FDA) and with academic researchers, biotechnology
companies, and large pharmaceutical companies. NIH, and especially
NIAID, has a broad capability to scout the emerging science that comes
from its investments. These teams will be responsible for scouring
grant portfolios for discoveries that could have applicability to
medical countermeasure development. They will be empowered to leverage
both additional funding and access to a wide range of NIH core services
to foster these potential solutions into promising medical
countermeasure candidates. Where necessary, staff could even play a
matchmaking function with other investment organizations, the Centers
for Innovation in Advanced Development and Manufacturing, or
biotechnology and pharmaceutical firms. Such an approach represents a
new and potentially transformational model of advancing our science
investments at NIH, and could enable benefits far beyond the realm of
MCMs. NIAID is in the process of identifying the number and level of
skilled personnel that need to be dedicated to this effort.
Modernizing Pandemic Influenza Vaccine Manufacturing
Fourth, we will invest in our domestic manufacturing surge
capacity.
The emergence of a novel pandemic strain of influenza virus is a
continuous threat to human health. In addition to the experiences of
2009, we are ever vigilant to the possibility that avian influenza H5N1
or other circulating virus strains may become highly transmissible and
virulent in humans. Our experience with 2009 H1N1 taught us that we
need to respond even faster to an emerging pandemic. Although we were
able to manufacture and distribute a safe vaccine faster than in
previous years, domestic manufacturing surge capacity needs to be
expanded and accelerated.
The MCM Enterprise review, along with a parallel study conducted by
the President's Council of Advisors on Science and Technology to
improve influenza vaccine manufacturing, identified immediate needs and
opportunities to shorten vaccine production timelines. We need better
methods for potency assays and sterility testing, optimized virus seed
strains, additional development of diagnostic devices, and expanded
capacity to fill and finish vaccine. The review also recommends that
HHS support the development of at least three new influenza vaccine
candidates whose manufacture does not depend on virus grown in eggs or
cells. This initiative is already underway through collaborative
efforts by ASPR/BARDA, NIH, FDA, CDC, and the industrial and academic
communities.
Strategic Investor Fund
The fifth initiative we have identified is a strategic investment
fund for new medical countermeasure technologies.
Biotechnology companies are often founded with a promising novel
technology, but without the resources and business acumen necessary to
fully develop and license their idea into a marketable product. As I
described above, the large manufacturers in the private sector often
choose to not invest the needed capital and management expertise in
these entrepreneurial endeavors due to the many risks inherent in
medical countermeasure development, especially with firms or
technologies whose products have no market outside that currently
needed for Federal Government stockpiles. We discovered that this same
set of problems led the intelligence community and the Department of
the Army to each establish ``strategic investor'' organizations, In-Q-
Tel and On Point, respectively, which help in partnering Federal
Government needs with companies that are developing technical
approaches that match those needs, and which are also capable of
producing commercially viable spinoffs, or multi-use products, based on
that technology.
The administration's fiscal year 2011 budget amendment transmitted
to Congress in August included authorization for HHS to use an
independent strategic investor that would nurture biotechnology
companies by providing the needed capital and business expertise to
yield a successful product for Government needs. The mission of the
envisioned MCM Strategic Investor (MCMSI) would be the development of
novel technologies that have the potential for sustainable commercial
applications to the commercial market and the MCM public health
enterprise. In addition to its own investments, the MCMSI could
potentially leverage other private capital, provide expert
consultation, and link promising companies with potential partners in
the private sector. The MCMSI is envisioned as a private, not-for-
profit corporation operating outside the Federal Government, but it
would still work closely with NIH, BARDA, DOD, and our other Federal
partners.
Management, Administration, and Accountability
The review also found that while some program management components
are working quite well, better management and administration would
provide more clarity and predictability, as well as less risk to
development partners. These include: improving coordination across the
agencies involved in the MCM enterprise, speeding up the contracting
process or using more flexible transaction authorities, clearly setting
and prioritizing broad enterprise goals, and coordinating the process
of product development itself, from initial concept development to
product use.
implementation of the recommendations
We have re-allocated $1.9 billion in funding already appropriated
for pandemic influenza and the procurement of medical countermeasures
under Project BioShield to begin implementing these recommendations.
This includes:
--$170 million to promote regulatory innovation and investment in
regulatory science at the FDA;
--$678 million to build domestic flexible manufacturing
infrastructure and advanced development core services;
--$33 million to support promising efforts and translation of
concepts and research at NIH;
--$822 million to address immediate development needs related to
pandemic influenza vaccines, antiviral drugs, and diagnostics;
and
--$200 million to explore alternative capital market mechanisms.
The administration has submitted an amendment to the fiscal year
2011 President's budget to provide new authorities where needed.
Specifically, new authority is required to support the efforts at FDA,
the efforts at DOD, and the MCMSI.
HHS has begun developing implementation plans for each of the
initiatives and enhancements described above. Some have progressed more
than others, based on the complexity and novelty of the new efforts.
The HHS senior leaders from CDC, FDA, NIAID and ASPR, working with
colleagues at DOD, have conducted strategic reviews of our major
product portfolios for smallpox, anthrax and radiological/nuclear
threats. They have identified priority actions to further enhance the
production and eventual distribution of these medical countermeasures,
looking as well at economies that can be realized so we may be better
stewards of the public funding for this capability. As previously
noted, BARDA released a draft solicitation to support Centers of
Innovation for Advanced Development and Manufacturing.
BARDA has also awarded new contracts recently for the development
of products that could be used as medical countermeasures to known or
unknown threats as well as having a possible commercial market. BARDA
awarded a contract to develop an antibiotic that could be used against
two possible types of bioterrorism (plague and tularemia) as well as
common infections that are becoming resistant to antibiotics. BARDA
also awarded a contract to continue developing a new way to treat an
illness caused by exposure to a nuclear blast; this treatment
potentially could be used for other blood disorders and complications
of cancer. BARDA is also expected to award a contract for the
development of a next-generation ventilator as part of all-hazards
preparedness generally, and pandemic influenza specifically.
As we transition to this improved approach to medical
countermeasure development, we see opportunities for advances in other
areas of public health--new vaccines for neglected diseases, rapid
response for emerging naturally occurring infectious diseases, and new
approaches to treating drug-resistant bacteria in hospitals or other
settings. This strategy aligns with our concepts under the National
Health Security Strategy,\2\ which was developed to galvanize efforts
to minimize the health consequences associated with significant health
incidents and achieve a national vision of health security. The
advances coming out of the medical countermeasure enterprise may
ultimately address day-to-day needs as well as the ever-widening
threats of biological, chemical, nuclear, and radiological hazards.
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\2\ Available online at: http://www.phe.gov/Preparedness/planning/
authority/nhss/Pages/default.aspx.
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conclusion
I called for a review of the MCM enterprise recognizing that we
need to incorporate 21st century technology along with 21st century
financial, legal, and regulatory frameworks in order to have the
medical countermeasures necessary to defend against the diverse threats
we face. The review focused primarily on our ability to take an idea or
concept in research and move it quickly to producing an approved
medical countermeasure. But, we recognize that our ability to respond
begins with the rapid identification of a new event through public
health or medical surveillance and the ability to identify the
requirements of an MCM--how much we will need, for what part or parts
of the population. A medical countermeasure is successful only if it
reaches the right population at the right time. We must rely on
surveillance capabilities and feedback from end--users incorporated at
the beginning of development cycle.
The review identifies a variety of initiatives and opportunities to
accomplish these intended goals with the ultimate vision of a nimble,
flexible capacity that the nation can rely on to produce medical
countermeasures rapidly in the face of any attack. As I mentioned
earlier, in the end, if a product fails to make it into our national
response capability, it should only be based on its failure to meet our
stringent standards for safety, efficacy or quality, and not because we
failed to provide the needed business, regulatory and technical support
for success. By moving toward a 21st century countermeasures enterprise
with a strong base of discovery, a clear regulatory pathway, and agile
manufacturing, we will be able to respond faster and more effectively
to public health threats.
Thank you for this opportunity to speak with you today on this
important subject. I look forward to answering your questions.
STRATEGIC INVESTOR FUND AND DEVELOPMENT AUTHORITY
Senator Harkin. Thank you, Madam Secretary, for that
statement. And thank you for taking the lead in this endeavor.
I think the plan is a good plan, from what I've been able
to read about it and to take a look at it. I'll be anxious to
follow its development to see what kind of input you get on
your request for proposals that you've put out there.
But, I do have some, kind of, concerns about a few elements
of this. Help me think about this. We worked very hard to
establish BARDA a few years ago, and this subcommittee has
funded it to get it going. But, I don't understand how this
fund--the Strategic Investor Fund----
Secretary Sebelius. Sure.
Senator Harkin [continuing]. I'm talking about--how that
would work different from BARDA, because BARDA was basically
set up to provide funds to small companies, promising companies
with good ideas. That was a lot of talk, we had a lot of
discussion about that. And so, it sounds like that's the same
thing as this Strategic Investor Fund (SRF). So, who--how does
it differ? And who runs it? Does BARDA run it, or does NIH run
it? I can't quite get a handle on that one.
Secretary Sebelius. Well, Mr. Chairman, the way that the
strategic investor fund is envisioned is similar to some
entities that exist in the national security realm, so the CIA
has In-Q-Tel, and NASA has the Red Planet Capital Fund. And
they are really to make capital investments at an earlier point
in the process.
BARDA will remain as the commitment to industry that there
is a purchaser for the products that are going to be developed.
I think the missing link--and Congress was wise to identify it
and fill it--was that there's very little appetite in the
commercial market for making a product unless there's some
indication that somebody will buy the product.
So, BARDA was funded and is still essential to demonstrate
that the Government is a willing buyer, that there are
resources set aside, that this won't be a commercial venture
without some ability to actually sell the product. And--what we
have found, though, is that some of these small companies
actually can't--don't have the capital to get to the
marketplace. They can't get the product idea all the way
through the pipeline. And some have a great idea, but lack the
business planning and strategy.
So, with the capital in the strategic investor, with a kind
of public-private partnership, using the assets of our NIH
scientists, of FDA, we would be able to actually streamline the
process, help move the ideas to the market, where BARDA could
become a purchaser. So, I think they actually are
complementary, not duplicative.
Senator Harkin. Okay. I think I get that. BARDA would be
the purchaser, but this fund would be the investor----
Secretary Sebelius. Or at least help--yes--direct capital,
business plans, ideas, marketing strategies.
Senator Harkin. Hmmm. Hmmm.
Secretary Sebelius. And, as I say, In-Q-Tel and a couple of
the other national security enterprises have done that very
successfully. The national security government officials
identify a missing piece of equipment or strategy. In-Q-Tel
helps to work with the private market to actually produce
what's needed; and then, at the end of the day, you know, the
DOD becomes the purchaser.
PANDEMIC INFLUENZA PREPAREDNESS ACTIVITIES
Senator Harkin. Let me just shift, a little bit, here, to
pandemic flu. We don't--obviously, we don't know what some of
these new strains of bugs that you mentioned in your
testimony--I may have mentioned in mine, too--that might come
down, or bioterrorism, or something. But, we do know flu is
here. We have the common strain of flu, that happens every
year, but we know there are a lot of other strains of flu out
there: the bird flu, H5N1, and H1N1, and a lot of variations
thereof. And we know they're floating around out there. So,
we're going to have that. I mean, we just know that that's
going to hit us. How big, we don't know. As I said, H1N1 wasn't
as big as we thought it was going to be, fortunately. But, we
don't know how big next--we know it's going to happen, we just
don't know how big.
Secretary Sebelius. Right.
Senator Harkin. So, therefore--I'm concerned, because this
subcommittee put a lot of money--$15 billion through this
subcommittee, since fiscal year 2006--for pandemic preparedness
activities. One-point-nine billion was used to develop cell-
based or recombinant vaccines. And I can remember visiting with
people a few years ago about that, and moving ahead. We put--
HHS awarded $487 million to Novartis for a cell-based
manufacturing facility in North Carolina. I thought--I heard
the plant was open, but now I'm told it won't be ready to
operate until 2013. Also, none of the influenza vaccines
licensed for use in the United States are cell-based, but they
are currently licensed in Europe.
So, why--what's the problem with getting them licensed in
the United States if they're licensed in Europe? And, why
aren't we further along in the area of cell-based or
recombinant-based vaccines, which can be turned around a lot
more rapidly, of course, than egg-based vaccines?
Secretary Sebelius. Well, Mr. Chairman, again, I think
you're absolutely right, that the subcommittee has been focused
on a series of investments, starting really in fiscal year
2006. And we do have doses of H5N1 purchased and in the
stockpile, knowing that that flu is still killing people, it is
circulating. There still isn't human-to-human transfer,
luckily, but we are very much aware that that's a very real
threat. So, some of the funding is actually preparing, in case
that were to be present here.
And, in terms of the cell-based technology that we're
moving ahead on currently, you're absolutely right, all of the
flu vaccine up to date has been developed with egg-based
technology. But, HHS did, with the pandemic funding that was
provided, support the construction of the new Novartis cell-
based manufacturing facility in North Carolina. The ribbon was
cut in November 2009. It is scheduled to be on line to apply
for licensure early in 2011, we hope in the first quarter of
next year, for cell-based, seasonal vaccine, and the licensed
vaccine is expected to be manufactured and marketed for the
2011-2012 flu season.
So, we're actually very much on track. They got to get it
up and running, they got to get it licensed. And it will be
capable of producing 150 million doses of vaccine within 6
months. So, this seriously ramps up our domestic capacity, and
that's also very good.
In terms of recombinant vaccine, we did issue a contract to
Protein Sciences in September 2009 for advanced development of
their recombinant protein vaccine, and the company is working
towards licensure again in 2011. We think that is on track.
They are expected to begin to manufacture and market their
vaccine again for the 2011-2012 flu season. Right now they're
saying they can produce 50 million doses in about 4 months.
So, both of those entities are up and running. It takes a
number of years in the pipeline, but your funding, several
years ago, has gotten us to that place. And, as I said, we just
issued a draft solicitation, this month, which will also come
out of the preparedness funding, to have these new centers of
innovation for advanced development and manufacturing that
Senator Specter has indicated a great deal of interest in.
What we find is that a flu-only facility is too limited.
What we're talking about looking at in the future, in two to
three centers, is what they call a ``flexible platform.'' So,
it could be used as surge capacity for flu vaccine, should that
be needed. It also could, essentially, begin with anthrax
vaccine, to H5N1 vaccine, to have another MCM. So, it wouldn't
be solely dedicated to the flu, but have the ability, really,
to mix and match, give us the ability to respond to something
that we don't really know is coming.
So, we plan to award the contracts by the--have the request
for proposal out by the end of this year. We want each of those
facilities to produce at least 50 million doses of cell-based
or recombinant vaccine within 4 months. So, that will be the
criteria around which we're looking. So, we're leaping over
egg-based to either cell, or ideally recombinant, and one is
in--already looking at licensure next year, and the other two
or three will be up and running, hopefully, fairly quickly.
Senator Harkin. Very good. Thank you, Madam Secretary.
Senator Cochran.
MCM SPEND PLAN
Senator Cochran. Madam Secretary, I was looking at the
funding amounts that this subcommittee has already recommended
and have been approved by Congress, and looking then at how the
funds have been used. You stated, in your testimony, that there
may be unspent funds that you are now attempting to reallocate,
or propose to reallocate.
Have you come to some understanding, with the leadership in
Congress, as to who goes first, who makes the decision? Do you
have to get approval? Or do you have license just to start a
program and start--sending this money out to beneficiaries or
hospitals or public health officials?
Secretary Sebelius. Senator Cochran, the plan that I just
outlined is based on reprogramming about $2 billion of the
preparedness funding which was dedicated to HHS by Congress and
has already been approved for preparedness. And what we're
doing, after our analysis of where the countermeasure pipeline
glitches exist, is suggesting that we would be better served,
rather than continuing to fund the traditional pipeline, to
look at areas where there were real gaps. So, more
manufacturing capacity in the United States regulatory science
in FDA and NIH, the areas where I outlined.
There are a couple of those areas, Senator, that we will
need specific congressional approval, because we don't have the
authorization; and that's the amendment that we requested as
part of the 2011 budget. So, until Congress actually gives us
the green light for the strategic investor or some of the new
authorities within the FDA, we will not be able to direct the
funds there. But, the rest of this funding is actually approved
for preparedness, and we have notified the appropriate
committees that that's the intent, and produced a spend plan to
go along with that.
H1N1 VACCINE
Senator Cochran. I'm curious, also, to know about how much
money we spent in defending against an H1N1 virus that may have
been over-advertised, in terms of its threat to general public
health. Did we waste a lot of money by sending money out to
State and local health authorities, or in letting them decide
how to use the money? Or was there a national plan, with
specifics included in the plan, as to how the funds were to be
spent?
Secretary Sebelius. Actually, Senator, I think that plan
that allowed us to move vaccine to about 85 million people in a
very rapid timeframe was based on years of planning that had
been done. I--as a former Governor, I was one of the
beneficiaries of preparedness funding, which allowed us to
gather private industry and our public health officials
together, and go through exercises: What if we had a pandemic?
Little did I know that I would be sworn in as Secretary when we
had the pandemic that I had been previously preparing for.
So, our plan with H1N1 followed, really, the strategies.
State and local health departments were major partners. And I
would say that the new part of the strategy was how we rapidly
enhanced the distribution system. We went from what was a
fairly limited number of providers who were used to giving
children vaccines in the past, to greatly enhancing that.
Because one of the key targets were children.
So, school-based clinics and mobile clinics and some of the
open doors, I think, were not ones that had been typically
planned for. But, there was definitely--at every point along
the way, States, in order to draw down funds, had to provide to
our Department very specific planning documents for what they
would do with the money, where it was going to go. Providers
had to be involved and included. We had weekly calls.
I think the good news is that, in spite of the very
alarming early days, where it appeared that, you know, this
could mirror a 1918 situation, the virus itself proved to be,
thank God, less lethal than it could have been. But, I don't
think there's any question that those partnerships, that
distribution system, the outreach network, was not only money
well spent for H1N1, but really helped to rebuild an
infrastructure for a public health system that will serve us
well, the next hurricane, flood, fire, or disaster that we're
going to have, because those are exactly the same folks who
need to respond.
Senator Cochran. I wonder, based on your experience so far
as Secretary of HHS, and also your experience as Governor, do
you have any recommendations to the subcommittee for language
that might be included in an appropriations bill that would
help improve the way we are using Federal dollars in an effort
to defend against influenza outbreaks, or any other public
health challenge that we may face?
Secretary Sebelius. Well, Senator, I think that some of the
strategies, that are outlined in some of the recommendations in
the lengthier report that we presented, at least deals with the
portion of the MCM response that is scientific discovery to
stockpile. What we're continuing to do is really this end-to-
end look. Is our surveillance system up to speed? I mean, do we
know about outbreaks quickly enough in the United States or
around the world? How do we get that information? What is that
public health infrastructure? All the way through to how we
distribute the products. You know, what's the fastest way to
get to people? I think that analysis is still going on.
And we would love to work with you. We will look for that
language and get it to you. Because I don't think there's any
question that each time we go through one of these
experiences--I mean, this was the first pandemic in 40 years--
that we need to be informed and make sure that we update all of
our systems along the way.
I can tell you, I am concerned, and continue to be
concerned, and pleased that there are funds again for the State
and local level. In this budget downturn, I don't think there's
any question that there's been a real hit on the public health
infrastructure around the country. A lot of State health
departments have less staff than they did; a lot of emergency
planners at the State and local level have been cut back. So,
that is of concern. And we are trying to pay close attention to
that as we anticipate what could come our way. Because--you
know, we can have all the great products and ideas here, but,
absent the ability to actually get them into communities across
this country in a rapid and efficient fashion, there's still a
real problem.
Senator Cochran. What was the name of that book? We had the
author of the book. Was it Barry who wrote about the influenza
100 years ago, or whatever----
Secretary Sebelius. Oh, the 1918? Yes.
Senator Cochran. And it was interesting experience,
learning from him, through his research and writing that book--
--
Secretary Sebelius. You bet.
Senator Cochran [continuing]. And everything, some of the
things that had been overlooked, that you would think a
civilized society, and advanced as we were, as wealthy as we
were, would have learned from that experience better than we
did. I wonder if you've had a chance to read that book. It's a
few years old now.
Secretary Sebelius. I have, and I've actually had a chance
to meet a bit with the author. We also talked, at the beginning
of the influenza outbreak, with a lot of the officials who were
involved in the 1970s with what appeared to be--it was a novel
strain of the flu. There was a major vaccination effort, and
the disease never spread anywhere.
So, to try and learn, again, how--you know, what they
learned, and didn't learn, I think it's wise to make sure that,
each time we have these experiences, we're better informed by
it, and, you know, update our strategies. And that's what this
is about, to use some of the money that had been appropriated
and allocated for preparedness, study what went right and what
went wrong, and try to redirect it to what we think are more
appropriate and timely opportunities.
Senator Cochran. Thank you very much.
Secretary Sebelius. Sure.
Senator Harkin. Well, Madam Secretary, thank you very much.
Like I said, we have--I've gone over this with our staff.
On your plan, it--there are a couple of things on which you do
need signoff here. I think that we'd be very supportive of the
plan, but, I must just tell you, forthrightly, so that you can
go back and tell the Office of Management and Budget (OMB),
that----
Senator Cochran. Nobody can tell OMB.
TRANSFERRING FUNDS FROM HHS TO DOD
Senator Harkin. Well--you can tell them this. You can tell
them that I just--that this proposed transfer to the DOD is one
exception, and that--I might as well just be up front with you,
I'm not going to sign off on it. That's $200 million. I just--
in all my years here, I've never heard of anything like
transferring money from HHS to DOD. I've heard it the other way
around, maybe, once in a while. But, never that way. And with
all of the demands that we have at NIH, at CDC, and all of the
other demands that we have here--we're having a hard time with
our budgets--I think DOD could come up with the $200 million. I
really do, Madam Secretary. I don't expect you to respond to
that, but I thought I would be fair and be up front with you so
that they would know that they would have to do some further
planning on that money.
Secretary Sebelius. I will convey your message----
Senator Harkin. I appreciate that----
Secretary Sebelius [continuing]. Mr. Chairman.
Senator Harkin [continuing]. Very much. Thank you very
much, Madam Secretary.
Secretary Sebelius. Thank you.
Senator Harkin. And if you have anything else to add to----
Secretary Sebelius. I just look forward to working with you
as we move along. We will certainly, as we continue this
review, continue to report back to the subcommittee. And again,
look forward to working with you on the authorities that we may
need for----
Senator Harkin. Great.
Secretary Sebelius [continuing]. Some of these----
Senator Harkin. Great.
Secretary Sebelius [continuing]. Novel ideas.
Senator Harkin. Thank you very much.
Secretary Sebelius. Thank you.
Senator Harkin. Thank you, Madam Secretary.
Now we'll move to our second panel. Colonel Randall Larsen,
U.S. Air Force, Retired. Colonel Larsen is the CEO of the
Weapons of Mass Destruction Center--a not-for-profit research
organization that he founded, along with former Senators Bob
Graham and Jim Talent. He previously served as the executive
director of the Congressional Commission on the Prevention of
Weapons of Mass Destruction, Proliferation, and Terrorism.
Colonel Larsen served for 32 years in both the Army and Air
Force; received his bachelor degree from Texas State University
and his master degree in national security studies from the
Naval Postgraduate School.
We have Dr. Eric Rose, M.D. Dr. Rose is the CEO and
chairman of Siga Technologies, which develops antivirals
against possible bioterrorism agents. He is also the co-chair
of the Alliance for Biosecurity. Dr. Rose received both his
undergraduate and medical degrees from Columbia University.
And Dr. Andrew T. Pavia is the Chief of the Division of
Pediatric Infectious Diseases at the University of Utah Health
Sciences Center. He's also the chair of the Pandemic Influenza
Task Force of the Infectious Disease Society of America. Dr.
Pavia received his B.A. and M.D. from Brown University.
Welcome. Thank you all for being here. And your testimonies
will be made a part of the record in their entirety. I ask if
you could sum them up in 5 minutes or so. I would appreciate
it. And we'll jut go in the order in which I said, here.
We'll start with Colonel Larsen first. Welcome to the
subcommittee. And thank you for all of your service.
Colonel Larsen.
STATEMENT OF COLONEL RANDALL J. LARSEN, USAF (RET.),
CHIEF EXECUTIVE OFFICER, WEAPONS OF MASS
DESTRUCTION CENTER, WASHINGTON, DC
Colonel Larsen. Mr. Chairman, vice chairman, you asked me
to provide an assessment on the threat of bioterrorism. Let me
be clear: Bioterrorism is a serious threat, and it will become
even more so if we don't take appropriate actions.
Senators Bob Graham, Jim Talent, and I agree with the
assessment in the National Security Council document signed by
President Obama in 2009. On page 1 of that document, it stated
that bioterrorism could place at risk the lives of hundreds of
thousands, and cause $1 trillion in economic disruption, per
event. The details of that threat are contained in my prepared
statement, so I won't focus on that in my oral testimony. But,
my concern is, Mr. Chairman, that there are a lot of senior
leaders--not this room--but there's a lot of senior leaders in
the legislative and executive branch that do not understand
this threat, that you and I know very well.
And I accept part of the responsibility for that. I'm an
educator, run a think tank, and that's what we're supposed to
be doing, is educating senior leaders, and make sure you have
the facts to make these very difficult decisions.
I get a lot of senior leaders asking me, ``Why don't we
just prevent this bioterrorism?'' Well, you and I know we can't
do that. That is the proper strategy for nuclear terrorism, but
it will not work against bioterrorism. The genie's out of the
bottle. We've known that since Dr. Josh Lederberg and George
Whiteside put out this report in 2001. This is nothing new. So,
we must focus on what Senator Graham calls the response side of
this equation. If Senator Graham was here, he'd have a big
chart up here like this, with his links about what we need to
do. He loves this chart and explains it very well.
What we can do, if we properly fund these programs, and
manage them, Mr. Chairman, vice chairman, we can push the
decimal point to the left, is how Senator Graham describes it.
We won't count casualties in hundreds of thousands, or tens of
thousands, or even thousands. We can push it down to a level of
what we lose on highways on 3-day weekends. Still be a tragedy
for those families, but it will not be a weapon of mass
destruction, and it won't change the course of history. That's
a realistic goal that we can achieve.
Now, let me give you two examples, since this is the
Appropriations Committee, where Senator Graham, Talent, and I
have a few problems with this. One of the things that Senator
Graham loves to talk about here is environmental cleanup. Now,
the reason that the President's document talked about $1
trillion per event--you know, if they put a pound of dry
powdered anthrax in New York City subway, we have no clue how
long it'll take to clean it up. We know that the British tested
anthrax weapons on the island of Gruinard, off the coast of
Scotland, in 1944. Took four decades to clean up that island.
Now, sir, do you know how much we're spending on clean-up
research at the Environmental Protection Agency (EPA) to clean
up anthrax? Half of what we will spend next year on Marine
Corps marching bands. Sir, I think we need to think about
priorities. Now sir, I'm a big fan of military bands, probably
the reason I spent 32 years in the military is because I saw
the Marine Corps Band when I was a young boy in the cornfields
of Indiana. But, sir, think about that. Half of what we spend
on Marine Corps marching bands is what we're going to spend to
figure out how to clean up the New York City subway. I think
it's 800 miles of subway up there.
That's one problem. The other one is, the funding of this
MCM. Now, we--you know, we gave an--WMD Commission gave an
``F'' to bioresponse preparedness, in the report card that came
out in January. The fact that we were using 60-year-old
technologies to make important vaccines like H1N1 was one of
the reasons that Senator Graham and Talent and the
commissioners gave that ``F''.
But, I have three questions about this initiative. Because
we think the strategy is great, and Senator Graham, Talent, and
I, we fully support it. But, three questions for you:
First of all, who's in charge? I believe that was the
question you asked the Secretary. I really would like to know.
In fact, I have a bigger question. Who's in charge, Mr.
Chairman, Mr. Vice Chairman, of the architecture, the
enterprise of biodefense for America? To the best of my ability
and study, there's about 24 presidentially appointed, Senate-
confirmed individuals with some responsibility for biodefense.
Not one of them has it for a full-time job, and nobody's in
charge.
Now, maybe it's because I spent 32 years in the military. I
like that authority, responsibility, and accountability. Kind
of easy to define, so you can do the oversight of that. With no
one in charge, I just don't know who's going to do that.
My second problem is, we don't have an integrated plan.
It's great strategy. And maybe they haven't had enough time, so
we'll give them a break on that. We need that integrated plan
to work with the private and public sector--there's a great
model for how we developed penicillin, just before World War
II, that made such a big difference in saving GIs' lives. We
need to figure out how to do that better. I'm sure these
gentlemen will talk about that.
And third, are we going to properly fund this? Now, Senator
Graham and Senator Talent, last year, sent letters to you, sent
letters to a lot of congressional leaders, and the White House,
saying, ``We think BARDA was only funded at 10 percent of what
were realistic requirements.'' Now, there were some people who
pushed back, and said, ``We know BARDA's doing--not doing a
very good job. They're not delivering products.'' Well, our
response to that was, ``If you funded the U.S. Air Force at 10
percent of their requirements, they probably wouldn't deliver
everything you wanted, either.''
Sir, I make these statements, not as a scientist or a
physician or as a public health expert--I spent many years,
like you did, flying airplanes--but, I have studied national
security for four decades. And, sir, the serious threats that
we'll face in the coming decade are not going to come from
missiles, tanks, or bullets, in my opinion; they're going to
come from infectious disease, going to come from Mother Nature.
We know that for a fact, and I think there's high probability
we're going to see attacks, manmade attacks, that'll cause
epidemics in our country.
PREPARED STATEMENT
Preparing for these events means we must develop faster
diagnostic capabilities, like the Secretary talked about,
better, safer, less expensive, and more rapidly produced
vaccines and therapeutics. Mr. Chairman, Mr. Vice Chairman,
they're critically important for our children and
grandchildren, whether we suffer a biological attack or not,
from terrorists. These will be no-regret investments that you
make in America.
Thank you.
[The statement follows:]
Prepared Statement of Colonel Randall J. Larsen, USAF (Ret.)
Mr. Chairman, I speak today on my own behalf, but based on
knowledge I have acquired during the past decade. I previously served
as the chairman, Department of Military Strategy and Operations at the
National War College, and the founding director of the Institute for
Homeland Security. Last year, I served as the executive director of the
Congressional Commission on the Prevention of Weapons of Mass
Destruction Proliferation and Terrorism, and currently serve as the CEO
of The WMD Center, a not--for--profit research and education
organization that former Senators Bob Graham (D-FL) and Jim Talent (R-
MO) created as a follow-on to continue the work of the WMD Commission--
and there is much work to do.
Our first mission at the WMD Center is to ensure that senior
leaders in both the public and private sectors understand the threat of
21st century bioterrorism--a subject not well understood by many
leaders in both the legislative and executive branches of Government. I
have concluded this based upon the actions and inactions of the Federal
Government.
In the past year, there have been numerous attempts to raid the
BioShield Strategic Reserve Fund for nondefense programs.
Organizations, such as the Food and Drug Administration (FDA) are
not seen as critical components on America's national security team.
Considering the threats we face, both from both from bioterrorism and
newly emerging diseases, FDA needs to be funded with the same vigor as
the Pentagon's latest weapons systems. Unfortunately, it's not.
No one is in charge of America's biodefense enterprise. No
individual has responsibility, authority, and accountability for a
program that is vital to America's long-term national security. To the
best of my knowledge, there are more than two dozen presidentially
appointed, Senate-confirmed individuals with some responsibility for
biodefense. Yet, not one of them has it for a full-time job, they
answer to no one in common, and no one is in charge. I do not think
that is the organizational structure that will lead to success.
Mr. Chairman, I am convinced that if senior leaders understood the
threat we face today, and even more importantly, the threat we will
face tomorrow, there would be someone in charge of America's biodefense
enterprise, and a clear policy and sufficient funds would be available
to properly defend America.
The threat of bioterrorism we face today is far different than that
of the 20th century. During the Cold War, only nation-states were
capable of producing sophisticated biological weapons. However, as the
biotechnical revolution began to accelerate in the latter days of the
20th century, the Defense Science Board (DSB)recognized the national
security implications of these rapid changes in the seminal DSB report,
Biological Defense, June 2001. The technology that had once been
limited to major powers was rapidly becoming available to small nations
and some non-state actors.
``. . . major impediments to the development of biological
weapons--strain availability, weaponization technology, and delivery
technology--have been largely eliminated in the last decade by the
rapid global spread of biotechnology. There is no way the United States
can control the spread of rapidly advancing biotechonology.'' (page 18)
What was unknown to the members of this DSB was the fact that while
they were preparing their report al Qaeda terrorists in Afghanistan and
Malaysia were in the process of developing anthrax weapons for use in
the United States. Thankfully, al Qaeda did not complete their weapons
development program before 9/11, and shortly after 9/11, U.S. troops
discovered and dismantled the laboratories.
Nobel Laureate, Dr. Joshua Lederberg and Dr. George Whitesides, the
former chairman of the chemistry department at Harvard University, co-
chaired this DSB task force. More than 9 years have passed since they
warned us about the national security implications of the rapid changes
in biotechnology. Those 9 years represent several generations--a great
leap forward in biotechnology. The vast majority of these new
capabilities represent good news for our families and Nation in terms
of medical care and public health; however, there is also a dark side
to this rapid progress.
Mr. Chairman, I am concerned that many leaders in the legislative
and executive branches of the Federal Government do not understand the
dark side of this progress--the nature of current and future threats of
bioterrorism. There are four key issues that are not well understood:
--history of biowarfare, including the former U.S. offensive
biowarfare program;
--the current technologies available to non-state actors;
--the interest of terrorist organizations in using biological
weapons; and
--and the fact that this is not an intractable problem.
For the past 11 years, I have provided briefings on bioterrorism in
a course sponsored by the Joint Staff's Anti-Terrorism and Force
Protection directorate (J-34) to more 3,500 senior military officers.
More than 70 percent of these officers filled out the critiques at the
end of my presentation, and by far, the most common statement on these
critiques is: ``Why hasn't anyone told me about this?''
Considering the fact that so many senior military officers are not
well versed on this threat, it should be of no surprise that
individuals outside the field of national security are even less well-
informed. To properly understand the threat of 21st century
bioterrorism, it is essential to have a basic understanding of the
history of the use of bioweapons.
In virtually all cases, biological weapons have been used in a
terroristic mode--to attack civilian populations. They are not reliable
weapons on the battlefield. They would be of little value if there was
a strong wind, bright sunlight, rain, or any combination thereof.
However, if one's goal is to attack a city, and there is no specific
date and time to do it, then they can become very effective tactical or
strategic weapons.
When I discuss 250 years of biological terrorism in my
presentations, beginning with British soldiers giving Native Americans
blankets contaminated with smallpox, to German agents attempting to
infect horses and mules in our ports during World War I, and the
Japanese dropping bombs filled with plague-infested fleas on Chinese
cities, I say that the theories of these early day bioterrorists were
sophisticated, but their technologies were not.
During the early days of the Cold War the United States, the Soviet
Union, Great Britain, and other nations reached a point where
technology finally caught up with the level of theory. This was
demonstrated in numerous tests in the United States, and by the fact
that in the 1960s, many of America's war plans included the use of
biological weapons.
I find it surprising how few citizens, and even senior military
officers, actually know that America had a powerful offensive
biological warfare capability until Richard Nixon unilaterally shut
down America's offensive of program on November 24, 1969.
When America's offensive biological warfare program began in the
1940s, it was low-tech and not capable of producing weapons of mass
destruction. Major investments were made in the 1950s and significant
advances were made in technical capabilities. By the late 1960s,
America's capabilities for the use of biological warfare was rapidly
approaching the equivalence of nuclear weapons (in terms of
casualties).
After America's unilateral disarmament in 1969, the United States
led the effort to get all nations to sign the Biological Warfare and
Toxin Convention. After signing this treaty, the Soviet Union then
ramped up their offensive program, eventually re aching a level almost
beyond imagination. With more than 50,000 scientists and engineers
working across 11 time zones in scores of facilities the Soviets
managed to hide most of this capability from Western intelligence
agencies. While the U.S. offensive program had produced hundreds of
pounds of weapons-grade pathogens, the Soviets were producing hundreds
of metric tons.
What is not well understood from this history is the fact that bio
warfare is not just theory. Tests conducted in the United States, the
Soviet Union and Great Britain confirmed beyond any doubt the
capability of pathogens to serve as either tactical or strategic
weapons against civilian targets--counter-value targets in Cold War
terminology. There is no question that in the 1960s, 1970s, and 1980s
this capability was only available to nation-states. What is not well
understood, however, is the same capability is now available to
virtually any nation, and for many terrorist organizations, both
international and domestic.
It was nearly a decade ago that Drs. Lederberg and Whitesides
stated that the rapid advances in biotechnology had reached the point
where non-State actors were capable of producing these terrible
weapons. The briefings given by various Government agencies to the WMD
Commission during the past 2 years made it clear that further advances
in the biotechnical revolution have made the production of
sophisticated biological weapons by non-State actors even less
challenging than in 2001. Those who say that it is still too difficult
for terrorists to produce and deliver sophisticated biological weapons
are either unaware of the extraordinary advances in biotechnology and
the recent Government studies that demonstrate these capabilities, or
have some other agenda that they wish to champion.
Mr. Chairman, four things must occur for a terrorist organization
to develop and deliver a sophisticated biological weapon. First they
must acquire a sample of the deadly pathogen such as anthrax or plague.
How would a terrorist organization acquire such deadly pathogens? For
the past few weeks there has been a naturally occurring outbreak of
anthrax in humans and cattle in Bangladesh. This is not terribly
uncommon in many developing countries. In fact, it even occurs in the
United States. In the summer of 2008, Ted Turner lost 278 buffalo to
anthrax on his ranch in Montana. The buffalo died because they ate
grass in a pasture that contained anthrax spores in the soil. On
Monday, a state of emergency was declared in a village in Southern
Russia's Krasnodar Territory over an anthrax outbreak in dairy cattle.
If terrorists wanted to find a sample of Yersinia pestis, the bacteria
that causes plague, they would not have great difficulty finding it in
many locations west of the Mississippi River in the United States.
Prairie dogs in West Texas and rats above the 5,000-foot level in the
Rocky Mountains often carry this deadly pathogen. Earlier this week,
the Chinese reported an outbreak of plague in humans in southwestern
Tibet.
Obtaining samples of deadly pathogens is not particularly
difficult. In fact, all but two of the 80+ pathogens on the Select
Agent List exist in nature. Pathogens that cause anthrax, plague,
tularemia, Ebola, Marburg, Venezuelan Equine Encephalitis, Q-Fever, and
dozens of others can be obtained and isolated from diseased animals or
humans.
The second step in creating a terrorist bioweapon is production.
Taking a small sample of one of these pathogens from nature and
producing enough material suitable for use as a weapon is a standard
process used in various industries including pharmaceutical,
agriculture, and pesticide. All of the equipment and supplies required
for production are available on various sites on the Internet at very
reasonable prices.
The third step, and the part that has always been most challenging
in creating a biological weapon, is getting material to the proper
particle size for airborne release. The most effective way to
disseminate a biological weapon is to spray either a liquid or dry
powdered form of a pathogen into the air. When in the proper particle
size, the pathogen will enter the human respiratory system and then
move directly into the blood stream where it leads to systemic illness.
In the 1960s and 1970s it took superpower technology to create the
proper particle size without causing harm to the bacteria or virus
being disseminated. Today it is standard off-the-shelf technology used
in the pharmaceutical and agriculture communities. Techniques far more
sophisticated than what was used in the highly classified U.S.
offensive program are now openly discussed in highly respected
scientific publications such as Journal of Aerosol Medicine and
Pulmonary Drug Delivery, and openly discussed at major conferences
hosted by organizations such as the American Association for Aerosol
Research (AAAR). The AAAR conference schedule for October in Portland,
Oregon, will include tutorials on Aerosol Mechanics I & II (http://
aaar.conference2010.org/content/tutorials).
These scientific publications and organizations are incredibly
important to medical research. They are important aspects of the
biotechnical revolution that will make the lives of our children and
grandchildren healthier and better protected from both chronic and
infectious diseases that plagued our parents and grandparents. But we
must understand, this same technology can be used to make weapons. We
must also remember what Drs. Lederberg and Whitesides told us in 2001:
``There is no way the United States can control the spread of rapidly
advancing biotechonology.'' (Nor should we try. It would only succeed
in reducing our defensive capabilities, and cause serious, perhaps
irreparable damage to our important biotech industries.)
The fourth and final step is delivery. In October 2001, the U.S.
Congress witnessed a very low-tech and generally ineffective method of
disseminating a biological weapon--the U.S. Postal Service. On the
other hand, using spray devices available in most agriculture stores,
and also available for sale on the Internet, to disseminate a few
pounds of dry-powdered anthrax, most particularly in an indoor
environment such as the subway or indoor sports arena, would have the
enormous consequences of a weapon of mass destruction.
What are those consequences? They were best stated on page 1 of the
November 2009 National Security Council document, National Strategy for
Countering Biological Threats.
``The effective dissemination of a lethal biological agent within
an unprotected population could place at risk the lives of hundreds of
thousands of people. The unmitigated consequences of such an event
could overwhelm our public health capabilities, potentially causing an
untold number of deaths. The economic cost could exceed one trillion
dollars for each such incident. In addition, there could be significant
societal and political consequences that would derive from the
incident's direct impact on our way of life and the public's trust in
Government.''
There are some who say terrorists prefer to use bombs, and point to
such recent attempts as we witnessed on Christmas Day and in May in
Times Square. Without question the vast majority of terrorists will
continue to use conventional weapons. Those weapons are certainly
capable of producing dramatic results for terrorists, such as what we
all watched unfold in Mumbai; however, terrorist use of conventional
weapons will not change course of history. An event, such as described
in the November 2009 NSC report would change the course of history--not
only for us, but for our children and grandchildren.
For those who say terrorists have no interest in biological
weapons, I guess they just ignore the Aum Shinrikyo attempts in 1994-
1995 to produce biological weapons in Japan and disregard the al Qaeda
bioweapons program. For a recent terrorist perspective on bioweapons, I
suggest you watch a short video at this Web site: http://
www.youtube.com/watch?v=M32M-2B2mz8. It was broadcast repeatedly on Al
Jazeera TV in February 2009 and has been viewed on the Internet more
than 80,000 times.
Perhaps some of the confusion comes from assessments by the
Intelligence Community (IC) on the bioterrorism threat. The IC will
tell you they have little or no information of any terrorist group
developing biological weapons capability. That should not be
surprising.
During 15 years of the Cold War, the IC failed to appropriately
identify the massive Soviet biowarfare program that consisted of 50,000
scientists and technicians working in scores of laboratories across 11
time zones. (This was the size of the Soviet's offensive biowarfare
program after they signed the Biological Warfare and Toxin Convention.)
The IC also missed al Qaeda's anthrax programs in Afghanistan and
Malaysia, and they missed the Aum Shinrikyo biowarfare and chemical
weapons programs. Thankfully, both of the Aum's weapons programs were
plagued with technical errors when they went from small-scale to large-
scale production.
Do we really think there is a high probability the IC will find a
half-dozen individuals working in a make-shift laboratory (standard bio
lab equipment purchased on the Internet in a facility no larger than a
two-car garage) in a remote village in the tribal regions of Pakistan
or Sana, Yemen, or the suburbs of New York City? That is the size and
scale of a facility required to produce bioweapons, according a study
(BACUS) done by the Defense Threat Reduction Agency in 1999 that
determined there would be no perceptible ``intelligence signature'' of
such an operation.
For the threat of bioterrorism, the IC can provide us with sound
strategic intelligence information on intent, but little or no tactical
level information: status of a bioweapons program of a specific
terrorist organization or the time and location of a planned attack.
I think we all understand that there are people and organizations
out there that want to kill large numbers of Americans. The WMD
Commission said there are two ways to do that, nuclear and biological,
and by far, biological is easier. If the senior leaders in the Congress
and administration understood the biological capabilities now
available--and even more troubling, what will be available in the next
couple of years--to small terrorist groups, there would be no
requirement for hearings such as these. Biodefense would be a top
priority, and we would be making rapid progress in defending our
cities, communities, and families.
I sometimes think the reason some leaders are hesitant to take the
recommended actions, is that they believe the problem is intractable-it
is so difficult and complex, that ``there is nothing we can do''. There
is no question that biodefense in the 21st century is difficult and
complex, but the fact is, there are actions we can take to remove
bioterrorism from the category of weapons of mass destruction (WMD).
We cannot realistically prevent bioterrorism, but if we develop
robust response capabilities, we will effectively remove bioterrorism
from the category of weapons of mass destruction. We will be able ``to
move the decimal point to left'' in that number from the November 2009
NSC report. We will not count casualties in the hundreds of thousands,
or tens of thousands, or even in the thousands. We can move the
casualty count down to the scale of what we lose on America's highway
on a 3-day weekend--most certainly it would still be a tragedy, but not
a WMD that would change the course of history.
The threat of bioterrorism will not diminish in the years ahead
unless we take the required actions to build a robust and nimble
resilience capability that includes:
--near real-time detection and diagnosis of disease outbreaks;
--situational awareness and effective communication of actionable
information, rapid development, and production of medical
countermeasures;
--timely countermeasure distribution and dispensing;
--surge medical care delivery to treat the sick and protect the well;
and
--environmental cleanup and remediation.
If Senators Bob Graham and Jim Talent were here today, they would
tell you that sufficient and continued funding in support of these
programs will not only lead us to a point where bioterrorism can be
removed from the category of WMD, it will also provide a deterrent
against attack, and just as importantly, that these are all ``no-regret
investments.'' Building a system that provides for rapid diagnosis of
disease, whether naturally occurring or manmade; better, faster, and
less expensive vaccines and therapeutics; and far greater capacity for
surge operations in our hospitals and clinics are the types of
investments we should be making for our children and grandchildren. On
that, we can all agree.
Last month the President recommended an initiative to improve our
system for developing MCMs. It is, perhaps, the single most important
factor for removing bioterrorism from the category of WMD, but to make
it work we need to understand that organizations responsible for this
new initiative--Health and Human Services/BARDA, National Institutes of
Health, and the Food and Drug Administration are now critical elements
of our national security community--no less important than the
Department of Defense, the IC, and the Federal Bureau of Investigation.
Mr. Chairman, the threat of bioterrorism is real and will only
increase over time. As Drs. Lederberg and Whitesides wrote back in
2001, there is no way to stop the biotechnical revolution that will
place ever-increasing asymmetric power in the hands of terrorists.
However, that same revolution in technology can be used by America to
remove bioterrorism from the category of WMD. The decision will be
yours.
I look forward to your questions.
Senator Harkin. Colonel Larsen, thank you very much. Very
stimulating presentation.
Dr. Rose.
STATEMENT OF ERIC A. ROSE, M.D., CHIEF EXECUTIVE
OFFICER AND CHAIRMAN, SIGA TECHNOLOGIES;
CO-CHAIR, ALLIANCE FOR BIOSECURITY,
WASHINGTON, DC
Dr. Rose. Mr. Chairman, Mr. Vice Chairman, I'm Eric Rose.
I'm the co-chair of the Alliance for Biosecurity and the CEO of
Siga Technologies. It's a pleasure to be with you today to
provide you with our impression of the HHS report on the PHEMCE
Enterprise review.
The Alliance for Biosecurity is a collaboration among
pharmaceutical and biotechnology companies that are focused on
biodefense countermeasures. My company, Siga Technologies, is
in late-stage development of a smallpox antiviral drug, and
therefore, I can give you a firsthand perspective of how well
our Federal Government is working with small, private-sector
biodefense companies like ours.
I've submitted written testimony for the record. At the
outset, I would like to make three simple points:
First, the BARDA Advanced Development Program is bearing
fruit. While many have criticized the perceived slow pace of
development of needed novel biodefense countermeasure, our
experience is that the Federal investment in biodefense is
generating important novel countermeasures less than 7 years
after BioShield enactment, and also just 4 years after the
creation of BARDA. And that, I think, you should take in a
context, that typical drug development now takes 10 to 15 years
for a new drug or vaccine. So, there is a trickle, but that
pipeline is beginning to flow. We, at Siga, are now producing
commercial-scale validation batches of our smallpox antiviral
drug candidate, which we hope will soon be added to the
strategic national stockpile.
Second, the administration's proposed enhancement of FDA
regulatory science innovation and capacity, along with
additional funding, is very welcome to our community. While the
FDA is not within the jurisdiction of this subcommittee, we do
want to note that we are particularly pleased with the emphasis
placed on the review on enhancing FDA's essential role.
Therefore, we strongly support the administration's August 20
budget amendment request to transfer available balances from
prior pandemic influenza appropriations to modernize FDA
regulatory science.
Third, full funding of the BioShield Strategic Reserve Fund
ensures that there is an oasis, and not a mirage, on the other
side of the valley of death of advanced development. And this
is absolutely critical to the success of small biotech
companies who rely on private investment to initiate product
development.
While we appreciate the need to find offsets for other new
spending in order to reduce the Federal budget deficit, I can
tell you that every time there is a proposal to transfer
unobligated balances out of the SRF for other purposes, it
sends shock waves through the private-sector companies involved
in this arena, and it shakes our investors' confidence that we
desperately rely upon to nurture these projects through the
early phases of development.
BARDA's rapidly growing advanced development pipeline is
indicative of the strong interest that small companies have in
biodefense. However, our success relies upon a reliable and a
committed customer. We share and support the overall goal of
the review, and the Alliance is thankful to have been consulted
by the ASPR, Dr. Nicky Lurie throughout the process. We are
particularly also pleased to see the review include plans for
HHS to increase transparency, communication, and predictability
within the contracting and procurement processes, and across
agencies. Further, we were encouraged that the review included
a commitment to develop a 5-year budget plan for the entire MCM
enterprise, expand the advanced development program, and
increase staff levels.
There are also some elements of concern to us. We were
disappointed that the review did not propose fully funding the
advanced development program that Colonel Larsen just referred
to--it's still grossly underfunded--nor outline a process for
restoring funding to the SRF beyond 2013, or otherwise
providing long-term and stable funding for the procurement of
MCM.
We support plans for the sustainability enterprise, but
caution that investments must be made up front in order to
guarantee success over the long term. In addition, to
reiterate, the SRF should not be depleted for other uses,
including proposals put forth in the review. For this reason
we're concerned that the administration's August 20 budget
amendment request included the transfer of $200 million to DOD
that you referred to, and we're delighted to hear your candid
and quick response.
And also, the $200 million transfer from the SRF to
establish a new countermeasures strategic investment firm.
We're supportive of a technical center of excellence, but, as
you've concluded, the transfer from DOD, we think, is just
wrong.
We think that an independent strategic investment firm for
innovation in MCM may have some merit, although little concrete
information has been provided to evaluate the value of this
initiative, and I think the whole nature of early stage
development of biological products, drugs, and vaccines is very
different from information technologies and electronics
technologies that are part of In-Q-Tel.
It seems highly misguided, however, to create a strategic
investment firm to incentivize entry into this space by de-
incentivizing private investment through depletion of the SRF.
That combination just does not make sense.
Particularly with the SRF, also, we were very pleased to
see the bipartisan effort on the part of 17 Senators, over the
summer, who wrote specifically to the Senate leadership about
the multiple--essentially to counter the multiple efforts to
raid the SRF, and we were very, very grateful for their
support.
PREPARED STATEMENT
Finally, we urge the subcommittee to work closely with the
administration to clarify, execute, and adequately fund the
programs needed to sustain the PHEMCE enterprise, and our
Alliance is committed to working with the Congress, the
administration, and others, of course, to make the
countermeasures enterprise a success.
We're very grateful for your attention and consideration,
and appreciate the invitation here.
[The statement follows:]
Prepared Statement of Eric A. Rose
summary
The Alliance for Biosecurity respectfully submits testimony to the
Senate Labor, Health and Human Services, and Education, and Related
Agencies Appropriations Subcommittee regarding the Department of Health
and Human Services' (HHS) report--Public Health Emergency Medical
Countermeasures Enterprise Review: Transforming the Enterprise to Meet
Long-Range National Needs (Countermeasure Enterprise Review) for the
``Defending Against Public Health Threats'' hearing on September 29,
2010.
We very much appreciate being invited to appear today before the
subcommittee to discuss this important report and thank you for the
consideration of our views. The Alliance for Biosecurity is a
collaboration among pharmaceutical and biotechnology companies that are
working in the public interest to improve prevention and treatment of
severe infectious diseases--particularly those diseases that present
global security challenges. The Alliance promotes a stronger, more
effective partnership between Government, the biopharmaceutical
industry, and other stakeholders in order to advance their shared goal
of developing critically needed medical countermeasures (MCMs).
Bioterrorism and emerging infectious diseases present an
extraordinary and potentially grave threat to public health and
national security. One of the most effective ways to improve our
national preparedness for these threats is through the development of
drugs, vaccines, and diagnostics, called MCMs, that can be distributed
in the event of an emergency. The Federal Government has a central role
to play in developing these MCMs and the Alliance stands ready to work
with the administration, Congress, industry, and other stakeholders in
our shared mission to identify, create, and obtain MCMs to protect
citizens against bioterrorist attacks and potentially destabilizing
emerging infectious diseases.
Positive Elements of the Countermeasure Enterprise Review
We share and support the goal of the Countermeasure Enterprise
Review, which is ``a modernized countermeasure production process where
we have more promising discoveries, more advanced development, more
robust manufacturing, better stockpiling, and more advanced
distribution practices.'' We support the intention of the Review and
look forward to working with the subcommittee and the administration to
further evaluate some of the initiatives included in the report as well
as other ideas that will help to sustain and further develop the
biodefense enterprise.
The Alliance is thankful to have been consulted by the Assistant
Secretary for Preparedness and Response, Dr. Nicole Lurie, throughout
the course of this important review. In addition to in-person meetings,
we submitted a White Paper on March 2, 2010, that incorporated a number
of core recommendations, including the need to (i) improve the
procurement and contracting process to more effectively promote
development of MCMs; (ii) improve the speed and efficiency of
regulatory interactions between private industry and the U.S.
Government; and (iii) improve coordination among the Food and Drug
Administration (FDA), Centers for Disease Control and Prevention,
Biomedical Advanced Research and Development Authority (BARDA), and
other relevant agencies around the development and approval of MCMs.
Therefore, the Alliance was particularly pleased to see the
Countermeasure Enterprise Review include plans for HHS to increase
transparency, communication, and predictability within the contracting
and procurement processes and across agencies. We hope that this
includes transparency regarding setting requirements and specific
information such as a target product profile as early as possible and
is publicly disclosing allowable requirement and population threat
analyses information.
Further, we were encouraged that the Review included a commitment
to develop a 5-year budget plan for the entire MCM enterprise, expand
the advanced development program, and increase staff levels. We welcome
these enhancements and feel strongly that the MCM enterprise and our
Nation's preparedness will benefit from increased communication,
development of a 5-year budget, continuity, and transparency. We hope
the administration will include such a coordinated long-range budget
plan as part of the 2012 President's budget.
The Alliance was also pleased with the emphasis placed on enhancing
FDA regulatory innovation, science, and capacity in the Review, as well
as the recognition of the importance of optimizing the legal and policy
framework for MCM oversight and approval. Therefore, we support the
administration's August 20 budget amendment request to make available
balances from prior pandemic influenza appropriations to modernize FDA
``regulatory science.'' We believe that this new approach to regulatory
science must focus on the agency's ``animal rule'' in order to make it
an effective mechanism for the approval of needed countermeasures in
the numerous instances where human testing of drugs and vaccines is
unfeasible and/or unethical. This focus requires the addition of
substantial manpower to the agency to meet the complex needs of this
space, and the training of regulatory personnel to facilitate their
understanding of the unique national security and public health issues
that chemical, biological, and nuclear threats represent.
Elements of Concern Regarding the Countermeasure Enterprise Review
The Alliance's March White Paper also included a core
recommendation to ``improve predictability and ensure the availability
of consistent, robust funding for the development of MCMs.'' Indeed,
this is essential to ensuring that the MCM enterprise is successful. We
were disappointed that the Countermeasure Enterprise Review did not
propose fully funding the advanced development program at BARDA, nor
outline a process for restoring funding to the Special Reserve Fund
(SRF) beyond 2013 or otherwise providing long-term and stable funding
for the procurement of MCMs. We support plans for the sustainability of
the Enterprise, but caution that investments must be made up front in
order to guarantee success over the long term.
As you know, in 2004, Congress--recognizing that the country was
relatively unprepared for the aftermath of an attack with CBRN agents--
passed the Project BioShield Act (Public Law 108-276), which
established the SRF. In the Project BioShield Act, Congress described
the purpose of the SRF as procuring products to ``treat, identify, or
prevent harm from any biological, chemical, radiological, or nuclear
agent that may cause a public health emergency affecting national
security.'' Congress appropriated $5.6 billion for this purpose in 2004
to remain available until 2013. Since that time several critical MCMs
have been purchased and stored in the Strategic National Stockpile with
SRF funds.
Predictability and availability of robust funding for the advanced
development and procurement of MCMs is one of the most important signs
to industry and to private investors that the Government is serious
about moving the MCM initiative forward. Although there are a number of
initiatives listed in the Review that may help the MCM enterprise in
the long term, there was little mentioned about immediate funding.
Since advanced development is the most expensive part of MCM
development, it must be funded at a higher level. In addition, the SRF
should not be depleted for other uses, including proposals put forth in
the Countermeasure Enterprise Review.
Private sector firms cannot invest in product development, which
requires 10 to 15 years and hundreds of millions of dollars, unless
they are reasonably certain that a market will exist for their product
when it is finished. The SRF serves as a concrete demonstration of the
Federal Government's commitment to procuring MCMs. Diminishing or
eliminating the SRF would call into question the credibility of that
commitment, and by doing so make it difficult for the private sector to
remain in the countermeasure business. While this would significantly
affect these companies and their employees, it would be a much larger
setback for the country as a whole.
For this reason, we are concerned that the administration's August
20 budget amendment request included the transfer of (i) $200 million
from the SRF to the Department of Defense (DOD) in order to establish a
Technical Center of Excellence for Advanced Development and
Manufacturing; and (ii) $200 million from the SRF to establish a new
MCM strategic investment firm.
Establishment of a ``Technical Center of Excellence'' for advanced
development and manufacturing of MCMs is a laudable goal. However, DOD
intends to dedicate significant funding to the development of platform
technologies and the advanced development and manufacturing of novel
countermeasures. We support this initiative but oppose transferring SRF
funds to support it. As previously stated, depleting the SRF now raises
a number of concerns. Any flexible manufacturing initiative should be
funded apart from the SRF with new resources, which do not compete with
funding for advanced development at BARDA. Lastly, it is important to
ensure that all existing manufacturing capacity is being effectively
and efficiently deployed before investing in the creation of new
capacity.
Likewise an independent strategic investment firm for innovation in
MCM, ``to provide necessary support for small innovators and increase
the odds of moving innovation into successful development'' may have
some merit although little concrete information has been provided to
evaluate the value of this initiative. It seems somewhat paradoxical,
however, to deplete the SRF--the primary signal of a Government market
for MCMs--in order to create a strategic investment firm to promote
innovation of MCMs. Such an action would send, at best, a confusing
signal to industry and private investors, and could have the impact of
discouraging further investment in MCMs under development.
Additionally, it is premature to transfer funds to create a new
investment firm when the administration has not decided on the model,
structure, or objectives of such a firm.
The Alliance urges the subcommittee to work closely with the
administration to clarify, execute an adequately fund the programs
needed to sustain the PHEMCE enterprise as the initiatives included in
the Countermeasure Enterprise Report are further developed and
implemented. The Alliance is committed to working with Congress, the
administration, and others to make the countermeasure enterprise a
success. We thank you for your attention and consideration.
Senator Harkin. Thank you very much, Dr. Rose.
And now we turn to Dr. Pavia.
Dr. Pavia.
STATEMENT OF ANDREW T. PAVIA, M.D., FAAP, FIDSA, CHIEF,
DIVISION OF PEDIATRIC INFECTIOUS DISEASES,
UNIVERSITY OF UTAH; CHAIR, INFECTIOUS
DISEASES SOCIETY OF AMERICA'S PANDEMIC
INFLUENZA TASK FORCE, SALT LAKE CITY, UTAH
Dr. Pavia. Senator Harkin, Senator Cochran, thank you very
much for this opportunity to speak to you on behalf of the
9,000 members of the Infectious Disease Society of America
(ISDA).
Unlike Colonel Larsen, I am an infectious disease
physician, a scientist, and a pediatrician--not much of a
pilot, but--I appreciate this opportunity to comment on the
matters before us.
IDSA commends Secretary Sebelius for undertaking the
comprehensive review of our MCM Enterprise. As a final report
makes abundantly clear, there are many components,
organizations, factors, and barriers that are vital to the
successful development of countermeasures, their deployment and
use. And, although it was intentionally left out of the review
because of its scope, investments in the U.S. public health
system at the Federal, State, and local level are urgently
needed.
The recent H1N1 pandemic demonstrated the importance of
being able to rapidly develop countermeasures--and these
include vaccines, antimicrobial drugs, and diagnostics--and the
importance that we be able to develop our responses to
biological threats, whether those be the ones that we
anticipate easily, such as pandemic influenza or anthrax, or
new and unrecognized threats. And an example that I want to
bring to your attention is the emergence of antimicrobial
resistance, whether it be influenza that's resistant to
Tamiflu, or bacteria that are resistant to all available
antibiotics.
There have been a number of recent reviews that have looked
at the MCM Enterprise, in addition to that done by the
Secretary. All have identified similar barriers and
opportunities for improvements. Many of these recommendations
mirror policy improvements that IDSA has suggested over the
past several years. We've put before you our reports from 2004
on ``Bad Bugs, No Drugs'' and on ``Pandemic Influenza''--
``Pandemic and Seasonal Influenza, Principles for Action,''
from 2007. Many of these recommendations will be critical if
they can be accomplished, but the proof is in their actual
implementation.
We're pleased that HHS is taking a comprehensive approach.
As you pointed out in your opening remarks, an effective
countermeasure system is one that doesn't focus on individual
agents, but that can flexibly respond to a variety of threats,
and do so quickly and efficiently, with good stewardship of our
resources.
We've recently experienced an influenza pandemic, which
was, thankfully, the mildest of the last 100 years. Part of why
it was mild was because of the investments that were made in
planning and preparation. We produced a vaccine in record time,
let's not forget, and yet, that still was not enough, and it
was not soon enough.
This was a mild pandemic, by all measures, but that means
that it only killed 9,000 to 18,000 Americans; it put some
300,000 in the hospital; it killed 1,200 children, some of whom
died in my hospital in front of my eyes.
So, a mild pandemic is still a major threat. A moderate or
severe pandemic is one that we have to be prepared for. And it
is indeed inevitable, as people have already mentioned. What we
don't know is when it will emerge and how severe it will be.
And what we have in our power to do something about is whether
or not we will be prepared for it.
The threat of antimicrobial resistance is, in fact,
intimately linked to the threat of pandemics and bioterrorism.
In influenza pandemics, people die of secondary bacterial
infections, not just of influenza virus; and in recent years,
Methicillin-resistant Staphylococcus aureus, or MRSA, has been
the major killer after influenza. Moreover, the antibiotic
resistance genes that are emerging naturally can fairly easily
be engineered into bioweapons, such as anthrax. And a
moderately competent graduate student can do it with a modicum
of funds and a decent laboratory.
Several factors have resulted in the dearth of new MCM in
development, and these include the lack of financial
incentives; insufficient risk-sharing, because of the high rate
of failure of new products; regulatory uncertainty;
insufficient federally supported research; and lack of
coordination across all components of the MCM measure, as
Colonel Larsen has mentioned.
To create sustainable MCM R&D, we have to determine the
right combination of financial incentives and risk-balancing
and -sharing that will allow industry to invest and to succeed.
The strategic investment firm envisioned by the MCM report is
one potential tool, and IDSA supports it. But, other mechanisms
are also needed. We caution, however, that the initial funding
level proposed for the strategic investment firm is unlikely to
result in useful countermeasures. Other funding and additional
mechanisms need to be integrated.
All reviews identify potential barriers from regulatory
uncertainty. FDA must develop clear and achievable regulatory
pathways for review and approval of new MCM. This will require
investment. While not the purview of this subcommittee, it's
critical that Congress fund the desperately needed improvements
in regulatory science and capacity for public health measures
at FDA.
The investments made over the past several years have
limited the impact of pandemic flu, but large gaps remain. IDSA
appreciates the generous funding that this subcommittee has
provided over recent years, as it did in the supplemental
appropriations bill. However, we strongly believe that
preparedness for influenza and other public health emergencies
requires a consistent and predictable stream of funding. We
support at least $1.7 billion in multiyear appropriations for
BARDA for fiscal year 2011 to fund the development of new
countermeasures.
We also recognize a need for a clinical-trials
infrastructure that will allow the further clinical development
of these MCM. Successful examples exist for HIV/AIDS and for
cancer. We need to learn from these examples that have been
successful, and integrate that into the MCM enterprise.
Improved management structure has already been mentioned.
It's featured in the Secretary's report. Some of the tools that
are laid out, including the early development teams at NIH and
the action teams proposed at FDA, are promising approaches, but
there does need to be coordinated leadership.
PREPARED STATEMENT
The danger posed to the United States by biological
threats, including pandemic influenza, biologic weapons,
emerging infections, is really very real and very great.
Continued thoughtful, efficient investment in the science, in
filling the pipeline, evaluating and licensing countermeasures,
and efficient management of the enterprise, will provide
Americans with the protection that they expect and deserve.
Thank you, and I'll be happy to answer any questions.
[The statement follows:]
Prepared Statement of Andrew T. Pavia
The Infectious Diseases Society of America (IDSA) appreciates this
opportunity to speak before the Senate Labor, Health and Human Services
(HHS), and Education, and Related Agencies Appropriations Subcommittee
as you examine our Nation's readiness and ability to deal with public
health threats, particularly through the development of countermeasures
to address biodefense, pandemic influenza, and emerging infectious
diseases. My name is Andrew Pavia, MD, FIDSA, FAAP. I am an infectious
diseases specialist and the George and Esther Gross Presidential
Professor and Chief of the Division of Pediatric Infectious Diseases at
the University of Utah. I am the chair of IDSA's Pandemic Influenza
Task Force. I am also a member of the National Biodefense Science
Board, which was created under the authority of the Pandemic and All-
Hazards Preparedness Act, to provide expert advice and guidance to the
HHS Secretary and the HHS Assistant Secretary for Preparedness and
Response (ASPR) to prepare for, and respond to, public health
emergencies resulting from chemical, biological, nuclear, and
radiological events, whether naturally occurring, accidental, or
deliberate.
IDSA represents more than 9,000 infectious diseases physicians and
scientists devoted to patient care, prevention, public health,
research, and education. Our members care for patients of all ages with
serious infections, including meningitis, pneumonia, tuberculosis (TB)
and HIV/AIDS, emerging infections like the 2009 H1N1 influenza virus,
food-borne diseases caused by salmonella, campylobacter, and
escherichia coli (E. coli), and diverse infections caused by
antimicrobial-resistant bacteria, such as methicillin-resistant
staphylococcus aureus (MRSA), enterococcus, E. coli, salmonella,
pseudomonas aeruginosa, klebsiella pneumoniae, acinetobacter baumannii,
and the newly emerging New Delhi metallo-beta-lactamase (NDM-1). NDM-1
is an enzyme that makes bacteria resistant to a broad range of
antibacterial drugs. It was first identified in December 2009 in a
patient hospitalized in New Delhi with an infection caused by
Klebsiella pneumoniae. It has since rapidly spread to other areas of
the world, and three cases recently have been reported in the United
States. IDSA's testimony will primarily focus on new medical
countermeasures essential to address pandemic influenza and
antimicrobial-resistant infections.
HHS' End-to-End Countermeasure Review
IDSA commends HHS Secretary Kathleen Sebelius and the
administration for undertaking the comprehensive end-to-end review of
our medical countermeasures enterprise. As the final report (The Public
Health Emergency Medical Countermeasure Enterprise Review: Transforming
the Enterprise to Meet Long Range National Needs), prepared by the
ASPR, Nicole Lurie, MD, MSPH and her staff, makes clear, there are many
components and organizations which are critical to the development,
deployment and use of medical countermeasures, including urgently
needed investments in the U.S. public health system. The goal of an
efficient and effective medical countermeasure enterprise is to be able
to rapidly produce effective responses, not only to known threats or
biologic attacks, but to previously unrecognized threats and emerging
infectious diseases.
We are pleased that the administration is taking a comprehensive
approach to developing a medical countermeasure strategy. Many of the
recommendations in HHS' end-to-end review mirror policy improvements
IDSA has suggested over the past several years, including in our 2004
report ``Bad Bugs, No Drugs: As Antibiotic Discovery Stagnates, a
Public Health Crisis Brews'', which called attention to the dry
antibacterial pipeline and the need for the U.S. Government to
financially support and incentivize the development of novel
antibacterial drugs. The administration's report also reflects several
recommendations found in IDSA's 2007 report, ``Pandemic and Seasonal
Influenza Principles for U.S. Action.'' In this report, IDSA
recommended that HHS and ASPR move quickly to:
--Strengthen pandemic vaccine efforts by establishing a Multinational
Pandemic Influenza Vaccine Master Program;
--Strengthen anti-infective pharmaceutical research and development
and stockpiling efforts;
--Improve quality and availability of diagnostic tools for influenza;
--Accelerate development of countermeasures to prevent, treat, and
diagnose pandemic influenza through additional legislative
action and continue to streamline regulatory approval
processes;
--Update plans for countermeasure distribution and prioritization of
use;
--Expand vaccine uptake, stabilize vaccine manufacture, and test and
evaluate vaccine distribution plans during annual influenza
seasons;
--Protect the healthcare workforce during a pandemic;
--Build national, regional, and local healthcare systems capable of
responding to mass casualty events;
--Develop and test community mitigation measures;
--Improve and coordinate influenza surveillance;
--Continue to strengthen leadership, international collaboration, and
communication; and
--Allocate significant and sustainable funding for long-term planning
and action.
The implementation of these policy improvements is essential to
reduce the threat Americans and the world community faces from the
public health threats of greatest concern. Copies of IDSA's Bad Bugs,
No Drugs report and the Pandemic and Seasonal Influenza Principles for
U.S. Action document are available through IDSA's Web site at: http://
www.idsociety.org/10x20.htm and http://www.idsociety.org/influenza.htm.
Additionally, IDSA is hosting a meeting on January 27-28, 2011,
``Seasonal and Pandemic Influenza 2011'', where the influenza
principles will be reviewed and further updated to include lessons
learned from the novel H1N1 influenza pandemic, with a focus on
specific actions and timelines.
Pandemic Influenza and Antimicrobial Resistance
Infectious diseases and public health experts believe that another
influenza pandemic is inevitable. The key questions that remain are
when it will occur, which influenza virus will cause the pandemic, how
severe it will be, and whether the world will be ready. Experts also
are extremely concerned about the growing threat of antimicrobial-
resistant infections. The need for novel products (drugs, diagnostics,
and vaccines) to address these threats is urgent.
There are three types of influenza viruses, classified as A, B, or
C, based on their protein composition. Public health experts are most
concerned with type A influenza virus. Pandemic influenza typically is
a virulent new strain of human influenza that causes a global outbreak
of serious illness. Four influenza pandemics have occurred during the
past 100 years: the 1918-1919 ``Spanish flu,'' the 1957-1958 ``Asian
flu,'' the 1968-69 pandemic or ``Hong Kong flu'' and the H1N1 pandemic
from 2009-2010. The 2009 H1N1 influenza pandemic proved to be the
mildest of these in overall deaths, killing an estimated 9,000 to
18,000 Americans according to CDC estimates. The virus did not develop
resistance to oseltamivir (Tamiflu), the only widely available
antiviral to treat influenza. Focusing solely on the number of deaths,
however, masks the overall impact of the H1N1 pandemic. More than 1,200
children younger than 18 died of H1N1 influenza and between 200,000 and
400,000 Americans were hospitalized.
The 2009 H1N1 influenza pandemic was perhaps a best case scenario.
If a pandemic similar in virulence to the 1918 influenza strain were to
occur, up to 2 million Americans could die and the number of
hospitalizations and need for intensive care unit beds would overwhelm
our healthcare system and cripple our infrastructure.
On the issue of antimicrobial-resistant infections, the CDC has
described antimicrobial resistance as ``one of the world's most
pressing health problems'', while the World Health Organization (WHO)
calls it ``one of the three greatest threats to human health.''
Infectious diseases physicians agree. NDM-1, for example, poses a new
threat of great concern and illustrates how antimicrobial-resistant
infections will continue to emerge wherever antimicrobial drugs are
used. NDM-1 also illustrates how a drug-resistant organism created in
one area of the world can quickly threaten all regions. The costs due
to antimicrobial resistance, both in the numbers of lives lost or
devastated and in economic terms, are exceedingly high. Drug-resistant
bacteria, such as MRSA-resistant E. coli, Acinetobacter baumannii and
Clostridium difficile (c. diff.) currently affect many hospitalized
patients and a growing number of people in the community, including
healthy athletes, parents, working people, and children. CDC reports
that nearly 2 million healthcare-associated infections (HAIs) and
90,000 HAI-related deaths occur annually in the United States. Most of
these infections and deaths involve antimicrobial-resistant bacteria.
The direct and indirect economic costs associated with antimicrobial-
resistant infections are also enormous in terms of dollars spent,
length of hospital stay, and loss of productivity. A recent study
indicated that annually in the U.S. antimicrobial-resistant infections
are responsible for more than $20 billion in excess healthcare costs,
more than $35 billion in societal costs, and more than 8 million
additional hospital days. Antimicrobial resistance is a critical issue
in viral diseases as well. In 2008, the dominant circulating seasonal
influenza strain had become resistant to oseltamivir (Tamiflu) leaving
limited options for treatment. For now, this strain has largely
disappeared, but if it re-emerges we have few drugs in the pipeline to
deal with the threat.
There also is an alarming connection between influenza and
antimicrobial-resistant bacterial infections. In addition to the
morbidity and mortality caused by the influenza virus itself, many
people with influenza will develop life-threatening secondary bacterial
infections, many of which are resistant to antibacterial drugs. In
recent years, MRSA has been the most lethal cause of postinfluenza
bacterial infections.
Re-engineering the Pandemic Influenza Vaccine Production Enterprise
As we stated in our 2007 Pandemic and Seasonal Influenza Principles
for U.S. Action, IDSA believes the widespread use of a pandemic vaccine
should be the central strategy for protection of human health during a
pandemic event. IDSA supports a coordinated effort led by the Federal
Government working with public and private partners and the
international community to outline a comprehensive approach that will
coordinate, and strengthen vaccine research and development, increase
production capacity, accelerate licensure, guarantee equitable global
distribution, and monitor vaccine performance and safety.
In August 2010, the President's Council of Advisors on Science and
Technology (PCAST) issued a report focused on re-engineering the
pandemic influenza vaccine production enterprise. In its report, the
PCAST emphasized that existing technology for influenza vaccine will
never deliver enough vaccine in time to respond to a pandemic. However,
they said that targeted investments in key areas could shorten by weeks
the time needed to produce enough doses. They found that the
development of new types of influenza vaccines is of critical
importance, and no single new technology has a high likelihood of
success. To ensure success of one, we must pursue several potential
vaccine strategies simultaneously. The PCAST recommendations provide a
blueprint to significantly increase our Nation's ability to produce
vaccine in a timely manner. The recommendations would speed up not only
flu vaccines, but also a number of other medical countermeasures
against infectious diseases that could emerge naturally or as the
result of a bioterrorism attack.
Although the PCAST did not determine anticipated costs for the
projects required to make the improvements necessary to re-engineer the
influenza vaccine production enterprise and has not attempted to
allocate the share of financial responsibility to be borne by the
governmental agencies or the companies, they did state that it is fair
to assume an initial $1 billion in Federal funds--and at least similar
sums over the subsequent few years--would be required to make the
changes that will allow the Nation to mount a vigorous effort that can
protect its population as well as possible in the event of another
pandemic, an event that could have catastrophic consequences.
On-going strong investment in pandemic vaccine technologies is
justified on a cost-benefit basis, in part because large numbers of
lives could be saved through relatively inexpensive improvements in
current methodologies and in part because Federal investments in
influenza pandemic response would speed development of technical
platforms and production facilities that would support medical
countermeasures against a variety of other dangerous pathogens.
Antimicrobial and Diagnostics Discovery and Development
The development of both antiviral and antibacterial drugs as well
as point-of-care diagnostics must be treated as priorities in the U.S.
medical countermeasure development strategy. In IDSA's view, there is
an urgent need to address the factors that have resulted in a dearth of
new antimicrobials and other countermeasures in development. These
include:
--Lack of financial incentives of sufficient strength to make
companies choose to engage;
--Regulatory uncertainty caused by the lack of consistent approval
pathways and limited regulatory scientific resources at the
Food and Drug Administration (FDA);
--Insufficient federally supported research and development efforts;
and
--Lack of a coordinated management structure.
In addition, as pointed out in the end-to-end medical
countermeasure review, lack of coordination between Federal agencies
and complex contracting regulations add additional barriers.
To create a sustainable, national and global medical
countermeasures R&D enterprise, it is necessary to determine the right
combination of financial incentives (``push'' and ``pull'' mechanisms)
to entice industry to invest and to help companies, big and small, with
innovative technology to succeed. Examples of the push incentives are
grants, contracts, and tax credits. Examples of the pull incentives are
milestone payments, guaranteed markets, liability protection, patent
extensions or data exclusivity, and prizes. These incentives are
intended to change the ``return on investment'' or net present value
calculation of countermeasures to make them more competitive with other
medical products. The strategic investment firm envisioned by the
medical countermeasure review report also supports the development of
high-priority products by sharing the risk of development with
companies. The HHS report highlights the need for the strategic
investment firm to first focus on novel antimicrobials to address drug-
resistant infections. IDSA wholeheartedly supports this effort. We
caution, however, that the proposed initial funding level for the
strategic investment firm is $200 million, which is wholly insufficient
to increase the likelihood of bringing successful antimicrobial drugs
and other medical countermeasures to the marketplace. We also strongly
believe that additional ``push'' and ``pull'' incentives are needed,
particularly to address the withering antibacterial pipeline, and urge
Congress to act quickly to pass strong legislation in this area. Risk
sharing and incentives that stimulate the development of new rapid
diagnostics also should be adopted.
FDA must quickly assure a clear regulatory pathway for the review
and approval of new countermeasures. For many years, industry
representatives have identified regulatory uncertainty as one of the
primary obstacles to new antibacterial development, in particular. IDSA
acknowledges the strong commitment expressed by current FDA leaders and
staff to address the multi-faceted problem of regulatory uncertainty.
Despite good faith meetings, workshops, and advisory committee
meetings, the situation today for antibacterial review and approval
appears no better than it was at this time last year. In some respects,
the level of uncertainty has increased. In its medical countermeasure
review report, HHS identified a critical need to upgrade FDA science
and regulatory capacity. HHS hopes to make a significant investment to
provide FDA scientists with the resources they need to develop faster
ways to analyze promising new discoveries and give innovators a clear
regulatory pathway to bring their products to market. This year, IDSA,
FDA, the National Institute of Allergy and Infectious Diseases (NIAID),
and pharmaceutical companies have begun to participate in an important
effort being led by the Foundation of the National Institutes of Health
(FNIH) to study new endpoints that will more easily demonstrate
antibacterial effectiveness. The FNIH effort is promising, but to
develop this knowledge and quickly implement changes in the regulatory
process requires people and money. This spring, IDSA testified in
support of additional funding to allow FDA to hire additional staff to
develop much needed clinical trial guidance documents and to fund
Critical Path Initiatives specific to antimicrobial drug development.
We also requested $13.25 million to support a focus on new antibiotics
within FDA's new regulatory science initiative with the National
Institutes of Health.
We recognize the strains on the Federal budget due to the economic
crisis and the budget deficit, but significantly increased Federal
research dollars are urgently needed to advance scientific knowledge
about pandemic influenza and antimicrobial resistance, as well as to
support countermeasure discovery and development. IDSA has for the past
several years supported consistently strong funding for these
activities throughout HHS. We appreciate that this subcommittee has
provided substantial funding for pandemic influenza response, as it did
last year in the supplemental appropriations bill. However, IDSA
strongly believes that some pandemic preparedness efforts require
funding over multiple years. For example, companies considering
investing in countermeasures development need assurance that the
financial commitment will be secure in future years or they will not
engage.
We strongly support significantly boosting funding for HHS'
Biomedical Advanced Research and Development Authority (BARDA). This
year, IDSA testified in support of at least $1.7 billion of multi-year
appropriations for BARDA in fiscal year 2011 to fund the development of
new therapeutics, diagnostics, vaccines, and other technologies,
including antimicrobials. Such funding would significantly enhance
BARDA's support of countermeasures through the advanced stages of
development, as well as BARDA's flexibility to partner effectively with
industry. IDSA also wishes to see BARDA take a much stronger role in
advancing the development of new antimicrobials and related diagnostics
to detect, identify, and treat pathogens that presently are affecting a
significant number of Americans in hospitals annually. With modern
molecular biology techniques, the resistance genes found in these
highly resistant ``superbugs'' can be readily introduced into
bioweapons such as anthrax or tularemia. Specific to NIAID research
funding for antibacterial resistance and antibacterial discovery
research, this year IDSA testified in support of a substantial funding
increase in these areas for fiscal year 2011 to a total of $500
million. Current NIAID funding levels in these areas are extremely
limited in IDSA's view and do not match the threats we face from
antibacterial-resistant infections.
Moreover, to further strengthen the countermeasures pipeline, we
must invest in appropriate infrastructure for clinical trials. Such
clinical trials infrastructure should be flexible and agile, with the
ability to rapidly respond to new or re-emerging infections as they
arise. Further, it must balance both pediatric and adult unmet
infectious diseases needs. We are gratified to see NIAID taking steps
to achieve part of this goal, as NIAID is broadening its AIDS Clinical
Trials Group (ACTG) to expand its tuberculosis and, likely, its
hepatitis C clinical research portfolios. Earlier this year, IDSA urged
NIAID to build clinical trials infrastructure in areas beyond HIV/AIDS
including to address serious bacterial, viral (particularly influenza),
and fungal infections. The creation of an NIAID-funded in-patient
clinical trials network in these areas will help to create an
environment supportive of high-quality research, incorporating
experienced investigators and study sites, robust statistical support,
specialized laboratories (e.g., pharmacokinetics, immunology) and
organizational structures to support clinical trials. Such additional
clinical trials infrastructure could contribute substantially to the
critical need for advancements in the diagnosis and treatment of drug-
resistant bacterial infections, pandemic and seasonal influenza, and
other serious infections. Furthermore, the clinical trial
infrastructure we have proposed fits squarely within and is supportive
of HHS' medical countermeasure review effort. IDSA believes such
additional infrastructure is urgently needed.
The global H1N1 pandemic is a striking reminder of the importance
of making sustained investments in research as well as public health
infrastructure. Investments made over the past several years in
surveillance, vaccine capacity and preparedness clearly limited the
impact of the H1N1 pandemic. However, in other areas the pandemic
showed our continued vulnerabilities. These include early international
detection, and rapid production and distribution of vaccines, and
antivirals that are appropriate for critically ill patients. The threat
of another pandemic remains. The Nation's public health system must
maintain robust disease surveillance, epidemiologic investigation,
education and outreach, and communications capacity.
Strengthening Leadership, Coordination, and Management Structure
In 2007, IDSA called for strengthened leadership and collaboration
in influenza preparedness. We called for HHS and the Federal Government
to clarify lines of authority and key responsibilities, involve
technical experts and stakeholders, issue and update national standards
for planning, and continue to lead international collaborative efforts
related to pandemic preparedness. HHS responded and many improvements
were considered and implemented. The PCAST report recommends that the
administration further strengthen its management structure by vesting
authority with the ASPR at HHS to coordinate and task component
agencies at HHS with supporting and implementing the influenza vaccine
recommendations. In addition, it recommends that HHS create a small
advisory committee comprised of representatives from the biotechnology,
pharmaceutical and investment communities, to guide the HHS's
engagement with industry. This coincides with the recommendation in
HHS's end-to-end medical countermeasure review that changes are needed
in how the enterprise is managed to greatly strengthen its
decisionmaking. The review suggests that HHS identify a leader who
would work with program leaders and managers across the span of medical
countermeasure development activities as well as with commercial
partners and other key stakeholders. The congruence of these three
recommendations emphasizes the critical role of integrated and
coordinated planning between all levels of government in pandemic
preparedness and medical countermeasure development.
Having the necessary infrastructure in place to both monitor and
respond to current and emerging antimicrobial-resistant infections also
will play a crucial role in ensuring that we are protecting the health
and safety of our citizens. Congress began to address this need several
years ago when it passed legislation that became section 319E,
``Combating Antimicrobial Resistance'' of the Public Health Service
Act. This law directed the Secretary to establish an Antimicrobial
Resistance Task Force to coordinate Federal programs relating to
antimicrobial resistance. This Task Force developed the Public Health
Service Action Plan to Combat Antimicrobial Resistance, published in
2001, which has not been sufficiently funded. Comprehensive legislation
introduced in the Senate during the last Congress and in the House of
Representatives in each of the last two Congresses, the Strategies to
Address Antimicrobial Resistance (STAAR) Act (H.R. 2400 in the 111th
Congress), will advance the key elements in the Federal Action Plan and
authorize adequate funding for these strategies. The STAAR Act
strengthens existing efforts by establishing within HHS an
Antimicrobial Resistance Office (ARO). The director of this new office
also will serve as the director of the existing interagency task force
to facilitate the coordination of activities. The legislation also
would establish a Public Health Antimicrobial Advisory Board comprised
of infectious diseases and public health experts who will provide much-
needed advice to the ARO director and interagency task force.
Finally, the bill, when enacted and sufficiently funded, will
strengthen existing surveillance, data collection, and research
activities as a means to reduce the inappropriate use of
antimicrobials, develop and test new interventions to limit the spread
of resistant organisms, and create new tools to detect, prevent, and
treat drug-resistant ``bad bugs.''
Conclusion
It is easy to dismiss hyperbolic news reports because of
sensationalism and inaccuracies, but the danger posed to the United
States by biological threats, including pandemic influenza, biologic
weapons and emerging infections, including antimicrobial-resistant
infections, is very real and very great. Continued thoughtful
investment in science, filling the pipeline, evaluating and licensing
countermeasures and efficient management of the enterprise will provide
Americans with the protection they expect and deserve. IDSA stands
ready to assist this subcommittee and the Federal Government in any way
that we can, and we are grateful for this opportunity to express our
views.
Thank you.
Senator Harkin. Thank you again, Dr. Pavia.
And thank all of you for your testimonies, and for your
work in this field, and your leadership in this field.
Colonel Larsen, is anthrax the major threat that we have
that we should be worried about with regard to bioterrorism? Is
it anthrax, or is it something maybe we don't know about?
Colonel Larsen. That's a very good question. It's very
difficult to answer. I worry about anthrax. It's the only one
that's really persistent.
Senator Harkin. Because what you just told me----
Colonel Larsen. We're going to have a hard time cleaning it
up. We don't know how to----
Senator Harkin [continuing]. About four decades, then----
Colonel Larsen. We don't know how to do it.
Senator Harkin. Yes.
Colonel Larsen. It's deadly. But, it's not contagious. You
know, Eric may tell you smallpox is the worst one, because--
I've run exercises that--with Senator Nunn, several years ago,
looking at smallpox. The fact that it's contagious, we're a
highly mobile society, unvaccinated; that is.
April, I was up in J. Craig Ventner Institute, and they
were showing me some of the amazing things they were doing up
there just a month before they announced that--you know, a new
organism that had a computer for a parent. I'm not worried
about people in caves doing that now. Those are the best
scientists in the world at the best laboratory. But, 5 years
from now? And the decisions you're going to make, in this next
year, are going to tell us what kind of defense we have in 5
years. So, I would feel--I would sleep better tonight if I know
we were ready for 1960-style bio-attacks, which is anthrax. Or
plague.
Senator Harkin. You can see that--obviously, the problem
that confronts us is, there are a lot of threats out there.
And, you know, you can't have 100 percent protection against
everything. I mean, you just--it's impossible. So, we have to
sort of think about what are the priority areas, knowing full
well that we can't guarantee absolute, 100-percent protection
against anything. But, we can try to lessen the possibility of
a bioterrorist attack. We can lessen that, but we can't
completely do away with it. And then we can do what we can to
build up our responses to it. That's what you're talking about:
how we respond to that.
Colonel Larsen. I'll go back to what I call my bible, what
Dr. Josh Lederberg, Nobel Prize winner, was talking about,
``Bug to Drug in 24 Hours.'' When he wrote that, in 2001, that
was science fiction. That does not have to remain science
fiction.
You know, when H1N1 was discovered in southern California,
within 2 weeks they did genetic mapping and had an antiviral
that was better than Tamiflu. In 2 weeks. That's a lot of
progress we've made in the last decade.
So, we can't build vaccines for everything that's out
there, you're absolutely right. But, we've got to figure out
how to respond quickly, and make vaccines and therapeutics a
lot faster, which is why--the one little statement I left out
here is, when it comes to national security, today the FDA,
NIH, and BARDA are just as important as DOD and the
intelligence community. And we need to understand that, and
fund them appropriately.
Senator Harkin. Yes. I----
Colonel Larsen. Because the funding you're going to approve
now is what kind of defense my kids and grandkids are going to
have 5, 10 years from now, sir.
Senator Harkin. Well, I agree with that. I--you know, we've
tried to get BARDA going, and now we've got this. And I'm still
wrestling with who's in charge.
Now--you said that, too, but who do you think should be in
charge?
Colonel Larsen. I'll give you two answers. Because I work
very closely with Senator Graham and Talent. They wrote a
letter to President Obama, and they said, ``This is so
important that the Vice President of the United States should
be in charge of all WMD activities here.''
I mentioned that in a hearing at the Judiciary Committee
last month, and Senator Kyl said, ``Well, you know, the Vice
President's a pretty busy guy.''
I said, ``I know that, but tell me one thing more important
than defending America against weapons of mass destruction.''
He's the only person that can look--because there are so
many Cabinet Secretaries involved in this enterprise of
biodefense--he's the only person in this town--other than the
President, and he is kind of busy--he's the only person that
can look at Cabinet Secretaries and say, ``Do this,'' and they
say, ``Yes, sir.'' Now, that's going a long way. He'd need more
of a staff. That's Senator Graham and Senator Talent's answer,
I thought I'd give you that, because they've written that
several times.
I would just like to see a special assistant for biodefense
in the White House. We had that in the Clinton administration,
we had that in the Bush administration. We don't have that
today. There is no special assistant to the President for
biodefense. That would be a good start. I'd be happy with that.
Somebody to coordinate that interagency community.
So, somewhere between Senator Graham and Senator Talent
saying the Vice President, and my recommendation is at least a
special assistant to the President.
Senator Harkin. And was it special assistant for
bioterrorism?
Colonel Larsen. For biodefense, yes, sir.
Senator Harkin. Oh, biodefense.
Colonel Larsen. Yes, sir. That was Dr. Ken Bernard, back in
the Clinton administration; Dr. Bob Kadlec, in the Bush
administration. That position doesn't exist today.
Senator Harkin. Okay.
For all three of you, I have been in this subcommittee
personally involved in trying to really promote cell-based and
recombinant-based vaccine production. Well, I get frustrated at
the slow pace of this, but I think things--they do take time.
I'll just ask you. How do you feel--all three of you--feel
about the state of our--right now, and where we are, in terms
of moving to cell-based and recombinant-based vaccine
production? Are we dragging our heels? Are we on track, sort
of? Could we be faster? How about this idea that cell-based are
licensed in Europe but not in the United States?
So, Dr. Rose, go ahead.
Dr. Rose. Yes. Sure. I think there's a disconnect between
the pace of advancement of the technology, which is rapid, and
the regulatory response to that technology, which I think has
been relatively slow. And I think that pace is quickening.
I visited a company in Israel, earlier this year, that has
portable, disposable bioreactors, using carrot cells and
tobacco cells, where they're making biological drugs in these
kinds of incubators, at cost that's about one-tenth the
production costs of similar agents made in mammalian cells.
The particular advantage, too, is that mammalian viruses,
animal viruses, don't contaminate vegetable cells. So, there's
a safety advantage to it. But, when the regulators look at
this, they still look at it from the perspective of safety
issues with regard to animal cells.
And the other issue is just with regard to safety, the
necessary clinical trials. Protein Sciences firm was alluded to
earlier by Secretary Sebelius. They've developed an insect-
cell-based flu vaccine that actually was rejected by a panel
when it was presented for use in seasonal flu, on the argument
that the several thousand patients in which it had been tested,
without a safety problem, was just simply not enough to reach
that conclusion. And I think--you know, licensure there, I
think, arguably, would have sped up, for the next flu pandemic,
the availability of the insect cell base, because it would have
allowed it to establish itself that much earlier, commercially.
Senator Harkin. Dr. Pavia?
Dr. Pavia. Yes. So, I would agree with the points that Dr.
Rose made about regulatory and clinical trials being a holdup.
There's also scientific hurdles that emerge. One recombinant
technology or another may sound terrific when it's first
demonstrated as a proof of concept. But, attempts to scale up
sometimes lead to antigen that doesn't work as well, difficulty
with contamination, so that when we go after one candidate, it
doesn't always deliver on the promise. Just like in drugs,
there's a high failure rate.
The other issues that we haven't really talked about are
the economics. Influenza vaccine, while not perfect, and slow
for seasonal use, is produced relatively efficiently. It's
inexpensive. The capital investment to bring some of these new
technologies to market is very large. The cost of a dose of
vaccine with the new technologies is going to be higher. And
the incentive hasn't always been there to bring out a somewhat
improved influenza vaccine that's going to cost more, when the
demand isn't clear, much as we need it for more rapid response
and for pandemic capacity.
Senator Harkin. Colonel Larsen.
Colonel Larsen. Sir, you've heard from two scientists. All
I can say is, the chief scientist at the WMD Commission last
October was 8 months pregnant, and in the State of Maryland,
she could not get an H1N1 vaccine, even though she was in the
highest risk group. So, from my perspective, we are not where
we need to be, sir.
Senator Harkin. Why aren't they licensed here? I'm sorry, I
should--why--what's the problem with licensure here? Someone--
--
Dr. Pavia. One would hear, you know, this perhaps more
clearly from the FDA, but when you produce a new vaccine in a
new technology, it usually requires a different way to measure
its potency. There are unanswered questions about the best way
to prove safety. And we just don't know what measures need to
be taken to look at the safety of something produced in insect
cells. And so, these regulatory hurdles in the United States
are set higher, perhaps for good reasons. But, FDA has not been
able to respond to these as quickly as they should, and in
part, as was pointed out in Secretary Sebelius's review, they
lack some of the scientific basis for making these decisions
right now.
Senator Harkin. I'll think about that.
Senator Cochran.
Senator Cochran. Mr. Rose, in your testimony you mention
that the Alliance for Biosecurity has been recommending to the
ASPR to improve predictability and assure availability of
funding for the development of MCM. What would be the impact of
the successful development of such a--an entity if a stable
funding stream is not provided by the Federal Government?
Dr. Rose. Right now, there's no question that the free
market is not enough of an incentive, or a funder, provider of
either capital for starting up, or funds for advanced
development, for companies to advance products in this space. I
think BARDA is a splendid and very effective addition, but
getting it started--it's not easy to spend $400 million a year
on advanced development, and do it wisely. But, the--BARDA has
a terrific leader, the size of the agency has grown
exponentially in just the last few years, and the size of its
research portfolio has increased dramatically.
I think you shouldn't underestimate the quality of the work
that you've already done to put this in motion. But, the nature
of this is such that making a new antiviral drug or a new
vaccine is not something that happens on a timeframe of weeks
and even years. It's a multiyear process that requires the
underlying science to be handled, the creation of new chemical
entities--be they proteins, vaccines, small molecules, and the
like--that target new targets that are abundant now, that have
been identified with basic research at institutes like the
NIAID. Then it requires setting up a manufacturing capability
and clinical trials to document effectiveness, or not. And in
the case of agents against things like smallpox and anthrax,
you can't do human efficacy testing, because it's not ethical
and it's not practical.
So, it is very, very complicated, complex, long-leadtime
work. And you've already, I think, had the good judgment to
fund it. I think, repeatedly, we see that people want to pull
the plug, thinking there's something wrong with this process
because you're not seeing, you know, drugs for Ebola, drugs for
some of the hemorrhagic fevers, and some of the newer vaccines,
that you want to see. But, they're coming. And they're a lot
further along than they were just a couple of years ago,
because of this mechanism. And, if anything, I'd say, stay the
course in that regard.
Senator Cochran. Thank you very much for that analysis.
Dr. Pavia, in your statement you mentioned the use of
pandemic vaccine in a widespread way should be the central
strategy, as I understood, it for the protection of human
health during a pandemic. Do you think the Federal Government
needs to be the lead on this, or should we create some other
body to be in charge?
Dr. Pavia. Senator, I think that--it's very clear that, in
a severe pandemic, we would need to be able to vaccinate
everyone in a rapid fashion, and that would require a very
large manufacturing capacity, as well as the platforms, the new
techniques that would produce the vaccine quickly enough. I
don't think that, at present, market forces will either deliver
a manufacturing capacity that would make 300 to 600 million
doses available a year, nor is it clear that it--that, all by
themselves, they will allow the development of these new
technologies. So, I think there's a vital role that the Federal
Government has to play in facilitating both the science that
will allow new products to be developed, and then nurturing
them along.
And, at the other end, I think the Federal Government has a
role in providing enough manufacturing capacity on U.S. soil
that we're not dependent on foreign manufacturers in the event
of an emergency. And you've already made investments in this.
And you should realize that the investment in egg-based
manufacturing, in Pennsylvania, paid off in a large way.
Without that, most of the domestic production that we had
during this last pandemic wouldn't have occurred. And two of
the foreign manufacturers with whom the Government contracted
did not deliver the full amount of vaccine that they contracted
for.
Senator Cochran. Colonel Larsen, what is your reaction to
that question?
Colonel Larsen. Well, sir, I--you know, I'm pretty
conservative on the fiscal side, being a fourth-generation
Indiana corn farmer, and--but, I tell you, how many B-2 bombers
would we have built if we had relied on the private-sector
free-market economy? There are certain things that are so
important for national security that that's what we have to do
up here. And I think we have to rely on the talent and the
brainpower and some of the creativity, but this is a national
security issue. We would never have built a single B-2 bomber
if we'd a just told those companies, ``Well, you can just go
out and do it all on your own, and if you get something the FAA
approves and the Air Force likes, then we'll give you your
first dollar.''
So, this--I mean, that's my point--this is a national
security issue. That's how I see it.
Senator Cochran. Well, thank you.
I think this was a very worthwhile hearing, and your
contributions have been very helpful. And I think we'll--I
hope--have some influence as we go about making the decisions
on priorities for funding and carrying out our duty to help
protect the security interests and the health of our American
public.
Thank you.
Senator Harkin. I would also say thank you to the panel,
and again for all the work that you do and the leadership you
provide.
I was reading your testimonies last night, and then
following you today, and then--I just--I can't help but think
that it's not streamlined enough, in terms of who's in charge,
and who does what, and who reports to whom, and who gets the
finances to do this. Kind of a mishmash of things. And, quite
frankly, I just--I think we're relying too much on the FDA.
Now, before all the press runs out of here and say,
``Harkin wants to diss the FDA''--we're about to pass a new
food safety bill. It's got great bipartisan support. It's being
held up a little bit, but it's going to pass. It's got industry
support and consumer support, and everybody, and it's long
overdue. We haven't done--had a food--a change in our
inspection systems--it's been over three decades. But, that job
goes--a lot of that goes--to FDA. It's not agriculture, it's
FDA. So, we're going to ask them to do more.
And we're not going to give them the funds or the personnel
to do that. It's--you know, we'll give them a little bit,
maybe, but not much. And it just seems to me, FDA's got so much
on their plate that they really can't give this the kind of
focus that it should.
So, I'm just--I'm just thinking out loud here--is it FDA,
or do we need to take something out of the FDA, something,
maybe, out of DOD, that would be put under BARDA, and let BARDA
be the one, the lead agency? At least that's what I thought the
concept was of BARDA, that they would be the lead agency,
working with scientists, manufacturers, people like the
colonel, and others, that think about all these things. And
then they would then have line-item authority, in terms of
looking at licensure, which I'm--still don't understand why we
can't get over that, why we can't have it faster--and doing
some of the things that FDA now is charged with the
responsibility of doing. Because FDA just--institutionally, I
don't know that they can do it. It's just--because they've got
so much to do, and they have other responsibilities, and mostly
they're focused on drugs that we take; you know, drug
development for new drugs for illnesses and things like that.
This is not the biggest thing on their plate. But, in terms of
the country itself, it's probably one of the biggest things
we've got confronting us right now.
So, I don't know, I just keep thinking that we need some
restructuring here--not for restructuring's sake, but to make
it more efficient, to make the line items--make the line
authority better, and to speed up some of the things that we
have to--we just have to speed these things up faster than what
we're doing.
So, I don't mean to just pick on FDA, but just recognizing
the reality that FDA simply can't do all the things we're
asking them to do. They just can't do it. And that's why, I
thought, we set up BARDA.
And so, I will be looking at that, both from the standpoint
of this subcommittee, but also the authorizing committee, in
the next reauthorization bill that comes up. When is that? Aha,
next year.
Senator Harkin. So, next year we'll look at the
reauthorization, because I just--I think now's time to take
stock and think, on the reauthorization, do we need to do some
realignment here? And I'll take into consideration the Vice
President. I never thought about that, the--maybe we don't
think about the Vice President that much. I mean, you know--
what's that old saw about----
Senator Cochran. I don't think I'm going to get into this.
Senator Harkin [continuing]. Some guy said that--he had two
sons--one went off to the South Pacific, and the other became
Vice President, and neither was heard from again.
Dr. Rose. Can I comment on the FDA?
Senator Harkin. Yes.
Dr. Rose. Because I think that your comments are thoughtful
and important, and where we are now is not working. But, I
think that the proposal that HHS is making now is a very
substantive and important change that they're proposing,
particularly the funding issue.
I mean, what we see, in our interactions with the FDA, is,
they're just quite short-handed, and their ability to respond
to real-time science is hampered by their lack of manpower.
This whole issue of regulatory science, I think, is an
important issue, but I think there's also an issue of
regulatory culture, because there are some things--particularly
if you're using things like the animal rule--the level of proof
of efficacy of a drug for a measure that you can't test in
humans is just not going to be the same standard of certainty.
That doesn't mean you can't make a judgment based on a body of
evidence. But, I think there's an enormous reluctance to
recognize the limitations and still act. And that culture
change, I think, needs to be part of the FDA change, as well.
But, delaying that, I think, would be a big problem.
Senator Harkin. See, now, you and I are coming at this a
little differently. You want to change the culture at FDA. And
I've been here long enough to think I'm not certain we can do
that. I mean, it's just--it's just very difficult to do that,
okay? It's just difficult.
Yes.
Colonel Larsen. Sir, I think leadership is one way to do
that. And I know Dr. Peggy Hamburg has said we've got to stop
looking at things in black and white and the various shades of
gray, which is some of the things that Eric's talking about.
And so, I have great confidence in what she's saying.
I am intrigued about your comments, though, because I went
through this, sir, with Goldwater Nichols, which is one of the
finest things that ever came out of the U.S. Senate, in terms
of national security. And we didn't do away with the Army, Air
Force, Navy, and Marines, but we did build a structure where
they could work together far better.
Senator Harkin. That's right.
Colonel Larsen. And maybe what FDA needs the most is enough
money to do the job properly. They're too small today. And you
said that yourself, sir.
Senator Harkin. That's absolutely true. For all that we put
on their plate.
Colonel Larsen. Yes.
Dr. Rose. I've proposed that the FDA actually create a
center for biodefense, like CDER, like CBER, where there's
actual leadership----
Senator Harkin. Okay.
Dr. Rose [continuing]. At a higher level. Because our
experience is that, when you bring these complicated products
to the FDA, by and large the review is done--I'm a surgeon by
trade--before it's done by the intern, instead of having senior
leadership engaged in the actual review early on, looking at
the raw data. And I think that having a full-blown center,
where there's a leader that is responsible for signing off and
guiding this, I think, could be very helpful.
Senator Harkin. Now, that's a good idea. I like that. You
got anything more on paper on that at all, any suggestions? Or
are you just----
Dr. Rose. We'll make sure you get it.
Senator Harkin. Or are you just thinking about that right
now?
Dr. Rose. No--well, I've proposed at the IOM in February,
but--there, it got shot down, but I hear it's getting some
traction.
I still think it's a good idea.
Senator Harkin. I kind of like it. Yes, get me some stuff
on that, will you?
Dr. Rose. Yes.
Senator Harkin. Get it to my staff?
Dr. Rose. Sure.
Senator Harkin. Before our reauthorization comes up.
Dr. Rose. Sure.
Senator Harkin. I'd like to start thinking about it now,
and looking at it.
Dr. Rose. Yes.
Senator Harkin. Yes. Okay. Well, anything else anybody want
to add to what we've said?
If not----
Yes.
Dr. Pavia. No, I'd echo what Eric Rose suggested, in that
you can't have the same people evaluating a drug for high blood
pressure that are evaluating a crucial drug for biodefense or
for an influenza pandemic, and yet, we need professionals to
look at the safety and efficacy. I think it can be done within
FDA, but not in the current structure. And I think Dr. Hamburg
has some very good ideas for redoing this. But, it may require
some statutory and legislative changes to let them do that and
to apply appropriate standards that match the risk that we're
facing.
CONCLUSION OF HEARING
Senator Harkin. Well, thank you all very much. I thought
this was very interesting and intellectually challenging, and
you gave us some good ideas and suggestions, and we appreciate
it very much.
And I look forward to getting that from you, Dr. Rose,
about this new structure.
So, thank you all very much.
Anything else? No.
The subcommittee will stand recessed.
[Whereupon, at 4:03 p.m., Thursday, September 29, the
hearing was concluded, and the subcommittee was recessed, to
reconvene subject to the call of the Chair.]
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